The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages
By J. Schulthess, S. Pandey, M. Capitani, Kevin C. Rue-Albrecht, I. Arnold, F. Franchini, Agnieszka Chomka, N. Ilott, Daniel G. W. Johnston, Elisabete Pires and 5 more. Immunity, 2019
903 citations recorded by the source corpus.
&NA; Host microbial cross‐talk is essential to maintain intestinal homeostasis. However, maladaptation of this response through microbial dysbiosis or defective host defense toward invasive intestinal bacteria can result in chronic inflammation. We have shown that macrophages differentiated in the presence of the bacterial metabolite butyrate display enhanced antimicrobial activity. Butyrate‐induced antimicrobial activity was associated with a shift in macrophage metabolism, a reduction in mTOR kinase activity, increased LC3‐associated host defense and anti‐microbial peptide production in the absence of an increased inflammatory cytokine response. Butyrate drove this monocyte to macrophage differentiation program through histone deacetylase 3 (HDAC3) inhibition. Administration of butyrate induced antimicrobial activity in intestinal macrophages in vivo and increased resistance to enteropathogens. Our data suggest that (1) increased intestinal butyrate might represent a strategy to bolster host defense without tissue damaging inflammation and (2) that pharmacological HDAC3 inhibition might drive selective macrophage functions toward antimicrobial host defense. Graphical Abstract Figure. No caption available. HighlightsButyrate induces differentiation of macrophages with potent antimicrobial functionEnhanced antimicrobial function is a consequence of glycolysis and mTOR inhibitionSingle‐cell RNA‐sequencing identifies butyrate‐induced antimicrobial peptidesButyrate inhibits HDAC3 to drive metabolic changes and microbicidal function &NA; Macrophages maintain gut homeostasis by eliminating invasive pathogens and regulating inflammatory responses. Schulthess et al. demonstrate that butyrate, a bacterial fermentation product, imprints potent antimicrobial activity during macrophage differentiation through HDAC3i function.
Subfields: Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/00bf607f0b8bd871595e15b97dba116853ecf323
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Citations in the corpus
- Short-chain fatty acids: linking diet, the microbiome and immunity (2024, positive): “In parallel to its anti-inflammatory properties, butyrate increases the production of antimicrobial peptides, including calprotectin, by macrophages through HDAC3 inhibition, thereby increasing macrophage antimicrobial activity against enteropathogens in vivo 52 .”
- Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases (2019, background): “Finally, bacterial butyrate imprints a host protection program via epigenetic remodeling during monocyte tomacrophage differentiation in the lamina propria (64).”
- SCFA: mechanisms and functional importance in the gut (2020, background): “Hence, upon stimulation, antimicrobial peptides belonging to the S100 family, ficolin and lysozyme are increased((148)).”
- Interaction between microbiota and immunity in health and disease (2020, background): “Moreover, butyrate can drive monocyte-to-macrophage differentiation through histone deacetylase 3 (HDAC3) inhibition, thereby amplifying antimicrobial host defense.(88) Recently, it has been demonstrated that a soluble microbiome-derived metabolite, trimethylamine N-oxide (TMAO), can drive murine ma”
- Diversity, Mechanisms and Significance of Macrophage Plasticity (2019, background): “It has recently been shown that the short chain fatty acid butyrrate, a bacterial metabolite, prepares macrophages with a set of antimicrobial molecules, but not inflammatory cytokines (27).”