Metabolite mimicry identifies butyrate analogs with select protective functions in the intestinal mucosa

Butyrate is a well-studied microbial short-chain fatty acid that regulates a number of mucosal pathways and is paramount in maintaining intestinal integrity. In health, it is a major source of energy for colonocytes and regulates gene transcription. The role of butyrate in disease is still controversial and not well understood. When butyrate is not metabolized or well-utilized (e.g. disease), it accumulates in intestinal stem cells leading to reduced cell proliferation and differentiation, thereby hampering intestinal barrier recovery. In this study, we describe a butyrate analog that enhances epithelial barrier formation and wound healing. Furthermore, as opposed to native butyrate, this butyrate analog is protective in a colitis mouse model and does not exhibit detrimental influences on intestinal stem cells.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-01-08
DOI
https://doi.org/10.64898/2026.01.07.697087
Primary Topic
Cancer, Hypoxia, and Metabolism
Type
article
Field-Weighted Citation Impact
0.00

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article

Metabolite mimicry identifies butyrate analogs with select protective functions in the intestinal mucosa

Caroline Hall, J. Adducci, Geetha Bhagavatula, Sean P. Colgan et al.
bioRxiv (Cold Spring Harbor Laboratory)
Cancer, Hypoxia, and Metabolism
article

Metabolite mimicry identifies butyrate analogs with select protective functions in the intestinal mucosa

Caroline Hall, J. Adducci, Geetha Bhagavatula, Sean P. Colgan, Rachel H Cohen, Joseph C. Onyiah, Liheng Zhou, Alexander S. Dowdell, Alfredo Ornelas, Jacob A. Countess, Faiz Minhajuddin, Kiranmayee Yenugudhati Vijaya Sai, Rebecca Roer, JiYeon Kim, Ian M Cartwright, Philip Reigan, Julia L.M. Dunn
article en

Abstract

Butyrate is a well-studied microbial short-chain fatty acid that regulates a number of mucosal pathways and is paramount in maintaining intestinal integrity. In health, it is a major source of energy for colonocytes and regulates gene transcription. The role of butyrate in disease is still controversial and not well understood. When butyrate is not metabolized or well-utilized (e.g. disease), it accumulates in intestinal stem cells leading to reduced cell proliferation and differentiation, thereby hampering intestinal barrier recovery. In this study, we describe a butyrate analog that enhances epithelial barrier formation and wound healing. Furthermore, as opposed to native butyrate, this butyrate analog is protective in a colitis mouse model and does not exhibit detrimental influences on intestinal stem cells.

bioRxiv (Cold Spring Harbor Laboratory)
University of Colorado Boulder (US), Children's Hospital Colorado (US), VIB-UGent Center for Inflammation Research (BE), Rocky Mountain MS Center (US), University of Montana (US), University of Colorado Denver (US)
Crohn's and Colitis Foundation, National Institutes of Health
Affordable and clean energy
Openalex Percentile: Top 94%
Cancer, Hypoxia, and Metabolism
DOIOpen Access PDFOpenAlex
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