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Access Type

WSU Access

Date of Award

January 2021

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Nutrition and Food Science

First Advisor

Kequan Zhou

Abstract

The prevalence of obesity is rising steadily across the world, which increases the risk of many metabolic diseases and life-threatening illnesses. A specific strain, Clostridium cochlearium (C. cochlearium), reported as a butyrate producer, could have potential probiotic effects against obesity. The objective of this study was to evaluate the effects of dietary supplementation of C. cochlearium on a high-fat diet-induced obese (DIO) mouse model. The 16S rRNA sequencing of mice gut microbiome was performed at the end of the experimental period to identify the changes in gut microbial composition, investigate possible functional genes, and elucidate potential mechanisms. Thirty-six C57BL/6 6-8 week old male mice were randomly separated into three groups (n = 12): low-fat diet control (LF) group, high-fat diet control (HF) group, and experimental group on a high-fat diet with C. cochlearium supplementation (CC). After 16 weeks of dietary supplementation, the results showed the CC group had a 17.29% body weight reduction relative to the HF group (P < 0.0001), while 20.82% of fat mass decrease was observed compared to the HF group (P < 0.0001). The AUC of OGTT and HOMA-IR in the CC group was significantly reduced by 60.20% (P < 0.0001), 47.21% (P < 0.01), respectively. Moreover, the resting energy expenditure (P < 0.05) and activity level (P < 0.05) showed a significant increase in the CC group. After performing alpha-and beta-diversity analyses, significant separation of the gut microbiome profile was observed between the HF and CC groups, which suggested the alteration of microbial compositions from the C. cochlearium supplementation. Additionally, the ratio of Firmicutes and Bacteroidetes (F/B) was significantly lower in the CC group compared to the HF group (P < 0.05). The family of Ruminococcaceae and Lachnospiraceae, as short-chain fatty acids (SCFAs) producers, significantly contributed to the gut community of the CC mice, which has been negatively associated with body weight. There was an increasing abundance of butyrate-producing enzymes and pathways observed from the CC group, which suggested a possible beneficial effect of a negative correlation with body weight gain. This study concluded that the administration of C. cochlearium had anti-obesity effects on reduced body weight gain and improve glucose homeostasis in the high-fat diet-induced obesity mouse model, which could be mediated through an increased abundance of SCFAs-producing bacteria and their related pathways. However, the butyrate (P < 0.0001) and acetate (P < 0.001) concentrations in the intestinal content showed a significant reduction in the CC group, which was unexpected and warranted further investigation of circulating SCFAs levels. This additional information may enhance our understanding of the probiotic effects of C. cochlearium supplementation.

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