Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice
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BACKGROUND: Intestinal bacteria are known to regulate bile acid (BA) homeostasis via intestinal biotransformation of BAs and stimulation of the expression of fibroblast growth factor 19 through intestinal nuclear farnesoid X receptor (FXR). On the other hand, BAs directly regulate the gut microbiota with their strong antimicrobial activities. It remains unclear, however, how mammalian BAs cross-talk with gut microbiome and shape microbial composition in a dynamic and interactive way. RESULTS: We quantitatively profiled small molecule metabolites derived from host-microbial co-metabolism in mice, demonstrating that BAs were the most significant factor correlated with microbial alterations among all types of endogenous metabolites. A high-fat diet (HFD) intervention resulted in a rapid and significant increase in the intestinal BA pool within 12 h, followed by an alteration in microbial composition at 24 h, providing supporting evidence that BAs are major dietary factors regulating gut microbiota. Feeding mice with BAs along with a normal diet induced an obese phenotype and obesity-associated gut microbial composition, similar to HFD-fed mice. Inhibition of hepatic BA biosynthesis under HFD conditions attenuated the HFD-induced gut microbiome alterations. Both inhibition of BAs and direct suppression of microbiota improved obese phenotypes. CONCLUSIONS: Our study highlights a liver-BA-gut microbiome metabolic axis that drives significant modifications of BA and microbiota compositions capable of triggering metabolic disorders, suggesting new therapeutic strategies targeting BA metabolism for metabolic diseases.
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In mice fed a high-fat diet, there is a significant change in the profile of intestinal bile acids, while total BAs, primary BAs, and secondary BAs, including CA, GCA, TDCA, DCA, and LCA, are greatly increased.
“In mice fed a high‐fat diet, there is a significant change in the profile of intestinal bile acids, while total BAs, primary BAs, and secondary BAs, including CA, GCA, TDCA, DCA, and LCA, are greatly increased (Zheng et al., 2017).”
From <i>Akkermansia muciniphila</i> alleviates <scp>high‐fat‐diet</scp> ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Zheng et al., 2017
The abundance of Bilophila and Blautia immediately increase after 1 day of intervention with a high-fat diet, which may be related to their ability to tolerate bile salts.
“The abundance of Bilophila and Blautia immediately increase after 1 day of intervention with a high‐fat diet, which may be related to their ability to tolerate bile salts (Zheng et al., 2017).”
From <i>Akkermansia muciniphila</i> alleviates <scp>high‐fat‐diet</scp> ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Zheng et al., 2017
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- Authors
- Zheng, X., Huang, F., Zhao, A., Lei, S., Zhang, Y., Xie, G., Chen, T., Qu, C., Rajani, C., Dong, B., Li, D., & Jia, W.
- Affiliations
- Shanghai Jiao Tong University (CN)
- University of Hawaii Cancer Center (US)
- China Agricultural University (CN)
- Corresponding author
- Jia, Wei
- ORCID
- Venue
- BMC Biology
- Published
- 2017-12
- Volume
- 15
- Issue
- 1
- Pages
- 120-120
- ISSN
- 1741-7007 (ISSN-L)
- PMC
- PMC5731064
- OpenAlex
- W2774287749
- Cited by
- 323
- References
- 40
- Citations by year
- 2026: 18 · 2025: 36 · 2024: 40 · 2023: 61 · 2022: 44 · 2021: 47 · 2020: 36 · 2019: 29 · 2018: 12
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (31500954)
- Science and Technology Committee of Shanghai Municipality Government (15YF1409100)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Keywords
- bile acids, gut microbiota, diet-induced obesity, high-fat diet, bile acid synthesis, FGF19, farnesoid X receptor, small molecule metabolites, metabolic disorders
- MeSH terms
- Gastrointestinal Microbiome, Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Isoxazoles, Male, Mice, Inbred C57BL, Mice, Obese, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Mice, Diet, High-Fat
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