Natural products from human-associated microbiota in human diseases

Covering: 1985 to 2026The human microbiota harbors abundant metabolic capacity, producing and transforming a chemically diverse array of small molecules that range from well-characterized classes, such as short-chain fatty acids, secondary bile acids, and indoles, to structurally complex ribosomal and non-ribosomal peptides. Several of these metabolites act on defined host receptors and signaling pathways, linking microbial metabolic activity to a broad spectrum of human diseases. Although individual compounds have increasingly been linked to defined host targets, this rapidly growing evidence remains scattered across disease areas. Here, we review bioactive compounds produced or transformed by human-associated microbiota, together with microbiota-associated co-metabolites, across four major disease categories, namely metabolic diseases, cancers, immune regulation, and other systemic and extraintestinal diseases. For each, we discuss the microbial species implicated, the compounds they produce, and the mechanistic evidence connecting individual molecules to disease-relevant biological processes. Altogether, we highlight the therapeutic potential of microbiota-derived metabolites and the rich opportunities for discovery within the largely untapped microbial chemical space by integrating chemistry, microbiology, and disease mechanisms. Beyond the disease-centered organization, we compare these molecules across structural and biosynthetic origins, taxonomic producer patterns, and emerging discovery strategies to identify recurring principles that cut across individual disease categories.