Microbiome-Derived Effectors and Convergent Host Pathways in Organ Injury and Fibrosis

The human microbiome functions as an endocrine-like biochemical network that generates metabolites, structural ligands, and peptides capable of shaping host physiology. Under physiological conditions, these microbiome-derived effectors contribute to epithelial integrity, immune homeostasis, metabolic regulation, and tissue resilience. During dysbiosis, however, the composition and systemic distribution of these effectors are altered, shifting host responses toward injury. Despite their chemical diversity, microbiome-derived signals converge on a limited set of host pathways, including pattern-recognition receptor activation, mitochondrial dysfunction, apoptosis and senescence, inflammatory amplification, and fibrosis, which collectively determine tissue vulnerability across organ systems. This framework links gut imbalance to disorders such as pulmonary fibrosis, acute lung injury, chronic kidney disease, and hepatobiliary inflammation. Microbial peptides represent an emerging layer of regulation. Among these peptides, corisin exemplifies how discrete microbial effectors can directly engage intracellular targets and amplify tissue injury. Together, these observations reframe microbiome-associated disease as a disorder of microbial chemistry and host pathway activation, thereby providing a foundation for mechanism-based biomarkers and targeted therapeutic strategies.