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Revisiting Metchnikoff: Age-related alterations in microbiota-gut-brain axis in the mouse
Open accessAbstract
Over the last decade, there has been increased interest in the role of the gut microbiome in health including brain health. This is by no means a new theory; Elie Metchnikoff proposed over a century ago that targeting the gut by consuming lactic acid bacteria such as those in yogurt, could improve or delay the onset of cognitive decline associated with ageing. However, there is limited information characterising the relationship between the behavioural and physiological sequelae of ageing and alterations in the gut microbiome. To this end, we assessed the behavioural, physiological and caecal microbiota profile of aged male mice. Older mice (20-21months old) exhibited deficits in spatial memory and increases in anxiety-like behaviours compared to younger mice (2-3months old). They also exhibited increased gut permeability, which was directly correlated with elevations in peripheral pro-inflammatory cytokines. Furthermore, stress exacerbated the gut permeability of aged mice. Examination of the caecal microbiota revealed significant increases in phylum TM7, family Porphyromonadaceae and genus Odoribacter of aged mice. This represents a shift of aged microbiota towards a profile previously associated with inflammatory disease, particularly gastrointestinal and liver disorders. Furthermore, Porphyromonadaceae, which has also been associated with cognitive decline and affective disorders, was directly correlated with anxiety-like behaviour in aged mice. These changes suggest that changes in the gut microbiota and associated increases in gut permeability and peripheral inflammation may be important mediators of the impairments in behavioural, affective and cognitive functions seen in ageing.
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“aged mice have a higher relative abundance of Porphyromonadaceae and that the levels of this family correlate with increased anxiety-like behavior”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Scott et al., 2017
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“Sequencing studies showing associations between particular gut microbiota profiles and various diseases in humans, along with studies modifying the gut bacterial composition in animal models, by probiotic administration or microbiota transfer, implicate the gut microbiota as a key regulator of systemic homeostasis, including neuroinflammation and behavioral disorders [16, 106].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [106]
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Metadata
- Authors
- Scott, K. A., Ida, M., Peterson, V. L., Prenderville, J. A., Moloney, G. M., Izumo, T., Murphy, K., Murphy, A., Ross, R. P., Stanton, C., Dinan, T. G., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Suntory (Japan) (JP)
- Teagasc - The Irish Agriculture and Food Development Authority (IE)
- Corresponding author
- Cryan, John F.
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 65
- Pages
- 20-32
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2585159410
- Cited by
- 202
- References
- 87
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 21 · 2023: 15 · 2022: 32 · 2021: 27 · 2020: 24 · 2019: 34 · 2018: 20 · 2017: 11
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 300 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Brain Behavior and Immunity (acceptedVersion)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (acceptedVersion)
- Cork Open Research Archive (University College Cork, Ireland) (submittedVersion, cc-by-nc-nd)
- Funders
- Science Foundation Ireland
- SFI
- Health Research Board (12)
- Department of Agriculture, Food & the Marine
- Enterprise Ireland
- APC Microbiome Institute
- University College Cork
- AstraZeneca
- Mead Johnson
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- gut microbiota, microbiota-gut-brain axis, aging, cognitive decline, spatial memory, anxiety-like behavior, intestinal permeability, peripheral inflammation, inflammatory cytokines, Porphyromonadaceae, Odoribacter, cecal microbiota, stress, lactic acid bacteria, mouse model
- MeSH terms
- Gastrointestinal Microbiome, Age Factors, Animals, Anxiety, Behavior, Animal, Brain, Cognition, Inflammation, Male, Mice, Inbred C57BL, Cytokines, Porphyromonas, Gastrointestinal Tract, Mice, Microbiota
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