The germ-organ theory of non-communicable diseases.

Gut dysbiosis is associated with many non-communicable human diseases, but the mechanisms maintaining homeostasis remain incompletely understood. Recent insights suggest that during homeostasis, epithelial hypoxia limits oxygen availability in the colon, thereby maintaining a balanced microbiota that functions as a microbial organ, producing metabolites contributing to host nutrition, immune education and niche protection. Dysbiosis is characterized by a shift in the microbial community structure from obligate to facultative anaerobes, suggesting oxygen as an important ecological driver of microbial organ dysfunction. The ensuing disruption of gut homeostasis can lead to non- communicable disease because microbiota-derived metabolites are either depleted or generated at harmful concentrations. This Opinion article describes the concept that host control over the microbial ecosystem in the colon is critical for the composition and function of our microbial organ, which provides a theoretical framework for linking microorganisms to non-communicable diseases.