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Microbiota How does the gut microbiota shape the composition and function of distal host organs, despite being segregated in the gut? Uchimura et al. used stable isotope tracing to show that microbial metabolites penetrate host tissues and fluids to influence host immunological and metabolic signaling networks. However, metabolite impact is modulated by a high rate of urinary excretion of microbial products. Furthermore, secretory immunoglobulin A antibodies limit bacterial dwell times in the small intestine, which also ameliorates host exposure to microbial metabolites. The joint effect contributes to resolving gut function as both nutrient gateway and barrier. Immunity 49 , 545 (2018).