Weizmannia coagulans JA845 modulates glucose and lipid metabolism via the gut microbiota-bile acid axis and FXR/TGR5 signaling to enhance GLP-1 secretion.

Authors

Haifei Guan, Yunlong Shang, Yansong Gao, Ge Yang, Wenrui Wang, Shengyu Li, Chuan Zhang

Published in

Food & function. Jul 21, 2026. Epub Jul 21, 2026.

Abstract

Type 2 diabetes mellitus (T2DM) is a globally prevalent metabolic disorder, commonly leading to serious complications such as cardiovascular diseases, renal failure, and neuropathy. This study took spore-forming probiotic Weizmannia coagulans JA845 isolated from fresh fermented sauerkraut as the research subject. By establishing T2DM mouse models combined with in vitro STC-1 cell assays, we systematically evaluated the therapeutic effects of this strain on T2DM and clarified its underlying molecular mechanisms governing glycolipid metabolism. The results showed that W. coagulans JA845 intervention significantly improved glucose metabolism, enhanced insulin sensitivity, and effectively alleviated hepatic lipid accumulation and systemic inflammation in T2DM mice induced by a high-fat diet combined with streptozotocin. 16S rRNA gene sequencing analysis revealed that W. coagulans JA845 significantly reshaped the gut microbiota (GM) composition, particularly by inhibiting the abundance of Ligilactobacillus, a bile salt hydrolase (BSH)-producing bacterium. Further mechanistic studies indicated that JA845 modulated BA metabolism by increasing the accumulation of tauro-β-muricholic acid (TβMCA) and taurolithocholic acid (TLCA) in the gut contents. Specifically, TβMCA improved lipid metabolism by antagonizing the farnesoid X receptor (FXR) signaling pathway and inhibiting the expression of the downstream target gene FGF15. In contrast, TLCA promoted GLP-1 synthesis and secretion by activating the TGR5/CREB/PCSK1/GCG signaling pathway, which further enhanced insulin secretion and glucose metabolism. In conclusion, this study is the first to reveal that W. coagulans JA845 improves glucose and lipid metabolism disorders in T2DM by modulating the gut microbiota-BAs-TGR5/FXR metabolic axis and promoting GLP-1 secretion, offering a new probiotic candidate for the management of T2DM.

PMID:
42478224
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.

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