title: Gut Microbial Metabolites Fuel Host Antibody Responses.
abstract: Antibody production is a metabolically demanding process that is regulated by gut microbiota, but the microbial products supporting B cell responses remain incompletely identified. We report that short-chain fatty acids (SCFAs), produced by gut microbiota as fermentation products of dietary fiber, support host antibody responses. In B cells, SCFAs increase acetyl-CoA and regulate metabolic sensors to increase oxidative phosphorylation, glycolysis, and fatty acid synthesis, which produce energy and building blocks supporting antibody production. In parallel, SCFAs control gene expression to express molecules necessary for plasma B cell differentiation. Mice with low SCFA production due to reduced dietary fiber consumption or microbial insufficiency are defective in homeostatic and pathogen-specific antibody responses, resulting in greater pathogen susceptibility. However, SCFA or dietary fiber intake restores this immune deficiency. This B cell-helping function of SCFAs is detected from the intestines to systemic tissues and conserved among mouse and human B cells, highlighting its importance.
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Myunghoo
authors.initials: M
authors.lastname: Kim
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Qie
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Jeongho
authors.initials: J
authors.lastname: Park
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Inflammation, Immunology, and Infectious Diseases, Purdue University, West Lafayette, IN 47907, USA; Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address: chkim@purdue.edu.
authors.forename: Chang H
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D004043:Dietary Fiber / Q000378:metabolism*; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D005285:Fermentation; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008810:Mice, Inbred C57BL
chemical_list: D004043:Dietary Fiber; D005232:Fatty Acids, Volatile
keywords: B cells; antibody; metabolism; short-chain fatty acids