Adjusting for age improves identification of gut microbiome alterations in multiple diseases
Open accessAbstract
Interaction between disease-microbiome associations and ageing has not been explored in detail. Here, using age/region-matched sub-sets, we analysed the gut microbiome differences across five major diseases in a multi-cohort dataset constituting more than 2500 individuals from 20 to 89 years old. We show that disease-microbiome associations display specific age-centric trends. Ageing-associated microbiome alterations towards a disease-like configuration occur in colorectal cancer patients, thereby masking disease signatures. We identified a microbiome disease response shared across multiple diseases in elderly subjects that is distinct from that in young/middle-aged individuals, but also a novel set of taxa consistently gained in disease across all age groups. A subset of these taxa was associated with increased frailty in subjects from the ELDERMET cohort. The relevant taxa differentially encode specific functions that are known to have disease associations.
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Members of the Bifidobacteriaceae, Akkermansiaceae, and Eubacteriaceae families are associated with beneficial effects on intestinal and extra-intestinal health in both mice and humans.
“Members of the Bifidobacteriaceae, Akkermansiaceae, and Eubacteriaceae families that are associated with beneficial effects on intestinal and extra-intestinal health in both mice and humans”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [43]
Some species within the Eubacteriaceae family are currently thought to modulate cholesterol and bile acid metabolism and are considered potential therapeutics.
“However, some species are currently thought to modulate cholesterol and bile acid metabolism and are considered potential therapeutics [43].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [43]
Age has been shown to improve microbiome predictions in colorectal cancer.
“Age was also added to the feature-set, as this covariate has been shown to improve microbiome predictions in CRC (Ghosh et al., 2020).”
From Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3 (2021) · cites this paper as Ghosh et al., 2020
The Enterocloster genus (E. aldensis, E. asparagiformis, and E. bolteae) represents a vancomycin-sensitive clade of immunosuppressive bacteria, dominant in the intestinal microbiota of people and patients suffering from aging and chronic inflammatory disorders including cancer.
“The Enterocloster genus (E. aldensis, E. asparagiformis, and E. bolteae) represents a vancomycin-sensitive clade of immunosuppressive bacteria, dominant in the intestinal microbiota of people and patients suffering from aging and chronic inflammatory disorders including cancer.39”
From Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome (2024) · cites this paper as [47]
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A metagenome-wide association study of gut microbiota in type 2 diabetes
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BackgroundMetaPhlAn2 for enhanced metagenomic taxonomic profiling
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MethodResultDisentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota
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InfluentialGut microbiome structure and metabolic activity in inflammatory bowel disease
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MethodResultInfluentialPrecision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile
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“Alterations in the gut microbiome have been reported for many diseases (Duvallet et al., 2017; Pasolli et al., 2016).”
BackgroundResultInfluentialRegional variation limits applications of healthy gut microbiome reference ranges and disease models
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BackgroundDeschasaux, M., Bouter, K. E., Prodan, A., Levin, E., Groen, A. K., Herrema, H., Tremaroli, V., Bakker, G. J., Attaye, I., Pinto-Sietsma, S.-J., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0160-1 · Cited by 695 · cited 2× · see citing works
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BackgroundMachine Learning Meta-analysis of Large Metagenomic Datasets: Tools and Biological Insights
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Accessible, curated metagenomic data through ExperimentHub
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“Comparing the list of these associations with a pre-compiled list of all known marker associations reported in the original studies (Figure 3—source data 3) (Feng et al., 2015; Franzosa et al., 2019; Karlsson et al., 2013; Qin et al., 2012; Qin et al., 2014; Vogtmann et al., 2016; Zeller et al., 2014), identified that…”
BackgroundMethodResultMicrobial modulation of insulin sensitivity
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“difficile) that is associated with microbiome alteration, large bowel cancer and insulin resistance (Fau et al., 1976; Khan et al., 2014), high level ethanol production in the gut has not only been linked to incidence of NAFLD, atherosclerosis and SIBO, but also to an increase in the levels of inflammatory markers (El…”
BackgroundSung, J., Kim, S., Cabatbat, J. J. T., Jang, S., Jin, Y., Jung, G. Y., Chia, N., & Kim, P. (2017) · Nature Communications · doi:10.1038/ncomms15393 · Cited by 249 · cited 1× · see citing works
“, 2018), as well as a recent method to search experimentally-verified functional profiles representing the production and consumption patterns of different metabolites in various gutassociated species (Sung et al., 2017).”
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Gut microbiota composition is associated with polypharmacy in elderly hospitalized patients
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“Similarly, production of acetone, ammonia (NH3) have been associated with increased cytotoxicity, small intestinal bacterial overgrowth, as well as insulin resistance (Baskaran et al., 1989; Ghoshal et al., 2017; Khan et al., 2014).”
BackgroundAnalysis of 1135 gut metagenomes identifies sex-specific resistome profiles
Sinha, T., Vich Vila, A., Garmaeva, S., Jankipersadsing, S. A., Imhann, F., Collij, V., Bonder, M. J., Jiang, X., Gurry, T., Alm, E. J., et al. (2019) · Gut Microbes · doi:10.1080/19490976.2018.1528822 · Cited by 208 · see citing works
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Early-onset Colorectal Cancer is Distinct From Traditional Colorectal Cancer
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“Recent meta-analyses have also shown a surprising degree of overlap of microbiome associations (both at the level of specific taxa as well as specific microbial metabolic pathways) (Armour et al., 2019; Duvallet et al., 2017; Pasolli et al., 2016).”
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“We first adopted a stepwise methodology to reduce the confounding effects of DNA sequencing/ extraction methodologies on the microbiome profiles from the different studies (See Materials and methods; Figure 1—figure supplement 1), and subsequently retained samples from individuals with age in the range of 20–89 years…”
MethodBile acid dysregulation, gut dysbiosis, and gastrointestinal cancer
Tsuei, J., Chau, T., Mills, D. A., & Wan, Y. Y. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214538743 · Cited by 118 · cited 2× · see citing works
“While p-cresol is a cytotoxic compound (produced by specific gut bacterial species including C. difficile) that is associated with microbiome alteration, large bowel cancer and insulin resistance (Fau et al., 1976; Khan et al., 2014), high level ethanol production in the gut has not only been linked to incidence of NA…”
BackgroundA vaccine and diagnostic target for Clostridium bolteae, an autism-associated bacterium
Pequegnat, B., Sagermann, M., Valliani, M., Toh, M. C. W., Chow, H. S., Allen‐Vercoe, E., & Monteiro, M. A. (2013) · Vaccine · doi:10.1016/j.vaccine.2013.04.018 · Cited by 65 · cited 1× · see citing works
“separate studies of different diseases and/or disease-like states (T2D, Polyps, CRC and autism) (Pequegnat et al., 2013; Qin et al., 2012; Sinha et al., 2019; Yu et al., 2017), but are shown here, for the first time to be part of a shared gain response across diseases.”
BackgroundFormation of methylglyoxal by bacteria isolated from human faeces
Baskaran, S., Rajan, D. P., & Balasubramanian, K. A. (1989) · Journal of Medical Microbiology · doi:10.1099/00222615-28-3-211 · Cited by 50 · cited 1× · see citing works
“Similarly, production of acetone, ammonia (NH3) have been associated with increased cytotoxicity, small intestinal bacterial overgrowth, as well as insulin resistance (Baskaran et al., 1989; Ghoshal et al., 2017; Khan et al., 2014).”
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Hallmarks of aging: An expanding universe
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“Frailty Ghosh et al.(46) (189) Ireland Shotgun Pathobionts with production capacity of multiple detrimental metabolites increased; SCFA producers decreased”
BackgroundSelf-citationGut microbiome pattern reflects healthy ageing and predicts survival in humans
Wilmanski, T. M., Diener, C., Rappaport, N., Patwardhan, S., Wiedrick, J. T., Lapidus, J., Earls, J. C., Zimmer, A., Glusman, G., Robinson, M., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00348-0 · Cited by 693 · see citing works
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“For example, age could be a common confounder due to its influence on the microbiome and on the risk of most health outcomes 32 .”
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“[409] Ghosh TS, Das M, Jeffery IB, O’Toole PW.”
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“Members of the Bifidobacteriaceae, Akkermansiaceae, and Eubacteriaceae families that are associated with beneficial effects on intestinal and extra-intestinal health in both mice and humans ([8, 38, 43, 73, 78, 81]) were more Fig.”
BackgroundThe Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence
DeJong, E. N., Surette, M. G., & Bowdish, D. M. E. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.07.013 · Cited by 370 · see citing works
Gut Microbiome in Progressive Multiple Sclerosis
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“The microbiome composition in adults is relatively stable and similar between young adults (20–40 years of age) and middleaged (40–60 years) adults, but can differ in adults older than 60 years.(77) To address this, we adjusted microbiota correlations with EDSS, MRI, and quality of life for age.”
BackgroundAbdolmaleky, H. M., & Zhou, J. (2024) · Antioxidants · doi:10.3390/antiox13080985 · Cited by 311 · see citing works
“In general, there is a trend toward decreased microbial diversity and increased abundance of pathogenic bacteria as we age [33,34].”
BackgroundRethinking healthy eating in light of the gut microbiome
Armet, A. M., Deehan, E. C., O’Sullivan, A. F., Mota, J. F., Field, C. J., Prado, C. M., Lucey, A. J., & Walter, J. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.04.016 · Cited by 252 · see citing works
Companys, J., Gosalbes, M. J., Pla‐Pagà, L., Calderón-Pérez, L., Llauradó, E., Pedret, A., Valls, R. M., Jiménez‐Hernández, N., Sandoval-Ramírez, B. A., Bas-Prior, J. M. D., et al. (2021) · Nutrients · doi:10.3390/nu13062032 · Cited by 199 · see citing works
“001), both groups were in the same range of age (adulthood) and no adjustments were performed, since it has been shown that subjects between 40 and 59 years (middle age) have similar gut microbiota compared with young adults or older adults [21].”
BackgroundDerosa, L., Iebba, V., Silva, C. A. C., Piccinno, G., Wu, G., Lordello, L., Routy, B., Zhao, N., Thelemaque, C., Birebent, R., et al. (2024) · Cell · doi:10.1016/j.cell.2024.05.029 · Cited by 198 · see citing works
Aging and InflammationPreprint
Singh, A., Schurman, S. H., Bektas, A., Kaileh, M., Roy, R., Wilson, D. M., Sen, R., & Ferrucci, L. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041197 · Cited by 194 · see citing works
The human gut microbiome and aging
Bradley, E. S., & Haran, J. P. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2359677 · Cited by 177 · see citing works
“61 It has been suggested that there are microbial taxa associated with healthy aging, and that loss of these may represent “taxonomic mile-stones” that contribute to or accompany physiologic decline and subsequent age-related disease.”
BackgroundZhou, Q., Zhang, Y., Wang, X., Yang, R., Zhu, X., Zhang, Y., Chen, C., Yuan, H., Yang, Z., & Sun, L. (2020) · Nutrition & Metabolism · doi:10.1186/s12986-020-00516-1 · Cited by 175 · see citing works
“One previous report showed that the aging-associated microbiome masked the microbial signatures of colorectal cancer because of the interactions between cancer-microbiome and aging [22].”
BackgroundMicrobiota-Centered Interventions: The Next Breakthrough in Immuno-Oncology?
Derosa, L., Routy, B., Desilets, A., Daillère, R., Terrisse, S., Kroemer, G., & Zitvogel, L. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0236 · Cited by 170 · see citing works
Nickols, W. A., Kuntz, T. M., Shen, J., Maharjan, S., Mallick, H., Franzosa, E. A., Thompson, K. N., Nearing, J. T., & Huttenhower, C. (2026) · Nature Methods · doi:10.1038/s41592-025-02923-9 · Cited by 165 · see citing works
Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy
Thomas, A. M., Fidelle, M., Routy, B., Kroemer, G., Wargo, J. A., Segata, N., & Zitvogel, L. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00785-8 · Cited by 141 · see citing works
Toward an improved definition of a healthy microbiome for healthy aging
Ghosh, T. S., Shanahan, F., & O’Toole, P. W. (2022) · Nature Aging · doi:10.1038/s43587-022-00306-9 · Cited by 128 · see citing works
“Reinvestigating the disease associations of the above set of 59 health- and diseaseassociated taxa (originally identified in(1)) in the newly included datasets of the current study (that is, not considered in Ghosh et al.(1)), indicated a high reproducibility of the disease associations of these taxa in the additional…”
BackgroundMethodResultInfluentialSelf-citationDysbiosis in the Gut Microbiota in Patients with Inflammatory Bowel Disease during Remission
Pisani, A., Rausch, P., Bang, C., Ellul, S., Tabone, T., Cordina, C. M., Zahra, G., Franke, A., & Ellul, P. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.00616-22 · Cited by 120 · see citing works
“This points toward a possible age-dependent decrease of colonization resistance or simply continuing succession of the bacterial communities (16, 17).”
BackgroundWu, R., Xiong, R., Li, Y., Chen, J., & Yan, R. (2023) · Journal of Autoimmunity · doi:10.1016/j.jaut.2023.103062 · Cited by 121 · see citing works
Chanda, D., & De, D. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2304900 · Cited by 116 · see citing works
Microbiomes other than the gut: inflammaging and age-related diseases
Santoro, A., Zhao, J., Wu, L. H., Carru, C., Biagi, E., & Franceschi, C. (2020) · Seminars in Immunopathology · doi:10.1007/s00281-020-00814-z · Cited by 106 · see citing works
“The GM undergoes both compositional and functional changes along with physiological modifications that characterize the advancement of age [38].”
BackgroundThe gut microbiota–brain axis in neurological disorders
You, M., Chen, N., Yang, Y., Cheng, L., He, H., Cai, Y., Liu, Y., Liu, H., & Hong, G. (2024) · MedComm · doi:10.1002/mco2.656 · Cited by 107 · see citing works
“18,176,177 The composition and relative abundance of gut bacteria from phylum to genus are different in AD patients compared with healthy people.”
BackgroundChen, Y., Wang, H., Lu, W., Wu, T., Yuan, W., Zhu, J., Lee, Y. K., Zhao, J., Zhang, H., & Chen, W. (2022) · Gut Microbes · doi:10.1080/19490976.2021.2025016 · Cited by 94 · see citing works
“clostridioforme, Clostridium hathewayi, Clostridium bolteae, Clostridium leptum, Clostridiales bacterium 1_7_47FAA and the pathway of pyruvate fermentation to acetone.(8) In addition, some indicators may clarify the collective characteristics of the gut environment.”
BackgroundInfluentialGut microbiota development across the lifespan: Disease links and health‐promoting interventions
Schoultz, I., Claesson, M. J., Domínguez-Bello, M. G., Hållenius, F. F., Konturek, P. C., Korpela, K., Laursen, M. F., Penders, J., Roager, H. M., Vatanen, T., et al. (2025) · Journal of Internal Medicine · doi:10.1111/joim.20089 · Cited by 93 · see citing works
“Based on this framework, adjusting for age could also allow for better identification of microbiome associations with a number of non-communicable diseases [137].”
Microbiome and health implications for ethnic minorities after enforced lifestyle changes
Keohane, D. M., Ghosh, T. S., Jeffery, I. B., Molloy, M. G., O’Toole, P. W., & Shanahan, F. (2020) · Nature Medicine · doi:10.1038/s41591-020-0963-8 · Cited by 87 · see citing works
Self-citationThe Role of Diet and Lifestyle in Early-Onset Colorectal Cancer: A Systematic Review
Puzzono, M., Mannucci, A., Grannò, S., Zuppardo, R. A., Galli, A., Danese, S., & Cavestro, G. M. (2021) · Cancers · doi:10.3390/cancers13235933 · Cited by 90 · see citing works
“In fact, a recent meta-analysis determined that the microbiota composition changes with age, even for healthy individuals [189].”
BackgroundBladder cancer, inflammageing and microbiomes
Martin, A., Woolbright, B. L., Umar, S., Ingersoll, M. A., & Taylor, J. A. (2022) · Nature Reviews Urology · doi:10.1038/s41585-022-00611-3 · Cited by 89 · see citing works
Reinold, J., Farahpour, F., Fehring, C., Dolff, S., Konik, M., Korth, J., van Baal, L., Hoffmann, D. E., Buer, J., Witzke, O., et al. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.747816 · Cited by 84 · see citing works
Risely, A., Wilhelm, K., Clutton-Brock, T. H., Manser, M. B., & Sommer, S. (2021) · Nature Communications · doi:10.1038/s41467-021-26298-5 · Cited by 78 · see citing works
Albrich, W. C., Ghosh, T. S., Ahearn-Ford, S., Mikaeloff, F., Lunjani, N., Forde, B. M., Suh, N., Kleger, G., Pietsch, U., Frischknecht, M., et al. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2073131 · Cited by 71 · see citing works
“In addition, acquisition of this subset of disease-associated taxa has been shown to shift the metabolic state to a disease-like state.(27) These changes in the microbiome may have happened gradually over time and could potentially make the host less resilient to SARS-CoV-2 infection.”
BackgroundMethodSelf-citationRole of gut microbiota in epigenetic regulation of colorectal Cancer
Zhao, Y., Wang, C., & Goel, A. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188490 · Cited by 68 · see citing works
Jing, Y., Yang, D., Bai, F., Wang, Q., Zhang, C., Yan, Y., Li, Z., Li, Y., Chen, Z., Li, J., et al. (2023) · npj Biofilms and Microbiomes · doi:10.1038/s41522-023-00466-5 · Cited by 67 · see citing works
“Thus, sex and different stages of the disease should be considered as variables in clinical trials of SCI, which may impact the characteristics of disease-related bacteria 48,49 .”
Emerging Targets and Treatments for Sarcopenia: A Narrative Review
Cacciatore, S., Calvani, R., Esposito, I., Massaro, C., Gava, G., Picca, A., Tosato, M., Marzetti, E., & Landi, F. (2024) · Nutrients · doi:10.3390/nu16193271 · Cited by 71 · see citing works
“Ghosh et al. [110] found that individuals over 60 years of age exhibited greater variation in gut microbiota composition than younger individuals.”
BackgroundGhosh, T. S., Arnoux, J., & O’Toole, P. W. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1822729 · Cited by 62 · see citing works
Self-citationSingh, J., Vanlallawmzuali, Singh, A. K., Biswal, S., Zomuansangi, R., Lalbiaktluangi, C., Singh, B. P., Singh, P. K., Vellingiri, B., Iyer, M., et al. (2024) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2024.104068 · Cited by 70 · see citing works
Pellanda, P., Ghosh, T. S., & O’Toole, P. W. (2020) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2020.11.001 · Cited by 59 · see citing works
Self-citationWest, K., Yin, X., Rutherford, E. M., Wee, B., Choi, J., Chrisman, B., Dunlap, K., Hannibal, R. L., Hartono, W., Lin, M., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-21327-9 · Cited by 64 · see citing works
Gut microbial features and circulating metabolomic signatures of frailty in older adults
Pu, Y., Sun, Z., Zhang, H., Huang, Q., Wang, Z., Mei, Z., Wang, P., Kong, M., Yang, W., Lin, C., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00678-0 · Cited by 62 · see citing works
“This observation supports previous research linking these species to unhealthy aging phenotypes, including frailty 43,47 .”
Ang, Q. Y., Alba, D., Upadhyay, V., Bisanz, J. E., Cai, J., Lee, H. L., Barajas, E., Wei, G., Noecker, C. A., Patterson, A. D., et al. (2021) · eLife · doi:10.7554/elife.70349 · Cited by 60 · see citing works
“…prior studies 167 (Falony et al., 2016), PERMANOVA analysis of our full 16S-seq dataset revealed that diabetes 168 (Forslund et al., 2015), age (Ghosh et al., 2020), metformin use (Wu et al., 2017), and statin 169 intake (Vieira-Silva et al., 2020) were significantly associated with variance…”
BackgroundMethodHuman Gut Microbiota in Coronary Artery Disease: A Systematic Review and Meta-Analysis
Choroszy, M., Litwinowicz, K., Bednarz, R., Roleder, T., Lerman, A., Toya, T., Kamiński, K. A., Sawicka, E., Niemira, M., & Sobieszczańska, B. (2022) · Metabolites · doi:10.3390/metabo12121165 · Cited by 56 · see citing works
Gut Microbiota in Psychiatric Disorders: A Systematic Review
Chen, L. L., Abbaspour, A., Mkoma, G. F., Bulik, C. M., Rück, C., & Djurfeldt, D. R. (2021) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000959 · Cited by 54 · see citing works
He, W., Luo, Y., Liu, J., Sun, N. L., Guo, D., Cui, L.-L., Zheng, P., Yao, S.-M., Yang, J.-F., & Wang, H. (2020) · Clinical Interventions in Aging · doi:10.2147/cia.s270887 · Cited by 52 · see citing works
Microbiome-based therapeutics towards healthier aging and longevity
Kadyan, S., Park, G., Singh, T. P., Patoine, C., Singar, S., Heise, T., Domeier, C., Ray, C. A., Kumar, M., Behare, P. V., et al. (2025) · Genome Medicine · doi:10.1186/s13073-025-01493-x · Cited by 55 · see citing works
Determinants and Interactions of Oral Bacterial and Fungal Microbiota in Healthy Chinese Adults
Cheung, M. K., Chan, J. Y. K., Wong, M. C. S., Wong, P. Y., Lei, P., Cai, L., Lan, L., Ho, W. C. S., Yeung, A. C. M., Chan, P. K. S., et al. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.02410-21 · Cited by 47 · see citing works
“Individuals were binned into three age groups, namely, young (18–39 yr), middle (40–59 yr) and elderly (60 yr or above) (22).”
MethodShrode, R. L., Knobbe, J. E., Cady, N. M., Yadav, M., Hoang, J., Cherwin, C. H., Curry, M. A., Garje, R., Vikas, P., Sugg, S. L., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-27436-3 · Cited by 43 · see citing works
Kedia, S., Ghosh, T. S., Jain, S., Desigamani, A., Kumar, A., Gupta, V., Bopanna, S., Yadav, D. P., Goyal, S., Makharia, G. K., et al. (2020) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15232 · Cited by 47 · see citing works
Self-citationSpinal cord injury and gut microbiota: A review
Jing, Y., Bai, F., & Yu, Y. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118865 · Cited by 48 · see citing works
Healthy aging and the human gut microbiome: why we cannot just turn back the clock
Wilmanski, T. M., Gibbons, S. M., & Price, N. D. (2022) · Nature Aging · doi:10.1038/s43587-022-00294-w · Cited by 47 · see citing works
Lian, W., Wang, F., Chen, Y., Tsai, M., Chao, H., Jahr, H., Wu, R., & Ko, J. (2022) · Biomedicines · doi:10.3390/biomedicines10040860 · Cited by 45 · see citing works
A gut aging clock using microbiome multi-view profiles is associated with health and frail risk
Wang, H., Chen, Y., Feng, L., Lu, S., Zhu, J., Zhao, J., Zhang, H., Chen, W., & Lu, W. (2024) · Gut Microbes · doi:10.1080/19490976.2023.2297852 · Cited by 44 · see citing works
“15 Specifically, validation samples were downloaded from the NCBI sequence data and annotated according to the following method.”
MethodThe role of the microbiota in glaucoma
Huang, L., Hong, Y., Fu, X., Tan, H., Chen, Y., Wang, Y., & Chen, D. (2023) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2023.101221 · Cited by 44 · see citing works
Almeida, H. M., Sardeli, A. V., Conway, J., Duggal, N. A., & Cavaglieri, C. R. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101773 · Cited by 43 · see citing works
Gut Microbiome Interactions with Oxidative Stress: Mechanisms and Consequences for Health
Semenova, N. V., Евгеньевна, Г. Н., Kolesnikov, S. I., Darenskaya, M. A., & Kolesnikova, L. (2024) · Pathophysiology · doi:10.3390/pathophysiology31030023 · Cited by 43 · see citing works
“The gut microbiome structure is affected by a variety of factors, including the environment, diet, age, and geographical location [2–6].”
BackgroundTierney, B. T., Tan, Y., Yang, Z., Shui, B., Walker, M. J., Kent, B. M., Kostic, A. D., & Patel, C. J. (2022) · PLoS Biology · doi:10.1371/journal.pbio.3001556 · Cited by 42 · see citing works
Early-onset Colon Cancer Shows a Distinct Intestinal Microbiome and a Host–Microbe Interaction
Adnan, D., Trinh, J. Q., Sharma, D., Alsayid, M., & Bishehsari, F. (2023) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-23-0091 · Cited by 41 · see citing works
Abdullah, M., Sukartini, N., Nursyirwan, S. A., Pribadi, R. R., Maulahela, H., Utari, A. P., Muzellina, V. N., Wiraatmadja, A., & Renaldi, K. (2021) · Digestion · doi:10.1159/000516689 · Cited by 41 · see citing works
Zhu, L., Chen, J., Pi, X., Li, J., Liu, W., Ding, Q., Wang, X., & Jia, W. (2021) · BMC Microbiology · doi:10.1186/s12866-021-02103-7 · Cited by 40 · see citing works
“We refer midlife as the people between 40 to 60 years old.[33, 34]”
MethodHuman microbiome variance is underestimated
Shanahan, F., Ghosh, T. S., & O’Toole, P. W. (2023) · Current Opinion in Microbiology · doi:10.1016/j.mib.2023.102288 · Cited by 40 · see citing works
Self-citationInfluence of human gut microbiome on the healthy and the neurodegenerative aging
Borrego-Ruiz, A., & Borrego, J. J. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112497 · Cited by 42 · see citing works
Zhang, X., Zhao, A., Sandhu, A. K., Edirisinghe, I., & Burton‐Freeman, B. M. (2020) · Nutrients · doi:10.3390/nu12113595 · Cited by 39 · see citing works
“suggested that younger people gain disease-causing microbes, whereas in older cohorts, the loss of beneficial bacteria may associate with disease [39].”
BackgroundResultInfluentialConvergent pathways of the gut microbiota–brain axis and neurodegenerative disorders
Gubert, C., Gasparotto, J., & Morais, L. H. (2022) · Gastroenterology report · doi:10.1093/gastro/goac017 · Cited by 40 · see citing works
“Taken together, these studies demonstrate that diet and disease status are important co-variates for aging-linked microbiota associations [120].”
Toward a health-associated core keystone index for the human gut microbiome
Goel, A., Shete, O., Goswami, S., Samal, A., C.B., L., Kedia, S., Ahuja, V., O’Toole, P. W., Shanahan, F., & Ghosh, T. S. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115378 · Cited by 37 · see citing works
Self-citationThe role of dietary strategies in the modulation of hallmarks of aging
de França, N. A. G., Rolland, Y., Guyonnet, S., & Barreto, P. D. S. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101908 · Cited by 38 · see citing works
Gut Microbiota and Aging: Traditional Chinese Medicine and Modern Medicine
Li, J., Li, D., Chen, Y., Chen, W., Xu, J., & Gao, L. (2023) · Clinical Interventions in Aging · doi:10.2147/cia.s414714 · Cited by 37 · see citing works
“Therefore, it is a significant challenge to clarify the relative contribution of age, drugs, diet and comorbidity to microbial dysbiosis.(60) Indeed, research on the elderly adjusted for diet, lifestyle and medication shows that age is a critical factor in the increase or decrease of the microbial species in the gut,(…”
Sadoughi, B., Schneider, D., Daniel, R., Schülke, O., & Ostner, J. (2022) · Microbiome · doi:10.1186/s40168-022-01283-2 · Cited by 37 · see citing works
“Disentangling the effect of age and frailty is complicated by their strong covariation because age-related changes in diet, medication, lifestyle, location, and concomitant diseases typically correlate [9, 23, 29, 31].”
BackgroundInfluentialFleischer, R., Schmid, D. W., Wasimuddin, Brändel, S. D., Rasche, A., Corman, V. M., Drosten, C., Tschapka, M., & Sommer, S. (2022) · Molecular Ecology · doi:10.1111/mec.16491 · Cited by 35 · see citing works
“Collectively, these results indicate age- specific MHC– microbiota relationships and altered immunomodulatory function of an ageing microbiome (Ghosh et al., 2020).”
BackgroundYou, X., Dadwal, U. C., Lenburg, M. E., Kacena, M. A., & Charles, J. F. (2022) · mSystems · doi:10.1128/msystems.01248-21 · Cited by 36 · see citing works
“For example, diet, medication, disease status, and duration of stay in a care facility may all impact the aging microbiome, yet data on these factors are frequently lacking in human aging microbiome research (15, 46).”
BackgroundDucloux, D., Legendre, M., Bamoulid, J., Saas, P., Courivaud, C., & Crépin, T. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.720402 · Cited by 34 · see citing works
Bidirectional relationships between the gut microbiome and sexual traits
del Castillo-Izquierdo, Á., Mayneris‐Perxachs, J., & Fernández‐Real, J. M. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00116.2022 · Cited by 34 · see citing works
“As Fusobacterium relative abundance also increases with age (Ghosh et al, 2020; Shanahan et al, 2021), gender-specific differences seem to confluence with age-specific changes leading to differential gender-specific susceptibility to a given disease.”
Zhuang, Y.-P., Zhou, H., Chen, H., Zheng, M.-Y., Liang, Y., Gu, Y.-T., Li, W., Qiu, W., & Zhou, H. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115040 · Cited by 33 · see citing works
Ravikrishnan, A., Wijaya, I., Png, E., Chng, K. R., Ho, E. X. P., Ng, A. H. Q., Naim, A. N. M., Gounot, J.-S., Guan, S. P., Lee, J. H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52097-9 · Cited by 39 · see citing works
“Several studies have also highlighted that frailty indices and healthy aging are linked to the state of the gut microbiome 16,17 , along with known gut-microbiome associations with aging-related diseases 18,19 .”
BackgroundMethodRooney, C. M., Jeffery, I. B., Mankia, K. S., Wilcox, M. H., & Emery, P. (2024) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2024-226362 · Cited by 33 · see citing works
“Due to the observed decrease in alpha diversity preceding RA onset (see online supplemental materials, page 44), pairwise dissimilarities between timepoints were assessed to examine gut microbiome stability using 16S rRNA amplicon sequencing.”
Self-citationType, Intensity, and Duration of Exercise as Regulator of Gut Microbiome Profile
Suryani, ., Alfaqih, M. S., Gunadi, J. W., Sylviana, N., Goenawan, H., Megantara, I., & Lesmana, R. (2022) · Current Sports Medicine Reports · doi:10.1249/jsr.0000000000000940 · Cited by 33 · see citing works
Carr, R. M., Li, Y., Chau, L., Friedman, E. S., Lee, J., Adorini, L., Erickson, M., Zaru, L., Shringarpure, R., MacConell, L., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000474 · Cited by 34 · see citing works
“Together with prior studies showing an association between gut microbiome composition, BMI, [42] and age, [45] these results provide additional evidence emphasizing the critical need to control for both BMI and age when investigating the role of the gut microbiome in NASH.”
ResultAraújo, J., Marques, C., Rodrigues, C., Calhau, C., & Faria, A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102451 · Cited by 29 · see citing works
Epigenetic Mechanisms in Aging: Extrinsic Factors and Gut Microbiome
Borrego-Ruiz, A., & Borrego, J. J. (2024) · Genes · doi:10.3390/genes15121599 · Cited by 33 · see citing works
“Table 3 shows the GM dysbiosis related to unhealthy aging due to several disorders (modified from [295,318–324]).”
Age-Related Cognitive Decline and Dementia: Interface of Microbiome–Immune–Neuronal Interactions
Prajapati, S. K., Jain, S., & Yadav, H. (2025) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaf038 · Cited by 35 · see citing works
Lapauw, L., Rutten, A., Dupont, J., Amini, N., Vercauteren, L., Derrien, M., Raes, J., & Gielen, E. (2024) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13569 · Cited by 28 · see citing works
A metagenomic study of gut viral markers in amyloid-positive Alzheimer’s disease patients
Ghorbani, M., Ferreira, D., & Maioli, S. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01285-8 · Cited by 27 · see citing works
Obesity is the main driver of altered gut microbiome functions in the metabolically unhealthy
de la Cuesta‐Zuluaga, J., Huus, K. E., Youngblut, N. D., Escobar, J. S., & Ley, R. E. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2246634 · Cited by 28 · see citing works
“57,58 In other words, accounting for common confounders might facilitate the comparison between studies by ameliorating biases introduced by the confounding variables.”
BackgroundGut microbiota–astrocyte axis: new insights into age-related cognitive decline
Zhang, L., Wei, J., Liu, X., Li, D., Pang, X., Chen, F., Cao, H., & Lei, P. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01776 · Cited by 27 · see citing works
“Among these metabolites, p-cresol has been demonstrated to be correlated with increased frailty and is linked to age-associated decline in elderly individuals (Ghosh et al., 2020).”
BackgroundUtilization of Host and Microbiome Features in Determination of Biological Aging
Ratiner, K., Abdeen, S. K., Goldenberg, K., & Elinav, E. (2022) · Microorganisms · doi:10.3390/microorganisms10030668 · Cited by 27 · see citing works
Exploring the Gut Microbiota–Retina Axis: Implications for Health and Disease
Schiavone, N., Isoldi, G., Calcagno, S., Rovida, E., Antiga, E., Almeida, C. V. D., & Lulli, M. (2025) · Microorganisms · doi:10.3390/microorganisms13051101 · Cited by 28 · see citing works
“The human gut microbial community plays a fundamental role in maintaining physiological homeostasis, yet its composition and function are subject to modifications over time [14].”
Manghi, P., Antonello, G., Schiffer, L., Golzato, D., Wokaty, A., Beghini, F., Mirzayi, C. A., Long, K., Gravel-Pucillo, K., Piccinno, G., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-66888-1 · Cited by 24 · see citing works
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Cross‐Cohort Gut Microbiome Signatures of Irritable Bowel Syndrome Presentation and Treatment
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Self-citationKrüger, K., Myeonghyun, Y., van der Wielen, N., Kok, D. E. G., Hooiveld, G. J. E. J., Keshtkar, S., Bruin, M. D.-D., Balvers, M. G. J., Grootte-Bromhaar, M., Mudde, K., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-75477-z · Cited by 24 · see citing works
Gut Microbiota–Related Biomarkers in Immuno-Oncology
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The gut microbiome and ageing trajectories: mechanisms and clinical implications
Ticinesi, A., Maggi, S., Nouvenne, A., Zuliani, G., & Franceschi, C. (2026) · Nature Reviews Endocrinology · doi:10.1038/s41574-026-01236-x · Cited by 25 · see citing works
“The biological process of ageing, however, shapes gut microbiome composition beyond the sum of the influences of lifetime exposures, inducing changes that tend to dysbiosis 65 .”
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“microbiome analysis results given that age-specific differences have been observed in gut microbial change-related diseases among individuals aged 20 to 89 years (13).”
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“Gut microbiota plays a pivotal role in upholding gut homeostasis but it is susceptible to both internal and external factors, including gene, dietary habits, exercise, and illnesses (Power et al., 2014; Ghosh et al., 2020; O ’ Sullivan et al., 2015).”
Discovering geroprotectors through the explainable artificial intelligence-based platform AgeXtend
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InfluentialSelf-citationMicrobial–Immune Crosstalk in Elderly-Onset Inflammatory Bowel Disease: Unchartered Territory
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Postbiotics: A Promising Approach to Combat Age-Related Diseases
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- Authors
- Ghosh, T. S., Das, M., Jeffery, I. B., & O'Toole, P. W.
- Affiliations
- University College Cork (IE)
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2020-03-11
- Volume
- 9
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC7065848
- OpenAlex
- W3011436618
- Cited by
- 233
- References
- 45
- Citations by year
- 2026: 30 · 2025: 29 · 2024: 56 · 2023: 38 · 2022: 37 · 2021: 23 · 2020: 20
- FWCI
- 9.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Funders
- Science Foundation Ireland (APC/SFI/12/RC/2273, 13/SIRG/2128)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, aging, age adjustment, colorectal cancer, frailty, multi-cohort analysis
- MeSH terms
- Gastrointestinal Microbiome, Adult, Age Factors, Aged, Aged, 80 and over, Data Interpretation, Statistical, Disease Susceptibility, Female, Humans, Male, Middle Aged, Reproducibility of Results, Computational Biology, Metagenome, Young Adult, Metagenomics, Microbiota, Dysbiosis
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