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.

Neurodegeneration and cancer are fundamentally distinct disorders: one signifies gradual neuronal loss while the latter signifies uncontrolled cell growth and survival. However, emerging evidence explores an inverse association between these conditions, suggesting that they do not arise from independent biological processes. Understanding the context-dependent behaviour of major pathways (for example, p53, PI3K/AKT/mTOR, Wnt, and immune–stress signaling) remains pivotal in elucidating the relationship between these two diseases. Pathways promoting early-life fitness, tissue repair, and tumor suppression in dividing cells can become detrimental later in life for post-mitotic neurons. Cross-species genomics studies reveal how evolution has repeatedly adapted these shared networks to balance cancer resistance with survival. Research on species exhibiting exceptional longevity and disease resistance, including naked mole rats and bowhead whales, shows that cancer resistance and longevity are not fixed traits but rather are controlled by precise regulatory mechanisms. In this review, we integrate insights from broad species genomics and multi-omic and single-cell studies to understand how evolutionarily conserved molecular crosstalks diverge at the interface of cancer and neurodegeneration.