Dysbiosis and the emerging role of intestinal microbiota in chronic enteropathies (Proceedings)

Molecular studies have determined that the intestines of dogs and cats harbor a complex population of commensal bacteria, referred to as the microbiota. Depending on its composition, the microbiota can be beneficial or harmful to the host. Evidence suggests that the bacterial composition of the intestinal ecosystem plays a role in the pathogenesis of acute and chronic enteropathies, including chronic inflammatory bowel disease (IBD). The pathogenesis of IBD likely involves complex interaction between the mucosal immune system and the intestinal microbiota.

Intestinal microbiota in health

The mammalian intestinal tract becomes colonized by commensal bacteria shortly after birth. These indigenous intestinal bacteria are vitally important for development and homeostasis of the host's mucosal immune system (i.e., gut-associated lymphoid tissue; GALT). The intestinal microbiota also helps to prevent colonization by enteropathogens by competing for oxygen, nutrients and mucosal adhesion sites, and through production of antibacterial substances (e.g., bacteriocins). Colonic bacteria ferment organic matter into short-chain fatty acids (SCFA; e.g., acetate, proprionate, butyrate), which serve as the main energy source for colonic epithelial cells. Bacteria-derived SCFA stimulate mucosal growth and epithelial cell proliferation. The pH lowering effect of SCFA also helps resistance to pathogens. The composition of the microbiota is dependent on host characteristics (age, genotype, health status), diet composition, and environmental factors. The total enteric ecosystem comprised of the resident microbial community together with the host cells they mutually interact with has been called the intestinal microbiome.

With recent advances in molecular microbiology, complex bacterial populations can be analyzed without bacterial culture. The ability to evaluate the composition of the intestinal microbiota by conventional bacterial culture is limited by the complexity of the bacterial population and the fact that the majority of the bacteria are nonculturable. For this reason the intestinal microbiota is best analyzed using molecular techniques that sequence bacterial subunit ribosomal RNA (16S rRNA) - the molecular identity “bar code” for microbes. Bacterial 16S rRNA sequencing has characterized the GI microbiota in healthy dogs. Several hundreds or even thousands of different bacterial species from 10 different bacterial phyla inhabit the canine and feline GI tract, as well as a variety of fungi. Each individual animal harbors a unique but diverse microbial population. Bacterial diversity is a key attribute of a healthy intestinal microbiota. The predominant and most diverse phylum of bacteria in healthy dogs and cats is Firmicutes (mostly Clostridiales and Lactobacillales). Other phyla present in high proportion are Bacteroidetes, Fusobacteria, and Proteobacteria. The bacterial populations differ between regions of the intestine (duodenum, jejunum, ileum, colon). Bacteria in the luminal contents (or feces) also differ from bacteria in the mucosa (or adherent mucus).

Intestinal dysbiosis in IBD

Molecular studies have revealed imbalances in the bacterial composition of the intestine in dogs and cats with IBD. This intestinal dysbiosis in IBD is characterized by a decrease in the overall diversity of the bacterial population in the intestine compared to healthy animals, and a flora shift from gram-positive to gram-negative bacteria. The altered bacterial composition in IBD is characterized by increased Enterobacteriaceae (E. coli) and other Proteobacteria, and decreased Firmicutes, Bacteroidetes, and Clostridium clusters XIVa and IV (Faecalibacterium, etc). The increased numbers of Enterobacteriaceae (E. coli and other gram negative bacteria) in both the luminal contents and adherent mucus layer appear to correlate with the severity of mucosal inflammation and clinical signs. It remains to be determined if these shifts and imbalances in microbiota composition are a cause or a consequence of the mucosal inflammation in IBD. Alterations in the microbiota may perpetuate intestinal inflammation, which would support treatment strategies that might control inflammation by modifying the intestinal bacterial population (e.g., antibiotics, probiotics, dietary modification). The association of dysbiosis with IBD may explain the responsiveness of IBD to antibiotics such as metronidazole and tylosin. In normal dogs tylosin has been shown to have prolonged effects on the composition and diversity of small intestinal microbiota.

Using bacterial 16S rRNA gene pyrosequencing technique, Suchodolski et al, 2011 have also identified intestinal dysbiosis in dogs with acute hemorrhagic diarrhea. As in chronic enteropathy, dysbiosis is characterized by higher proportions of Proteobacteria (gram negatives) and lower proportions of Firmicutes (e.g., Clostridium and Faecalibacterium spp).

Probiotics and prebiotics

Considering the emerging importance of the intestinal microbiota in intestinal disease, there is growing interest in the role of intervention using probiotics and prebiotics. Probiotics are neutraceuticals containing live microorganisms that beneficially affect host health by improving the intestinal microbial balance. To have an effect, probiotics must contain adequate numbers of viable bacteria that survive transit into the intestine. Loss of viability in processing is a significant issue for over-the-counter probiotic products, but the quality of commercial brand name veterinary probiotics is excellent. Prebiotics are nondigestible food ingredients (e.g., fructans, lactulose, galactooligosaccharides) that beneficially affect the host by selectively promoting the growth and/or activity of desireable populations of intestinal bacteria.            Numerous studies are published that demonstrate the effects of probiotics and prebiotics on fecal microbiota, fermentation endproducts, and fecal consistency in healthy dogs and cats, but placebo-controlled studies to establish efficacy in gastrointestinal disease are lacking. Using molecular techniques it has been shown in dogs and cats treated with a multistrain probiotic that the increased numbers of the probiotic species are detectable in the feces throughout the treatment period, but this effect rapidly disappears after discontinuation of treatment and the microbiota returns to baseline. Probiotics are extremely safe and free of adverse side effects. This presentation will review some of the evidence for probiotics in canine and feline GI disease. It is important to recognize that the results obtained with one probiotic strain may not be equivalent to the effects of other probiotics strains. Also, beneficial effects of a probiotic in one particular disease or condition does not necessarily mean the probiotic will be effective in other diseases.

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