ArticleDevelopmental cell2024
The evolutionarily ancient FOXA transcription factors shape the murine gut microbiome via control of epithelial glycosylation.
Article in Developmental cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- VNN1, upregulated by FOXA1, suppresses osteogenic differentiation and promotes inflammation in LPS-induced periodontal ligament stem cells.Odontology · 2026Article
- Dismissing-then-recruiting: a unique mechanism for symbiont recruitment and lignocellulose degradation in gut of black soldier fly larvae.Microbiome · 2026Article
- FUT2-mediated intestinal fucosylation: a master regulator of host-microbiota symbiosis in health and disease.Frontiers in microbiology · 2026Review
- Genes, guts, and microbes: decoding host-driven microbial regulation using intestine-specific conditional knockouts.Frontiers in immunology · 2025Review
- Metabolic regulation of intestinal homeostasis: molecular and cellular mechanisms and diseases.MedComm · 2024Review
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Authors and funding
13 authors.
Funding
Abstract
Evolutionary adaptation of multicellular organisms to a closed gut created an internal microbiome differing from that of the environment. Although the composition of the gut microbiome is impacted by diet and disease state, we hypothesized that vertebrates promote colonization by commensal bacteria through shaping of the apical surface of the intestinal epithelium. Here, we determine that the evolutionarily ancient FOXA transcription factors control the composition of the gut microbiome by establishing favorable glycosylation on the colonic epithelial surface. FOXA proteins bind to regulatory elements of a network of glycosylation enzymes, which become deregulated when Foxa1 and Foxa2 are deleted from the intestinal epithelium. As a direct consequence, microbial composition shifts dramatically, and spontaneous inflammatory bowel disease ensues. Microbiome dysbiosis was quickly reversed upon fecal transplant into wild-type mice, establishing a dominant role for the host epithelium, in part mediated by FOXA factors, in controlling symbiosis in the vertebrate holobiont.
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Registered trials
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