Human gut microbial aromatic amino acid and related metabolites prevent obesity through intestinal immune control

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.

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Publication Details

Journal
Nature Metabolism
Published
2025-03-14
DOI
https://doi.org/10.1038/s42255-025-01246-5
Citations
42
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
33.85
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article

Human gut microbial aromatic amino acid and related metabolites prevent obesity through intestinal immune control

Yuhui Feng, Liang Tao, Yuanqing Fu, Danyang Li et al.
42 citations
Nature Metabolism
Gut microbiota and health
33.85
article

Human gut microbial aromatic amino acid and related metabolites prevent obesity through intestinal immune control

Yuhui Feng, Liang Tao, Yuanqing Fu, Danyang Li, Yuhui Liang, Zengliang Jiang, Diyin Li, Liuqing He, Ju‐Sheng Zheng, Yu‐Ming Chen, Jianhua Luo, Lingjun Chen, Rui-Qi Shi, Lai‐Bao Zhuo, Xiao Congmei
article en
42 citations

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.

Nature MetabolismVol. 7(4)
Sun Yat-sen University (CN), Westlake University (CN), Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine (CN), Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences, Zhejiang University (CN)
Zero hunger
Openalex Percentile: Top 0%
Gut microbiota and health
33.85
DOIOpen Access PDFOpenAlex
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