From the rhizosphere to systemic circulation: cross-kingdom signaling and health effects of soil microbial metabolites

Abstract

Plant roots and soil microorganisms engage in continuous, complex chemical dialogues at the rhizosphere-a highly dynamic interface. The rhizosphere not only serves as a “black box” where root exudates and microbial metabolites converge but also functions as a critical site for shaping microbial community structure. Small-molecule metabolites produced by either plant roots or microbes mediate plant-microbe interactions locally and can further influence shoot physiology through systemic signaling. Similarly, in animal and human systems, gut microbes produce bioactive metabolites – such as short-chain fatty acids, indole derivatives, and secondary bile acids – that enter systemic circulation and participate in host metabolic regulation, immune modulation, and even neural function. Although the rhizosphere and gut belong to distinct ecosystems, they exhibit remarkable parallels in metabolite-mediated cross-kingdom signaling mechanisms: microbial metabolites in both systems can traverse biological barriers, enter systemic circulation, and modulate host phenotypes. Thus, from the rhizosphere to systemic circulation, soil (or gut) microbial metabolites are being redefined as pivotal mediators linking environment, microbiota, and host health. Elucidating the chemical nature, transmission pathways, and biological effects of these metabolic signals will not only advance the development of green, microbiome-based inputs for sustainable agriculture but also offer novel ecological perspectives for understanding human metabolic and neurodegenerative diseases.