Stable isotope tracing in vivo reveals a metabolic bridge linking the microbiota to host histone acetylation

作者：Peder J. Lund, Leah A. Gates, Marylène Leboeuf, Sarah Ann Smith, Lillian Chau, Mariana de Camargo Lopes, Elliot S. Friedman, Yedidya Saiman, Min Soo Kim, Clarissa A. Shoffler, Christopher J. Petucci, C. David Allis, Gary D. Wu, Benjamin Aaron Garcia · 发表于：Cell Reports · 年份：2022 · DOI：10.1016/j.celrep.2022.111809 · 被引用次数：62 · 研究领域：Gut microbiota and health、Epigenetics and DNA Methylation、Metabolomics and Mass Spectrometry Studies

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 13 C-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.