Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice
Open accessAbstract
Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study gut microbiota from young or old conventional mice was transferred to young germ-free mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer’s patches, and mesenteric lymph nodes from conventionalized germ-free mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here we show by transferring aged microbiota to young germ-free mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the germ-free mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young germ-free mice.
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Changes in the aging intestinal microbiota can adversely affect host metabolism and immunity and are associated with development of cardiovascular, autoimmune, metabolic, and neurodegenerative disorders.
“These changes can adversely affect the host metabolism and immunity [25–27, 40, 64, 86, 110, 112, 118] and are associated with the development of cardiovascular, autoimmune, metabolic, and neurodegenerative disorders [17, 90, 122, 132].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [40]
Declining immune cell function and immunosenescence, together with increased epithelial barrier permeability, promotes elevated systemic inflammation termed inflammaging, contributing to functional decline in the intestine and CNS in old age.
“This, together with declining immune cell function and immunosenescence, promotes a state of elevated systemic inflammation termed “inflammaging” [39, 40, 118], contributing to the functional decline in the intestine and CNS in old age [10, 13, 48].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [40]
The observation that microbiota from aged donors exacerbates paracellular permeability and inflammation in germ-free mice is in agreement with the study's findings and interpretation.
“In agreement with our findings and interpretation is the observation that the microbiota from aged donors exacerbates paracellular permeability and inflammation in germ-free mice [40, 118].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [40]
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References 50 · Cited by 403
- Authors
- Fransen, F., van Beek, A. A., Borghuis, T., Aidy, S. E., Hugenholtz, F., van der Gaast – de Jongh, C., Savelkoul, H. F. J., De Jonge, M. I., Boekschoten, M. V., Smidt, H., Faas, M. M., & de Vos, P.
- Affiliations
- University Medical Center Groningen (NL)
- University of Groningen (NL)
- Wageningen University & Research (NL)
- Corresponding author
- Fransen, Floris
- ORCID
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2017-11-02
- Volume
- 8
- Pages
- 1385-1385
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC5674680
- OpenAlex
- W2765279273
- Cited by
- 403
- References
- 50
- Citations by year
- 2026: 38 · 2025: 43 · 2024: 46 · 2023: 45 · 2022: 62 · 2021: 62 · 2020: 49 · 2019: 41 · 2018: 16
- FWCI
- 11.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- Socio-Environmental Systems Modeling (acceptedVersion, cc-by)
- Socio-Environmental Systems Modeling (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- inflammaging, microbiota transfer, germ-free mice, Akkermansia, Proteobacteria, intestinal inflammation, bacterial translocation, T cell activation, Peyer's patches, mesenteric lymph nodes, ileal gene expression
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