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Fecal IgA Levels Are Determined by Strain-Level Differences in Bacteroides ovatus and Are Modifiable by Gut Microbiota Manipulation
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Abstract
Fecal IgA production depends on colonization by a gut microbiota. However, the bacterial strains that drive gut IgA production remain largely unknown. Here, we assessed the IgA-inducing capacity of a diverse set of human gut microbial strains by monocolonizing mice with each strain. 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 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.
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“There is now ample evidence that intraspecies variation of gut microbiota can substantially change their effect on hosts, first described for enteric pathogens (for example, Escherichia coli 56 ) but more recently demonstrated for immunomodulatory commensals 57,58 , providing further conceptual support for this notion.”
From A gut microbial signature for combination immune checkpoint blockade across cancer types (2024) · cites this paper as [57]
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Metadata
- Authors
- Yang, C., Mogno, I., Contijoch, E. J., Borgerding, J. N., Aggarwala, V., Li, Z., Siu, S., Grasset, E. K., Helmus, D. S., Dubinsky, M. C., Mehandru, S., Cerutti, A., & Faith, J. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Karolinska University Hospital (SE)
- Mount Sinai Hospital (US)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Faith, Jeremiah J.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 27
- Issue
- 3
- Pages
- 467-475.e6
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC7213796
- OpenAlex
- W3007217849
- Cited by
- 221
- References
- 78
- Citations by year
- 2026: 22 · 2025: 33 · 2024: 38 · 2023: 29 · 2022: 38 · 2021: 40 · 2020: 21
- FWCI
- 10.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Janssen Research and Development LLC
- National Institute of General Medical Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Center for Complementary and Integrative Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- fecal IgA, Bacteroides ovatus, strain-level diversity, gut microbiota, mucosal immunity, T cell-dependent B cell activation, microbial transplantation, large intestine
- MeSH terms
- Gastrointestinal Microbiome, Animals, B-Lymphocytes, Bacteroides, Feces, Germ-Free Life, Humans, Immunoglobulin A, Intestine, Large, Mice, Inbred C57BL, CD4-Positive T-Lymphocytes, Mice
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