Document Type

Thesis - Open Access

Award Date

2021

Degree Name

Doctor of Philosophy (PhD)

Department / School

Veterinary and Biomedical Sciences

First Advisor

Joy Scaria

Abstract

Aberrant gut microbiota composition is found to be associated with several human diseases such as inflammatory bowel diseases (IBD). Reduction in butyrate producing bacteria is one of the characteristic features of such dysbiotic bacterial community in the gut. Modulation of gut microbiota to bring the dysbiotic state back to normal healthy state is a promising therapeutic strategy to cure several diseases like recurrent Clostridium difficile infection (rCDI) and IBD where traditional therapies using pharmacological substances fails to make a difference. Restoration of butyrate producers is found to be an effective method of such gut microbiota modulation. The potential to produce butyrate is phylogenetically diverse and not even present in all members of the same family. Hence the number of identified bacteria that can produce butyrate is not vast and most of them were not explored for their functional roles towards host health benefits. Low abundance and the difficulty to culture these strictly anaerobic organisms are the few reasons of their under exploration. Here we examine the immunomodulatory properties of four butyrate producing human gut bacterial species as a defined mix using gnotobiotic mouse as a model. Our study shows, these allochthonous bacterial strains assemble in the germ-free mouse gut and produce butyrate as one of the short chain fatty acids. Without causing any pathological changes, successful colonization of these bacteria fortifies the innate immune defense system by enhancing the expression of regenerating islet-derived protein 3 beta (Reg3b), regenerating islet-derived protein 3 gamma (Reg3g), mucin 2 (Muc2) and defensin beta (Defb) genes in the colon and modulating the adaptive immune cell populations at the systemic levels. However, precolonization of these bacteria did not show any significant changes in pro and antiinflammatory responses in gnotobiotic mice compared to germ free mice under colitis induced by Dextran sulfate sodium (DSS). But a better gross and histopathological appearance of colon in gnotobiotic mice indicates that these bacteria have some role in attenuating colitis rather aggravating it and thus can be considered as candidates of bacterial therapeutics.

Library of Congress Subject Headings

Gastrointestinal system -- Microbiology.
Butyrates.
Germfree animals.
Mice as laboratory animals.

Format

application/pdf

Number of Pages

143

Publisher

South Dakota State University

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Included in

Microbiology Commons

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Rights Statement

In Copyright