Metabolic crosstalk between intestinal microbiota and dendritic cells: from homeostasis to inflammation

The intestinal microbiota plays critical roles in regulating immunity and inflammation through intricate interactions between microbial metabolites and diverse immune cells. Dendritic cells (DCs), the most potent professional antigen-presenting cells, are essential for sensing the complicated microbiota environment and subsequently initiating and regulating adaptive immune responses. While the commensal microbiota typically mediates DC-triggered immune tolerance and thus the maintenance of intestinal homeostasis, epithelial injury or pathogenic infection generally drives the proinflammatory function of DCs, contributing to harmful inflammation and intestinal disorders. Various microbiota metabolites (such as short-chain fatty acids, bile acids, and tryptophan derivatives) play critical roles in modulating the developmental and functional diversity of DCs through metabolic, epigenetic, or signaling reprogramming. In this review, we discuss the metabolic crosstalk between the intestinal microbiota and DCs and its pivotal function in orchestrating the balance between intestinal homeostasis and pathogenic inflammation. We also discuss future directions to better elucidate the microbiota-DC dialog in intestinal immunity and develop therapeutic approaches for manipulating the microbiota-DC axis against inflammatory disorders.