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Access Type

WSU Access

Date of Award

January 2018

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Nutrition and Food Science

First Advisor

Kai-Lin Catherine Jen

Second Advisor

Kequan Zhou

Abstract

THE EXPLORATION OF CHARACTERISTICS OF AKKERMANSIA MUCINIPHILA, AND EVALUATION OF ITS PROBIOTIC EFFECTS ON DIABETES BY USING C57BL/6 MOUSE MODEL

by

JIANGQI TANG

December 2018

Advisor: Dr. Kai-Lin Catherine Jen

Major: Nutrition and food science

Degree: Doctor of Philosophy

The prevalence of type 2 diabetes (T2D) is increasing continuously worldwide. The incidence of T2D is highly correlated with poor diet, physical inactivity and occurrence of obesity. Recent studies reported possible interaction between T2D and gut microbiome, which revealed different composition of gut microbiome. A specific strain Akkermansia muciniphila (A. muciniphila) was reported with significantly lower abundance even prior to the incidence of diabetes. This study was designed to discover the optimal growth conditions based on characteristics of A. muciniphila and determine appropriate encapsulation method to ensure sufficient bioactivity through gastrointestinal tract. C57BL/6 mice model was further used to explore in-vivo benefits of A. muciniphila supplementation. Results showed medium adjusted to pH 6.5 could promote the best growth of A. muciniphila at 37 °C. Isomaltooligosaccharide was proved to be the best prebiotic ingredient. In order to manufacture in large quantity, fructose, sucrose and dextrose were able to promote the highest viability, especially with the concentration of 0.5%. Bile salt hydrolase activity was discovered in A. muciniphila with an intermediate level, which helped to improve its tolerance to digestion system with high concentration of bile salts. Extruded beads of A. muciniphila was shown to be an outstanding protection through simulated stomach and GIT. After diet induced mice were supplemented with A. muciniphila for six months, results showed no significant change in mice body weight or daily food intake; however, improvement on glucose homeostasis was noticed including fasting blood glucose and glucose tolerance. In addition, mice supplemented with A. muciniphila showed a higher energy loss in feces while no difference was found in energy expenditure or body composition. A. muciniphila has been proved to be safe after a supplementation for six months. Future studies would investigate the benefits of A. muciniphila with increased dosage and its possible mechanism in the host.

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