Postbiotics as Multifunctional Bioactives: Mechanistic Insights and Translational Applications in Host Physiology and Microbial Ecosystem Modulation.

Postbiotics are increasingly recognized as a predominant group of biotherapeutic agents sourced from the microbial secretome, offering functional benefits, while circumventing the safety concerns associated with the application of live microbial consortia. These microbial derivatives are emerging as promising approaches for tackling complex diseases, encompassing cancer, autoimmune diseases, and metabolic disorders, through modulation of host cell signalling pathways, including G protein-coupled receptors (GPCRs), the NF-κB (Nuclear Factor Kappa B) pathway, and epigenetic regulatory pathways. Besides systemic effects, postbiotics may also have localized effects, such as epithelial regeneration, modulation of fibroblast functions, and control of collagen remodelling. Eventually, the scale-up in the production of postbiotics has initiated new avenues in improving sustainable agriculture and environmental biotechnology. This comprehensive review attempts to integrate mechanistic insights and translational applications, highlighting the therapeutic potential of postbiotics across biomedical and ecological domains. These observations could pave the way to bridge the gap between microbiome regulation, precision medicine, and sustainable biotechnology, thereby positioning postbiotics as a versatile tool addressing some of the most pressing health and sustainability challenges of the 21st century.