Gut immune maturation depends on colonization with a host-specific microbiota
Open accessAbstract
Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4(+) and CD8(+) T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression--all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system.
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Difficulty in maintaining new (non-native) microbiota in recipient mice, whether germ-free or those in which gut microbiota suppression was initially performed with oral mixture of poorly absorbed antibiotics, has been reported in other studies.
“Difficulty in maintaining new (non-native) microbiota in recipient mice, whether germ-free or those in which gut microbiota suppression was initially performed with oral mixture of poorly absorbed antibiotics, has been reported in other studies (30-32).”
From Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation (2015) · cites this paper as [32]
Deficits in germ-free mice can be corrected by colonization with diverse commensal bacteria, but this is age-dependent, suggesting composition and timing of colonization are critical for immune education.
“These deficits can be corrected by colonization with diverse commensal bacteria; however, this has been shown to be age-dependent, suggesting that both composition and timing of colonization are critical for the education of the immune system [16–18].”
From The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders (2018) · cites this paper as [16]
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- Authors
- Chung, H., Pamp, S. J., Hill, J. A., Surana, N. K., Edelman, S. M., Troy, E. B., Reading, N. C., Villablanca, E. J., Wang, S., Mora, J. R., Umesaki, Y., Mathis, D., Benoist, C., Relman, D. A., & Kasper, D. L.
- Affiliations
- Brigham and Women's Hospital (US)
- VA Palo Alto Health Care System (US)
- Harvard University (US)
- Yakult Central Institute (JP)
- Corresponding author
- Kasper, Dennis L.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 149
- Issue
- 7
- Pages
- 1578-1593
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3442780
- OpenAlex
- W2170925079
- Cited by
- 1,241
- References
- 66
- Citations by year
- 2026: 48 · 2025: 77 · 2024: 88 · 2023: 78 · 2022: 78 · 2021: 122 · 2020: 115 · 2019: 109 · 2018: 99 · 2017: 91 · 2016: 83 · 2015: 77 · 2014: 83 · 2013: 78 · 2012: 15
- FWCI
- 32.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- Funders
- National Institutes of Health (DP1OD000964)
- National Institute of Allergy and Infectious Diseases (R21AI090102, F32AI091104, T32AI007061)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD055148)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- gut microbiota, host-microbe mutualism, immune system maturation, germ-free mice, human microbiota, intestinal T cells, dendritic cells, antimicrobial peptides, segmented filamentous bacteria, Firmicutes, salmonellosis, host specificity
- MeSH terms
- Animals, Bacteria, Female, Germ-Free Life, Humans, Immunity, Innate, Intestines, Male, Salmonella Infections, Species Specificity, Specific Pathogen-Free Organisms, Symbiosis, T-Lymphocytes, Rats, Sprague-Dawley, Cell Proliferation, Mice, Rats, Metagenome
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