Gut Microbiota Metabolites Modulate Inflammation in Non-alcoholic Fatty Liver Disease
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 ... read moredescribed 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
Thesis (Ph.D.)--Tufts University, 2018.
Submitted to the Dept. of Chemical and Biological Engineering.
Advisor: Kyongbum Lee.
Committee: David Sherr, Carol Kumamoto, and Nikhil Nair.
Keyword: Chemical engineering.read less