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Dissertation/Thesis Abstract

Gut Microbiota Metabolites Modulate Inflammation in Non- Alcoholic Fatty Liver Disease
by Krishnan, Smitha, Ph.D., Tufts University, 2018, 234; 10812893
Abstract (Summary)

Recent findings, including our own work, demonstrated that intestinal microbiota species produce bioactive metabolites that engage host cellular pathways. Microbiota-derived metabolites have also been detected in circulation and in the, setting up the intriguing possibility that these bacterial products could directly interact with host cellular pathways at distant sites. The study described in this abstract investigates the hypothesis that gut microbiota dysbiosis perturbs the balance of immunomodulatory microbiota metabolites, which exacerbates liver inflammation in steatosis. We utilize a multi-omic approach to identify microbiota-dependent immunomodulatory metabolites and characterize their effects on liver inflammation and metabolic function. In summary, we show that the levels of AAA-derived microbiota metabolites are significantly depleted in a diet model of liver steatosis, and that these metabolite can act directly on hepatocytes to modulate inflammatory pathways. Our results also show that the microbiota metabolites are ligands for the AhR, which could provide a mechanistic link for the observed anti-inflammatory effects. Taken together, our findings support the hypothesis that dysbiosis of the gut microbiota could predispose the liver to inflammation in diet-induced steatosis through an altered microbiota metabolite profile. Prospectively, additional insights into the mechanisms underlying the link between microbiota dysbiosis and NAFLD could provide novel strategies to treat or prevent the progression of fatty liver diseases through the use of probiotics or postbiotics.

Indexing (document details)
Advisor: Lee, Kyongbum
Commitee: Kumamoto, Carol, Nair, Nikhil U., Sherr, David H.
School: Tufts University
Department: Chemical and Biological Engineering
School Location: United States -- Massachusetts
Source: DAI-B 79/10(E), Dissertation Abstracts International
Subjects: Chemical engineering
Keywords: Aryl hydrocarbon receptor, Fatty liver disease, Gut microbiota, Indole-3-acetate, Inflammation, Steatosis
Publication Number: 10812893
ISBN: 978-0-438-02097-9
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