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Nirello, Vinícius Dias, Araújo, Nathália, de Assis, Helder Carvalho, Moreno-Gonzalez, Mar, Ruiz, Paula, Castro, Pollyana Ribeiro, Shealy, Nicolas G., Shelton, Catherine, Fernandes, Mariane Font, de Oliveira, Sarah, Boroni, Mariana, Ryffel, Bernhard, Byndloss, Mariana Xavier, Beraza, Naiara 
ORCID: https://orcid.org/0000-0003-0718-0940, Vinolo, Marco Aurélio Ramirez and Varga-Weisz, Patrick
(2025)
Microbiota shape the colon epithelium controlling inter-crypt absorptive goblet cells via butyrate–GP R109A signalling.
Gut Microbes, 17 (1).
ISSN 1949-0976
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Abstract
The colonic epithelium is a key interface between the gut microbiota and the host. How microbiota-derived signals influence epithelial cell identity and function remains incompletely understood. Here, we used single-cell transcriptomics, antibiotic-mediated microbiota depletion, germ-free mice and colonization experiments in mice to uncover cell-type-specific responses to microbiota changes, highlighting changes in the cell composition and functional diversities in enterocytes. Our analysis demonstrates that the microbiota control the absorptive profile of the colon epithelial cells and reveals non-canonical inter-crypt goblet cells as microbiota-responsive constituents that combine absorptive and secretory features and whose abundance is regulated by the gut microbiota. We found that their number is suppressed through the short-chain fatty acid butyrate and its receptor GPR109A. Analysis in mouse and humans indicates that the expansion of this hybrid population increases with age and that this expansion is driven by microbiome changes. Our work reveals a previously unrecognized level of epithelial plasticity driven by microbial triggers and highlights butyrate, acting as a signaling molecule that shapes the colon micro-anatomy.
| Item Type: | Article |
|---|---|
| Additional Information: | Data availability statement: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Sequence data generated in this study have been uploaded to the NCBI repository BioProject: PRJNA1136851, 16S amplicon sequencing of Antibiotic-Induced Microbiome-Depleted and Specific Pathogen Free Mice; BioProject: PRJNA1136828, Single-Cell Gene Expression Profiling of Intestinal Epithelial Cells in Colon Tissue from Antibiotic-Induced Microbiome-Depleted, Specific Pathogen Free, and Germ-Free Mice |
| Uncontrolled Keywords: | gpr109a,hcar2,single-cell transcriptomics,aging,butyrate,colon epithelium,microbiology,gastroenterology,microbiology (medical),infectious diseases,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2404 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 14 Aug 2026 11:52 |
| Last Modified: | 14 Aug 2026 11:52 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/104140 |
| DOI: | 10.1080/19490976.2025.2573045 |
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