Molecular crosstalk of probiotics in gut health: A chemical perspective on metabolite-mediated pathways.

Intestinal diseases, encompassing conditions like inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, represent a significant global health burden. Their pathogenesis is intricately linked to gut microbiota dysbiosis, which disrupts intestinal barrier integrity and immune homeostasis. Probiotics, as live beneficial microorganisms, have emerged as promising therapeutic agents to restore gut ecological balance and alleviate disease symptoms. This review comprehensively synthesizes current knowledge on the multifaceted mechanisms of action of probiotics against intestinal diseases. It delves into their ability to regulate gut microbial composition, strengthen the intestinal barrier, modulate immune and inflammatory responses, influence host-microbe co-metabolism (e.g., SCFAs, bile acids, tryptophan), and alleviate oxidative stress. Furthermore, it evaluates their clinical applications across a spectrum of intestinal disorders and discusses emerging strategies such as engineered probiotics and postbiotics. Probiotics exert their beneficial effects through a complex interplay of mechanisms, including competitive exclusion of pathogens, production of antimicrobial compounds, and immunomodulation. Preclinical models demonstrate their considerable potential in ameliorating disease-specific pathologies by restoring microbial balance and enhancing gut barrier function. Future perspectives highlight the potential of precision interventions via strain synergy optimization, genetic engineering, and harnessing microbial metabolites, positioning probiotics as next-generation, targeted therapeutics for intestinal health management.