A research team led by Jin Wenbing, a professor of life sciences at Xiamen University, published a groundbreaking study titled "Microbiota-derived bile acids antagonize the host androgen receptor and drive anti-tumor immunity" in the prestigious Cell Journal on April 15, revealing the latest advances in anti-tumor immune modulation.

Using an approach combining bioinformatics, bile acids (BA) metabolomics, and microbial genetics, the team uncovered a series of novel bile acids widely present in the gut. Through activity screening, they identified a class of bile acids with potent androgen receptor (AR) antagonistic properties. It was confirmed that these bile acids can modulate anti-tumor immunity by antagonizing AR in CD8+ T cells within the host.

By integrating BA metabolomics and synthetic biology, the researchers conducted functional analysis on 207 potential microbial BAs hydroxysteroid dehydrogenases (HSDHs). They successfully identified 56 novel BAs, many of which are detected in humans and mammals. Notably, a subset of these BAs are potent antagonists of the human androgen receptor (hAR). They inhibit AR-related gene expression and are human-relevant. As a proof-of-principle, the team demonstrated that one of these BAs suppresses tumor progression and potentiates the efficacy of anti-PD-1 treatment in an AR-dependent manner.

The study was led by Professor Jin (co-primary author and corresponding author) and Xiao Leyi, a doctoral student at Cornell University in the United States. Co-corresponding authors included Nicholas Collins, David Artis, and Professor Guo Chunjun from Cornell University.