Mining the human gut microbiota for effector strains that shape the immune system
Open accessAbstract
The gut microbiota codevelops with the immune system beginning at birth. Mining the microbiota for bacterial strains responsible for shaping the structure and dynamic operations of the innate and adaptive arms of the immune system represents a formidable combinatorial problem but one that needs to be overcome to advance mechanistic understanding of microbial community and immune system coregulation and to develop new diagnostic and therapeutic approaches that promote health. Here, we discuss a scalable, less biased approach for identifying effector strains in complex microbial communities that impact immune function. The approach begins by identifying uncultured human fecal microbiota samples that transmit immune phenotypes to germ-free mice. Clonally arrayed sequenced collections of bacterial strains are constructed from representative donor microbiota. If the collection transmits phenotypes, effector strains are identified by testing randomly generated subsets with overlapping membership in individually housed germ-free animals. Detailed mechanistic studies of effector strain-host interactions can then be performed.
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Microbial manipulations and supplementation of microbial metabolites are being considered as emerging preventive and therapeutic medicines for numerous disorders including those with gut barrier dysfunction and dysbiosis.
“Microbial manipulations and supplementation of microbial metabolites are being considered as emerging preventive and therapeutic medicines for numerous disorders185, 186, 187 including those with gut barrier dysfunction and dysbiosis.”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [185]
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- Authors
- Ahern, P. P., Faith, J. J., & Gordon, J. I.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Gordon, Jeffrey I.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 40
- Issue
- 6
- Pages
- 815-823
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4118768
- OpenAlex
- W2067445465
- Cited by
- 123
- References
- 39
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 7 · 2019: 11 · 2018: 13 · 2017: 13 · 2016: 13 · 2015: 15 · 2014: 8
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust
- Crohn's and Colitis Foundation
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK030292, DK-30292, DK 70977, R01DK070977, R01DK030292)
- 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
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- gut microbiota, immune system development, germ-free mice, fecal microbiota transplantation, innate immunity, adaptive immunity, uncultured bacteria
- MeSH terms
- Animals, Feces, Germ-Free Life, Humans, Immune System, Immunity, Innate, Gastrointestinal Tract, T-Lymphocytes, Regulatory, Mice, Adaptive Immunity, Microbial Consortia, Microbiota
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