The evolutionarily ancient FOXA transcription factors shape the murine gut microbiome via control of epithelial glycosylation.

Autor:	Swisa A; Department of Genetics and Center for Molecular Studies in Liver and Digestive Diseases, Perelman School of Medicine, University of Pennsylvania, 12-126 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5156, USA., Kieckhaefer J; Department of Genetics and Center for Molecular Studies in Liver and Digestive Diseases, Perelman School of Medicine, University of Pennsylvania, 12-126 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5156, USA., Daniel SG; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA., El-Mekkoussi H; Department of Genetics and Center for Molecular Studies in Liver and Digestive Diseases, Perelman School of Medicine, University of Pennsylvania, 12-126 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5156, USA., Kolev HM; Department of Genetics and Center for Molecular Studies in Liver and Digestive Diseases, Perelman School of Medicine, University of Pennsylvania, 12-126 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5156, USA., Tigue M; Department of Genetics and Center for Molecular Studies in Liver and Digestive Diseases, Perelman School of Medicine, University of Pennsylvania, 12-126 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5156, USA., Jin C; Department of Medical Biochemistry, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Assenmacher CA; Comparative Pathology Core, Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA., Dohnalová L; Microbiology Department, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Thaiss CA; Microbiology Department, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Karlsson NG; Department of Medical Biochemistry, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Life Sciences and Health, Faculty of Health Sciences, Oslo Metropolitan University, 0130 Oslo, Norway., Bittinger K; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Kaestner KH; Department of Genetics and Center for Molecular Studies in Liver and Digestive Diseases, Perelman School of Medicine, University of Pennsylvania, 12-126 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5156, USA. Electronic address: kaestner@pennmedicine.upenn.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Aug 19; Vol. 59 (16), pp. 2069-2084.e8. Date of Electronic Publication: 2024 May 30.
DOI:	10.1016/j.devcel.2024.05.006
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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