{"title":"Human gut microbial aromatic amino acid and related metabolites prevent obesity through intestinal immune control","authors":"Zengliang Jiang, Liuqing He, Diyin Li, Laibao Zhuo, Lingjun Chen, Rui-Qi Shi, Jianhua Luo, Yuhui Feng, Yuhui Liang, Danyang Li, Xiao Congmei, Yuanqing Fu, Yu-ming Chen, Ju-Sheng Zheng, Liang Tao","doi":"10.1038/s42255-025-01246-5","DOIUrl":null,"url":null,"abstract":"<p>Obesity affects millions of people in the world. The gut microbiome influences body fat accumulation, but the mechanisms remain to be investigated. Here, we show an association between microbial aromatic amino acid metabolites in serum and body fat accumulation in a large Chinese longitudinal cohort. We next identify that 4-hydroxyphenylacetic acid (4HPAA) and its analogues effectively protect male mice from high-fat-diet-induced obesity. These metabolites act on intestinal mucosa to regulate the immune response and control lipid uptake, which protects against obesity. We further demonstrate that T cells and B cells are not vital for 4HPAA-mediated obesity prevention, and innate lymphoid cells have antagonistic roles. Together, these findings reveal specific microbial metabolites as pivotal molecules to prohibit obesity through immune control, establishing mechanisms of host modulation by gut microbial metabolites.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"183 1","pages":""},"PeriodicalIF":18.9000,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s42255-025-01246-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Obesity affects millions of people in the world. The gut microbiome influences body fat accumulation, but the mechanisms remain to be investigated. Here, we show an association between microbial aromatic amino acid metabolites in serum and body fat accumulation in a large Chinese longitudinal cohort. We next identify that 4-hydroxyphenylacetic acid (4HPAA) and its analogues effectively protect male mice from high-fat-diet-induced obesity. These metabolites act on intestinal mucosa to regulate the immune response and control lipid uptake, which protects against obesity. We further demonstrate that T cells and B cells are not vital for 4HPAA-mediated obesity prevention, and innate lymphoid cells have antagonistic roles. Together, these findings reveal specific microbial metabolites as pivotal molecules to prohibit obesity through immune control, establishing mechanisms of host modulation by gut microbial metabolites.
期刊介绍：
Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.
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