Fecal microbiome sequensing of mice treated with microbial aromatic amino acids metabolites

Obesity is an important public health issue that affects millions of people in the world. The gut microbiome is a vital factor influencing body fat accumulation, while the mechanisms remain to be investigated. Here, we started by analyzing data sets from a large-scale human cohort in the Chinese population (Guangzhou Nutrition and Health Study, GNHS). We found a strong association between specific microbial aromatic amino acids (AAA) metabolites in serum and host body fat accumulation. We next identified 4-hydroxyphenylacetic acid (4HPAA) and its structurally related analogs, 3-hydroxyphenylpropionic acid (3HPP) and 4-hydroxyphenylpropionic acid (4HPP), that effectively protected male mice from a high-fat diet (HFD)-induced obesity via oral feeding at a low dose. These metabolites directly act on the intestinal mucosa to regulate the immune response and thus control lipid uptake.