Access Type

Open Access Dissertation

Date of Award

January 2021

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Nutrition and Food Science

First Advisor

Kequan Zhou

Abstract

ABSTRACTCHARACTERIZATION OF CLOSTRIDIUM COCHLEARIUM AS A POTENTIAL PROBIOTIC FOR OBESITY MANAGEMENT

ByPABA EDIRISURIYA MAY 2021 Advisor: Dr. Kequan Zhou Major: Nutrition and food science Degree: Doctor of Philosophy Emerging evidence indicates that manipulation of gut microflora is a potential therapeutic approach for managing obesity. Probiotic effects on host weight reduction have repeatedly been revealed through previous studies. Clostridium cochlearium is a butyrate-producing, spore-forming bacteria that have been reported to present in the mammalian gut. Our simulated Invitro digestion model revealed that C. cochlearium could survive in the unfavorable conditions of the human gastrointestinal tract, including low pH (pH2), high bile salts (1.5% w/v), and in the presence of enteric digestive enzymes. Daily Oral administration of C. cochlearium (109 CFU) for 14 weeks showed 18% bodyweight reduction in DIO (C57BL/6) mice primarily via fat mass reduction. Obesity-related other metabolic deteriorations, including hyperglycemia, serum glucose, and insulin intolerance, hypercholesteremia, liver steatosis, were also improved. A significant decrease in host energy expenditure and alteration of hot bile acid composition were observed in the C. cochlearium treated group. In addition, C. cochlearium treatment significantly upregulated gene expressions related to reverse cholesterol clearance and bile acids synthesis. C. cochlearium administration increased bile acid deconjugation and fecal bile acid excretion, thus reducing intestinal bile acid absorption consequently derepressed FXR/FGF15 inhibition circuit of CYP7A1. Along with the modulation of bile acid metabolism, we observed parallel regulation of reverse cholesterol transport. These finding indicated that the anti-obesity activity of C. cochlearium occurred through altered bile acid composition, that increased energy expenditure and cholesterol turnover which ultimately improved host lipid and glucose metabolism. Thus, C. cochlearium could be a potential therapeutic probiotic for managing obesity, diabetes, and hypercholesteremia. Further studies are needed to understand the impact of C. cochlearium on the gut microbiome and the association of C. cochlearium mediated microbiome with bile acid composition and FXR/fgf15 singling pathway.

Share

COinS