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

Peder J. Lund, Leah A. Gates, Marylene Leboeuf, Sarah A. Smith, Lillian Chau, Mariana Lopes, Elliot S. Friedman, Yedidya Saiman, Min Soo Kim, Clarissa A. Shoffler, Christopher Petucci, C. David Allis, Gary D. Wu, Benjamin A. Garcia

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish
Article number111809
JournalCell Reports
Issue number11
StatePublished - Dec 13 2022


  • CP: Microbiology
  • colitis
  • epigenetics
  • fatty acid metabolism
  • histone acetylation
  • host-microbiota interactions


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