From Microbial Ecology to Functional Components in Microbe–Host Interactions

Microbiome research is shifting from a focus on "whole microorganisms" to an emphasis on microbial functional components. This review systematically describes how the effects of microbial communities on the host are mediated by bioactive functional components released by microbes. These components primarily exert their effects through interactions with host Pattern Recognition Receptors (PRRs) and metabolic sensing receptors, thereby regulating host immune, metabolic, and barrier function networks. The biological effects of these functional components are highly context-dependent. Under homeostasis, metabolites such as SCFAs and bile acids promote mucosal immune tolerance and maintain epithelial barrier integrity. However, the same signals can become deleterious under dysbiosis, driving inflammation and contributing to colorectal tumorigenesis. Mechanistic dissection of individual components, such as lipopolysaccharide (LPS), is now propelling a transition in clinical translation from whole-microbe-based interventions toward component-oriented diagnostics and therapeutics. Component-oriented diagnostics and therapeutics use defined microbial molecules rather than whole microorganisms. Microbial nucleic acids (e.g., HPV DNA), metabolites (e.g., SCFAs), and proteins can serve as biomarkers for disease risk, diagnosis, and prognosis. Therapeutic strategies include targeted modulation of beneficial components, neutralization of harmful molecules, and engineered microbial delivery.