Summary:
Obesity is a major public health concern, with rates tripling since 1975. Obesity increases the risk of chronic diseases like heart disease, diabetes, and cancer. Research shows that the gut microbiome plays a role in obesity, influencing metabolism and the immune system and that some bacteria and their metabolites help prevent weight gain while others contribute to it. This study analyzed gut microbiome metabolism in a large group of people and then tested specific bacterial metabolites (4HPAA, 3HPP, and 4HPP) on mice. These compounds prevented obesity in high-fat diet-fed mice by reducing fat absorption and lowering intestinal inflammation. The findings suggest that gut bacteria and their metabolites could be used to develop new anti-obesity treatments. Further research is needed to identify bacteria that naturally produce these beneficial metabolites and explore their potential as dietary supplements or probiotics, but this study highlights the gut microbiome’s role in regulating body weight and its potential for preventing obesity-related diseases.
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.
Article Publication Date: 14/03/2025
DOI: 10.1038/s42255-025-01246-5
