Gut commensal bifidobacteria are associated with restrained inflammatory reprogramming in human monocyte-derived dendritic cells

The gut commensal microbiota helps calibrate systemic innate immunity in humans. Here, we investigated whether gut bifidobacteria are associated with altered inflammatory responsiveness in human monocyte-derived dendritic cells (moDCs) from healthy adults. Higher abundance of gut-resident Bifidobacterium correlated with lower moDC inflammatory responses to multiple bacterial stimuli. In vitro , priming monocytes with Bifidobacterium before differentiation into moDCs induced transcriptomic and H3K4me1-associated chromatin remodeling and reduced inflammatory cytokine production upon rechallenge, while preserving the induction of selected phenotypic markers. These findings support an association between commensal bifidobacteria and restrained inflammatory reprogramming in human moDCs, characterized by attenuated inflammatory output without global loss of responsiveness under the conditions tested. Although our cohort and in vitro analyses do not establish causality, their convergence supports the biological plausibility of bifidobacterial modulation of monocyte-derived cell responses.