Microbial metabolites control gut inflammatory responses

An estimated 100 trillion bacteria populate the human gut and are separated by a single layer of intestinal epithelial cells (IECs) from the innate and adaptive immune cells of the lamina propria. Considering that both commensal and pathogenic microbes share many molecular features and that these features are detected by pattern recognition receptors (PRRs) displayed by immune cells, it is necessary to understand how appropriate inflammatory responses against pathogens are coordinated in the presence of such high numbers of innocuous bacteria. Current thinking holds that the mucosal immune system tolerates commensal microbes while maintaining the ability to mount a robust protective response against pathogens. This process must operate within the context of a dynamic equilibrium of microbial diversity that rapidly fluctuates in response to an environment of ingested dietary materials (1). Lack of response to pathogenic onslaught leaves the host vulnerable to barrier penetration and systemic infection, whereas aberrant inflammatory responses against the commensal community result in tissue damage and dysbiosis that perturbs the microbial community and facilitates inflammatory bowel disease (IBD). It has long been appreciated that commensal bacteria are necessary for digestion of plant-derived starches, bile acid production, and vitamin acquisition. Observations that byproducts of these processes are reduced in IBD patients have led many groups to test whether these microbial metabolites shape intestinal immunity. In PNAS, Chang et al. (2) show that a short-chain fatty acid (SCFA), n-butyrate, produced as an end product of bacterial anaerobic fermentation of starches, has potent anti-inflammatory properties and inhibits proinflammatory responses by intestinal macrophages. These data indicate, along with an additional emerging body of evidence, that certain bacterial species communicate with the immune system through their metabolites to influence both the magnitude and the quality of the immune response (Fig. 1).