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    Bile Acid Metabolism and Gastrointestinal Microbiota in Dogs with Chronic Inflammatory Enteropathy

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    GIARETTA-DISSERTATION-2019.pdf (3.273Mb)
    Date
    2019-04-04
    Author
    Giaretta, Paula Roberta
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    Abstract
    Chronic inflammatory enteropathy (CIE) is a common cause of gastrointestinal signs in dogs, but its etiology is poorly understood. Dogs with CIE have imbalances in their bile acid (BA) metabolism and gastrointestinal microbiota. The objective of this study was to investigate a particular BA receptor, BA transporter, and the mucosal microbiota in canine CIE. In the first part of this study, the distribution of the BA receptor Takeda-G-protein-receptor-5 (TGR5) was characterized along the canine gastrointestinal tract. In control dogs, TGR5 was ubiquitously found in cells of epithelial, neural, muscular, endothelial, and endocrine origin in the gastrointestinal tube, liver, and pancreas. The expression of TGR5 protein in the intestine of dogs with CIE was similar to that of control dogs. Second, the distribution of the apical sodium-dependent BA transporter (ASBT) was described along the canine gastrointestinal tract. In control dogs, expression of ASBT was observed mainly in the ileum, the major site for BA reabsorption. Dogs with CIE had decreased expression of ASBT protein in the ileum, which was negatively correlated with inflammation. An increased proportion of primary BAs versus secondary BAs was observed in the feces of dogs with CIE. The proportion of fecal secondary BAs was correlated with the fecal dysbiosis index and abundance of Clostridium hiranonis, supporting that the intestinal microbiota is critical for BA biotransformation. The final part of this study analyzed the microbiota in the colonic mucosa and feces of dogs with CIE using fluorescence in situ hybridization (FISH) and qPCR, respectively. Dogs with CIE had fecal and mucosal dysbiosis, with decreased number of total bacteria within their colonic crypts. The depleted cryptal microbiota in the colon was composed mainly by Helicobacter spp. Dogs with CIE had decreased number of Akkermansia spp. and increased Escherichia coli on the colonic surface and within the crypts. In conclusion, this study demonstrated that BA dysmetabolism in dogs with CIE is associated with altered expression of the intestinal transporter, which might be relevant for the pathogenesis of CIE. The dysbiosis associated with CIE involves both the feces and the niches closely associated with the host, such as the colonic crypts.
    URI
    http://hdl.handle.net/1969.1/185086
    Subject
    Bile acids
    Inflammatory bowel disease
    Microbiota
    Dogs
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    • Electronic Theses, Dissertations, and Records of Study (2002– )
    Citation
    Giaretta, Paula Roberta (2019). Bile Acid Metabolism and Gastrointestinal Microbiota in Dogs with Chronic Inflammatory Enteropathy. Doctoral dissertation, Texas A & M University. Available electronically from http : / /hdl .handle .net /1969 .1 /185086.

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