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Microbial metabolites refer to the bioactive molecules generated by microorganisms during their metabolic processes, including primary metabolites and secondary metabolites. Microbial secondary metabolites represent a crucial source of clinical drugs, exemplified by penicillin, bleomycin, and cyclosporine. The gut microbiota, the most intricate microbial community residing in the human host, produces a variety of metabolites that potentially mediate critical host-microbe and microbe-microbe interactions. However, existing research has predominantly concentrated on primary metabolites, whose functional mechanisms are relatively wellelucidated. In contrast, investigations into secondary metabolites derived from the gut microbiota remain comparatively scarce. A suite of integrated discovery technologies is progressively unlocking this microbial "dark matter", providing unprecedented opportunities for in-depth analysis of the mechanisms by which these metabolites regulate both the microbiome and host physiology. This review summarizes the reported categories of secondary metabolites derived from the gut microbiota, describes the key methods employed for their identification and characterization, explores their potential physiological functions and translational medicine prospects, and elaborates on the trajectory of gut microbial metabolites-from "dark matter" to characterized molecules, and further to novel drugs and therapeutic strategies.
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Zhang et al. (2026) studied this question.
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