Burgeoning momentum: the present and future of hyodeoxycholic acid in host microbiome dynamics

This review critically examines the emerging role of hyodeoxycholic acid (HDCA) in metabolic and inflammatory disorders. We analyze the current understanding of HDCA biosynthesis, highlighting species-specific differences and challenges in identifying HDCA-producing bacteria. The study evaluated the signaling mechanism by which HDCA simultaneously activates intestinal G protein-coupled bile acid receptor 1 (TGR5) and farnesoid X receptor (FXR), challenging the traditional paradigm of bile acid （BA）signaling. We assess HDCA's immunomodulatory effects, particularly its Toll-like receptor 4 (TLR4) inhibition, and discuss potential therapeutic applications in metabolic diseases and sepsis. The review addresses challenges in translating rodent studies to human applications and explores future directions, including the development of HDCA derivatives and integration with microbiome modulation strategies. Ethical and regulatory considerations for microbiome-derived therapeutics are also discussed. We propose that HDCA research may catalyze paradigm shifts in understanding host-microbiome-BA interactions, calling for interdisciplinary approaches to harness its potential fully.