Page 654 - Clinical Small Animal Internal Medicine

622 Section 6 Gastrointestinal Disease

the micriobiota) include Spirochaetes, Tenericutes, and changes in bacterial groups, and/or changes in the func-
VetBooks.ir Verrucomicrobia. The Firmicutes can be divided into tional and immunomodulatory properties of the gastro-
intestinal microbiota. All these forms overlap to some
several subgroups on a family and genus level. It com-
prises many phylogenetically distinct bacterial groups.
There are several physiologic mechanisms that regu-
These groups (e.g., Ruminococcus spp., Faecalibacterium extent.
spp., Dorea), together with Bacteroidetes and late microbial colonization in the GI tract. Gastric acid,
Actinobacteria (i.e., Bifidobacterium) are producers of bile, and pancreatic enzymes all have antibacterial roles
metabolites that have direct impacts on host health. For and eliminate a proportion of ingested organisms.
example, bacteria can utilize complex carbohydrates Intestinal motility is an important regulator of bacterial
(e.g., starch, cellulose, pectin, and inulin) as nutrient adhesion to the mucosa in the small intestine. Microbes
sources, and their fermentation produces SCFA (e.g., that are unable to adhere to the epithelium will be pushed
acetate, propionate, and butyrate). These act as energy to the large intestine, which has a more stagnant motility
sources for the host, regulate intestinal motility, and are and therefore higher bacterial numbers. The ileocolic
important growth factors for epithelial cells. SCFA are valve is a natural barrier that prevents retrograde migra-
also important antiinflammatory molecules, as they tion of bacteria from the large to the small intestine.
induce immunoregulatory T cells (T reg ). Other bacteria‐ Any changes in these mechanisms may lead to dysbio-
derived metabolites, such as indoles (a byproduct of sis, but whether this leads to disease will depend on the
tryptophan degradation) or secondary bile acids, are also susceptibility of the individual, as not every animal
antiinflammatory, thereby maintaining immune homeo- exposed to these risk factors will develop disease. For
stasis and strengthening intestinal barrier function. example, acid suppression therapy increases gastric and
The microbiota primes the immune system, aids in the duodenal bacterial counts in humans, but not all patients
defense against potential intestinal pathogens, and show clinical signs. Similarly, dogs with experimentally
provides nutritional benefits to the host. Bacteria com- induced exocrine pancreatic insufficiency (EPI) have
municate with the host’s innate immune system through increased bacterial numbers in the proximal small intes-
cell‐associated receptors such as Toll‐like receptors tine. Rapid diet changes, dietary indiscretion, changes in
(TLR) and dendritic cells. The resident intestinal micro- the architecture of the intestine, or changes in intestinal
biota is also a crucial part of the intestinal barrier, due to motility (i.e., surgical creation of intestinal loops, short
the phenomenon of “colonization resistance” which bowel syndrome, and resection of the ileocolic valve) are
protects the host from invading pathogens through com- also associated with dysbiosis. The development of dys-
petition for oxygen, nutrients, and adhesion sites on the biosis may then lead to changes in gastrointestinal physi-
mucosa. ology that will negatively impact function of the GI tract.
Examples are an altered intestinal barrier with increased
intestinal permeability and direct damage to the intesti-
The Gastrointestinal Microbiota nal brush border and enterocytes leading to nutrient and
in Disease vitamin malabsorption. An overgrowth in specific bacte-
rial groups may lead to increased competition for nutri-
There is clear evidence that altered microbial communi- ents and vitamins and to increased deconjugation of bile
ties play a role in the pathophysiology of various disorders. acids, resulting in the creation of potentially deleterious
Chronic dysbiosis is likely an important environmental metabolites.
risk factor for development of several chronic diseases in The intestinal microbiota also plays a role in the patho-
genetically susceptible individuals. For example, recent genesis of IBD. Intestinal inflammation leads to a shift
epidemiologic studies in humans have linked antibiotic towards gram‐negative bacteria (i.e., Proteobacteria)
administration in early childhood with an increased risk that may perpetuate the disease. Existing dysbiosis may
for development of allergies and obesity. Also, antibiotic‐ trigger alterations in the immune system, which in turn
induced reductions in gut microbiota diversity were a diminish the colonization resistance of the resident
risk factor for higher mortality outcomes in allogeneic microbiota. Several studies in dogs and cats have
hematopoietic stem cell transplantation. These initial reported increases in Enterobacteriaceae in the GI tract
data in humans suggest that dysbiosis is clinically rele- of dogs and cats, and these are associated with inflam-
vant and the correction of dysbiosis would appear to be a mation and altered mucosal architecture. In contrast, a
prudent therapeutic goal. However, at this time, there are reduction in some major bacterial groups (i.e.,
still only limited clinical data available to guide specific Lachnospiraceae, Ruminococcaceae, Faecalibacterium
treatments for correction of dysbiosis in dogs and cats. prausnitzii and Clostridium coccoides subgroups) occurs
Dysbiosis occurs in various forms; it may be due to in GI disease, suggesting a loss of normal and protective
overgrowth of specific pathogens, or due to more general microbiota in GI disease (Figure 58.1).