Dataset Information

Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia.

ABSTRACT:

Background

Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipidemic donors (FMT-dd) to study the causal role of gut microbiota in diet-induced dyslipidemia.

Results

We demonstrated that FMT-dd reshaped the gut microbiota of mice by increasing Faecalibaculum and Ruminococcaceae UCG-010, which then elevated serum cholicacid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA), reduced bile acid synthesis and increased cholesterol accumulation via the hepatic farnesoid X receptor-small heterodimer partner (FXR-SHP) axis. Nevertheless, high-fat diet led to decreased Muribaculum in the humanized dyslipidemia mice induced by FMT-dd, which resulted in reduced intestinal hyodeoxycholic acid (HDCA), raised bile acid synthesis and increased lipid absorption via the intestinal farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis.

Conclusions

Our studies implicated that intestinal FXR is responsible for the regulation of lipid metabolism in diet-induced dyslipidemia mediated by gut microbiota-bile acid crosstalk. Video Abstract.

SUBMITTER: Xu H

PROVIDER: S-EPMC10675972 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia.

Xu Hongtao H Fang Fang F Wu Kaizhang K Song Jiangping J Li Yaqian Y Lu Xingyu X Liu Juncheng J Zhou Liuyang L Yu Wenqing W Yu Fei F Gao Jie J

Microbiome 20231125 1

<h4>Background</h4>Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipidemic donors (FMT-dd) to study the causal role of gut microbiota in diet-induced dyslipidemia.<h4>Results</h4>We demonstrated that FMT-dd reshaped the gut microbiota of mice by increasing Faecalibaculum ...[more]

PMID: 38001551

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Project description:BackgroundBariatric surgery remains the most effective therapy for adiposity reduction and remission of type 2 diabetes. Although different bariatric procedures associate with pronounced shifts in the gut microbiota, their functional role in the regulation of energetic and metabolic benefits achieved with the surgery are not clear.MethodsTo evaluate the causal as well as the inherent therapeutic character of the surgery-altered gut microbiome in improved energy and metabolic control in diet-induced obesity, an antibiotic cocktail was used to eliminate the gut microbiota in diet-induced obese rats after gastric bypass surgery, and gastric bypass-shaped gut microbiota was transplanted into obese littermates. Thorough metabolic profiling was combined with omics technologies on samples collected from cecum and plasma to identify adaptions in gut microbiota-host signaling, which control improved energy balance and metabolic profile after surgery.ResultsIn this study, we first demonstrate that depletion of the gut microbiota largely reversed the beneficial effects of gastric bypass surgery on negative energy balance and improved glucolipid metabolism. Further, we show that the gastric bypass-shaped gut microbiota reduces adiposity in diet-induced obese recipients by re-activating energy expenditure from metabolic active brown adipose tissue. These beneficial effects were linked to improved glucose homeostasis, lipid control, and improved fatty liver disease. Mechanistically, these effects were triggered by modulation of taurine metabolism by the gastric bypass gut microbiota, fostering an increased abundance of intestinal and circulating taurine-conjugated bile acid species. In turn, these bile acids activated gut-restricted FXR and systemic TGR5 signaling to stimulate adaptive thermogenesis.ConclusionOur results establish the role of the gut microbiome in the weight loss and metabolic success of gastric bypass surgery. We here identify a signaling cascade that entails altered bile acid receptor signaling resulting from a collective, hitherto undescribed change in the metabolic activity of a cluster of bacteria, thereby readjusting energy imbalance and metabolic disease in the obese host. These findings strengthen the rationale for microbiota-targeted strategies to improve and refine current therapies of obesity and metabolic syndrome. Video Abstract Bariatric Surgery (i.e. RYGB) or the repeated fecal microbiota transfer (FMT) from RYGB donors into DIO (diet-induced obesity) animals induces shifts in the intestinal microbiome, an effect that can be impaired by oral application of antibiotics (ABx). Our current study shows that RYGB-dependent alterations in the intestinal microbiome result in an increase in the luminal and systemic pool of Taurine-conjugated Bile acids (TCBAs) by various cellular mechanisms acting in the intestine and the liver. TCBAs induce signaling via two different receptors, farnesoid X receptor (FXR, specifically in the intestines) and the G-protein-coupled bile acid receptor TGR5 (systemically), finally resulting in metabolic improvement and advanced weight management. BSH, bile salt hydrolase; BAT brown adipose tissue.

Dataset Information

Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia.

Background

Results

Conclusions

Publications

Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia.

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