SID / SIBO / Microbiome
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 or maladaptation on or inside the body, such as an impaired microbiota.
August 2020 Effect of Metronidazole on the Fecal Microbiome and Metabolome of Healthy Dogs
( It is now advised to NOT use Metronidazole )
Sept 2019 Long-Term Impact of Tylosin on Fecal Microbiota and Fecal Bile Acids of Healthy Dogs
Jan 14, 2020 The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease
May 2019 SCFA (Short Chain Fatty Acids) and Dogs with CE (Chronic Enteropathy
Sept 2018 – Bile Acid
For information regarding the Regulation of Bile Acids… please click here: https://www.hindawi.com/journals/ppar/2009/501739/
For information regarding Bile Acid Disorders ….. please click here: https://rarediseases.org/rare-diseases/bile-acid-synthesis-disorders/
Nov 23, 2017 Canine Gastrointestinal Microbiome
by Dr. Patrick Barko and Dr. David A. Williams, M.A. McMichael and K.S. Swanson
An excellent and current all-encompassing piece on the canine microbiome. Much of effectively managing EPI for life includes keeping the canine microbiota imbalance under good control… not an easy task. This publication explains the issues, mechanisms and possible treatments.
To read the entire publication and/or print, see below:
2017 EPI Dogs Fecal Chart
(to read the smaller print on the chart… just expand the text with the “zoom” button)
2017 EPI Dogs Lactate Chart
(to read the smaller print on the chart… just expand the text with the “zoom” button)
Epi4Dogs collaborated and co-authored with Texas A&M Gastrointestinal Lab on TWO research projects.
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.
The Fecal Microbiome of Dogs with EPI
Small intestinal dysbiosis is an alteration of the small intestinal microbiota in either composition or numbers. There are several different terms that describe similar clinical conditions: antibiotic-responsive diarrhea, tylosin-responsive diarrhea, small intestinal bacterial overgrowth (SIBO), and intestinal dysbiosis. At the current time it is unclear whether all 4 terms describe essentially the same condition or if one of these terms would be more appropriate than the other three is most or even all situations.
Antibiotic-responsive diarrhea is a case of diarrhea that responds to antibiotic therapy. Similarly, tylosin-responsive diarrhea describes a case of diarrhea responsive to tylosin treatment. This term was coined by a Finnish group after they had done several studies in dogs with chronic diarrhea. The dogs showed poor response to several different antibiotics, but all responded to tylosin. The reasons for these findings are unclear. One explanation is that tylosin has an optimal antibiotic spectrum against the intestinal bacteria that are responsible for the diarrhea. Another explanation is that tylosin has other properties in addition to its antibiotic properties. Small intestinal bacterial overgrowth refers to an expansion of unfavorable bacteria in the small intestinal tract. Finally, small intestinal dysbiosis refers to a qualitative and/or quantitative derangement of the small intestinal microbiota that leads to clinical signs of small bowel diarrhea. Again, it is unclear whether these conditions can really be separated, and for a lack of better understanding in the following text, the term small intestinal dysbiosis is used as an overarching term for all four conditions.
The intestinal microbiota is made up of a wide variety of microorganisms, including bacteria, viruses, and fungal organisms. Most attention has been given to the intestinal bacterial ecosystem, which is made up of a complex mixture of a wide variety of bacterial species. Traditional studies describing the intestinal bacterial ecosystem have employed traditional culture techniques. However, the true diversity of the intestinal bacterial ecosystem became evident only recently with the advent of new micromolecular techniques. These newer techniques have revealed a far greater diversity of the bacterial ecosystem in the intestinal tract than previously assumed and have also shown that fungal organisms, such as Pichia spp., Cryptococcus spp., Candida spp., and Trichosporon spp. are far more frequently present in the intestinal tract of healthy dogs than previously believed. Using these new methodologies, it has now been estimated that the intestinal bacterial ecosystem is made up of more than 1,000 different bacterial species.
Physiologic Importance of the Intestinal Bacterial Ecosystem
The intestinal bacterial ecosystem is initially established during birth and continues to develop during suckling. The impact of the intestinal microbiota and the bacterial ecosystem has been well established by studies in germ-free rodents. These rodents show a wide variety of morphological and physiological alterations that overall equate to a state of compromised intestinal function and immunity. In healthy animals, the physiologic microbiota, and most prominently the bacterial ecosystem, has several important functions. Firstly, it protects the host against pathogenic bacteria by competing for oxygen, luminal substrates, and space, but also by synthesizing and releasing substances that inhibit bacterial growth, so-called bacteriocins. Intestinal bacteria also produce short-chain fatty acids by metabolizing dietary components that are often non-digestible for the host. In turn, these short-chain fatty acids serve as an important energy source for the intestinal mucosa, leading to epithelial cell proliferation and mucosal growth. Members of the intestinal bacterial ecosystem also synthesize a variety of vitamins, including riboflavin (vitamin B2), biotin (vitamin B7), folic acid (vitamin B9), cobalamin (vitamin B12), and vitamin K. It is important to note, however, that physiologically, the synthesis of some of these vitamins, for example cobalamin, is not of significance to the host as the synthesis may occur distally to where the vitamin can be absorbed. Finally, intestinal bacteria also play a crucial role in the development of the intestinal immune system. They stimulate said intestinal immune system, which plays a crucial role in overall host defense throughout all stages of life.
It has long been known that some dogs and cats with acute or chronic diarrhea respond to antibiotic therapy. While some of these patients may be infected with a primary gastrointestinal pathogen, such as Salmonella spp. or some pathogenic Campylobacter strains, a specific causative organism can’t be identified in most of these patients. A response to antibiotics would suggest that these patients are affected by an alteration of the intestinal bacterial ecosystem that leads to diarrhea and that modification of the intestinal bacterial ecosystem can lead to improvement of clinical signs.
Small intestinal dysbiosis is caused by an abnormal proliferation of bacteria and/or the change in bacterial species present in the small intestinal lumen. However, dysbiosis should not be considered a primary disorder in most if not all patients with this disorder. There are several protective mechanisms that prevent a patient from dysbiosis. Gastric acid, intestinal motility and antibacterial activity of pancreatic juice all limit the bacterial numbers in the small intestine. Gastric acid directly destroys bacteria that are ingested with the diet and also decreases the pH of the ingesta, leading to a lower pH in the proximal small intestine. However, the lack of gastric acid secretion alone is not sufficient for dysbiosis to develop. Propulsive movements of the small intestine are probably the most important protective factor since there is no physical barrier between the large intestine and the small intestine that would prevent retrograde cultivation of the small intestine by the large intestinal microbiota. The antibacterial properties of pancreatic juice are not well understood. Pancreatic digestive enzymes may be partly responsible for the antibacterial action of pancreatic juice. Any disease process that affects one or more of the protective mechanisms discussed can ultimately lead to small intestinal dysbiosis.
Small intestinal dysbiosis in dogs and cats leads to chronic small bowel diarrhea that is often intermittent. Weight loss can be present in some cases. Other clinical signs may be due to the primary underlying disease process, such as partial obstruction, exocrine pancreatic insufficiency, or others.
Part of the controversy about small intestinal dysbiosis is due to the fact that this disorder is difficult to diagnose. Traditionally, the gold standard for assessment of the small intestinal bacterial ecosystem is the culture of duodenal juice. However, not only is the collection of duodenal juice challenging, but also the culture of duodenal juice once collected is difficult, time-consuming, and expensive and requires a laboratory that has experience in this area. Also, bacterial culture methods grossly underestimate the bacterial diversity of the small intestinal bacterial ecosystem. Therefore, culture of duodenal juice is not suggested. It remains to be seen whether molecular-based methods allow for a better assessment of the small intestinal microbiota.
Noninvasive Diagnostic Tests
Serum folate concentration – As pointed out previously folic acid is synthesized by enteric bacteria and is available for absorption. In dogs with small intestinal dysbiosis for a long period of time, serum folate concentration increases. While an increased serum folate concentration is fairly specific for small intestinal dysbiosis, it is not very sensitive. In one study, only 50% of all dogs with small intestinal dysbiosis had increased serum folate concentrations.
Serum cobalamin concentration – Many species of bacteria utilize cobalamin and compete with the body for dietary supplies. Unlike an increased serum folate concentration, a decreased serum cobalamin concentration is not specific for small intestinal dysbiosis. Any severe small intestinal disease involving the ileum can lead to cobalamin deficiency. Also, a lack of intrinsic factor and digestive proteases in dogs with exocrine pancreatic insufficiency can cause cobalamin deficiency. A decreased serum cobalamin concentration is rather insensitive for small intestinal dysbiosis and in one study, only 25% of dogs with small intestinal dysbiosis had decreased serum cobalamin concentration. A combination of a decreased serum cobalamin and an increased serum folate concentration is highly specific for small intestinal dysbiosis but rather insensitive. These two parameters are, to date, the most practical diagnostic tools for the diagnosis of small intestinal dysbiosis.
Other noninvasive diagnostic tests, previously evaluated for the diagnosis of small intestinal dysbiosis, such as unconjugated bile acid concentration in serum, breath hydrogen concentration, 13C-xylose, and 13C-bile acid tests have not shown to be consistently useful for the diagnosis of this condition.
The therapeutic goal in dogs with small intestinal dysbiosis is the identification and treatment of the inciting cause. For example, serum TLI concentration should be evaluated. Dogs with EPI and secondary small intestinal dysbiosis usually do not require specific therapy for small intestinal dysbiosis once they are treated with enzyme supplementation. If a primary cause cannot be identified, one of several therapeutic strategies or a combination thereof should be employed.
Prebiotics are substances that preferentially support the resident bacterial ecosystem of the intestine. Basically, prebiotics are nondigestible food components (dietary fiber) 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. While this has not been evaluated as of yet, other prebiotics, such as inulin or beet-pulp, may also prove to be beneficial.
In one study, dogs with dysbiosis diagnosed based on clinical signs and serum folate and cobalamin concentrations were divided into two groups. One group was treated with an antibiotic for 6 weeks and the other group was switched to a diet containing FOS. Both groups of dogs responded equally with normalization of fecal quality among improvement of other parameters, but many of the dogs treated with the antibiotic showed a relapse after the antibiotic therapy was stopped, while the beneficial effect of the diet was maintained.
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 or cats are: 1) the probiotic must be safe; 2) the probiotic must be stable; and 3) the probiotic must be efficacious. In an older study, 8 veterinary and 5 human probiotics were evaluated, and only 2 of the 13 products contained the strains and concentrations of those strains were indicated on the label. Several of the products contained bacterial species that could potentially act as enteropathogens. One may suspect that these issues were related to start-up issues when probiotics first entered the marketplace. However, a recent study showed that of 22 veterinary products evaluated only 2 contained in it what the label stated. Part of the problem may be that many of the products offered are manufactured by small companies that may not have the technological capabilities to manufacture a stable product. The probiotic also must be stable throughout transport and storage until the product is being administered by the pet-owner. 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 resistant and bile acid resistant. 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 for the host. Several studies have been conducted in dogs that show that certain probiotics carry health benefits in dogs with gastrointestinal disorders. Scenarios for which there is good evidence of a beneficial effect of probiotics are the prevention of stress-related diarrhea, treatment of stress-related diarrhea, and acute nonspecific diarrhea. The effects of probiotics in dogs and cats with idiopathic inflammatory disease or dysbiosis have not been sufficiently studied, though a beneficial effect in patients with small intestinal dysbiosis would seem logical.
Synbiotics are combinations of prebiotics and probiotics. There are three different approaches to synbiotic use. Some boutique pet foods are fortified with a prebiotic and are sprayed with a probiotic. Even though most of these pet foods use bacterial spores that show much greater resilience to environmental factors, this mode is likely unrealistic, as the bacterial load is small and the bacterial spores may not be stable enough to reach the patient. Another approach is to use a pet food fortified with a prebiotic and also use a probiotic nutraceutical concurrently. This is likely the most realistic synbiotic approach. The use of a nutraceutical that contains both the pre- and the probiotic may be realistic in cats and small dogs, but in large dogs the amount of prebiotic in the supplement is likely not sufficient to show any prebiotic effect.
In humans with chronic intestinal disease, there has been some experience with fecal transplantation. While in patients with chronic colitis application of the transplant by enema may be efficacious, in patients with small intestinal dysbiosis the transplant would need to be used through some oral route. Experience in dogs and cats with small intestinal dysbiosis is limited, and great care would need to be taken to transplant enteropathogens, especially in donors that are subclinically infected.
Oxytetracycline used to be the therapy of choice for small intestinal dysbiosis, but oxytetracycline for oral use has become largely unavailable. Tylosin (25 mg/kg q12h for 6 weeks) is the new antibiotic agent of choice. Tylosin is extremely safe and is not used in humans for the most part – thus, creating resistant bacterial strains is not a big concern. In one study, a group of dogs was treated with 400 mg/kg daily for a period of 2 years and none of them developed any side-effects. The superb efficacy of tylosin has been well-demonstrated in studies from Finland. Some of those newer studies would suggest that smaller dosages may also be beneficial, but these findings will need to be verified. Other antibiotics, such as metronidazole, can also be used. Some patients respond to therapy rapidly and do not have a recurrence. However, other patients 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 patients 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 patients 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 or if cobalamin is in the very low end of the reference range, cobalamin should be supplemented.
(click the speaker’s name to view other papers and abstracts submitted by this speaker)Jörg M. Steiner, DrMedVet, PhD, DACVIM, DECVIM-CA, AGAF
Texas A&M University
College Station, TX, USA
Microbes and Gastrointestinal Health of Dogs and Cats
Dr. Jan Suchdolski 2014
2015 Small Bowel Diarrhea- -IBD not the most Common Cause
Michael Willard, DVM, MS, DACVIM-SA
College of Veterinary Medicine
Texas A&M University, College Station, TX
SIBO or ARD: What’s in a Name?
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 109cfu/mL being reported in clinically healthy dogs. Yet when bacterial numbers in the duodenum of cats were first reported as up to 1 x 109cfu/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.
DOES SIBO EXIST?
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.
DOES IDIOPATHIC SIBO EXIST?
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.
WHAT IS ARD?
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.
WHAT CAUSES IDIOPATHIC SIBO / ARD?
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:
- competition for nutrients
- damage to brush border enzymes
- deconjugation of bile salts impairing fat absorption
- hydroxylation of fatty acids; these products and deconjugated bile salts stimulate colonic secretion.
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.
Serum Folate and Cobalamin
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.
Unconjugated Bile Salts
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.
E.J. Hall, School of Clinical Veterinary Science, University of Bristol, Langford, Bristol, England.
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- 5. Peters IR, Helps CR, Calvert E, Hall EJ, Day MJ. Cytokine mRNA quantification in duodenal mucosa from dogs with chronic enteropathies by real-time reverse transcriptase polymerase chain reaction. J Vet Intern Med 2005;19; 644-653.
- 6. Peters IR, Helps CR, Calvert EL, Hall EJ, Day MJ. Identification of four allelic variants of the dog IGHA gene. Immunogenet 2004; 56:254-260.
- 7. Westermarck E, Skrzypczak T, Harmoinen J, et al.Tylosin-responsive chronic diarrhea in dogs. J Vet Intern Med 2005; 19:177-186.
SIBO “Small Intestinal Bacterial Overgrowth” 2009
Masterfoods, Mars Inc.
Waltham-on-the-Wolds, Leicestershire, UK
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 H2breath 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.
An 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
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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.
“ARD” Antibiotic-Responsive Diarrhea …. otherwise known as “SIBO”
F.P. Gaschen Email: email@example.com
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.).