Small intestinal dysbiosis (Proceedings)

Aug 01, 2011

A 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 the most appropriate.

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 Finish 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 microbiota

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. Unfortunately, such studies are associated with problems in reproducibility. For example, a variety of studies reported the physiologic bacterial ecosystem in the proximal small intestine of dogs, but different studies found a preponderance of different bacterial species. It has since been recognized that a variety of factors, such as location, breed, age, collection method, culture media, culture conditions, and others all play an important role in the results of culture-based studies. 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 1000 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 have 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.