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Heterochronic faecal transplantation boosts gut germinal centres in aged mice
Open accessAbstract
Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system; however, it is not clear whether there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer’s patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli.
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“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 [112]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the defective germinal center reaction in Peyer's patches of aged mice can be rescued by FMT from younger animals without affecting germinal center reactions in peripheral lymph nodes.”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [288]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“| Dysbiosis | Mouse | Fecal microbiota transplantation | Improved germinal centre reactions in lymph nodes | 288 |”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [288]
Experimental — accuracy not yet measuredIn the citing paper
“Similar beneficial effects have been reported in aged mice receiving microbiota from young mice to extend life span [8, 61] or halt the functional decline in the mucosal immune system [112].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [112]
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“obese or aged vs young) can lead to important metabolic changes.(105) These results imply that animals from the same experimental group must be in the same cage, as cross-contamination could occur and affect the results.”
ResultShin, J., Noh, J., Choe, D., Lee, N., Song, Y., Cho, S., Kang, E., Go, M., Ha, S. K., Chang, D., et al. (2021) · Microbiome · doi:10.1186/s40168-021-01189-5 · Cited by 119
“Although FMT has shown potential in the treatment of several diseases [32, 40], it is a complex biological intervention and has intrinsic limitations, that is, it can use only feces from healthy donors that are free from diseases.”
BackgroundMethodBacterial induction of B cell senescence promotes age-related changes in the gut microbiota
Kawamoto, S., Uemura, K., Hori, N., Takayasu, L., Konishi, Y., Katoh, K., Matsumoto, T., Suzuki, M., Sakai, Y., Matsudaira, T., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01145-5 · Cited by 91
Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging
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MethodGut, oral and skin microbiome of Indian patrilineal families reveal perceptible association with age
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“FMT from young mice into older recipients can restore defective GC reactions in PPs, although the restorative effect did not extend to peripheral lymph nodes, suggesting a localized effect (Stebegg et al., 2019).”
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“showed that heterochronic FMT from young into old mice and vice versa, boosts germinal center (GC) reaction in Peyer’s patches irrespective of age directionality (19).”
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“FMT has been shown to rejuvenate aged HSCs [194], rescue ageing-associated germinal center deficiency [373], and enhance healthspan and lifespan in progeroid mouse models [191], thereby providing a potential therapy to rejuvenate aged immune system.”
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“Given the accumulating evidence of the role of the gut microbiota on overall health, life quality and/or expectancy could potentially be improved by remodeling the gut microbiome through interventions for probiotic/prebiotic regulation or fecal microbiota transplantation (FMT) (Smith et al., 2017; Vaiserman et al., 20…”
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The cellular factors that impair the germinal center in advanced age
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Self-citationFecal microbiota transplantation holds the secret to youth
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Establishment and Resilience of Transplanted Gut Microbiota in Aged MicePreprint
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Additional file 1 of Gut microbiota of the young ameliorates physical fitness of the aged in mice
Kim, K. H., Chung, Y., Huh, J.-W., Park, D. J., Cho, Y., Oh, Y., Jeong, H., Yoon, J., Kang, J.-H., Shin, H.-S., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22602284
Modeling Hormone Receptor Positive Breast Cancer in Immunocompetent Mice
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Berbudi, A., Riswari, S. F., & Kwarteng, A. (2026) · Journal of Tropical Medicine · doi:10.1155/jotm/3767562 · Cited by 2
“…t h e i r i n t e r a c t i o n w i t h t h e i n t e s t i n a l e p i t h e l i u m , t h e r e b y n e u t r a l i z i n g p o t e n t i a l t h r e a t s [ 55 – 59 ] T h e p r e s e n c e o f c e r t a i n c o mm e n s a l b a c t e r i a h a s b ee n l i n k e d t o i n c r e a s e d T G F - β”
Metadata
- Authors
- Stebegg, M., Silva-Cayetano, A., Innocentin, S., Jenkins, T. P., Cantacessi, C., Gilbert, C., & Linterman, M. A.
- Affiliations
- Babraham Institute (GB)
- University of Cambridge (GB)
- Corresponding author
- Linterman, Michelle A.
- ORCID
- Venue
- Nature Communications
- Published
- 2019-06-04
- Volume
- 10
- Issue
- 1
- Pages
- 2443-2443
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6547660
- OpenAlex
- W2948768639
- Cited by
- 107
- References
- 53
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 16 · 2023: 17 · 2022: 17 · 2021: 18 · 2020: 14 · 2019: 3
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Apollo (cc-by)
- Funders
- Wellcome Trust
- European Commission (675395)
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0407, BBS/E/B/000C0427)
- H2020 European Research Council (637801)
- 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 › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- Peyer's patches, gut-associated lymphoid tissue, gut microbiota, immunosenescence, frailty, systemic inflammation, aged mice
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Aging, Animals, Cholera Toxin, Female, Immunoglobulin A, Immunization, Nitrophenols, Peyer's Patches, Phenylacetates, Germinal Center, Mice, Dysbiosis
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