The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression

• Type of Material: Article
• Authors: Abdul Malik Tyagi, Emory University; Mingcan Yu, Emory University; Trevor M. Darby, Emory University; Chiara Vaccaro, Emory University; Jau-Yi Li, Emory University; Joshua A. Owens, Emory University; Emory Hsu, Emory University; Jonathan Adams, Emory University; M. Neale Weitzmann, Emory University; Rheinallt Jones, Emory University; Roberto Pacifici, Emory University
• Language: English
• Date: 2018-12-18
• Publisher: Elsevier (Cell Press)
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.immuni.2018.10.013
• Title of Journal or Parent Work: Immunity
• ISSN: 1074-7613
• Volume: 49
• Issue: 6
• Start Page: 1116
• End Page: +
• Grant/Funding Information: M.N.W. was also supported by a grant from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (5I01BX000105).; T.M.D. is a recipient of the Research Fellowship award from the Crohn’s and Colitis Foundation of America (CCFA).; The Emory Gnotobiotic Animal Core is supported by the Georgia Clinical & Translational Science Alliance and the Emory University School of Medicine.; The Emory Integrated Core Facilities are supported by the Emory Neuroscience NINDS Core Facilities, the Georgia Clinical & Translational Science Alliance, and the Emory University School of Medicine.; This study was supported by grants from the National Institutes of Health (DK112946, DK108842, and RR028009 to R.P.; DK108735 to E.H.; DK098391 to R.M.J.; AR070091, AR068157, and AG062334 to M.N.W.).
• Keywords: Science & Technology; Life Sciences & Biomedicine; PARATHYROID-HORMONE; BACTERIA; ANABOLIC ACTIVITY; PTH; OSTEOBLAST; DIVERSITY; CHAIN FATTY-ACIDS; DEPLETION; PROLIFERATION; DIFFERENTIATION; Immunology
• Research Categories: Health Sciences, Pathology; Biology, Molecular; Health Sciences, Immunology

Abstract

Tyagi et al. show that oral supplementation with the widely used probiotic, Lactobacillus rhamnosus GG (LGG), increases bone mass in mice by increasing the serum levels of the short chain fatty acid butyrate. LGG or butyrate increase the frequency of regulatory T (Treg) cells in the intestine and in the bone marrow. Treg cells stimulate CD8 + T cells to secrete the Wnt ligand Wnt10b, which stimulates bone formation by activating Wnt signaling in osteoblasts. Therefore, LGG and butyrate may represent new interventions for the prevention and treatment of osteoporosis.