@article{ce5b8b010ebf4d9aaa2f3b3755bf6b52,
title = "Stable isotope tracing in vivo reveals a metabolic bridge linking the microbiota to host histone acetylation",
abstract = "The gut microbiota influences acetylation on host histones by fermenting dietary fiber into butyrate. Although butyrate could promote histone acetylation by inhibiting histone deacetylases, it may also undergo oxidation to acetyl-coenzyme A (CoA), a necessary cofactor for histone acetyltransferases. Here, we find that epithelial cells from germ-free mice harbor a loss of histone H4 acetylation across the genome except at promoter regions. Using stable isotope tracing in vivo with 13C-labeled fiber, we demonstrate that the microbiota supplies carbon for histone acetylation. Subsequent metabolomic profiling revealed hundreds of labeled molecules and supported a microbial contribution to host fatty acid metabolism, which declined in response to colitis and correlated with reduced expression of genes involved in fatty acid oxidation. These results illuminate the flow of carbon from the diet to the host via the microbiota, disruptions to which may affect energy homeostasis in the distal gut and contribute to the development of colitis.",
keywords = "colitis, CP: Microbiology, epigenetics, fatty acid metabolism, histone acetylation, host-microbiota interactions",
author = "Lund, {Peder J.} and Gates, {Leah A.} and Marylene Leboeuf and Smith, {Sarah A.} and Lillian Chau and Mariana Lopes and Friedman, {Elliot S.} and Yedidya Saiman and Kim, {Min Soo} and Shoffler, {Clarissa A.} and Christopher Petucci and Allis, {C. David} and Wu, {Gary D.} and Garcia, {Benjamin A.}",
note = "Funding Information: Funding is generously acknowledged from the Crohn's and Colitis Foundation (RFA 598467 to P.J.L.), the Crohn's and Colitis Foundation Microbiome Initiative, the PennCHOP Microbiome Program, the Penn Center for Nutritional Science and Medicine (PenNSAM), The Rockefeller University (C.D.A.), the Shapiro-Silverberg Fund for the Advancement of Translational Research at The Rockefeller University (L.A.G.), the St. Jude Children's Research Hospital Chromatin Consortium, the Host-Microbial Analytic and Repository Core of the Center for Molecular Studies in Digestive and Liver Diseases (P30 DK050306), and the National Institutes of Health (T32CA009140 to P.J.L.; F32GM134560 and K99GM143550 to L.A.G.; P01CA196539, R01AI118891, and R01HD106051 to B.A.G.; R01GM40922 to C.D.A.). The authors wish to thank Johayra Simithy, Sophie Trefely, Kevin Janssen, Simone Sidoli, Greg Donahue, Pau Pascual-Garcia, Nathaniel W. Snyder, and Meenakshi Bewtra for assistance. P.J.L. acknowledges Warren Pear for additional support and mentoring. P.J.L. participated in project conception, performed experiments, analyzed data, and drafted the original manuscript. L.G. M.L. S.A.S. L.C. E.S.F. Y.S. M.L. M.S.K. C.A.S. and C.P. performed experiments and assisted with sample preparation. C.D.A. G.D.W. and B.A.G. participated in project conception and supervision. All authors assisted with review and editing of the manuscript. The authors declare no competing interests. Funding Information: Funding is generously acknowledged from the Crohn's and Colitis Foundation ( RFA 598467 to P.J.L.), the Crohn{\textquoteright}s and Colitis Foundation Microbiome Initiative , the PennCHOP Microbiome Program , the Penn Center for Nutritional Science and Medicine (PenNSAM), The Rockefeller University (C.D.A.), the Shapiro-Silverberg Fund for the Advancement of Translational Research at The Rockefeller University (L.A.G.), the St. Jude Children{\textquoteright}s Research Hospital Chromatin Consortium , the Host-Microbial Analytic and Repository Core of the Center for Molecular Studies in Digestive and Liver Diseases ( P30 DK050306 ), and the National Institutes of Health ( T32CA009140 to P.J.L.; F32GM134560 and K99GM143550 to L.A.G.; P01CA196539 , R01AI118891 , and R01HD106051 to B.A.G.; R01GM40922 to C.D.A.). The authors wish to thank Johayra Simithy, Sophie Trefely, Kevin Janssen, Simone Sidoli, Greg Donahue, Pau Pascual-Garcia, Nathaniel W. Snyder, and Meenakshi Bewtra for assistance. P.J.L. acknowledges Warren Pear for additional support and mentoring. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = dec,
day = "13",
doi = "10.1016/j.celrep.2022.111809",
language = "English",
volume = "41",
journal = "Cell Reports",
issn = "2211-1247",
number = "11",
}