Microbiome-derived bioactive molecules regulate host signaling and therapeutic responses in cancer and metabolic diseases

The human microbiome is a complex ecosystem that produces a diverse repertoire of bioactive molecules essential for maintaining physiological homeostasis. Growing evidence indicates that microbiome-derived metabolites, including secondary bile acids, short-chain fatty acids (SCFAs), polyamines, vitamins, tryptophan-derived metabolites and microbial bioactive compounds, play vital roles not only in modulating immune responses and metabolic pathways but also in maintaining epithelial integrity and regulating systemic inflammation. Through their effects on host signaling pathways, these molecules act as key mediators in the development and progression of metabolic diseases and cancer. This review discusses how such molecules influence the tumor microenvironment, regulate epigenetic processes, such as histone deacetylase inhibition, and modulate metabolic pathways, including lipid homeostasis, adipogenesis, and insulin sensitivity. Emerging therapeutic approaches, including probiotics, postbiotics, and fecal microbiota transplantation, highlight the translational potential of microbiome-targeted interventions. Postbiotics comprise preparations of inanimate microorganisms and/or their components that confer health benefits and should be distinguished from purified microbial metabolites. Despite advancements in this field, challenges remain, including the standardization of metabolites and inter-individual variability in the microbiome, which can hinder widespread application. Future perspectives emphasize not only multi-omics technology but also the significant impact of personalized microbiome medicine, bioprospecting for novel metabolites, and computational modeling. Collectively, these findings highlight the therapeutic landscape of microbiome-derived molecules and their potential to transform interventional strategies for metabolic diseases and even cancer. This review synthesizes current knowledge on major classes of microbiome-derived metabolites, emphasizing their origins, mechanisms of action, and roles in disease modulation.