Exposure to short chain fatty acids in early-life leaves a life-long epigenetic imprint on hematopoietic stem and progenitor cells 2328904

Abstract

Abstract Introduction Early life is a critical window during which the gut microbiota sculpts immunity and long-term susceptibility to allergic disease. Methods Using neonatal antibiotic administration and bone marrow transplantation assays, we show that depletion of short chain fatty acid (SCFA)-producing bacteria alters gene expression in hematopoietic stem and progenitor cells (HSPCs) and imprints a persistent, transplantable atopic immune phenotype. Results Bone marrow transplants from exposed mice generate recipients with elevated serum IgE, downstream increased IgE bound to basophils, and exacerbated allergic lung inflammation following papain challenge. H3K27 ChIP-seq analyses further reveals differential histone acetylation in HSPCs, consistent with a SCFA-mediated epigenetic regulatory mechanism. Conclusion Collectively, these findings establish a link between gut microbiota composition, hematopoiesis, and long-term immune function, offering a mechanistic explanation for microbiota-driven susceptibility to atopic disease and hematopoietic dysfunction. Funding Source CIHR Topic Categories Mucosal and Regional Immunology (MUC)