Strain-level differences in gut microbiome composition determine fecal IgA levels and are modifiable by gut microbiota manipulation
Strain-level differences in gut microbiome composition determine fecal IgA levels and are modifiable by gut microbiota manipulation
Summary Fecal IgA production depends on colonization by a gut microbiota. However, the bacterial strains that drive gut IgA production remain largely unknown. By accessing the IgA-inducing capacity of a diverse set of human gut microbial strains, we identified Bacteroides ovatus as the species that best induced gut IgA production. However, this induction varied bimodally across different B. ovatus strains. The high IgA-inducing B. ovatus strains preferentially elicited more IgA production in the large intestine largely through the T-cell-dependent B cell-activation pathway. Remarkably, a low-IgA phenotype in mice could be robustly and consistently converted into a high-IgA phenotype by transplanting a multiplex cocktail of high IgA-inducing B. ovatus strains but not individual ones. Our results highlight the critical importance of microbial strains in driving phenotype variation in the mucosal immune system and provide a strategy to robustly modify a gut immune phenotype, including IgA production.
Faith Jeremiah J.、Mogno Ilaria、Aggarwala Varun、Siu Sophia Y.、Helmus Drew S.、Dubinsky Marla C.、Cerutti Andrea、Grasset Emilie K.、Contijoch Eduardo J.、Li Zhihua、Borgerding Joshua N.、Yang Chao、Mehandru Saurabh
Precision Immunology Institute, Icahn School of Medicine at Mount Sinai||Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount Sinai||Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount Sinai||Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiPediatric Gastroenterology and Hepatology, Department of Pediatrics, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount SinaiPediatric Gastroenterology and Hepatology, Department of Pediatrics, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount Sinai||Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d?ˉInvestigacions Mediques (IMIM)||Catalan Institute for Advanced Studies (ICREA)Precision Immunology Institute, Icahn School of Medicine at Mount Sinai||Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University HospitalPrecision Immunology Institute, Icahn School of Medicine at Mount Sinai||Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount Sinai||Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount Sinai
微生物学基础医学
Gut microbiotaImmunoglobulin ABacteroides ovatusFecal Microbiota TransplantationImmune modulation
Faith Jeremiah J.,Mogno Ilaria,Aggarwala Varun,Siu Sophia Y.,Helmus Drew S.,Dubinsky Marla C.,Cerutti Andrea,Grasset Emilie K.,Contijoch Eduardo J.,Li Zhihua,Borgerding Joshua N.,Yang Chao,Mehandru Saurabh.Strain-level differences in gut microbiome composition determine fecal IgA levels and are modifiable by gut microbiota manipulation[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/544015.点此复制
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