Figure 1.

IECs immune programs are mutually beneficial for the host and microbiome. Perception of microbiome via pattern recognition receptors (PRRs) signaling promotes secretion of antimicrobial peptides (AMPs) and erection of a mucus barrier directly supporting beneficial mucus‐foraging bacteria and indirectly via colonization resistance to pathogens of other commensal bacteria (A). Microbiome sensing via luminal antigen uptake informs diurnal adjustment of intestinal barrier properties maintaining immunological tolerance towards microbiome around the clock and calibrates proliferative activity of intestinal stem cells (ISCs) promoting host‐microbiome homeostasis (B). Uptake of microbiome‐derived short‐chain fatty acids (SCFAs) promotes maintenance of an anaerobic environment required for homeostasis of commensal bacteria and protects against facultatively anaerobic pathogens (C). The figure was created using BioRender.com.