Abstract

Akkermansia muciniphila (A. muciniphila) is a promising probiotic candidate owing to its health-promoting properties. A previous study reported that the pasteurized form of A. muciniphila strains isolated from human stool samples had a beneficial impact on high-fat diet-induced obese mice. On the other hand, the differences in the probiotic effects between live and pasteurized A. muciniphila on the metabolism and immune system of the host are still inconclusive. This study examines the differences between the live and pasteurized forms of A. muciniphila strains on the lipid and glucose metabolism and on regulating the inflammatory immune responses using a HFD-fed obese mouse model. The animals were administered the live and pasteurized forms of two A. muciniphila strains five times per week for the entire study period of 12 weeks. Both forms of the bacterial strains improved the HFD-induced obesity and metabolic dysregulation in the mice by preventing body-weight gains after one week. In addition, they cause a decrease in the weights of the major adipose tissues, adipogenesis/lipogenesis and serum TC levels, improvement in glucose homeostasis and suppression of inflammatory insults. Furthermore, these treatments restored the damaged gut architecture and integrity and improved the hepatic structure and function in HFD-induced animals. On the other hand, for both bacterial strains, the pasteurized form was more potent in improving glucose tolerance than the live form. Moreover, specific A. muciniphila preparations with either live or pasteurized bacteria decreased the number and population (%) of splenic Treg cells (CD4+ Foxp3+) significantly in the HFD-fed animals, further supporting the anti-inflammatory properties of these bacteria.

Highlights

  • Metabolic dysregulation represents a cluster of metabolic abnormalities, such as hyperglycemia, hyperinsulinemia and hyperlipidemia

  • Our results further revealed that the serum glucose area under the curve (AUC) in the high-fat diet (HFD)-treated mice2A)

  • SREBP-1c primarily regulates the genes involved in de novo lipogenesis and triglyceride synthesis, including ACC, which plays an essential role in modulating fatty acid synthesis and degradation [46,47]

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Summary

Introduction

Metabolic dysregulation represents a cluster of metabolic abnormalities, such as hyperglycemia, hyperinsulinemia and hyperlipidemia. It is a vital measure of obesity-related diseases, such as fatty liver disease, insulin resistance and type 2 diabetes [1]. In addition to systemic inflammation, metabolic dysregulation is considered a key complication of obesity [2], a complex disease characterized by the excessive accumulation of body fat that appears to be a major global health problem.

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