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The Gut Microbiome, Aging, and Longevity: A Systematic Review
Open accessAbstract
Aging is determined by complex interactions among genetic and environmental factors. Increasing evidence suggests that the gut microbiome lies at the core of many age-associated changes, including immune system dysregulation and susceptibility to diseases. The gut microbiota undergoes extensive changes across the lifespan, and age-related processes may influence the gut microbiota and its related metabolic alterations. The aim of this systematic review was to summarize the current literature on aging-associated alterations in diversity, composition, and functional features of the gut microbiota. We identified 27 empirical human studies of normal and successful aging suitable for inclusion. Alpha diversity of microbial taxa, functional pathways, and metabolites was higher in older adults, particularly among the oldest-old adults, compared to younger individuals. Beta diversity distances significantly differed across various developmental stages and were different even between oldest-old and younger-old adults. Differences in taxonomic composition and functional potential varied across studies, but Akkermansia was most consistently reported to be relatively more abundant with aging, whereas Faecalibacterium, Bacteroidaceae, and Lachnospiraceae were relatively reduced. Older adults have reduced pathways related to carbohydrate metabolism and amino acid synthesis; however, oldest-old adults exhibited functional differences that distinguished their microbiota from that of young-old adults, such as greater potential for short-chain fatty acid production and increased butyrate derivatives. Although a definitive interpretation is limited by the cross-sectional design of published reports, we integrated findings of microbial composition and downstream functional pathways and metabolites, offering possible explanations regarding age-related processes.
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![Figure 2 Microbial taxa reported to be differentially abundant in long-living individuals across reviewed studies. Area represents proportion of studies reporting each taxon. Color indicates the direction and net strength of observed findings. Data in this figure are based on nine studies [19,20,21,22,23,24,25,26,34].](/paper-figures/3196547cf8d249b5a06aadaaf7f49a56/the-gut-microbiome-aging-and-longevity-a-systematic-review-figure-2.jpg)
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“Studies in the past decade have demonstrated that gut microbiome composition changes with age, that exceptionally long-lived individuals have a different microbiome composition from average older adults131–133, and that certain microorganisms131,134,135 and the metabolites they produce132,134,136 are beneficial to human health.”
From Measuring biological age using omics data (2022) · cites this paper as [131]
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Self-citationLinking long-term dietary patterns with gut microbial enterotypes
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Self-citationInflamm‐aging: An Evolutionary Perspective on Immunosenescence
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Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
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Self-citationInflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
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Measuring biological age using omics data
Rutledge, J., Oh, H., & Wyss-Coray, T. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00511-7 · Cited by 570
Chronic inflammation and the hallmarks of aging
Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101755 · Cited by 471
The aging gut microbiome and its impact on host immunity
Bosco, N., & Noti, M. (2021) · Genes and Immunity · doi:10.1038/s41435-021-00126-8 · Cited by 435
Short-chain fatty acids as modulators of redox signaling in health and disease
González‐Bosch, C., Boorman, E., Zunszain, P. A., & Mann, G. E. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102165 · Cited by 298
Gut bacterial profiles in Parkinson's disease: A systematic review
Li, Z., Liang, H., Lu, L., Lu, L., Zheng, C., Fan, Y., Wu, B., Zou, T., Luo, X., Xinchun, Z., et al. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13990 · Cited by 224
Metadata
- Authors
- Badal, V. D., Vaccariello, E. D., Murray, E. R., Yu, K. E., Knight, R., Jeste, D. V., & Nguyen, T. T.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Nguyen, Tanya T.
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2020-12-07
- Volume
- 12
- Issue
- 12
- Pages
- 3759
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC7762384
- OpenAlex
- W3110715890
- Cited by
- 551
- References
- 91
- Citations by year
- 2026: 108 · 2025: 122 · 2024: 122 · 2023: 96 · 2022: 73 · 2021: 29
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (K23 MH118435-01A1, 5T32 MH019934-24)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- gut microbiota, aging, longevity, oldest old, microbial diversity, Akkermansia, Faecalibacterium, Bacteroidaceae, Lachnospiraceae, short-chain fatty acids, butyrate, carbohydrate metabolism, amino acid synthesis, immune dysregulation
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Aged, 80 and over, Aging, Amino Acids, Cross-Sectional Studies, Feces, Female, Humans, Longevity, Male, Middle Aged, Protein Biosynthesis, Signal Transduction, Carbohydrate Metabolism
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