The DOI matches its Crossref record; 201 of the 201 references it cites were found in a registry or an index.
Gut microbiome and aging: Physiological and mechanistic insights
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) and is exposed to innumerable microorganisms from the mother as well as the surrounding environment. Concurrently, the host responses to these microbes during early life manifest during the development of an otherwise hitherto immature immune system. The human gut microbiome, which comprises an extremely diverse and complex community of microorganisms inhabiting the intestinal tract, keeps on fluctuating during different stages of life. While these deviations are largely natural, inevitable and benign, recent studies show that unsolicited perturbations in gut microbiota configuration could have strong impact on several features of host health and disease. Our microbiota undergoes the most prominent deviations during infancy and old age and, interestingly, our immune health is also in its weakest and most unstable state during these two critical stages of life, indicating that our microbiota and health develop and age hand-in-hand. However, the mechanisms underlying these interactions are only now beginning to be revealed. The present review summarizes the evidences related to the age-associated changes in intestinal microbiota and vice-versa, mechanisms involved in this bi-directional relationship, and the prospective for development of microbiota-based interventions such as probiotics for healthy aging.
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![Fig.2 Age-related changes in the human gut microbial ecosystem, and potential factors that could affect microbiota composition at different stages of life. α-diversity: species (taxa) richness within a single host/microbial environment; β-diversity: diversity in microbial community (taxonomic abundance profiles) between different environments/samples) [4, 23, 31, 34, 73].](/paper-figures/f1107e493be446d099d9073fb5de9aaf/gut-microbiome-and-aging-physiological-and-mechanistic-insights-figure-2.jpg)
![Fig.3 Features of the homeostatic intestinal environment (eubiosis) (A), and how a perturbed microbiota (dysbiosis) and gut barrier may instigate aging-related maladies (B). Under homeostatic conditions (eubiosis), the epithelial cells produce antimicrobial peptides (AMPs) in response to interleukins (e.g. IL-22) and also express pattern recognition receptors (e.g. Toll-like receptors; TLR). The gut microbes regulate mucous secretion and AMPs production and also regulate/enhance the gut barrier integrity via producing short-chain fatty acids (SCFAs). Goblet cells produce mucus to constrain pathobiont invasion. Lymphoid cells (e.g. TH17 cells) play a role in host defense by producing controlled arrays of IL-22. Dendritic cells (DCs) induce the activation and differentiation of naive B cells to produce plasma cells that produce commensal-specific IgA in the lamina propria. IgA is transported into the gut lumen as secreted IgA (sIgA) via (polymeric immunoglobulin receptor pIgR) receptors, where after sIgA binds to commensal microbes and soluble antigens, thereby restraining their adherence to the host epithelium and leakage through the gut barrier. However, under dysbiosis and/or senescent milieus, the altered microbiota composition and weakened/perturbed gut permeability may lead to increased adherence and leakage of various microbes and microbial by-products through the gut barrier thereby instigating hyper-inflammatory responses eventually increasing the host susceptibility to various gut-related as well as systemic ailments via perturbations in the magnitude of gut-brain axis, gut-liver axis etc. [7, 36, 63, 84, 124, 127, 128, 132, 133, 147].](/paper-figures/bf7bb29546ad4c58a27a5eccfe094eb4/gut-microbiome-and-aging-physiological-and-mechanistic-insights-figure-3.jpg)
![Fig.4 Schematic illustration of putative pathway(s) by which aging-related alterations in gut microbiome and entero-neuro-endocrine system may affect brain health via deteriorated gut-brain communication signaling. In healthy adult host, the balanced gut microbiome configuration and intestinal barrier integrity help in maintaining balanced arrays of microbes, microbial by-products (e.g. short-chain fatty acids; SCFAs) and other entities such as neurotransmitters across the gut wall thereby maintaining a balanced enteric-immune and -inflammatory system through controlled proliferation of dendritic cells and macrophages which eventually helps in keeping the gut-brain communication and the functioning of central nervous system (CNS) under control. In old age, the altered gut microbiota diversity and weakened gut barrier integrity may perturb the microbial and biochemical environment across the intestinal epithelial cell lining via abnormal levels of SCFAs, lipopolysaccharide (LPS), secretory Immunoglobulin A (sIgA), histamins, serotonin (5-hydroxytryptamine; 5-HT), etc. thereby instigating an abnormal (hyper) inflammatory responses eventually affecting (disturbing) the gut-brain communication [84, 90, 93, 103, 104, 109, 112, 124, 158].](/paper-figures/579c46006245475ba84247bd494a4d03/gut-microbiome-and-aging-physiological-and-mechanistic-insights-figure-4.jpg)
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“The microbiota change drastically over the course of host’s lifetime, and aging is correlated with a reduction in microbial diversity and alterations in microbiota composition (24,44).”
From Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice (2021) · cites this paper as [44]
In the citing paper
“Although continued development of the microbiota in adolescence has been indicated in some studies, a core, albeit individualized, microbial profile develops in adulthood that is relatively stable and resilient in the absence of extreme external stressors (e.g., dietary changes or antibiotic treatment) (233-235).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [235]
In the citing paper
“In general, microbial diversity decreases and numbers of beneficial bacteria (bifidobacteria, lactobacilli, Clostridium cluster XIVa, F. prausnitzii) reduce, whereas facultative anaerobes and opportunists or even proinflammatory pathogenic bacteria (Escherichia spp., Enterobacteriaceae spp., Bacteroides spp., C. difficile, etc.) increase when compared with younger individuals (235, 295, 296).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [235]
In the citing paper
“The gut microbiome can modulate many of the host physiological processes including metabolism, cognitive function, innate immunity as well as cellular senescence, thereby potentially contributing to frailty, dysfunction, and disease (44,47).”
From Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice (2021) · cites this paper as [44]
In the citing paper
“Emerging evidence suggests that the gut microbiota imbalance (dysbiosis) is associated with the development of age-associated disorders and reduced survival (44).”
From Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice (2021) · cites this paper as [44]
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Citations
Cites
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Cited by
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Malnutrition in Older Adults—Recent Advances and Remaining Challenges
Norman, K., Haß, U., & Pirlich, M. (2021) · Nutrients · doi:10.3390/nu13082764 · Cited by 905
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Metadata
- Authors
- Nagpal, R., Mainali, R., Ahmadi, S., Wang, S., Singh, R., Kavanagh, K., Kitzman, D. W., Kushugulova, A., Marotta, F., & Yadav, H.
- Affiliations
- Atrium Health Wake Forest Baptist (US)
- Wake Forest University Health Sciences (US)
- Nazarbayev University (KZ)
- ReGenera Research and Development for Aging Interventions, and San Babila Clinic, Corso Matteotti 1/A, Milano, Italy
- Corresponding author
- Yadav, Hariom
- ORCID
- Venue
- Nutrition and Healthy Aging
- Publisher
- SAGE Publications
- Published
- 2017-11-06
- Volume
- 4
- Issue
- 4
- Pages
- 267-285
- ISSN
- 2451-9480 (ISSN-L)
- 2451-9502
- PMC
- PMC6004897
- OpenAlex
- W2767624273
- Cited by
- 670
- References
- 200
- Citations by year
- 2026: 44 · 2025: 69 · 2024: 93 · 2023: 73 · 2022: 103 · 2021: 118 · 2020: 116 · 2019: 48 · 2018: 6
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nutrition and Healthy Aging (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Nazarbayev University Repository (Nazarbayev University) (submittedVersion)
- Funders
- National Institutes of Health (P30AG12232, R01AG18915)
- Wake Forest School of Medicine
- National Institute on Aging (R01AG018915, R37AG018915, P30AG021332)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- gut microbiota, aging, microbiota-immune interactions, immune system development, infancy, probiotics, microbiota-targeted interventions, healthy aging
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