May 24, 2017 Epi4Dogs "Managing SID in EPI dogs"
The topic of managing SID (small intestinal dysbiosis) formerly known as SIBO, in EPI dogs is vast, variable and ever evolving. Over the years, working with veterinarian researchers around the world and also listening to over 3,000 actual EPI pet parents, much information has passed through this website. We, at Epi4Dogs are proud of the fact that we can and do revise information when more advanced technology is available, more in depth research is done, and as soon as we have permission to do so, we can share the findings with you.
Epi4Dogs objective is to present the very best and most thorough information on EPI by including as much actual and pertinent veterinarian research supporting what we suggest. Too many sites will give recommendations as absolute truths based on human studies and although there are many similarities between the dog and human... there are differences that do affect how things are processed. This is why Epi4Dogs cites veterinarian canine studies, preferably related to EPI when possible. We also strongly recommend that pet owners share with their vets everything that is suggested. We may be the largest resource of EPI and have the only EPI database, however this does not take the place of a vet. An EPI patient's vet and owner best knows that individual EPI patient' history and any other possible health concerns, contraindications, etc. An EPI dog (or cat) will best be served when everyone works together and shares information.
With regards to managing SID. Years ago, vets prescribed Metronidazole (in the USA) that sometimes worked and sometimes didn't. Back then they didn't know what else to try. They now know more.... much more! Over the years, Tylosin Tartrate (Tylan) has evolved as a better antibiotic in most cases to address the bugs in the gut. Although at that time it was presumed that the gut was overloaded with bad bacteria. Since then they have further discovered that is not true either. Now they understand that there is an imbalance of bacteria and that the health of the host and it's interaction / synergy with the gut flora is also key. However, with antibiotics that do work on SID, sometimes once the course of antibiotics is completed there is a relapse called ARD (Antibiotic Responsive Diarrhea) or TRD (Tylosin Responsive Diarrhea). When SID continues to return, Epi4Dogs recommends a repeat course of antibiotics (Tylan is the preferred drug, given twice a day for 6 weeks) and a change in the diet. These recommendations are from multiple veterinarian research, that is also included on this site. It has also been observed that sometimes instead of stopping the antibiotics completly when the antibiotic course is completed, some dogs do better if slowly withdrawn from the antibiotic. Another point of interest is if the dog does not show noticeable improvement within 7 to 10 days on the antibiotic prescribed (usually Tylan) then continue the course of antibiotic with a different antibiotic (usually Metronidazole). The opposite is also advised. If starting with Metronidazole and there is no noticeable improvement within 7 to 10 days, then stop the Metro and continue the antibiotic course with Tylan. Sometimes, even after trying all of the above, some dogs simply have to be placed on a reduced maintenance dose of antibiotics for life. However, in a recent study, dogs with SID were divided into two treatment groups. 1/2 received FOS (Fructooligosaccharides) a dietary prebiotic, 1/2 received Tylan (antibiotic). Both groups improved. However some in the antibiotic group relapsed, but those in the FOS group continued to do well. Is FOS a possibility? maybe.
Epi4Dogs and various Veterinarian Medical Schools continue to together in an effort to find maybe even a better way to address SID than with antibiotics.
As you can see, "how to" manage SID is a work in progress! With the onset of the study of Microbiome they are now discovering amazing things but realize they have so much more to discover. For example, even bacteria that we considered "bad" has it's place (in the correct concentration) in the gut. The other thing they have very recently discovered is that some of the bacteria strains that are overall key to good health in the dog.... are different from humans. In sick dogs, the variety of bacteria strains are less, what you feed a dog does make a difference and can change the gut flora composition, different composition preferences appear with different diseases, not all diseases will respond accordingly to the same set of probitoics. Some life situations that occur may forever destroy certain bacteria strains, and yet not affect others.
The premise of probiotics sounds good, but they may or may not work depending on the individual dog's gut flora and health situation. Most probiotic research is based on humans, not dogs and they now know there is a difference between the two. Obviously more studies are needed specifically on dogs so that there is a better understanding of which probiotics might be more appropriate for which condition, habits, and dietary concerns. If probiotics are given, what is known is to also give a prebiotic for a much better response.
Prebiotics have been shown to make a difference with SID in dogs. A major difference between probiotic and prebiotics is that prebiotics do not depend on the specific gut flora composition like probiotics do. Prebiotics is a food source for probiotics and it also manufactures it's own necessary probiotics too. However, as beneficial as prebiotics are, too much can also cause a gastrointestinal issues/discomfort. There are different types of prebiotics, some commercial diets currently include FOS ( Fructooligosaccharides ) in moderation which may benefit a dog with SID. Slippery Elm has prebiotic properties but to what degree and why it appears to help in most but not all cases. Is it the prebiotic composition? the vitamins & minerals?, the mucilage? or the SCFA "Butyrate" in the composition? Further investigation is needed.
And last but not least.... veterinarian researchers well versed in Microbiome studies are re-visiting fecal transplants as another option to treating SID. This is mostly based on successful trials with humans dealing with SID and some cases of fecal transplants in dogs. But how often does this affordable procedure need to be done? We don't know yet, just that we are seeing success with the cases that have been done.
There are now many more choices on how to manage SID in the EPI dog.... but there are no guarantees. Please read the research articles on this site as there is a wealth of information, and much that is not readily known but may be beneficial. The best treatment any EPI dog (or cat) can receive is when both the vet and the pet owner work together sharing valid, veterinarian research. Assess an individual dog's application, observe, keep notes and ascertain what works and what doesn't for that individual dog.
Olesia Kennedy, President, Epi4Dogs
May 24, 2017
June 2017 Epi4Dogs collaborated and co-authored with Texas A&M Gastrointestinal Lab on TWO research projects. Abstracts below:
1. Dogs with Exocrine Pancreatic Insufficiency have Dysbiosis and Abnormal Fecal Lactate and Bile Acid Concentrations
A.B. Blake1, B.C. Guard1, J.B. Honneffer1, F.G. Kumro1, O.C. Kennedy2, J.A. Lidbury3, J.M. Steiner1, J.S. Suchodolski3
1Gastrointestinal Laboratory, College of Veterinary Medicine, Texas A&M University, College station, Texas, USA, College Station, TX, USA, 2Epi4Dogs Foundation, Inc., Farmville, VA, Farmville, VA, USA, 3Gastrointestinal Laboratory, Texas A&M University, College station, TX, USA
It has been reported that dogs with exocrine pancreatic insufficiency (EPI) commonly have intestinal dysbiosis. However, the effects of EPI on microbial metabolism are poorly understood. The aim of this study was to compare fecal dysbiosis as well as fecal lactate and bile acid concentrations between dogs with EPI and healthy control dogs.
Fecal samples were collected from eleven dogs with EPI that had not received antibiotics for at least 3 weeks and had been on enzyme supplementation for 0.5–10 years (median 5 years). Fecal samples from healthy dogs (n = 18), collected for three consecutive days and pooled, served as control samples. DNA was extracted and analyzed by qPCR for selected bacterial groups and data expressed as Dysbiosis Index (as previously reported). Fecal lactate was measured by enzymatic methods (D-/L-lactic acid kit, R-Biopharm) and bile acids were quantified with gas chromatography/mass spectrometry from lyophilized feces. The Mann-Whitney U test was used to compare the Dysbiosis Index and fecal lactate and bile acid concentrations between dogs with EPI and healthy control dogs. Correlations were assessed using Spearman's correlation coefficient and significance was set at P < 0.05.
Dogs with EPI had a higher Dysbiosis Index (median [min-max]: +3.08 [−7.29 to +7.62]) than healthy control dogs (−3.81 [−7.57 to +3.32]; P = 0.0232). Total fecal lactate concentrations were increased in dogs with EPI (3.44 mM [0.71–158.30 mM]) compared to healthy control dogs (1.14 mM [0.54–6.64 mM]; P = 0.0037). The proportion of secondary bile acid was lower in dogs with EPI (70% [6–96%]) compared to healthy control dogs (93% [12–97%]; P = 0.0431). There was no correlation between any measurements and duration of enzyme therapy.
In conclusion, this study identified differences in the fecal microbiota as well as fecal lactate and bile acid concentrations between dogs with EPI and healthy control dogs.
2. Fecal Fatty Acid Concentrations in Dogs with Exocrine Pancreatic Insufficiency Receiving Enzyme Supplementation
J.B. Honneffer1, A.B. Blake1, J.C. Parambeth1, O.C. Kennedy2, B.C. Guard1, J.A. Lidbury3, J.M. Steiner1, J.S. Suchodolski3
1Gastrointestinal Laboratory, College of Veterinary Medicine, Texas A&M University, College station, Texas, USA, College Station, TX, USA, 2Epi4Dogs Foundation, Inc., Farmville, VA, Farmville, VA, USA, 3Gastrointestinal Laboratory, Texas A&M University, College station, TX, USA
Exocrine pancreatic insufficiency (EPI) is a disease characterized by insufficient synthesis and secretion of pancreatic enzymes by the exocrine pancreas, resulting in malassimilation of macro-nutrients. For example, insufficient pancreatic lipase prevents normal digestion of dietary fat. Consequently, EPI would be expected to be associated with excessive fat (e.g., fatty acids) remaining in the feces. Treatment of EPI includes oral supplementation of pancreatic digestive enzymes and is often effective at decreasing severity of clinical signs, but it is unclear if assimilation normalizes concomitantly. This study evaluated fecal fatty acid (FA) concentrations in dogs with EPI undergoing enzyme supplementation. The hypothesis of this study was that fecal fatty acid concentrations would be increased in dogs with EPI compared to those of healthy dogs, even when being treated with enzyme supplementation.
Fatty acid concentrations were quantified in fecal samples from 34 dogs diagnosed with EPI that were being treated with pancreatic enzyme supplements and from 82 healthy control dogs using an in-house gas chromatography/mass spectrometry (GC/MS) assay. Target analytes included palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1ω9), linoleic acid (18:2ω6), α-linolenic acid (18:3ω3), gondoic acid (20:1ω9), and erucic acid (22:1ω9). A Mann-Whitney U test was used for comparison between groups. P-values were adjusted for multiple comparisons and statistical significance was set at P < 0.05.
Fecal FAs were significantly increased in the feces of dogs with EPI (all P < 0.001). Concentrations of FAs for dogs with EPI vs. healthy control dogs were (median [min-max] μg/mg of lyophilized feces): palmitic acid (12.0 [1.6–48.4] vs. 4.2 [1.3–13.4]), stearic acid (6.6 [1.1–43.2] vs. 2.3 [0.9–14.4]), oleic acid (13.8 [1.8–70.2] vs. 4.0 [0.3–16.9]), linoleic acid (10.3 [1.7–34.5] vs. 4.0 [0.4–29.7]), α-linolenic acid (1.0 [0.2–5.5] vs. 0.4 [0.1–3.5]), gondoic acid (0.69 [0.10–2.36] vs. 0.19 [0.03–0.61]), and erucic acid (0.07 [0.02–0.96] vs. 0.03 [0.01–0.27]). The sum of measured fecal FAs was 46.8 [9.0–174.6] vs. 15.3 [4.0–61.3].
Fecal fatty acid concentrations were increased in dogs with EPI, even while being treated with pancreatic enzyme supplementation. These data are consistent with malassimilation of fat in these patients.
ANTIBIOTICS (supporting research)
9/2013 Tylan dosing has been revised to Tylosin (25 mg/kg BID for 6 weeks)
Epi4Dogs has and will continue to recommend/suggest Tylan twice a day for 30-45 days based on TAMU's EPI / SID protocol... and we will continue to refer to the research publication by Dr. Jorg Steiner/TAMU (article on our SID/SIBO page that references this) unitl new/better research suggests otherwise. http://www.epi4dogs.com/sidsibo.htm
2015 SMALL INTESTINAL DYSBIOSIS (by Dr. Jorg Steiner (TAMU: Texas A&M Gastrointestinal Lab/ USA) (below) presented at IVIS Conf
HOW I TREAT - SMALL INTESTINAL DYSBACTERIOSIS http://www.vin.com/apputil/content/defaultadv1.aspx?pId=12886&catId=57109&id=7054720
Jörg M. Steiner, Dr.med.vet., PhD, DACVIM, DECVIM-CA
College Station, Texas, USA
Oxytetracycline (10-20 mg/kg BID to TID for 4-6 weeks) used to be the therapy of choice. Unfortunately, oxytetracycline for oral use has become largely unavailable. Tylosin (25 mg/kg BID for 6 weeks) is the new antibiotic agent of choice...... (see below for complete presentation.
April 9-11, 2015 IVIS conf, Dr. Jorg Steiner, TAMU Gastrointestinal Lab presented the following on SID/SIBO (prevalent in EPI dogs) http://www.ivis.org/proceedings/voorjaarsdagen/2015/30.pdf
2009 Study by Dr. Jan Suchodolski from Texas A&M Gastrointestinal Lab
Accessed from BMC Microbiology. Open Access
he effect of the macrolide antibiotic tylosin on microbial diversity in the canine small intestine as demonstrated by massive parallel 16S rRNA gene sequencing
Department of Clinical Veterinary Sciences, Helsinki University, Helsinki, Finland
BMC Microbiology 2009, 9:210 doi:10.1186/1471-2180-9-210
The electronic version of this article is the complete one and can be found online at:http://www.biomedcentral.com/1471-2180/9/210
Tylosin-responsive diarrhea (TRD) is a syndrome that includes all cases in which tylosin antibiotic treatment has had a positive effect on treating dogs with intermittent or chronic diarrhea. Antibiotic treatment often leads to resolution of clinical gastrointestinal (GI) signs, and thus the term antibiotic-responsive diarrhea (ARD) was coined. Recently, trials have been published in which tylosin proved to be particularly effective in treating dogs with chronic or intermittent diarrhea, with the effect of tylosin differing from that of other antibiotics, thus indicating that the more newly established term TRD is more appropriate than ARD.
Tylosin is a macrolid, bacteriostatic antibiotic that has activity against most Gram-positive and Gram-negative cocci, Gram-positive rods and Mycoplasma. However, the Gram-negative bacteria Escherichia coli and Salmonella spp. are intrinsically tylosin-resistant. Tylosin is used only in veterinary medicine, and its most common indications are treating pigs with diarrhea or poultry with chronic respiratory diseases. Tylosin has also been used as a feed additive in food animal production, and it has been shown to increase gain and feed efficiency, especially in pigs. Debate about the mechanisms underlying tylosin-mediated growth enhancement is ongoing.
Tylosin is usually used in powder form for pigs and poultry. In Finland and in some other countries, tylosin is also available in tablet form, facilitating its use in dogs.
Our experience with tylosin is derived from numerous studies with dogs suffering from exocrine pancreatic insufficiency (EPI).These studies have clearly shown that tylosin has a favorable effect as a supportive therapy on dogs with EPI.
In Finland, tylosin has for years been the most common drug in the treatment of unspecific intermittent or chronic diarrhea in dogs. Anecdotal reports by veterinarians and dog owners reveal that many dogs with diarrhea respond well and quickly to tylosin treatment, generally within a few days of initiation of treatment. When treatment is discontinued, however, diarrhea reappears in many dogs within a matter of weeks or months. Some dogs need a treatment over very long period. Even so, the effect of controlling diarrheal signs does not appear to diminish with time, and thus there is no need to increase the dosage of the medication. No apparent tylosin-associated adverse effects have been reported.
TRD can affect dogs from all breeds and ages but is most often seen in middle-aged, large-breed dogs. The diarrea signs appear often as intermittent but progressivly become more frequent and end as persistent diarrhea. Abnormal loose fecal consistency is the predominant sign. The majority of the owners describe their dogs' feces as watery and/or mucoid indicating that TRD affects both the small and large bowel. Increased frequency of borborygmus and flatulence are also typically seen. Vomiting is occasionally seen during the diarrheal outbreaks.
In dogs with TRD the blood parameters are usually normal. Also the abnormal findings in diagnostic imaging studies and histological examination of intestinal biopsies, are only mild or completely absent.
Only a few studies on treating diarrheal signs in dogs with tylosin have been published. Van Kruiningen, (1976) reported more than 30 years ago that tylosin had a good effect in treatment of unspecific canine diarrhea. Recently, our study group performed two clinical trials to obtain more information on TRD. The first study included 14 adult pet dogs of 12 different breeds. Each dog's diet remained unchanged throughout the study. The dogs had shown chronic or intermittent diarrheal signs for a period of more than one year. Diarrhea had been successfully treated with tylosin for at least six months, and the treatment had been discontinued at least twice but the signs had always occured. When the study commenced, all dogs had been on tylosin for at least one month and were otherwise healthy. Thereafter, tylosin was discontinued and the dogs were monitored for a period of up to one month to determine whether signs of diarrhea would reappear, as suggested by the clinical history. Diarrhea reappeared in 12/14 dogs (85.7%) within 30 days. During the treatment trial diarrhea ceased with tylosin in all dogs within three days and in most dogs within 24 hours. In contrast, prednisone did not completely resolve diarrheal signs, and the probiotic Lactobacillus rhamnosus GG did not prevent the relapse of diarrhea in any of the dogs.
In the second study in an experimental dog colony, seven beagles showed signs of chronic diarrhea for at least one month. The dogs were treated with tylosin for ten days. During the treatment period the feces became significantly firmer, although they remained unacceptably loose. When the treatment was discontinued, diarrhea reappeared within three weeks. Treatment with other antibiotics (metronidazole, trimethoprim-sulfadiazine, or doxycycline) or with prednisone had almost no effect on fecal consistency, the feces remaining abnormally loose in all dogs. The diet was then changed for a ten-day period from a highly digestible moist pet food to a dry food developed for normal adult dogs. The feces again became significantly firmer, although they remained loose in some dogs. The dry food period was then extended to three months, but the fecal consistency continued to fluctuate from ideal to diarrhea. Since the consistency was not satisfactory, the dogs were treated a second time with tylosin for ten days. The feces then became normal in consistency and remained so throughout the entire three-month follow-up time. The study revealed that in the experimental dogs with chronic diarrhea the fecal consistency became significantly firmer both with tylosin treatment and with dietary modification. Neither of the treatments alone was sufficient to obtain ideal fecal consistency, but when the dogs were treated simultaneously with both regimes, permanent ideal fecal consistency was attained. The study thus indicated that tylosin and feeding regimes have synergic effects.
The etiology of TRD remains obscure. Since tylosin is an antimicrobial agent, it has been speculated that some pathogenic bacteria are likely responsible for the diarrheal signs. Based on negative culture results and ELISA tests, we have excluded such common enteropathogenic bacteria as Clostridium perfringens, Clostridium difficle, Salmonella spp., Campylobacter spp. , and Yersinia spp. as causative factors for the diarrheal signs occurring in TRD. Less well-defined species causing diarrhea in dogs, such as Plesiomonas shigelloides, Lawsoni intracellularis, and Brachyspira spp., have also been excluded.
Our ongoing studies have revealed that administration of tylosin leads to significant but transient changes in the composition of the small intestinal microflora. The results support the hypothesis that tylosin promotes the growth of beneficial commensal bacteria, while suppressing deleterious bacteria.
Besides antibacterial properties, tylosin may possess anti-inflammatory properties, contributing to its effectiveness in treating canine diarrhea. The mode of action must differ, however, from the immunomodulatory effect of prednisone because prednisone treatment did not completely resolve diarrheal signs in the same dogs that responded to tylosin.
The diagnostic protocol used for dogs with chronic diarrhea by the Faculty of Veterinary Medicine, University of Helsinki, is represented in Figure 1. In patients with chronic diarrhea, every effort should be made to achieve a diagnosis to enable a specific therapy. Unfortunately, this is not always possible in which case empirical therapeutic trials are used in the workup of these patients. There are conflicting opinions about how long an empirical therapy should be attempted. We recommend ten days if a dog has chronic diarrhea or if the interval between intermittent diarrheal episodes is only a few days. If signs of diarrhea disappear or are relieved during this period, the treatment should be continued another 2-6 weeks. When the interval between episodes of intermittent diarrhea is long, i.e. more than one week, the length of the empirical treatment period should be prolonged. The workup protocol displayed in Figure 1 for patients with chronic or intermittent diarrhea is applicable to most veterinary practices. It is also useful regardless of whether the clinical signs are typical of large- or small-intestine disease. The prevalence of diseases that can simultaneously affect the small and large intestines is high.
The initial evaluation (A) comprises obtaining a thorough case history (A1), conducting a physical examination (A2), and taking the basic laboratory tests, including a complete blood count, a serum chemistry profile, and measurement of serum concentrations of trypsin-like immunoreactivity (TLI) (A3). According to the initial examination, the patients are then divided into two groups. The first group includes patients showing clinical abnormalities in addition to diarrhea (Group B), while the second group shows no obvious abnormalities other than diarrhea (Group C).
Patients with obvious abnormalities (B) suffering from systemic disorders with secondary diarrhea (B1a), such as hepatic failure, renal failure, hypoadrenocorticism, and EPI (B1b), should be identified before starting trial therapies. Also if hypoproteinemia (B1c), melena and/or anemia (B1d), or abnormal palpation findings (B1e) are found, the reason for these abnormalities should be examined.
Dogs with diarrhea but no other abnormalities (C) are treated orally with fenbendazol 50 mg/kg for three days (C1) to rule out endoparasites as the causative factor for GI signs.
Food is probably the most common cause of diarrhea (C2), and adverse food reaction should always be excluded before empirical treatment trials with different drugs are initiated. Opinions vary widely about how the diet should be changed for a dietary treatment trial. Unfortunately, current recommendations are largely based on anecdotal evidence rather than on controlled trials. The most common recommendation is to use a diet with novel protein and carbohydrate sources, with the former restricted to a single animal source.
If modifying the feeding regime fails to produce a satisfactory fecal consistency, the next step is to treat the dog with tylosin 25 mg/kg BW q24h (C3). Dogs responding to tylosin treatment will usually do so within 3-5 days, and diarrhea will remain absent as long as treatment continues. In many dogs, diarrhea will reappear within some weeks upon discontinuation of treatment. If diarrheal signs reappear, the dog owner should change the dog's diet once again to make sure that the feeding regime is not involved in the etiology of the signs. If diarrheal signs continue, tylosin treatment is re-initiated. The effect of tylosin does not appear to diminish even in dogs that have been treated for years. The dose of tylosin for long-term use should be tapered to the lowest possible dose that controls clinical signs. Many dogs need only half of the recommended dose.
Although no adverse effects during tylosin treatment have been reported, efforts should be made to reduce the use of tylosin. This is because our recently conducted studies have indicated that tylosin causes wide resistance to antibiotics in the intestine (unpublished results). Certain probiotic lactic acid bacteria (LAB) have been shown to be effective in the prevention and treatment of a variety of diarrheal disorders in humans and in experimental mouse models. Hopefully in the future a probiotic LAB can be used instead of tylosin to treat or prevent chronic diarrhea in dogs with TRD.
With dogs not responding positively to dietary modification or tylosin treatment diagnostic imaging studies (D) should be performed and the workup continued as displayed in Figure 1.
Figure 1. Diagnostic approach to dogs presenting with chronic diarrhea at the Veterinary School in Helsinki, Finland. (click on figure to enlarge)
1. Westermarck E, Skrzypczak T, Harmoinen J, Steiner JM, Ruaux C, Williams DA, Eerola E, Sundbäck P, Rinkinen M. Tylosin-responsive chronic diarrhea in dogs. J Vet Intern Med 2005;19:177-186.
2. Westermarck E, Frias R, Skrzypczak T. Effect of diet and tylosin on chronic diarrhea in beagles. J Vet Intern Med 2005;19:822-827.
3. Westermarck E, Wiberg M. Exocrine pancreatic insufficiency in dogs. Vet Clin Small Anim 2003; 33: 1165-1179.
4. Van Kruiningen HJ. Clinical efficacy of tylosin in canine inflammatory bowel disease. J Am Anim Hosp Assoc 1976;12:498-501.
** For EPI dogs with SID (SIBO) the current "general" recommendation (in the USA) is a 30-45 day course of Tylan (first choice) to treat SID ...also referred to as SIBO / ARD /TRD **
9/30/2013 Revised Tylan dosage recommendation
TYLAN DOSING TABLE
Weight of Dog
Amount of Tylan to be given 2x/day
Mgs per tsp
New dosing recommendation
Maintenance ? as low as 5mg/kg **
Really Big Dogs
Aria the Tiger
* Conversion ratio is 2.2lbs=1kg. Numbers have been rounded. It should be noted that Tylan is very forgiving.
** For dogs that need to stay on Tylan for longer periods, you can try to get the dose as low as possible.
Dr. Westermarck "suggests" that a level as low as 5 mg/kg (2.5 mg/lb) once daily could work for some dogs.
In cats, the usual Tylan dose is 2.5 to 5 mg per pound (5 to 10 mg/kg) every 12 hours.
(previously recommended dose) Tylan Dosage for Dogs (administer twice daily with food) ....with 100g Tylan powder
30 lbs - 1/8 tsp
60 lb - 1/4 tsp
90 lb - 3/8 tsp
120 lb - 1/2 tsp
1/8 teaspoon of Tylan powder = 375mg
The new recommendation is Tylosin (25 mg/kg BID for 6 weeks)
For those interested in ordering Tylan in capsules, you can request to have this done at a "compounding pharmacy" in your area. To find a compounding pharmacy in your area (in the USA) please click on this "Pharmacy Compounding Accredited Board" link which lists them according to state: http://www.pcab.info/find-a-pharmacy.shtml
Encapsulating powder yourself is also an option. For examples of encapsulating machines see this forum thread: http://www.epi4dogs.com/apps/forums/topics/show/4148905-capsule-production-lab
Read more: Metronidazole Dose for Dogs | eHow.com http://www.ehow.com/about_5471971_metronidazole-dose-dogs.html#ixzz1aOG5iDPw
Metronidazole (Flagyl) Dosage for Dogs (administer twice daily with food) Vets usually recommend dosing dogs with 15 mg of metronidazole per kilo weight (2.2 lbs.) of the animal twice a day. This means that a 40-pound dog will can take 250mg of Metronidazole (technically 272 mg) twice a day with food 12 hours apart
TREATMENT (by Dr. Jorg Steiner - May 2010)
HOW I TREAT - SMALL INTESTINAL DYSBACTERIOSIS
Jörg M. Steiner, Dr.med.vet., PhD, DACVIM, DECVIM-CA
College Station, Texas, USA
Oxytetracycline (10-20 mg/kg BID to TID for 4-6 weeks) used to be the therapy of choice. Unfortunately, oxytetracycline for oral use has become largely unavailable. Tylosin (25 mg/kg BID for 6 weeks) is the new antibiotic agent of choice. Other antibiotics, such as metronidazole can also be used. Some dogs respond to therapy rapidly and do not have a recurrence. However, other dogs do not respond to antibiotic therapy alone. If there is no marked improvement after 2 weeks of appropriate antibiotic therapy further work-up is necessary. Some dogs may respond to therapy with a complete resolution of clinical signs but may have a recurrence of clinical signs as soon as antibiotic therapy is discontinued. These patients require further diagnostic work-up. In some of these patients a specific underlying cause of the dysbiosis can be identified and treated accordingly. However, in some dogs no specific cause can be identified and prolonged, maybe even life-long, antimicrobial therapy is required.
If serum cobalamin concentration is decreased below the lower limit of the reference range
cobalamin should be supplemented parenterally.
Probiotics have garnered a lot of interest in both human and veterinary medicine. Initially, probiotics were mostly embraced by holistic physicians and veterinarians and the expectations for probiotics were dramatic, with probiotics being hypothesized to be of benefit in disorders ranging from stress to gastrointestinal health, weight management, and even the prevention of cancer. These unrealistic expectations have been replaced with well-defined requirements for probiotics and controlled studies of their beneficial effects.
The three key requirements for a probiotic for use in dogs are:
1) the probiotic must be safe;
2) the probiotic must be stable; and
3) the probiotic must be efficacious.
In a recent study, 8 veterinary and 5 human probiotics were evaluated and only 2 of the 13 products contained the strains and concentrations of those strains indicated on the label.2 Several of the products contained bacterial species that could potentially act as pathogens. Thus, in order to ensure safety, the probiotic product should adhere to strict production and storage requirements. The probiotic also must be stable throughout transport and storage until the product is being administered by the pet-owner. In order to ensure that a certain number of colonies are administered to the patient, the colonies in the product should neither proliferate nor die.
Finally, a probiotic must be efficacious. In order to be efficacious, the bacteria must reach the intestinal lumen. This requires that the bacterial species being used in the formulation are both acid- and bile-acidresistant. Also, the bacterial species of the probiotic preparation should adhere to the intestinal mucosa to prolong the time of interaction. Finally, the presence of the probiotic species must have beneficial effects in the host. Several controlled studies have been conducted in dogs that also show that certain probiotics carry health benefits in dogs with gastrointestinal disorders.
Prebiotics are substances that preferentially support the resident bacterial ecosystem of the
intestine. Basically, prebiotics are non-digestible food components (dietary fibre) that are being
fermented by intestinal bacteria. This can lead to normalization of the intestinal microbiota. In a
recent study the use of fructooligosaccharides (FOS) in the diet showed a lasting advantageous
effect.1 While this has not been evaluated as of yet, other prebiotics, such as inulin or beet-pulp
may also prove to be beneficial.
SIBO or ARD: What's in a Name?
E.J. Hall, School of Clinical Veterinary Science, University of Bristol, Langford, Bristol, England.
FROM: NAVC Proceedings 2007, North American Veterinary Conference (Eds). Publisher: NAVC (www.tnavc.org). Internet Publisher: International Veterinary Information Service, Ithaca NY (www.ivis.org),
Last updated: 13-Jan-2007.
The upper small intestine is supposed to be relatively sterile, and increased numbers of bacteria have been incriminated as a cause of intestinal dysfunction. This process has been called "small intestinal bacterial overgrowth" (SIBO), and is likely to occur secondary to partial obstructions, blind loops and exocrine pancreatic insufficiency (EPI), when bacteria can accumulate and ferment undigested food. Yet an idiopathic form of SIBO has been claimed in large breed dogs, especially young German shepherd dogs. The belief now is that true overgrowth does not exist in this syndrome, and that a more accurate term is "antibiotic-responsive diarrhea" (ARD) because it is characterized by the positive response to antibiotic therapy.
It is agreed that in all monogastric species, including dogs and cats, bacterial numbers in the intestine gradually increase towards the ileocolic valve, with the colon containing approximately 1013 organisms per gram of feces. The composition of the flora as well as numbers also changes along the tract, with a progressively increasing proportion of gram-negative and obligate anaerobic bacteria. Yet the assumption that the proximal small intestine in dogs is virtually sterile has been extrapolated from human gastroenterology. The numerical cut-off for normality of 1 x 105 colony forming units per milliliter (cfu/mL) total bacterial numbers or 1 x 104 cfu/mL anaerobes was based inappropriately on the numbers found in the human small intestine. While this is not quite as erroneous as believing that counting bacterial numbers in feces is representative of the situation in the small intestine, it has focused our attention on the wrong etiology.
Initially these cut-off numbers were considered valid because they matched results that were obtained by a methodology that was unfortunately flawed: duodenal juice samples were placed in transport medium and posted to a laboratory for enumeration, and undoubtedly, the number of viable organisms initially present were underestimated. Other workers then struggled to confirm this cut-off, with numbers up to 1 x 109 cfu/mL being reported in clinically healthy dogs. Yet when bacterial numbers in the duodenum of cats were first reported as up to 1 x 109 cfu/ml it was assumed that this was because cats were different, and that their carnivorous diet encouraged the growth of anaerobes, especially Clostridia, rather than the fact that the numbers actually reflected the true situation more closely because of better technique.
The technique of culturing and counting the numbers of organisms in the duodenum has been considered the ?gold standard? for diagnosing SIBO, but is actually technically demanding and prone to significant error.
Collection of duodenal juice is difficult, because in the anesthetized patient there is often very little fluid present endoscopically. The duodenum is a relatively smooth tube in dogs and cats, in contrast to the human duodenum where annular folds trap pockets of fluid. So at times when a lot of fluid is found, it seems most likely that this is recently secreted gastric, pancreatic or biliary fluid, and therefore not truly representative. It is also not uncommon to suck up tissue and blood when trying to collect juice, but the alternatives of flushing with sterile saline or trying to culture adherent bacteria from endoscopic biopsy specimens are also flawed if it is the absolute numbers of bacteria in the juice that are important. And even when a representative juice sample is obtained, unless it is collected and transported under anaerobic conditions for immediate plating-out many organisms, especially anaerobes, will die. Furthermore, counting is done manually on serial dilutions of samples and requires excellent microbiological technique. Finally, recent molecular techniques analyzing 16S bacterial rRNA in duodenal juice has identified a large number of organisms that are unculturable by conventional techniques.
In summary, the technique of bacterial quantitation of duodenal juice is so difficult and prone to error, not to mention labor-intensive and expensive, that it is not a technique that should be contemplated in practice.
Even ignoring the problems of methodology, is there any evidence that a true increase in bacterial numbers, ie, SIBO, can exist? In humans with blind intestinal loops constructed by radical bypass surgery, there is good evidence for numbers as high as 1012 cfu/mL, and clinical consequences (eg, diarrhea, raised serum folate, low serum cobalamin) are well documented. Similar overgrowth is seen when strictures (benign or neoplastic) prevent passage of ingesta. Blind loops are very uncommon in small animal gastroenterology but overgrowth probably occurs when partial obstructions in dogs and cats cause luminal contents to stagnate. Antibiotic-responsive diarrhea can be seen with a focal annular adenocarcinoma when the limited extent of the tumor would not be expected to compromise the residual intestine?s ability to compensate. Overgrowth has also been described in 100% of dogs with EPI, although these results were still based on quantitative duodenal juice culture. However, the lack of antibacterial pancreatic secretions and the presence of undigested food seem logical reasons for SIBO to develop, and the requirement for antibiotics in some patients with EPI before an optimal response to enzyme replacement support the idea of secondary SIBO.
There is general agreement that SIBO can occur secondary to blind loops, partial obstruction and EPI. The controversy exists concerning the syndrome seen in large breed dogs, previously termed idiopathic SIBO.
It has become evident that there is a great variation in bacterial numbers between individuals and even within individual patients on a daily basis. The influence of coprophagy on duodenal bacterial numbers has also largely been ignored.
But even if we could rely on duodenal juice culture for reliable results, the finding of similar numbers in clinically healthy dogs questions the relevance of absolute numbers. It has been suggested that it is the type of flora and/or how the host and flora interact that are more important than numbers. Indeed, dogs treated successfully with antibiotics do not necessarily show a decrease in duodenal bacterial numbers. Established reference ranges in cats are set higher, and idiopathic SIBO is not recognized. Hence idiopathic SIBO is probably a misnomer, although there are clearly dogs with diarrhea that respond to antibiotics.
Although we cannot confirm idiopathic SIBO by bacterial numbers, a characteristic syndrome is recognized in dogs, where no underlying cause for gastrointestinal signs can be found but the signs are controlled by antibiotics. It therefore seems more logical to refer to this syndrome as antibiotic-responsive diarrhea (ARD), because that is what it truly is, whilst the evidence for true SIBO is lacking. It is likely that the syndromes of ARD and SIBO are not strictly identical: some cases of ARD may actually have a specific but undiagnosed infection. However, the term ARD is more appropriate than idiopathic SIBO as we cannot reliably count bacterial numbers but we can see a response to antibiotics.
The causes of idiopathic / ARD are uncertain, but IgA deficiency is one potential mechanism that has been studied. Confusing reports concerning serum IgA concentrations in German shepherds are probably irrelevant, as it is the mucosal secretion of IgA that is clinically important. However, conflicting studies about whether fecal IgA deficiency exists have also been published. Recently four allotypes (A?D) of the canine IgHA gene, encoding IgA heavy chains with potentially different functionality, have been found in dogs. All German shepherds studied so far are variant C and no association between variant and disease has yet been shown.
Molecular studies have also suggested that ARD is associated with increases in pro-inflammatory cytokine mRNA expression yet without histologic evidence of inflammation. This has lead to the hypothesis that SIBO is a precursor of inflammatory bowel disease (IBD), although this remains supposition. Indeed quantification of cytokine mRNA expression by real-time RT-PCR, has cast doubt on those earlier, semi-quantitative studies.
The development of diarrhea is believed to be related to a number of mechanisms:
The syndrome originally termed idiopathic SIBO is characteristically a problem of young, large-breed dogs, especially German shepherds. It is not recognized in small dogs or aged dogs. It has also never been definitively identified in cats, although the efficacy of metronidazole in mild cases of IBD has never been fully explained. Chronic or recurrent diarrhea is typical, but some dogs show colitis-like signs. Most dogs are polyphagic and often coprophagic, but anorexia is sometimes seen and may be related to acquired cobalamin deficiency. Weight loss and/or stunting are seen in more severely affected dogs.
The diagnosis of SIBO is difficult as quantitative duodenal juice culture is flawed. In contrast, ARD is readily defined by the response to antibiotic, and the recent reports of tylosin-responsive diarrhea, are probably no more than another manifestation of ARD or an undiagnosed infection.
There have been attempts to find indirect tests for SIBO but none have been shown to be reliable markers of antibiotic responsiveness.
Historically SIBO was first identified in a group of dogs with chronic diarrhea all showing increased folate and decreased cobalamin serum concentrations. This resembled the pattern seen in humans with blind intestinal loops. All of the dogs were subsequently found to have increased bacterial numbers, and a specificity of 100% was claimed. However, further studies showed that this pattern of folate/cobalamin was only present in 5% of dogs with culture-proven SIBO. Thus with such a poor sensitivity, folate and cobalamin cannot be used to diagnose SIBO, although a low serum cobalamin does have a value as an indication to treat.
Intestinal bacteria are the sole source of breath hydrogen. Theoretically SIBO should cause increased breath hydrogen or at least an early peak of hydrogen excretion following ingestion of carbohydrate. Unfortunately the technique is technically demanding, and other causes of carbohydrate malabsorption and increased intestinal transit rate will cause similar abnormal results.
Intestinal bacteria can deconjugate bile salts, which are absorbed but then are poorly extracted by the liver and are therefore measurable in serum. Theoretically SIBO should cause increased serum unconjugated bile acids (SUCA). Unfortunately, SUCA concentrations fluctuate significantly after a meal, and since Lactobacilli are one of the major organisms able to deconjugate bile acids their relevance to disease is questionable.
The treatment of secondary SIBO depends first on treating any underlying cause, such as EPI. Idiopathic SIBO/ARD is treated simply by antibiotics. Oxytetracycline is the first choice in the UK but metronidazole, tylosin or amoxicillin may be equally effective. A response should be seen within 7 to 10 days and, if positive, antibiotics should be continued for up to 6 weeks. Some cases never relapse on cessation of treatment, others relapse months later and require a second course of antibiotics. But typically, dogs relapse within days of treatment finishing. In these cases an underlying cause should again be looked for, but ultimately repeated courses or continuous antibiotic therapy may be required. Surprisingly, it may be possible to reduce the dose and dosage interval. Whilst this is not considered best practice for antibiotic usage, and resistance is likely to develop, in reality it works.
Adjunctive therapy may be helpful, and mild cases may be controlled by diet alone. A highly digestible, low fat diet seems beneficial, but the inclusion of prebiotics such as fructo-oligosaccharides are logical although not yet proven. This syndrome is also a potential target for probiotic therapy. Acquired cobalamin deficiency should be treated with parenteral vitamin B12.
The following are May 2013 photo's of Cristina's EPI dog, Sadie's poo before and after treatment with Tylan for SIBO:
Sadie's poo prior to treatment with Tylan:
Sadie's poo after 1 week on Tylan:
Going forward, Tylan will now be available by prescription only!
Elanco confirmed that a script will now be required to purchase Tylan Powder in all USA states.
The FDA began an initiative in late 2013 because the label recommendation is for chickens, swine and honey bees (See FDA Regulation http://www.fda.gov/downloads/animalveterinary/guidancecomplianceenforcement/complianceenforcement/ucm113433.pdf
(Scroll to page 40 for specific mention of Tylan USDA Residue listed as one of these drugs.)
The new required label detail is as follows: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=520.2640
There are multiple regulations and references on this matter with the FDA. Please feel free to click on the links above for more detailed information.
Previous scripts required by the state of California were regulated by the state and not the FDA.
Tylan is a Bacteriostat listed in the Macrolide Antibiotic Classification.
From what we have been told, places that are still selling Tylan which do not require a script, is nothing more than the overlap in stock and once that stock is used up scripts will be required.
With regards to the generic Tylan “Tylovet” a prescription is not required but this too may change.
Epi4Dogs is sharing this information with everyone as many purchase Tylan (tartrate) powder via a variety of on-line sources . Many depend on Tylan to keep EPI pets at optimal health. If you useTylan, please have a conversation with your vet with regards to prescription Tylan going forward. Please share with your vet the research that supports using Tylan for SID in EPI pets: http://www.epi4dogs.com/sidsibo.htm
In addition to Tylan antibiotic powder...... there is also Tylan capsules available ... if interested.... please have your vet look into Wedgewood Tylan capsules at:
In the USA, Tylan Soluble Powder (Tylosin Tartrate) is available through your veterinarian or can be purchased on-line at Amazon.com or most Pet Supply sites such as Lamberts to name a few.
If your vet in the USA does not carry Tylan (antibiotic for SIBO) you can still order it from the following places:
Lambert Vet Supply http://www.lambertvetsupply.com/Tylan_Soluble_Powder_100_gm-P39033.aspx
GENERIC TYLAN is also available:
GENERIC TYLAN AS A NON-PRESCRIPTION ANTIBIOTIC (same brand) also available:
Wedgewood TYLOSIN CAPSULES (USA) is now available in various strengths. Please have your vet contact Wedgewood for the proper dose: http://www.wedgewoodpetrx.com/items/tylosin-capsule.html
However.... locating a Tylan source outside the USA may be difficult.
EUROPE Attached is a medical list of various versions and strengths of Tylan from a European Medical Library (thank you Ann!!!!).
If you live in Europe and your vet is having difficulty locating Tylan Soluble Powder... please share this list with your vet and have your vet (and /or pharmacist) identify the most closely aligned version of Tylan to the USA source "Elanco Tylan (Tylosin Tartrate) Soluble Powder 100 grams tylosin base and for your vet or pharmacist to work out the proper dose - - as many of the Tylan products on this list are either Tylan phosphate or Tylan tartrate but also in many different strengths.
The proper dosing strength for the Elanco Tylan Soluble Powder 100 gram is located on a Tylan Dosing Chart on this page.
If you are in the UK..... you can get Tylan from the following places.... with a prescription from your vet (Thank you Esme for this information!)
Or have your vet directly contact the Bristol Vet School for a consult in EPi and a prescrip for Tylan powder for SID (SIBO). http://www.bristol.ac.uk/vetscience/
If you are in Australia and your vet does not think Tylan is available..... please have your vet check this out (Thanks Craig!!!):
Some manufacturer details for your vet if they need it (their rep should be able to get it easily. It is prescription only in Australia). Costs $80-90 and lasts ages.
Tylan Soluble 100
Elanco Animal Health.
A division of Eli Lilly Australia Pty. Ltd.
112 Wharf Road, West Ryde, N.S.W. 2114
Telephone Toll Free 1800 226 324
If you are in India...... you have access to 2 different products of Tylosin.. BUT you will need to talk to your pharmacist or vet to re-calculate the dosage since both of these other Tylosin products ARE NOT the same potency as the USA Elanco's "Tylan Powder"... hence why you will need your vet or pharmacist to re-calculate the dosage equivalent to the USA Elanco's "Tylan Powder".
2. Virbac; TROX SOLUBLE Powder Composition Tylosin Tartrate IP
(if the link below does not work... please copy it and paste in your browser and then it should work)
Copied from DiamondBack Pharmacy ( a Compounding Pharmacy) website and written by Giano Panzarella:
Tylosin’s strong anti-inflammatory properties come from it being made from natural bacteria. The drug works by interfering with the protein-manufacturing abilities of other bacteria, and it does this while not impacting the patient’s own ability to manufacture protein. Because Tylosin is a bacteriostatic antibiotic, it doesn’t kill off the bacteria in the patient’s bowel, it simply prevents it from growing and reproducing. By limiting the growth of the bacteria, the drug helps the patient to manage the infection using his or her own immune system.
*** Tylan is nasty tasting, so it can be either prepared for one at a compounding pharmacy such as DiamondBack or you can purchase the powder on-line or through your vet. ONLY THE POWDER FORM IS USED FOR SID/SIBO. There are multiple ways to camouflage the taste when giving to your dog or cat (see examples below on this page) ***
For years we have called it SIBO (Small Intestinal Bacterial Overgrowth).... but as more research has been THANKFULLY done..... it has been observed that there is a lot of "idiopathic SIBO" happening that does not exactly fit the SIBO criteria. So to better capture all cases of dogs and cats struggling with this condition, the veterinarian community has now renamed SIBO as SID. SID means "small intestinal dysbiosis". Dysbiosis means that there is a microbial imbalance.
Excellent article on SID and recent findings with regards to the microbials in the gut in dogs and cats in the
Journal of Animal Science by J.S. Suchodolski at Texas A&M :
MICROBES AND GASTROINTESTINAL HEALTH OF DOGS AND CATS
Tylan is very nasty - bitter tasting... some dogs will take it mixed in their meals... others will not...
Here on the epi4dogs forum we share creative ideas... often tips on saving money. Below is a great home-made idea by Maureen, Byrnn's mom on how to encapsulate Tylan powder without spending a lot of money:
Thanks Maureen... great idea!
"Here is a way to get Tylan down instead of putting it in the food. My Brynn stopped eating very early on because Tylan was on her food. So I got "00" gelatin capsules from a compound pharmacy, a block of florist foam from the dollarstore (and poked holes in it with a pencil), used a cake decorator tip as a funnel and measure out 1/8 tsp Tylan per capsule. There is still some room to add a pinch more if needed. I just pop these down her throat right before her meal. " - Maureen.
Similarly, inexpensive encapsulators and gel caps are available from health food stores or online at retailers like Amazon.
One size "00" size capsule equals 1/8 teaspoon of Tylan powder.
In some rare cases .... some dogs "may" have an adverse reaction to Metronidazole... especially if used long-term. The treatment is to stop the Metronidazole immediately.... but Valium may also be used as an antidote to Metronidazole poisoning. The following is an actual example of an Metronidazole poisoning with an EPI dog:
Dave & Linda, owners of Sasha
Our GSD, Sasha, was taking Metronidazole and was on her third round. I let her outside in the late evening to do her business before bedtime. Walking back to the house, she began to stumble and stagger, barely making it up the back porch steps. The best way to describe her walk was as if she were in a drunken stupor. Then when she came inside, she threw up four times. The fact that she had a hard time standing and walking really scared us, so my husband took her to an emergency vet center since it was already 10 p.m. After racking up a $1258 bill there, we received a call at 8 a.m. (Sasha was left there overnight) the next morning informing us our dog was getting worse, now not being able to stand at all and her eyeballs were rolling around in her head. They suggested we come pick her up and take her to another hospital to see a neurologist. Our poor Sasha had to be rolled out on a gourney and lifted and put in the back seat of our car.
After the 25 mile drive to the other hospital, techs lifted Sash out of our car and carried her in on a stretcher! She laid sideways on a mat on the floor as her eyes continued to roll in her head. It was heartbreaking, and we thought for sure we would lose her. The neurologist suspected Metronidazole toxicity but said he wanted to rule out a brain tumor or spinal infection so told us he wanted to perform an MRI on her head and do a spinal tap. We agreed to this but are always hesitant about anesthesia, especially with a dog in this condition.
This is where we made another costly mistake. In retrospect, looking up the side effects of Metronidazole, a rare side effect is built-up toxicity from it, of which Sasha had the exact symptoms - vomiting, unable to walk or stand, disorientation, the eyes rolling. Time and Valium is the antidote.
The MRI and spinal tap came back normal. so the vet started Sasha on Valium, and within 24 hours she made a remarkable improvement. We picked her up the next day and could not believe that was the same very sick dog we left there, as she waked right up to us with her tail wagging!
This was a $3,900 lesson. My point is if your pet is on Metronidazole and you notice any side effects that affect the central nervous system, Stop the metro immediately. Go to your vet for the Valium. We could have saved a lot of money if we would have gone this route at first. If after a day of the Valium there was no improvement, then the MRI and spinal tap would have been needed.
Hope our story helps someone. These scary and horrible side effects from the Metronidazole are rare, but they do happen, so be mindful of them if you pet is on this medication. I am also happy to add that Sasha doesn't appear to have any residual effects and was totally back to her normal self within a few days.
2014... Fecal Transplantation....a new old possibility .....
(please see page dedicated to this procedure: http://www.epi4dogs.com/fecaltransplant.htm
Clostridium perfringens is commonly recognized as a cause of diarrhea with mucus and blood in the dog. The purpose of this study was to determine if fecal transplantation could be used to cure Clostridium perfringnes infections that were not cured by treatment with Metronidazole and Amoxicillan trihydrate/clavulanate potassium.
PREBIOTICS, PROBIOTICS (supporting research)
Reprinted with Permission from Dr. Jean Dodds:
Please click on the "download article tab" to download the entire article for printing and sharing or just read the pages here... well worth it!
Taken in it's entirety from "Veterinary Practice News"
Posted: June 22, 2011, 2:40 p.m., EDT
While prebiotics and probiotics are often confused or thought of as one and the same, their commonalities end with their stint in the intestine.
Prebiotics are fiber that feeds the beneficial microorganisms residing in the intestine. Probiotics are live microorganisms that when ingested, can enhance intestinal microbial balance.
Prebiotics have been used in pet foods for decades, probably without pet owners even knowing it. But probiotics’ delicate handling needs means they’re sold in sachets and capsules. They are in something of a state of hibernation, according to Grace Long, DVM, MS, MBA, director of veterinary technical marketing for Nestlé Purina PetCare in St. Louis. The microorganisms become active when they enter the intestine.
“Probiotics are heat and moisture sensitive, so it would be very difficult to incorporate them directly into the kibble,” Dr. Long says.
“The most effective way of keeping probiotics alive in the packaging process is in a cool, dry environment away from air exposure. Not all probiotics sold in the veterinary market have evidence to support their claims, so veterinarians should make sure that the levels of microorganisms are guaranteed and that the manufacturer can provide support of efficacy.”
Label accuracy concerns prompted J. Scott Weese, DVM, DVSc, Dipl. ACVIM, associate professor in the department of pathobiology at Ontario Veterinary College, University of Guelph, in Ontario, Canada, to evaluate labels and bacterial contents of commercial probiotics marketed for use with animals.
In Dr. Weese’s study, 25 animal-marketed probiotics were purchased, labels were evaluated and bacterial contents were counted. Weese found that 21 products listed specific microorganisms. Expected bacterial numbers were listed for 15 products. To add to the suspicion of questionable probiotic efficacy, one or more organisms were misspelled on the labels of seven products.
Only four of 15 products tested met or exceeded their labels’ claims. Only two of these also had a label that properly described the contents, Weese says. He concluded that deficiencies in veterinary probiotic quality remain.
“Veterinary probiotics are less regulated than drugs,” says Joseph Bartges, DVM, PhD, Dipl. ACVIM, Dipl. ACVN, professor of medicine and nutrition at the University of Tennessee in Knoxville. “There’s less confidence that you are getting what the label claims. I believe in using probiotics in animals but I prefer to use one called VSL#3 marketed for human use because it contains 450 billion live bacteria per packet. This probiotic is manufactured by VSL Pharmaceuticals Inc.”
Animal food and supplement manufacturers interested in providing efficacious and effective probiotics perform in-house tests, sometimes evaluating hundreds of beneficial bacteria species before deciding which to use.
“We deal with one strain of bacteria in our probiotic,” says Amy Dicke, DVM, technical services veterinarian for P&G PetCare in Cincinnati. “After looking at 500 species and three clinical trials, bifidobacterium animalis AHC7 met our requirements for Prostora Max.”
In a Purina study, Enterococcus faecium SF68 (FortiFlora) minimized the incidence of diarrhea in a naturally occurring outbreak in kittens. While 60 percent of kittens fed the control diet developed diarrhea severe enough to be treated, only 9.5 percent of the kittens eating SF68 required treatment.
|Bifidobacterium animalis AHC7|
Photo courtesy of P&G PetCare
Probiotics are considered nutritional supplements as opposed to drugs. Although some veterinarians prefer to use medication to control diarrhea in patients, probiotics can be used in conjunction with medication or alone. Probiotics are finding their way into the standard protocol for managing dogs and cats with diarrhea.
“We are also encouraging veterinarians to recommend that clients keep a proven probiotic on hand for diarrhea, especially if their pets are prone to GI upset,” Long says.
Long points out that probiotics can even be used as a regular part of an animal’s diet to help support a good immune system. This is especially important in the young, the elderly and any pet with compromised health.
Probiotics are considered a nutritional supplement rather than a drug. Although some veterinarians prefer medication for controlling patients’ existing diarrhea issues, probiotics can be used in conjunction with medication or alone.
“We are trying to communicate to veterinarians that keeping a proven probiotic on hand for diarrhea is just like keeping Imodium in the cupboard,” Long says.
“Sometimes it’s hard for a veterinarian to develop a new habit when you are used to treating a condition in a certain way. When considering treatment for a patient with diarrhea, sometimes medicine can be faster, but probiotics can be used with drugs like Metronidazole.”
Long points out that probiotics can even be used to help support a good immune system.
“FortiFlora is packaged to be effective on any-sized animal,” Long says. “The only exception might be a veterinary recommendation to use two packets on a very large dog like a great Dane.”
Veterinarians and veterinary nutritionists say giant breed dogs generally have a poorer stool quality when compared to smaller breed dogs, making larger dogs another target group to benefit from probiotics.
“Large and giant breed dogs have decreased digestibility compared to small- and medium-size dogs,” says Brent Mayabb, DVM, manager of education and development of Royal Canin U.S. in St. Charles, Mo.
“About 7 percent of a small or medium dog’s weight is its GI tract, whereas a large or giant breed dog’s GI tract is only 2.5 percent of its entire weight, so it doesn’t have the same ratio as other dogs and generally has looser stools.
“Junctions between large-breed dogs’ intestinal cells allow minerals to pass back into the intestinal lumen after absorption. The minerals draw water with them, resulting in loose stools. A probiotic and a healthy diet containing prebiotics can help all dogs, and especially larger, dogs have better quality stools, in turn having a healthier GI tract.”
Dr. Mayabb says clients continue to ask their veterinarians about diet options and brand advice, which means veterinarians will be expected to be able to relay nutrition information to serve a variety of patient needs.
“Nutrition talk isn’t done enough during veterinary visits,” Mayabb says.
“In part, I think it’s because in the past, nutrition wasn’t a large part of veterinary school curriculum. Nutrition would be talked about in correlation with helping with certain diseases, but that’s about it. Now new grads focus more on preventive care, in which nutrition plays a huge role. I think we’ll see more of a shift in veterinary interest and subsequent owner interest in a healthy GI tract.”
“Think of prebiotics as functional food,” Dr. Dicke says.
“The right prebiotic will be resistant to digestive juices, selectively increase the number and activity of good bacteria and provide a health benefit. Prebiotics also have to stay in the intestine long enough for the bacteria to break it apart, basically attacking and fermenting it. This process releases short-chain fatty acids.
“Prebiotics are key components for intestinal cells, which create a barrier in the intestinal tract. This lining is important because it helps to keep bacteria in the intestinal tract and doesn’t allow it to travel to other areas of the body.”
While most everyone in the industry is optimistic about what probiotics can offer veterinary patients, there isn’t a consensus about the parameters.
For Kittens and Puppies
Nutramax Laboratories Inc., in Edgewood, Md., which markets Proviable–DC (capsules) and Proviable-KP (paste) for dogs and cats, says it learned that even puppies in the same litter had different microflora.
“Since different microflora is found even within the same litter of puppies, some may benefit from one bacteria while others benefit from another, so we use seven types of bacteria in our probiotic,” says Robert Devlin, DVM, senior director of the veterinary sciences division, Lancaster, S.C. “We have used our probiotic every day for 21 days in studies and found no change in bloodwork that shows a negative effect.”
The company also markets Bactaquin, an over-the-counter digestive health supplement for dogs that contains one bacteria strain.
“Everyone has a price-point,” Dr. Devlin says. “With inflated fuel prices and the bad economy, owners might make cutbacks. But effective probiotics that deliver 2 billion bacteria can be given for about 50 cents a day.”
Dicke says using puppy and kitten formulations containing prebiotics is an important part of ensuring a healthy GI tract from the beginning.
“Kittens’ and puppies’ intestinal bacterial balance begins forming when their mom licks them,” Dicke says. “The bacteria accumulated in the first couple of weeks of an animal’s life can ultimately affect their long-term bacteria colonization. When animals are orphaned or even when they have loose stools, a probiotic can help remedy the situation.”
Probiotics have an immune-boosting effect that is often discussed secondarily to their benefits in treating diarrhea, Long says.
“Very young animals have a fragile immune system and it’s not uncommon for them to have soft stools,” Long says. “Diarrhea can be very dangerous for young animals and providing a probiotic can help stablize the GI tract.”
Joseph Wakshlag, DVM, PhD, Dipl. ACVN, Dipl. ACVSMR, assistant professor of clinical nutrition at Cornell University College of Veterinary Medicine in New York, says that because little research exists about using probiotics in pediatric animals, veterinarians have to turn to research conducted in human medicine to make assumptions.
“Pediatric literature suggests that transdermal migration can cause sepsis in children who have used probiotics,” Dr. Wakshlag says.
“There hasn’t been documentation of this in veterinary medicine to date, but it just means it’s not impossible that there can be a negative to probiotic use. There’s been much more evidence to support the use of prebiotics than probiotics. But even there, some manufacturers throw everything but the kitchen sink in their products and pet owners may think that makes it a good food when it doesn’t. Manufacturers sometimes have ingredients in their foods that naturally contain prebiotics, but they add more like fructooligosaccharides and mannanoligosaccharides because owners are looking for that on the ingredients list.”
Dr. Bartges says additional evidence from human medicine suggests that asthma and other immune disease symptoms may decrease with probiotic use.
“No one knows for sure why or how probiotics help immune diseases aside from its role in changing GI tract bacteria,” Bartges says. “It’s possible the benefit comes from the immune system’s reaction and the systemic response.”
Manufacturers say ongoing research continues to improve existing products, broaden uses and enhance benefits. They say using proven products now will be an asset to any veterinarian’s tool box.
“We’re all still in the learning process with probiotics and how they can help with skin allergies and other issues that spur an inflammatory response,” Dicke says. “Certain probiotics or symbiotic combinations may be more effective on different medical conditions, but work is being done to find new ways to feed pets and use probiotics.”
The following is a list of "some" probiotics that have been used successfully with EPI dogs.... HOWEVER.... please note that not all probiotics will have the same result with every dog.... effectiveness depends on each individual dog's gut flora.... and unfortunately, they can vary dramatically from one dog to another.
What we at epi4dogs found what works best is to "try" a probiotic...... start with 1/2 the recommended dose and work up to a full dose within a week or two ... some dogs will have loose stools from the probiotic.. so you need to start slow. ALWAYS give probiotics 2-4 hours away from any antibiotic given. If your dog seems to be extra sensitive and not able to handle any of the suggested canine probiotic..... then start with a single strain "Acidophulis" (you can use human grade Acidophulis).... this particular probiotic strain seems to be tolerable by most all dogs....
Some of the Probiotic products used are as follows:
Acid reflux, wet burps, slight regurgitation…… sometimes our EPI dogs struggle with this and the easiest response is to just offer acid reduction drugs……. BUT this may not always be the best solution. It all depends on why the acid reflux issue is happening. What is not told to us is that some of these “acid reducers” often permanently alter the inhibition of gastric acid secretion, which is not such a good thing.
Acid is supposed to be in the stomach. Oftentimes, the real issue isn’t too much acid in the stomach, but rather too little of the right type of acid….. Of course there is much more to acid reflux such as why is the esophagus shortening, where is that acid going and why is it going there, sometimes there is a malfunctioning stomach valve, but for purposes of managing acid reflux in EPI patients, we will focus on the most common causes:
The two most common causes of acid reflux are:
· Inadequate stomach acid not able to process the food properly
· Inadequate digestive enzymes leading to improper digestion of food
Some triggers of acid reflux can be things like:
· Food sensitivities/allergies
· Gut flora imbalance (hmmmmmm…. Sound familiar???!)
· Some antibiotics
· Ileocecal valve dysfunction
· Environmental toxicities
· Blood sugar imbalances
What to try to help reduce the acid reflux???
Please be sure to try any of the "acid reducers" treatments above one at a time… give it 3-5 days to see if there is a positive or no change at all. As mentioned above, the most common cause of acid reflux is not too much acid, but not enough of the right acid…. HOWEVER….. If none of the above works, then the problem is more likely the less common cause of acid reflux, too much acid, in which case, an acid reducer is needed. Please talk to your vet about which product might be best suited for your pup: Pepcid AC (famotidine), Prilosec (omeprazole), ranitidine, cimetidine, sucralfate, etc....
Slippery Elm Resources:
In the USA:
(Buy loose powder in bulk)
STARWEST BOTANICALS: https://www.starwest-botanicals.com/category/slippery-elm-bark/?gclid=EAIaIQobChMIybqTiavP1AIVxiSBCh2iLQzQEAAYAiAAEgJQRfD_BwE
(Buy loose powder)
NOW (at AMAZON.COM) https://www.amazon.com/NOW-Slippery-Elm-Powder-4-Ounce/dp/B000UE25XQ/ref=sr_1_8_a_it?ie=UTF8&qid=1498061974&sr=8-8&keywords=slippery+elm
Slippery Elm "loose" powder is also available at Health Food Stores, Supermarkets that also cater to Health Food sections, and can be ordered from on-line Supplement Resources such as VitaCost, Swansons, etc.
In the UK:
(Buy loose powder)
NATURAL HEALTH FOR LIFE: http://www.naturalhealth4life.co.uk/medicinal-powders/98-slippery-elm-powder-various-weights.html
HOLLAND & BARRETT: http://www.hollandandbarrett.com/shop/vitamins-supplements/supplements/plant-sourced-supplements/slippery-elm/
Here is a recipe on how to make Slippery Elm Soup or Slippery Elm Tea as noted by a Holistic Vet, by Dr Yasson’s Guidelines for GastroIntestinal Troubles taken from this website: http://www.holvet.net/slippery_soup.html
ü **Slippery Soup™ / Slippery Elm Tea. I use this herb more than any other in my practice! It provides superb relief, and has kept many patients from hospitalization. It is a soothing nutritive herb which is perfectly suited for sensitive or inflamed mucous membrane lining of the digestive system. The bark contains mucilage and tannins that act as demulcent, emollient, protectorant, and astringent. You might think of it as a soothing internal bandage coating the digestive tract for its entire length. Imagine the relief for your pet to have a jelly-like coating soothing in an eosophagus (food pipe) burned by acrid vomitus, or in an ulcerated colon. This herb makes a huge difference. It is easy to make and has a very bland taste which makes it easy to add to tasty things.
ü Slippery Soup™ Preparation and Administration: You can find the herb in a dry powder form in capsules, as dried leaf in tea bags, or as loose dried leaf in the “bulk” products section of many health food stores. Any of these forms will do. Do not use the tincture (which already comes as a liquid in a dropper bottle). It may help in a few cases but it will not have all the healing physical properties of the brewed tea. The same goes for mixing the dried herb directly into the food. It will not give all the benefits of the brewed tea.
1. Simple Tea Method. You’ll prepare this medication just like a tea you might drink yourself. First, put a heaping teaspoon of dried herb in a coffee mug, and add 8-12 oz of boiling water or diluted broth. Allow to cool. If using capsules, open them up, discarding the shells, and note that it may take a bit less to get good results.
2. Long-Brew Method. To get more out of your supply or to create a thicker medicine use the same amounts of herb and water listed above and simmer for 10-20 minutes.
3. The resultant liquid, once cooled, should be somewhat thicker than water. If it is as thin as water double the dry herb amount next time, or try the long-brew method. If it is thick like jelly, that’s fine. You can use half of the dosages listed below. This makes it much easier to spoon feed reluctant patients! Do not worry about any loose herb in the liquid. It does not have to be filtered out. This infusion or decoction will keep for about 5 days in the fridge.
4. Add the liquid to the food at mealtimes, or add to the water bowl, or give as a treat. The goal is 4 doses per day, but even once daily will provide some relief. I hate to force feed anything. But this is one treatment that is probably worth it if you must. If force feeding is your only choice use the stove top brewing method and aim for a thicker, jellylike consistency so you can administer less physical amount for the same beneficial effect.
5. Palatability Tricks. To give Slippery Soup™ as a treat (my preferred way!) you can do several things. You can mix the liquid 50/50 withbroth, soup, a favorite canned food, milk, tuna juice, or baby food. It may not smell great to you, but these soups are highly appreciated by pets! You can also add it to yogurt or cottage cheese if dairy is not an issue.
6. Dose size (goal is 4 doses per day): We at epi4dogs find that giving 1 teaspoon of Slippery Elm once a day to a medium / large size dog and 1/2 teaspoon to small dogs works just as well- -there is no harm but also no need to give the below extra-large doses- -we also recommend Slippery Elm powder over Slippery Elm capsules.
Cats and Dogs under 25 lbs 1-2 Tablespoons
Dogs 25-50 lbs 2-4 Tablespoons
Dogs 50 lbs and up ¼ to ½ cup
ü Epilogue I. Slippery Elm is a very safe herb. It can literally be a life saver by preventing dehydration from continued vomiting or diarrhea. It is virtually impossible to overdose, and it can be used for extended periods of time. However, if you find your pet needs this treatment for several weeks and the symptoms still reappear when you attempt to wean off or discontinue, this is a sign of significant chronic disease and you shouldseek professional veterinary care.
ü Epilogue II. I am a Natural Health Coach for people as well. These first aid guidelines are solid recommendations for humans as well. This includes the Slippery Elm information. You can count human adults as “Dogs 50 lbs and up” : ) for dosing.
Copied directly in it's entirety from Open Journal of Veterinary Medicine at this link:
Vol. 3 No. 3 (2013) , Article ID: 34284 , 7 pages DOI:10.4236/ojvm.2013.33036
Expedited Management of Canine and Feline Vomiting and Diarrhea. Observational Study in 3952 Dogs and 2248 Cats Using Sucralfate-Like Potency-Enhanced Polyanionic Phyto-Saccharide—Elm Mucilage
Ricky W. McCullough
Mueller Medical International Translational Medicine Research Center, Foster, USA
Email: [email protected]
Copyright © 2013 Ricky W. McCullough. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received November 30, 2012; revised January 30, 2013; accepted March 5, 2013
Keywords: Canine; Feline; Vomiting; Diarrhea; Slippery Elm; Sucralfate
A potency-enhanced polyanionic phyto-saccharide of elm mucilage (PEPPS) was prescribed by 197 small animal veterinarians in an open-labeled field trial. Clients provided informed consent to veterinarians to prescribe PEPPS to 3952 dogs and 2248 cats. A 2 day/4 dose response rate, determined by veterinarians’ consensus, provided clinical threshold for a significant clinical outcome. Data was collected through phone interviews conducted over a period of 3.5 years from June 2003 through December 2006. 82% of 1928 vomiting dogs and 77% of 1064 vomiting cats responded to PEPPS within 2 days or four doses. 93% of 2024 dogs and 79% of 1184 cats with diarrhea responded to PEPPS within 2 days or four doses. PEPPS appears useful for managing vomiting and diarrhea in dogs and cats. However, a randomized blinded placebo controlled trial is needed to quantify true clinical efficacy.
Timely management of disruptive gastrointestinal (GI) symptoms poses a challenge to both veterinary and medical physcians alike [1,2]. Restoration of normal GI function requires effective means to mitigate nausea, vomiting, diarrhea, in dogs and cats  as well as colicky pain and ulcerations in horses . Current approaches in managing nausea (usually observed as inappetence), vomiting and diarrhea in small animals involve supportive care, bowel rest, pancreatic enzyme supplementation and/or appropriate anti-microbials . Management of mucosal erosions and ulceration in small companion animals centers on control of acidity, either by neutralization with antacids, reduction with histamine-2 blockers (e.g., ranitidine, cimetidine, famotidine) or inhibition with proton pump inhibitors (e.g., omeprazole, lanzoprazole, raberazole). A simplified approach in managing disparate GI symptoms would be useful for clinical veterinary practice were it safe, efficient and minimally burdensome [3,4].
The scale of the problem is significant. According to American Medical Veterinary Association  there are 150 - 197 million annual visits to small animal veterinarians in the US. Lund et al.  reported that in the US, 8.3% of veterinarian visits are for unexplained vomiting and diarrhea in dogs and cats. This translates into 12 to 16 million dog and cat visits (Appendix A) that involve diagnostic workups and treatment plans for vomiting and diarrhea. This volume however only reflects the owners who actively utilize veterinarian services. A recent survey of dog and cat owners  revealed that 40% of owners reported pet vomiting, diarrhea, inappetence and bloating yet only 17% of dog owners and 20% of cat owners actually consult a veterinarian. The survey implies that the estimated number of annual visits represents an undersized minority of animals that are actually affected. Given such a pervasive problem, any therapeutic intervention that improves management of disruptive GI symptoms would be a positive development.
Veterinary use of phyto-mucilages, particularly slippery elm, for gastrointestinal have been suggested by some [8,9]. A potency-enhanced version of elm USP, requiring less than 10% of suggested daily doses, has been prescribed by veterinarians since 2003. Veterinarians were familiar with the 2002 original formulation of canine/feline Gastrafate® which contained 5% high potency sucralfate as the active ingredient. Following successful preliminary testing  high potency sucralfate was replaced in January 2003 with magnesium chelated elm mucilage. This report presents observational data from the use of polyanionic phyto-saccharide of elm mucilage (PEPPS) in practice-based settings of small animal veterinarians.
2.1. Potency Enhanced Polyanionic Phyto-Sac Charide
Elm mucilage USP is a polyanionic phyto-saccharide . Unlike sucralfate, PEPPS contains no aluminum or sulfate. Chiefly a high molecular weight mucilage (>200,000 Daltons), it is comprised of galactose-rhamnose disaccharides. Potency-enhanced elm phyto-saccharide is prepared by suspending elm mucilage in an anion-cation solution similar to that used to formulate high potency sucralfate (HPS) . The resultant potency-enhanced phyto-saccharide (PEPPS) is muco-specific and capable of attaining augmented surface concentration of slippery elm. With sucralfate, potency enhancement ranges from 7 - 23 fold 3 hours post-administration, having a lower fold increase on normal GI lining and higher fold increase on inflamed or injured mucosa. The exact postadministration surface concentration of PEPPS is unknown. However, with PEPPS the concentration of elm USP administered is less than 8% the slippery elm dose recommended by holistic veterinarians [8,9]. The formulation strength of Elm USP in PEPPS for small animals is 0.9%. Administration of PEPPS was in accordance to weight. On average dogs or cats weighing less than 25 lbs received daily doses upwards of 72 mg, (b) animals between 25 - 50 lbs received 85 mg and (c) over 50 lbs received 120 mg.
2.2. Dosing Administration
Participating veterinarians prescribed PEPPS in accordance to weight-dose chart in label instructions. PEPPS was given twice daily with food for the majority of the patients. In the cases where vomiting and diarrhea disrupted eating and require intravenous hydration, PEPPS was given orally without food.
3.1. Study Design—Observational Trial
This study was an open labeled non-blinded observational trial. Information was collected regarding (a) weight of the dog or cat and (b) the nature and length of their GI symptoms at time of adding PEPPS. The length of illness is not reported.
As an observational study, treatment intervention was not randomized. By design, differences in outcomes are observed without regard to similarities or dissimilarities of patient characteristics prior to treatment. In fact, in this type of study, treatment decisions were made by veterinarians prior to use of PEPPS, the selection of PEPPS being made by the veterinarian due to concern that prePEPPS treatments were ineffectual. In this trial the question addressed is not one of the efficacy of PEPPS. Instead the question addressed is one of the relative merits of PEPPS as a competing treatment or intervention. Outcome of merit is relative to the expectation of the participating veterinarians. As discussed below a clinical response of 2 days or 4 doses merited note to the veterinarians involved. This study reports the percentage of dogs and cats with vomiting and diarrhea who responded to PEPPS while on failing therapies.
3.2. Comparative Control
As an observational study, there were no control groups. To provide a comparative “control” experience, each veterinarian was asked to reflect on their respective experience and select from a choice of a clinical response times which they would deem to deviate significantly from the expectations of their clinical experience. Most of the small animal veterinarians (85%) felt that a clinical response of 2 days or 4 doses would mark a significant departure from their clinical expectations and this was based on their experience managing vomiting and diarrhea in dogs and cats. This consensus of significant departure from expected time of clinical response was used to benchmark the primary outcome and a meaningful response. In essence, expectations of past clinical experience (replete with interventions requiring more time to work) served as a “comparative control” albeit a subjective one.
All animals were privately owned and owners’ consent was obtained by veterinarians.
3.4. Veterinarians Participating in the Study
Veterinarians placing orders for commercially available PEPPS were recruited to participate in this open-labeled trial. Each had more than 5 years of professional practice. Veterinarians were recruited from June 2003 through December 2006. All veterinarians prescribing PEPPS were engaged exclusively in primary care of small companion animals. They were experienced in the standards of care in treating vomiting and diarrhea in dogs and cats. Out of 256 small animal veterinarians, 197 practicing in 48 states completed the study, the remainder lost to follow up due to their inability to complete the protocol. Veterinarians received no honorarium for their participation.
3.5. Sequential Participation
Participation in the study was sequential, determined solely by the order of spontaneous requests for product made by veterinarians responding to notification of product’s availability. The veterinarians were self-selected. Information prompting orders pertain to the usefulness of PEPPS in the management of vomiting and diarrhea in small animals.
3.6. Inclusion/Exclusion Criterion for Dogs and Cats
Dogs and cats were brought to the veterinarian by clients primarily due to vomiting and/or diarrhea. Included in the trial were dogs and cats with vomiting and/or diarrhea for more than 3 days with or without bleeding and dehydration. Animal’s symptoms were attributed to gastrointestinal infections from viral, bacterial and protozoan agents or to exposure to environmental toxins. Notable inclusions were animals described by veterinarians as having hemorrhagic gastroenteritis, parvovirus enterocolitis, gastritis, intestinal “flare-ups”, and pancreatic “flare-ups”. Cases of food intolerance were included. No cases of medication induced vomiting or diarrhea included. Excluded were animals requiring surgical intervention.
3.7. Test Population
Animals included dogs and cats of varied age, breeds and weights. The size of the test population was 3952 dogs wherein 1928 were vomiting-dominant and 2024 diarrhea-dominant. Vomiting-dominant and diarrhea-dominant was defined by the major concern of the client who initiated the visit. Also included were 2248 cats wherein 1064 were vomiting-dominant and 1184 were diarrheadominant. All patients were studied across multiple office-based practices. The population was also geographically diverse with input provided from 48 out 50 states of the US.
3.8. Conditions Managed
Inappetence, vomiting and diarrhea fail owners’ attempts to adjust the pets’ diet. Following evaluation by physical exam, lab tests and in some cases x-rays the clinical impressions of veterinarian covered a broad range of diagnoses that included hemorrhagic gastroenteritis, parvovirus enterocolitis, gastritis, reflux, suspected ulcer, intestinal “flare-ups”, pancreatic “flare-ups” and “stomach issues”. The severity of GI symptoms or the presence of other (non-surgical) disorders did not preclude patients’ involvement in the study. Cases of food intolerance were included. There were no cases of medication induced vomiting or diarrhea in this study. Both dogs and cats were brought to the veterinarian due to vomiting and/or diarrhea.
3.9. Existing Treatment Regimens in Dogs and Cats
Methods of management for small animals were diverse. Existing treatment regimens for dogs and cats prior to PEPPS varied widely and included antibiotics, anti-emetics, acid reducers, pancreatic enzyme supplementation, bismuth preparations, plain sucralfate and dietary changes. To these diverse regimens PEPPS was added. Veterinarians in the study opted to add PEPPS to existing regimens that had been deemed inadequate or insufficient by them. There was no PEPPS only test group.
3.10. Primary Outcome Measure in Dogs and Cats
There were two symptom-related primary outcome measures for this trial—the cessation of diarrhea and the cessation of vomiting. The cessation of these symptoms within 2 days or 4 doses of PEPPS represented a positive outcome. This veterinarian-defined response to therapy was accepted as a meaningful clinical response (as described in section on Study Design) for the management of vomiting and diarrhea in dogs and cats in this study. Clinical observations made by veterinarians were reported by phone for data collection.
The hypothesis is that a majority of animals with serious and disruptive GI symptoms (of non-surgical etiology) when given PEPPS will experience resolution of symptoms within a timeframe (or dose administration) significant and relevant to the collective historical experience of practicing veterinarians who routinely manage such symptoms. This was a timeframe was 2 days or 4 doses.
Results are based on a per protocol analysis of the data. Chi-square analyses were performed to compare percent response between weight subgroups in dogs and cats at confidence level of 95% and 99% for confidence intervals and alpha level of 0.05.
3.13. Conduct of Observational Field Tests
The study was conducted from June 2003 through December 2006. Clinical observations made by veterinaryans were reported by phone for data collection. Phone interviews were conducted with veterinarian staff to collect results of adding PEPPS to existing treatment regimens. Results were tabulated as either a positive or negative outcome.
4.1. Dogs with Vomiting and Diarrhea ....to see actual charts please go to the website link:
The were dogs grouped roughly according to five weight categories—less than 6 lbs, 6 - 14 lbs, 14.1 - 29 lbs, 29.1 - 50 lbs and greater than 50 lbs. All dogs eventually responded to PEPPS with various clinical response times extending beyond 2 days. However, Table 1 show that 82% [CI 3.9 (CL 99%)] of 1,928 dogs with vomiting responded to PEPPS within 2 days or 4 doses, while 93% [CI 1.46 (CL 99%)] of 2024 dogs with diarrhea responded to PEPPS within 2 days or 4 doses. The collective percent response to PEPPS for vomiting and diarrhea in dogs was 88%. High percent response to PEPPS in 2 days or with 4 doses was similar across all weight classes of dogs regardless of symptom (Table 2). There were no weight-based differences in the percent response in dogs to PEPPS.
4.2. Cats with Vomiting and Diarrhea to see actual charts please go to the website link:
Cats were grouped according to 3 weight categories— less than 6 lbs, 6 to 11 lbs, and greater than 11 lbs. All cats eventually responded to PEPPS with varying clinical response times that extended beyond 2 days. However, Table 3 shows that 77% [CI 3.3 (CL 99%)] of 1064 cats with vomiting responded to PEPPS within 2 days or 4 doses. Similarly 79% [CI 3.05 (CL 99%)] of 1184 cats with diarrhea responded to PEPPS within 2 days or 4 doses. The ability for PEPPS to stop diarrhea and vomiting in 2 days or with 4 doses in cats was the same across all weight classes. Table 4 shows that there were no weight-based differences in the percent response in cats to PEPPS.
5.1. General Impressions
There are limited outpatient options for the treatment of acute vomiting and diarrhea in companion animals. For the most part, evidence-based guidance is drawn largely from human clinical trials, experimental studies in dogs and cats [13,14] and the collective clinical experience of small animal practitioners. Often what is recommended (and practiced) is manipulation of diet alone or concur-Table 1. Veterinary response to PEPPS prescribed to dogs.
Table 2. Chi-Square values comparing percent treatment response in dogs by weight.
Table 3. Veterinary response to PEPPS prescribed cats.
Table 4. Chi-square values comparing percent treatment response in cats by weight.
rently with the use of medications . Few randomized placebo controlled trials exist that offer evidence sufficient support national practice guidelines.
In this study, potency-enhanced polyanionic phytosaccharide was prescribed to 3952 dogs and 2248 cats in the private practices of 197 small animal veterinarians in the US over a 3.5 year period. The data from this study showed an association between the use of PEPPS and the resolution of vomiting and diarrhea in dogs and cats whose symptoms had failed pre-existing therapies. Causality would require a randomized, blinded, placebocontrolled trial. As in must observational trials, a standard control group was not used. Instead, the study used as its “control” the historical experience of veterinarians whose prior management of vomiting and diarrhea did not include PEPPS. Vomiting and diarrhea resolved within 2 days or 4 doses in a majority of dogs (over 80%) and cats (nearly 80%) that received PEPPS. The data supported the original hypothesis that majority of dogs and cats with serious and disruptive GI symptoms when given PEPPS will have symptom resolution within a timeframe significantly less than anticipated from the private practice experiences of the veterinarians involved. In dogs and cats with vomiting and/or diarrhea for more than 3 days with or without bleeding and dehydration the animal’s symptoms were attributable to gastrointestinal infections from viral, bacterial and protozoan agents or to environmental toxins. Notable inclusions were animals described by veterinarians as having hemorrhagic gastroenteritis, parvovirus enterocolitis, gastritis, intestinal “flare-ups”, and pancreatic “flare-ups” who were on failing treatments. The majority of these animals responded to PEPPS with the cessation of symptoms between 2 to 4 days. This study does not rule out whether on not the patients would have improved otherwise. Neither does the study exclude the possibility that patients’ improvement was from other causes, such as premature disqualification of existing treatment regimens or the combination of PEPPS with existing regimens led to improvement. It does support a plausible proof of principle. The study did demonstrate that PEPPS was associated with a 2 - 4 day cessation of vomiting and diarrhea in the majority of dogs and cats that received PEPPS twice daily by direct administration or with their food.
5.2. Disadvantages of Observational Studies
There are obvious disadvantages to an observational study of this nature. Firstly, there are no traditional control groups, the lack of which precludes objective quantification of the efficacy. What is known from this study is that a large majority of the patients got better sooner than 85% of the study’s small animal veterinarians would have thought possible based on their collective past clinical experience. The historical experience of each veterinarian and their consensus of what constitute a significant deviation from that experience are subjective. Consequently, the data offers little predictive value of efficacy. The study design, at best, provides an affirmative proof-of-concept supporting the plausible utility of PEPPS in the management of disruptive GI symptoms in dogs and cats.
A second disadvantage of this study is that the manner of recruitment gives rise to bias. Practitioners were selfselected by virtue of responding to advertisements regarding a new gastrointestinal protectant which is resold at profit if the product is prescribed to a patient. Data obtained utilizing this method of recruitment is vulnerable to a self-selection bias that is profit driven. In general, an appropriately randomized, placebo-controlled blinded investigation would best quantify the efficacy of PEPPS and thereby provide a better basis on which to predict the benefit of PEPPS in managing vomiting and diarrhea.
5.3. Strengths of This Observational Study
Despite the aforementioned drawbacks due to design, there are a number of strengths that provide a significant context for the positive results reported here, results that imply positive benefits in using PEPPS to manage unexplained diarrhea or vomiting in small animals.
The first strength of this study the is the geographic diversity of state-licensed veterinarians involved. The data reflected a nationwide experience among small animal practitioners in 48 of the 50 states. The positive findings were not a coincidence of geography but rather a reflection of generalized experience.
In addition, a study involving thousands animals across 48 contiguous states imply that response to PEPPS was not likely influenced by geographic life-styles (rural versus urban settings) of ownership, diversity of breed, client-companion animal relationships or seasonality (having been conducted over 42 months). The majority of patients demonstrated a high PEPPS response regardless of these factors.
5.4. Implications of Findings
The positive results of this study have implications regarding the physical origin of symptom-states of the GI tract. PEPPS is non-systemic agent. The entirety of its clinical effects is attributed solely to a topical action in coating the mucosal lining. Physical engagement of surface elements accessible to PEPPS as it layers along the gut lining result in a therapeutic effect. Similarly, sucralfate, another agent whose therapeutic effect is limited to engagement of the mucosal lining has been shown as well to reverse nausea, vomiting and diarrhea in small animals . Thus the positive clinical effect of PEPPS and similar surface-active agents (e.g. sucralfate) to reverse symptom-states of vomiting and diarrhea in dogs and cats, imply that those symptom-states are controlled by or to some degree, significantly influenced by physical elements associated with the mucosa onto which these agents are layered. Causal links of mucosal elements to symptom-states of the GI tract has been mentioned elsewhere, in cases involving human patients suffering from functional bowel syndromes that presenting with intestinal symptoms of nausea, vomiting, diarrhea or even constipation [17,18]. The use of surface-active agents to manage symptom-states by engagement of surface elements of the mucosal raises the question as to the nature of those elements so associated. Surely those elements should be targets for the design of other therapeutic agents.
The majority of 3952 dogs and 2248 cats with vomiting and diarrhea treated with PEPPS were observed to have unexpectedly shortened clinical course unanticipated by experienced small animal veterinarians practicing in 48 out 50 states in the US. While all patients eventually responded to PEPPS, most dogs and cats with vomiting and diarrhea responded within 2 days or 4 doses. Data from this 42-month-long observational study supports the notion that PEPPS may be useful in the practice setting to manage vomiting and diarrhea of common etiologies in small companion animals. However, blinded, randomized, placebo-controlled trials are needed to assess the true efficacy of PEPPS.
Fieldwork and data collection were funded as part of Mueller Medical International LLC research on polyanionic saccharides as in-vivo surface active agents for epithelial mediated processes in animals and humans. Thanks to Jeremiah McCullough of University of Connecticut for his assistance in the preparation of this manuscript.
Volume for office visits was calculated from data by Lund et al.  who reported that 8.3% of dog and cat visits per year for either vomiting or diarrhea. This number was multiplied by 196 million annual veterinarian visits reported in 2007 AVMA Pet ownership sourcebook, then further multiplied by 0.85 as the proportion of total small animal veterinarian visits by dogs and cats.
Sometimes when SID/SIBO is in play and the dog is already on antibiotics..... which may be keeping the SID/SIBO at a minimum, but it is just not being fully eradicated.... sometimes it is because of a certain food in the diet that is perpetuating the SID, or what may be going on in addition to EPI is either IBD or IBS (food sensitivities). There is a new test by Dr. Jean Dodds that has been performed on some of our member dogs with great success. If you are interested, check out the Nutri scan test http://www.nutriscan.org/knowledge-center/food-sensitivities.html
Very often, when our dog are first diagnosed.... we get the right enzymes, change their diet to something more suited to them, their "SID" (SIBO) is treated and appears resolved and if needed their B12 is taken care of.. and things are fine..... for a while................................................
But then.... some dogs start to have wet burps after they eat. This is not something to get overly upset about but rather... something you just need to find the cause of in your dog and make the necessary adjustments.
When they have wet burps there are a couple of different things to try.....PLEASE try one thing at a time and wait 3-5 days to see if it had a positive effect or not (with the poo and wet burps).
Here are some things you can try (in no particular order) to alleviate them wet-burps:
1. reduce the enzymes just a wee bit. If you are giving 1 level teaspoon of the pancreatic powdered enzymes per 1 cup of food.......and have been doing this for a while AND if the poos are ggreat and have been great for a while on this does..... then... try reducing the enzymes by 1/8 or even just 1/16th of a tsp... try this for 3 days... see if the burps subside AND also watch the poos to make sure that they are still good...The reason why i am suggesting this is because when we first start treating EPI dogs with enzymes you need to hit them hard and heavy with enzymes... but once they become stable, it is recommended to try and reduce the amount of enzymes to the lowest dose possible while still yielding good results (translation= good poo!) ....so if you haven't tried this yet... it might be that your dog doesn't need as much enzymes anymore now that he/she is stable and this might be the cause of the burping......However, please know that not all EPI dogs can have the enzymes dosage reduced even after they become stable....
2. try Tylan antibiotic ... often... wet burps are because of SID (SIBO) brewing......or sometimes it is because not the right amount of Tylan is being given.... the standard recommendation has been:
Tylan Dosage for Dogs (administer twice daily with food) ....with 100g Tylan powder which means: 5-10mg per pound (or 10-20mg/kg) every 12 hours for 4-6 weeks:
But now there is a newer recommendation (2010) from Dr. Jorg Steiner at TAMU where they have actually increased the amount of Tylan (slightly):
Tylosin (25 mg/kg BID for 6 weeks) is the new antibiotic agent of choice. (for the breakdown in teaspoons per weight.. please see the SIBO page: http://www.epi4dogs.com/sidsibo.htm
So.... with the latest on Tylan being slightly increased and with more insistence on longer duration..... I think either or is fine, your choice which you want to follow.. but what it does indicate to me is that if you give a little too much Tylan that no harm will come of it since they have since upped things.
3. Add a little fiber like pure canned pumpkin (1/2 teaspoon and work up to 1 level teaspoon)... or... there is a new product out called "Diggin Your Dog Firm Up" which can be purchased thru Amazon.com (or charity donation SMILE AMAZON.com) http://smile.amazon.com/gp/product/B006CBD7UQ?psc=1&redirect=true&ref_=oh_aui_detailpage_o03_s00
4. B12 is needed.... is yet another possibility because the B12 is not holding or needs to be upped....this could be why (if it is SID / SIBO is brewing... )
5. Change the food.... sometimes this happens if for some reason, the food just is not agreeing, might be a food intolerance or something.
6. Add Slippery Elm Powder... this is a mucilage that coats the insides and helps with any intestinal lining damage or bacterial imbalance that is often the cause of acid reflux. Start with 1/2 or 1 level tsp per day with a meal. This usually is enough.
7. Add probiotics/prebiotics to the regimen. Although this is a trial and error thingy that will take time... and money obviously trying different products....but when you happen upon the right pre-probiotic for YOUR dog... it helps with any gut flora imbalance which causes SID (SIBO)
8. Try acid reducers work, but bear in mind that one type of acid reducer may work in one EPI dog but not another, so if one type doesn't work, always feel free to talk to your vet about trying a different stomach coater or acid reducer. Some options are: Pepcid AC (famotidine), Prilosec (omeprazole), ranitidine, cimetidine, sucralafate, etc.... but ALWAYS... discuss with your vet before using any of these drugs. We are actually finding great success with Slippery Elm vs. most of the acid reducers.
9. Other things to watch for are as follows:
10. And the last option that i know of to look into if this just doesn't clear up and or gets worse and goes on and on and on is to then talk to the vet about using short-term steroids to straighten it out.... but i always save this as a last possibility..... i know steroids work wonders many, many times... but i am of the opinion that if you don't have to use them it is always great to see if you can resolve the problem another way..... but then this is just my personal opinion.... ALWAYS talk to your vet about what the best option is for your individual pet!
A general guideline to reading "poo"
(re-printed with permission from a Pancreatitis group)
Yellow or greenish stool -- indicates rapid transit (small bowel).
Black, Tarry stool -- indicates bleeding in the upper digestive tract.
Bloody stool -- red blood or clots indicate bleeding in the colon.
Orange stool - type of food, infection, bile duct issue, hemolytic issue
Pasty, light-colored stool -- indicates lack of bile (liver disease).
Large, gray, rancid-smelling stool -- indicates inadequate digestion or absorption (malabsorption syndrome).
Watery stool -- indicates small bowel wall irritation (toxins and severe infections).
Foamy stool -- suggests a bacterial infection.
Greasy stool -- often with oil on the air around the anus: indicates malabsorption.
Excessive mucus -- a glistening or jelly like appearance: indicates colonic origin.
(the more watery the stool, the greater the odor)
Food like or smelling like sour milk -- suggests both rapid transit and malabsorption.
Putrid smelling -- suggests an intestinal infection.
Several in an hour, each small, with straining -- suggests colitis
Three or four times a day each large -- suggests malabsorption or small bowel disorder.
Condition of Dog
Weight loss, malnutrition -- suggests small bowel disorder.
Normal appetite, minimal weight loss -- suggests large bowel disorder.
Vomiting - small bowel origin, except for colitis.
SIBO "Small Intestinal Bacterial Overgrowth"
The proximal small intestine normally contains few bacteria.In small intestinal bacterial overgrowth (SIBO) there is proliferation of abnormal numbers of bacteria in the lumen of the upper small intestine. The definition of what is considered an abnormal number of bacteria in the dog is still under discussion. It is classically stated that in normal household pet dogs no more than 104 to 105 bacteria per mL of juice are present in the lumen of the upper small intestine. Although recent reviews have questioned the accuracy of this upper limit of normal, some of the reported variation may reflect inclusion of dogs not from household environments rather than pet dogs. However, it is generally accepted that species normally present in the proximal small intestine of dogs include E. coli, enterococci and lactobacilli, and that obligate anaerobic species are rare. In dogs with SIBO there are not only increased numbers of intraluminal bacteria, but the composition of the flora also changes to a predominantly anaerobic one, resembling that of the colon.
SIBO in the dog has been infrequently reported, probably because of the difficulty in establishing the diagnosis, and initial descriptions were limited to its occurrence in German Shepherd Dogs. However, in recent years it has been described as a common finding in dogs with chronic small intestinal disease, either as a cause or a consequence of their disease. This condition in the dog has been controversial because of difficulties in defining its aetiology and pathogenesis. There have been suggestions that it be renamed antibiotic-responsive diarrhoea (ARD) until more is known about its aetiopathogenesis. However, this does not apply to all cases since it is not always associated with diarrhoea; indeed, weight loss alone can be the only presenting sign.
Accumulated data on clinical cases indicate that SIBO should be considered an important emerging syndrome that may occur in many breeds of dog. It typically presents in young animals as chronic intermittent small bowel diarrhoea, which may be accompanied by loss of body weight or failure to gain weight. Clinical signs are variable and some animals may only exhibit weight loss, while others may have intermittent vomiting or signs suggestive of mild colitis.
SIBO may develop if the normal host defence mechanisms, such as gastric acid secretion, intestinal peristalsis, the ileocaecal valve, intestinal immunoglobulin secretion, and mucus barrier are impaired. In people, SIBO is usually associated with intestinal stasis (blind loop syndrome). Small intestinal dysmotility, as evidenced by reduced migrating motor complex activity, is probably responsible for the prevalence of SIBO in elderly human patients. In dogs, there is rarely evidence for stasis, and the cause of SIBO is often unknown. A naturally developing enteropathy associated with SIBO was first described in German Shepherd Dogs, and it has been postulated that this is related to an apparent relative deficiency of IgA in this breed. SIBO may also develop secondary to exocrine pancreatic insufficiency, and has been reported in asymptomatic laboratory Beagles. We have documented SIBO by culture of duodenal juice in over half of dogs with chronic intestinal disease; dogs of many breeds are affected, although there is a predominance of German Shepherd Dogs. Serum IgA levels in these dogs have been variable. Predisposing conditions usually cannot be identified, although it remains important to rule out causes of intestinal stasis, such as neoplasia and intussusception. Increased numbers of pathogenic E. coli have been demonstrated in the duodenal juice of these dogs, and these may also play a role in the development of this condition. SIBO may furthermore be a secondary complication of many intestinal diseases due to altered intestinal motility and/or local immunity; in addition, malabsorption of nutrients may cause an environment favourable for bacterial proliferation. Conversely, bacterial antigens gaining access to the lamina propria also may cause an inflammatory reaction, although this tends to be milder.
Bacteria or their secreted products can directly damage the mucosa or indirectly impair absorption by competing for nutrients and by changing intraluminal factors such as the concentration of conjugated bile acids. This results in diarrhoea and steatorrhoea, competition with the host for nutrients, and weight loss. Enterocyte damage is often not visible on light microscopy, but may be demonstrated using biochemical or ultrastructural studies, or by measurement of intestinal permeability. Increased mucosal production of interleukin-6, a cytokine that plays a central role in the regulation of inflammatory and immune reactions, has been demonstrated in people with SIBO, suggesting heightened mucosal immune activity.
The species of bacteria in duodenal juice of dogs with SIBO varies markedly, with coliforms, staphylococci, enterococci, and Clostridium and Bacteroides spp predominating. Anaerobic overgrowth is most common, found in approximately 70% of dogs with SIBO. This is of clinical significance, since anaerobic bacteria have a much greater potential to damage the intestinal brush borderand cause malabsorption; in addition, anaerobes, especially Bacteroides, are the major cause of bile salt deconjugation resulting in fat malabsorption and steatorrhoea.
Symptomatic SIBO typically presents in young animals as chronic intermittent small bowel diarrhoea, which may be accompanied by loss of body weight or failure to gain weight. Diarrhoea often has been present since puppyhood, and gradually worsens. Some dogs also may have signs of a mild colitis, due to colonic irritation by bacterial metabolites, and these dogs may be erroneously diagnosed as having primary colitis. Weight loss may be severe, and is in some dogs the only sign. Appetite is often reduced. Vomiting is not typically associated with bacterial overgrowth; its presence suggests concurrent inflammatory bowel disease. Some dogs with SIBO are presented because of excessive intestinal gas.
CBC and biochemical profile should be performed to rule out systemic disease. Faeces should be examined for parasites and cultured for enteric pathogens. Abdominal radiography and especially ultrasound can be helpful to rule out partial obstruction, particularly in young (intussusception) or older (neoplasia) animals. Subsequently, exocrine pancreatic insufficiency (EPI) should be ruled out by assay of serum TLI activity.
Serum folate and cobalamin
Assays of serum folate and cobalamin appear to be the most helpful aids to the diagnosis of SIBO in the dog for use in general practice, although they have poor sensitivity (i.e., many affected dogs do not have abnormal test results). Normal serum vitamin concentrations do not exclude the possibility of SIBO, because alterations depend on the type and numbers of organisms present, the severity of any secondary mucosal damage that may interfere with folate absorption despite high intraluminal concentration, and depletion of body stores. If pancreatic function is normal (i.e., serum TLI is normal) then finding a decreased serum cobalamin concentration or increased serum folate is supportive of SIBO. If both of these are found together, SIBO is extremely likely; however, this combination occurs infrequently. High serum folate may also be a consequence of high folate intake, such as a high-folate diet or coprophagia. Demonstration of low serum cobalamin is the more useful finding, since it is less influenced by diet and coprophagia and appears to relate more to the severity of clinical disease
Measurement of intestinal permeability is a sensitive tool for the detection of mucosal damage, but it does not tell you about the underlying cause. However, these tests are useful to detect and assess the severity of mucosal damage in dogs with overgrowth. Increased intestinal permeability can be demonstrated using a differential sugar absorption test in 50-60% of clinical cases with SIBO, even when there are no histologic abnormalities. In addition, changes in intestinal permeability following antibiotics may be used to monitor response to treatment. Normalization of intestinal permeability following antibiotic therapy suggests successful treatment, and antibiotics may be discontinued. Antibiotics possibly should be continued longer if permeability remains high despite apparent response to treatment; in addition, other causes of intestinal disease should be suspected and investigated (e.g., dietary sensitivity). Persistent high permeability in dogs with a poor clinical response should prompt one to look for underlying disease, such as a primary inflammatory bowel disease.
Breath hydrogen testing
Breath tests measure the breath excretion of CO2 or hydrogen (H2) produced by intraluminal bacterial metabolism of an administered substrate. They appear to be the one of the most sensitive and specific tests available for the diagnosis of SIBO, although they are not yet technically feasible in most veterinary practices. The H2 breath test has been used most often in both human and veterinary medicine. It has been used not only for diagnosis of SIBO but also for detection of carbohydrate malassimilation and measurement of oro-caecal transit time. The time after ingestion of the test substrate at which increased breath H2 concentrations are first detected is used to distinguish between SIBO and carbohydrate malabsorption. In SIBO, elevated breath H2 concentrations occur within 1 to 2 hours after ingestion of the test substrate. An H2 breath test using a multiple sugar solution has been used successfully for detection of SIBO in dogs and has the advantage that it simultaneously allows for quantification of intestinal permeability. A limitation of breath H2 tests in people is that 15-20% of the human population have intestinal flora that does not produce hydrogen, and therefore cannot demonstrate a positive test result if bacterial overgrowth develops. The same probably applies to the dog, since there are significant numbers of dogs with culture-proven overgrowth but persistently negative breath tests.
The H2 breath test is more sensitive than serum folate and cobalamin assay, and has been useful to identify cases of SIBO with a falsely negative duodenal juice culture. A positive breath H2 test is very suggestive of SIBO, and there is no need to culture duodenal juice in these cases. However, a negative test does not rule it out, and culture of duodenal juice remains necessary in these patients.
Culture of duodenal juice
Definitive diagnosis of SIBO is based on results of microbiologic culture of duodenal juice, obtained usually at endoscopy or alternatively via intra-operative permucosal aspiration. Juice culture is still the gold standard for the diagnosis of SIBO, but it is technically difficult, time-consuming and expensive, and it may still not identify all cases of SIBO (for example when this is in the more distal portions of the small intestine or in isolated pockets). However, intestinal biopsies can be taken at the same time as the juice collection, and these are useful to rule out primary mucosal disease as the cause of malabsorption. Duodenal biopsy in SIBO is often normal. Over 75% of clinical cases with SIBO will have no histologic abnormalities, whereas mild to moderate lymphocytic infiltrates occur in up to 25%. Mild lymphocytic-plasmacytic enteritis can occur as a consequence of SIBO, and may resolve following appropriate antibiotic treatment.
Duodenal bacterial counts may be influenced by environmental factors, such as housing conditions (kennelled dogs tend to have higher bacterial numbers, perhaps associated with coprophagia) and infective load (such as endoparasites and naturally occurring enteropathogens in hot climates). This should be taken into account when defining bacterial levels deemed diagnostic of bacterial overgrowth.
Bacterial deconjugation of bile salts may result in increased serum concentrations of unconjugated bile acids. Unlike the conjugated bile acids normally present in the small intestinal lumen, these unconjugated bile acids (UBA) diffuse across the intestinal mucosa into the blood. Dogs with SIBO have been shown to have significantly higher serum concentrations of UBA. This test has also proven useful to identify dogs with culture proven SIBO that did not have abnormal serum vitamin concentrations. Until now, this test was technically too complicated for routine use, but new developments should lead to this becoming more available in the near future. It may therefore become a useful addition to the battery of diagnostic tests required to diagnose SIBO.
Response to treatment with antibiotics may also help in the tentative diagnosis of SIBO. However, lack of response does not rule it out, since prolonged treatment may be required in some dogs before clinical improvement is manifest.
SIBO can be a subclinical intestinal abnormality, as has been reported in man, German Shepherd dogs and laboratory Beagles. Development of clinical signs in these individuals probably depends on the nature of the bacterial population (for instance, colonization with anaerobes is more likely to result in signs) and the effect of the overgrowth flora on the local immune system. These patients may be identified on basis of abnormalities in serum folate and/or cobalamin concentrations, a positive hydrogen breath test, or by culture of duodenal juice aspirated in the course of other investigations. Treatment is not required as long as they are asymptomatic; however, they are at risk for developing signs once the delicate balance in their intestinal ecosystem is disturbed. Progressive decreases in serum cobalamin concentration in dogs with asymptomatic SIBO often precede development of clinical signs.
TreatmentAn attempt should be made to identify and correct an underlying cause, such as partial obstruction due to intussusception, tumours or foreign bodies. Detection of dysmotility is more difficult and often not feasible; however, motility modifying agents such as cisapride or low-dose erythromycin may empirically be used in refractory patients. In many dogs with SIBO a cause cannot be found, and long-term oral antibiotic treatment is required. Oxytetracycline (10-20 mg/kg TID for 28 days) is used initially, and may need to be continued for extended periods if clinical signs recur on withdrawal of medication. Its mechanism of action may involve more than just pure antibacterial action (e.g., direct influence on the mucosa), although this is not certain. Metronidazole (10-20 mg/kg TID) and tylosin (20 mg/kg BID) are good alternative choices and are used if dogs fail to respond to oxytetracycline. Broad-spectrum bactericidal antibiotics tend to be less effective.
Dietary management with a low fat diet may also be valuable, because this can minimize the secretory diarrhoea, which is a consequence of bacterial metabolism of fatty acids and bile salts. Since intestinal permeability is often increased in SIBO, a restricted antigen diet may be of value to reduce the incidence of secondary dietary sensitivities. Dietary supplementation with fructo-oligosaccharides has been suggested as a means of modifying bacterial counts in the small intestine in German Shepherd Dogs with asymptomatic naturally occurring bacterial overgrowth. However, since these compounds are more likely to affect the large rather than the small intestine, further studies in clinical cases are required to assess the efficacy of prebiotics in the management of canine SIBO.
Probiotics are a mixture of non-pathogenic bacteria, often containing Lactobacillus, which can change intestinal pathobiology by preventing enteric infections, modifying metabolic actions of intestinal bacteria, and promoting nutrition. They also may promote local mucosal and systemic immune response. Probiotics are extensively used in large animals, and have also been advocated as a means of modulating gut flora in people with gastrointestinal disease.
Parenteral cobalamin (e.g., 500µg/month for 6 months) may help dogs with apparent cobalamin deficiency. It may have to be given more frequently if serum cobalamin levels remain subnormal. Persistently low serum cobalamin levels are often associated with a poor clinical response to treatment.
Prolonged antibiotic therapy is often required in treatment of dogs with idiopathic SIBO, and serial measurement of intestinal permeability and breath H2 testing are helpful in monitoring response to treatment. Some dogs with SIBO relapse as soon after antibiotics are discontinued. In these patients long-term antibiotic treatment will be required, but empiric reduction of the dose to well below the recommended level may be effective in controlling signs.
In dogs with moderate to marked inflammatory bowel disease, corticosteroids should be added to the treatment regimen if response to antibiotics alone is inadequate. Corticosteroids are not recommended in the initial treatment of dogs with lymphocytic/plasmacytic enteritis and SIBO because in our experience they appear to worsen clinical signs associated with SIBO.
Chronic SIBO may cause permanent functional damage to the intestinal mucosa. This may explain the poor response to treatment of some dogs, and also the need for indefinite dietary management with controlled diets after apparent successful antibiotic therapy in some dogs with chronic SIBO.
1. 1.Rutgers HC, Batt RM, Elwood CM, Lamport A. Small intestinal bacterial overgrowth in dogs with chronic intestinal disease. J Am Vet Med Assoc 1995;206:187-19
2. 2.Rutgers HC, Batt RM, Proud FJ, et al. Intestinal permeability and function in dogs with small intestinal bacterial overgrowth. J Sm Anim Pract 1996;37:428-434
3. 3.Bissett SA, Guilford WG, Spohr A. Breath hydrogen testing in small animal practice. Comp Cont Educ 1997;19:916-931
4. Ludlow CL, Davenport DJ. Small intestinal bacterial overgrowth. In: Bonagura JD, ed. Current Veterinary Therapy XIII. Philadelphia, WB Saunders, 1999: 637-641
5. Melgarejo T, Williams DA, O'Connell NC, Setchell KD. Serum unconjugated bile acids as a test for intestinal bacterial overgrowth in dogs. Dig Dis Sci 2000; 45:407-414
(click the speaker's name to view other papers and abstracts submitted by this speaker)
Roger M Batt
Masterfoods, Mars Inc.
Waltham-on-the-Wolds, Leicestershire, UK
Roger Batt qualified as a veterinarian from Bristol University in 1972 and obtained his PhD at the Royal Postgraduate Medical School in London. In 1980 he moved to the University of Liverpool where he established a comparative gastroenterology research group. In 1990 he was appointed Professor of Veterinary Medicine at the Royal Veterinary College in London. In 1998 he moved to the Waltham Centre for Pet Nutrition to become Head of Research and in 2001 was given the status of Visiting Professor at the University of Bristol.
His research has focused on gastrointestinal disease in specific breeds of dog. He has over 300 publications, and for his research has received a 1989 Ralston Purina Award from the American Veterinary Medical Association, the 1990 Walter-Frei Prize from the University of Zurich, the 1991 Woodrow Award from the British Small Animal Veterinary Association, and the 1997 Oscar W. Schalm Award from Davis, University of California. In 1993 he became the first President of the European Society of Comparative Gastroenterology.
F.P. Gaschen Email: [email protected]
School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
In humans small intestinal bacterial overgrowth (SIBO) is most frequently a secondary phenomenon associated to anatomical abnormalities that facilitate migration of large intestinal bacteria towards the small intestine or preventing the normal bacterial clearance, or to functional problems associated with disturbed intestinal motility. Multifactorial causes have also been reported (eg, immunodeficiency, etc.).
In dogs, secondary proliferations have been described in association with gastric and intestinal surgery or with exocrine pancreatic insufficiency. However, the existence of a primary, idiopathic SIBO is subject to controversy, although the syndrome has been the object of numerous scientific publications during the 1980s and 1990s. The diagnosis and definition of SIBO are complicated. The recognized diagnostic gold standard is anaerobic and aerobic bacteriologic culture of intestinal juice. The method is work intensive and requires the immediate proximity of an adequately equipped bacteriologic laboratory since numerous bacteria do not survive snap freezing. Previously, concentrations of more than 105 colony forming units (CFU)/mL intestinal juice were considered diagnostic of SIBO. Currently, it is believed that small intestinal bacterial concentrations up to 107 CFU/mL may be physiological in dogs.
In a recent publication, intestinal juice was cultivated in dogs with chronic enteropathies. The bacterial concentrations detected in the small intestinal juice of dogs which later responded to antibiotics (antibiotic responsive diarrhea or ARD) were not higher than those found in the dogs that did not respond to antibiotics. The etiology of ARD is not known, a bacterial infection with unidentified bacteria cannot be ruled out. The work intensive procedure of quantitative small intestinal bacterial culture is of questionable value in the diagnosis of chronic canine enteropathies. Other less complicated and less accurate diagnostic methods are available to detect bacterial proliferation in the small intestine. Serum folic acid levels may increase in dogs with SIBO because numerous bacteria synthesize folic acid. On the other hand, serum vitamin B12 (cobalamine) concentration is often decreased in association with intestinal malabsorption. However, these parameters cannot distinguish dogs that will respond to antibiotic treatment from those who will not. Bile acids are produced in the liver and conjugated to proteins before they are excreted in the biliary tree and undergo enterohepatic circulation. Some of the bacteria involved in SIBO are able to deconjugate these bile acids in the intestinal lumen. Serum concentrations of deconjugated bile acids are used in human medicine in the diagnosis of SIBO; however, they have proven useless in dogs.
ARD may affect young dogs. German shepherd dogs may be predisposed to that disease due to a disorder in the production of immunoglobulin A (IgA). In a case study from Finland, middle-aged large breed dogs were affected with ARD and only responded to tylosin. Clinical signs associated with ARD may vary considerably: chronic recurring, mostly small intestinal diarrhea is frequent (although large intestinal signs may also occur). Additionally, dogs with ARD may show borborygmus, flatulence, dysorexia and weight loss.
What are the implications of these findings for clinical practice? Even though the very existence of canine idiopathic SIBO is questioned, a number of dogs with chronic enteropathies do respond favorably to antibiotic treatment. This suggests that imbalances of the small intestinal bacterial flora could play an important role in the pathogenesis of IBD. This is why a global and systematic approach is necessary in dogs with chronic recurring diarrhea. Diseases known to cause secondary SIBO such as exocrine pancreatic insufficiency must be ruled out. Once identifiable causes of chronic enteropathies have been excluded, the remaining differential diagnoses include food intolerance or allergy, ARD and IBD. A pragmatic approach according to the severity of clinical signs is recommended. In mild cases, changing to a "hypoallergenic" diet is recommended. If this approach fails after 3 to 4 weeks, oral antimicrobial treatment with metronidazole (10–20 mg/kg BID), tylosine (10–20 mg/kg once daily or BID) or tetracycline (10–20 mg/kg TID) should be considered. Interestingly these three substances may have immunomodulating or even antiinflammatory effects in addition to their antimicrobial properties. In the more severe cases or in dogs that do not respond to the above treatment, additional exams must be recommended (abdominal ultrasound, endoscopy of the digestive tract with sampling of mucosal biopsies, etc.).