Gut Microbiota & Aging

Version 1. F1000Res. 2018; 7: F1000 Faculty Rev-1086.
Published online 2018 Jul 16. doi: 10.12688/f1000research.15121.1
PMCID: PMC6051225
PMID: 30057748

The role of the gut microbiome during host ageing

Jens Seidel, Investigation, Methodology, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing1and Dario Riccardo Valenzano, Conceptualization, Funding Acquisition, Methodology, Project Administration, Resources, Supervision, Visualization, Writing – Original Draft Preparation, Writing – Review & Editinga,1,2


In hundreds of millions of years of co-evolution, commensal microbial communities and their hosts have adapted to one another, becoming strictly inter-dependent. A sophisticated metabolic cross-talk between microbes and their multi-cellular hosts ensures balanced homeostasis and finely regulates most physiological processes. During ageing, the complex interaction between host and its associated microbial communities—termed “microbiota”—undergoes important changes, which can result in dramatic phenotypic consequences for the host, including dysbiosis, infections and overall functional decline. However, what the triggers are of this age-related host-microbiota imbalance is still poorly understood. While a young and healthy immune system is capable of efficiently maintaining a taxonomically diverse commensal microbiota, age-related immune dysfunction—that is, immunosenescence 1—could reduce the selection on commensal and pathogenic microbial taxa, allowing proliferation of pathobiont and pathogenic bacteria. On the other hand, ecological (species-species competitive interactions) and evolutionary (emergence of novel strains within a species) dynamics in the microbial communities of the gut could also trigger age-dependent host demise. Rather than being mutually exclusive, a combination of immunosenescence and microbiota-intrinsic population and evolutionary dynamics could lead to irreversible host dysfunctions, resulting in rapid deterioration of health and increased risk for age-related pathologies and ultimately death ( Figure 1).

Figure 1.

Age-dependent changes in gut microbiota.

Evolutionary and ecological community changes during host ageing may play fundamental roles in shaping age-specific microbial communities. ( Above) De novo mutations (asterisk) or horizontal gene transfer in young-associated commensal bacterial species may lead to the evolution of highly fit bacterial strains that become more abundant in aged individuals, eventually leading to age-related pathogenicity. ( Middle) Species-species bacterial ecological interactions could affect community dynamics that shape microbiota composition throughout host life span, ultimately affecting host physiology during ageing. ( Bottom) An age-dependent decline in immune function may cause decreased surveillance over microbial communities over time, leading to age-dependent dysbiosis. On the other hand, a healthy microbiota itself could be necessary to preserve a healthy immune function during ageing.

Ageing and the microbiota

Biological ageing is a multi-factorial phenomenon, consisting of the loss of homeostasis at multiple scales of biological complexity, from the molecular (for example, DNA and proteins) to the organelle, cell, tissue, organ and metabolic/system level. Both genetic and environmental factors determine ageing progression in different species. Research in laboratory model organisms has demonstrated that single gene mutations (for example, in genes in the insulin–insulin-like growth factor 1 [insulin- IGF1], AMPK and TOR pathways) significantly affect life expectancy and ageing 25. Additionally, important gene variants (for example, in the FOXO3 gene) have been associated in humans with extreme longevity 6. On the other hand, environmental interventions, such as dietary restriction, changes in nutrient sensing, stress and changes in temperature, can also modulate life span and ageing in experimental model organisms 710.

Dwelling at the interface between organisms and the external environment, commensal microbes participate in several processes, including nutrient absorption 11, synthesis of essential vitamins, drug processing, pathogenicity, organ development 12, 13, circadian rhythms 14, and immune system maturation and modulation 15. Among all organs, the human gut lumen harbours the largest amount and diversity of commensal microbes, whose composition and function have been importantly associated with the modulation of the insulin signalling pathway and in general with the overall metabolic state of the host 16. Dramatic compositional changes occur with development in the human gut microbiota during early childhood, and the community becomes richer and more stable afterwards 17, 18. Despite being diverse in composition across healthy individuals, the adult gut microbial composition is considered functionally stable and involved in essential processes, such as protein translation, carbon metabolism, adhesion, amino acid and vitamin synthesis 19. Age-related frailty is importantly associated in humans with the loss of diversity in the core microbiota groups 20. Transplantations of microbes from obese individuals into mice raised in germ-free conditions lead to dramatic effects in recipient mice, including higher adiposity and differences in fatty acids and amino acid metabolism 21. Notably, gut microbes can effectively tune host inflammatory responses and several gut microbial taxa play a powerful anti-microbial action, suggesting a potential immune role of the gut microbiota, which can help fight infections by pathogenic bacterial species. For instance, faecal material transfer from healthy donors is successfully used in the clinic to resolve acute Clostridium difficile infections 22. Probiotic diets have been associated with beneficial life span effects in a mouse study 23, and human centenarians and ultra-centenarians are characterised by a gut microbial composition enriched in health-associated bacteria 24. Studies in yeast, flies and mice humans have shown that the gut microbiota undergoes dramatic changes during the ageing process 20, 2527, raising the question of whether these changes are a consequence or a cause of ageing. Experimental work in flies showed that, upon ageing, commensal microbes can lead to dysbiosis, which is followed by loss of barrier function and ultimately host demise 28. Recent work in nematode worms demonstrated that feeding worms with different bacterial species and with Escherichia coli mutant strains significantly tunes host life span 29, 30. Remarkably, despite the extensive influence of commensal microbes on host biology, very little is known about whether and how the complex microbial communities associated with vertebrate intestines affect ageing and whether they can be used to modulate ageing and life span.

A recent study conducted in a naturally short-lived vertebrate, the turquoise killifish ( Nothobranchius furzeri) 31, 32, showed that heterochronic gut microbiota transfer from young subjects to middle-aged individuals led to life span extension and delayed motor decline 33. Turquoise killifish undergo a wide range of age-related transformations that resemble human ageing-related phenotypes, including cancer, loss of pigmentation, reduced fecundity, neurodegeneration, cognitive decline, and cellular senescence, offering a unique opportunity to study ageing in a short-lived vertebrate 32, 34. Notably, unlike invertebrate model organisms, such as worms and flies, captive killifish have a very complex gut microbial community, consisting of hundreds of bacterial taxa, similar in complexity to other vertebrates, including mammals 33. Although young-derived gut microbiota can extend life span and delay ageing in this short-lived vertebrate model, several important questions still need to be answered. Is the life span modulatory role of the gut microbes amplified in short-lived species or is this a more general mechanism that applies broadly to other vertebrates, including mammals? Do gut microbes modulate host ageing in vertebrates via conserved ageing pathways or via novel mechanisms?

Possible mechanisms by which the gut microbiota can modulate host ageing

Pioneering work in nematode worms showed that mitochondrial unfolded protein response is the target of a key microbial metabolite, colanic acid, whose production leads to extended worm longevity 29. Mice raised on a life-long dietary restriction regime—typically associated with longer life span—have a significantly altered gut microbiota, characterised by lower abundance of bacterial taxa negatively associated with life span and a higher representation of bacteria of the genus Lactobacillus 35, 36. Transfer of germ-free mice with conventional specific pathogen-free microbiota induces high levels of serum IGF1, suggesting a direct connection between gut microbiota and the metabolic activation of canonical ageing pathways 37. Similarly, high levels of health-beneficial short-chain fatty acids lead to serum upregulation of IGF1, further supporting a strong mechanistic link between the insulin- IGF1 pathway and gut microbial metabolism 37. Short-chain fatty acids generated by commensal gut microbes induce anti-inflammatory responses 38, protecting from bacterial and fungal infections 39 and leading to life span extension in worms40. Through similar mechanisms, young-associated gut microbes may induce a healthier state and a slower ageing rate 41. The health-span–promoting drug rapamycin also has anti-inflammatory actions 42 and, when transiently administered to middle-life mice, significantly reshapes the gut microbiota, leading to increased abundance of segmented filamentous bacteria in the small intestine 43. The gut microbiota could in fact affect ageing and life span via its action on the immune system, modulating pro- and anti-inflammatory responses, importantly associated with host ageing 44. Studies in gnotobiotic mice have helped elucidate the contribution of different components of complex gut microbiota in modulating host’s metabolism and physiology (for instance, in the case of inflammatory bowel disease–induced dysbiosis) 45. In gnotobiotic mice, single microbial taxa (for example, Bacteroides thetaiotamicron and Faecalibacterium prausnitzii) play complementary roles in the gut and can lead to specific metabolic alterations in gut epithelial mucus production and in short-chain fatty acid synthesis and consumption, which could be importantly linked with the risk for ageing-related pathologies 46. Colonising the gastrointestinal tract of laboratory mice with microbiota from wild mice, investigators were able to reduce inflammation, promoting host fitness and survival after lethal viral infections and against colitis-associated tumorigenesis47. These results raise the question of whether similar effects could be induced by maintaining a highly diverse, young-associated intestinal microbiota throughout mice ageing. A functioning inflammasome and B-cell compartment are key to shaping the gut microbiota composition, as shown in experiments conducted in mice lacking Nlrp6 and RAG2, respectively 45. Specifically, inflammasome and adaptive immune function were essential to shaping the microbiota in the presence of pro-inflammatory bacteria 45. It is possible that, during ageing, immune function shifts towards inflammatory responses against commensal bacteria, leading to host-microbiota disbalance. Similarly, chronic inflammation is associated with a higher risk for age-associated diseases 44. In the context of infection, immune tolerance for commensal bacteria indeed shifts towards inflammation, compromising this delicate host-microbiota balance 48. Systemic translocation of the gut pathobiont Enterococcus gallinarum in a mouse model predisposed to autoimmunity has been causally associated with triggering of autoimmune responses, further providing a mechanistic connection between microbiota composition and host immune status 49.

Immunosenescence may indeed lead to a failure in maintaining commensal microbiota structure and function; on the other hand, microbial-intrinsic population dynamics—which could lead to the emergence of more pathogenic bacteria—may trigger immune failure and eventually induce functional decline in the host. Longitudinal studies in human samples over a six-month period have shown that gut microbial communities are rather stable, and within-host bacterial evolution is the consequence of horizontal gene transfer among bacterial strains from the same microbiota rather than occurring from de novo mutations or introgression from bacteria resident in other hosts 50. If this approach is extended to the study of bacteria throughout host life span, it could be possible to ask whether microbes evolve during host ageing and whether higher virulence—associated with pathogenicity in older subjects—is the consequence of the microbial evolution to evade immune surveillance.

Overall, the study of the host-microbiota dynamics throughout ageing can help reveal novel physiological and molecular mechanisms that contribute to the maintenance of homeostasis and ultimately help design powerful and personalised interventions that target the microbiota as a novel fundamental player implicated in the regulation of host ageing processes.

Open questions

The intimate connection between host physiology and commensal microbial function supports the implication of host-associated microbiota in the majority—if not the entirety—of biological processes of the host, including ageing. The study of the microbiota in the context of host ageing is a novel field of research and sets itself at the interface of several fields of investigation, including medical microbiology, immunology, ecology, evolutionary and population genetics, tissue and cell biology, physiology, nutrition, and metabolic research. Several confounders affect the microbiota changes occurring during human ageing, including age-dependent dietary changes, drug use, changes in mobility and housing conditions (community dwelling or elderly care facilities). Beyond descriptive connections between microbial composition and host health status, very few studies to date have dissected the causal role of the gut microbiota during ageing. To unweave the complex functional connection between host and microbiota in the context of ageing, it will be of paramount importance to study the role of not only bacteria but also archaea, viruses, fungi and microbial eukaryotes living between complex multi-cellular hosts and their environment. This holistic understanding of community dynamics can help reveal the intricate ecology of health, disease and ageing processes. To this end, it will be key to adopt novel experimental and analytical approaches to study the impact of different complex microbial communities on the host. Ultimately, by acting on microbial composition, nutrition and the immune system, it will be possible to test the efficacy of novel interventions to beneficially impact ageing and delay the onset of age-related pathologies.


We would like to thank our collaborators and all current and past members of the Valenzano lab at the Max Planck Institute for Biology of Ageing for their continual inspiration and invaluable feedback. We are thankful to our two reviewers for their constrictive comments and suggestions.


[version 1; referees: 2 approved]

Funding Statement

This work was supported by the Max Planck Institute for Biology of Ageing and by the Deutsche Forschungsgemeinschaft (DFG) CRC 1310.


Editorial Note on the Review Process

F1000 Faculty Reviews are commissioned from members of the prestigious F1000 Faculty and are edited as a service to readers. In order to make these reviews as comprehensive and accessible as possible, the referees provide input before publication and only the final, revised version is published. The referees who approved the final version are listed with their names and affiliations but without their reports on earlier versions (any comments will already have been addressed in the published version).

The referees who approved this article are:

  • Eran Elinav, Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

    No competing interests were disclosed.
  • Dominic S Raj, Division of Renal Diseases and Hypertension, The George Washington University, Washington, USA

    No competing interests were disclosed.


1. Franceschi C, Valensin S, Fagnoni F, et al. : Biomarkers of immunosenescence within an evolutionary perspective: the challenge of heterogeneity and the role of antigenic load. Exp Gerontol. 1999;34(8):911–21. 10.1016/S0531-5565(99)00068-6 [PubMed] [CrossRef] [Google Scholar]
2. Kapahi P, Chen D, Rogers AN, et al. : With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab. 2010;11(6):453–65. 10.1016/j.cmet.2010.05.001[PMC free article] [PubMed] [CrossRef] [Google Scholar]
3. Kenyon C, Chang J, Gensch E, et al. : A C. elegans mutant that lives twice as long as wild type. Nature.1993;366(6454):461–4. 10.1038/366461a0 [PubMed] [CrossRef] [Google Scholar]
4. Lapierre LR, Hansen M: Lessons from C. elegans: signaling pathways for longevity. Trends Endocrinol Metab. 2012;23(12):637–44. 10.1016/j.tem.2012.07.007 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
5. Weir HJ, Yao P, Huynh FK, et al. : Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling. Cell Metab. 2017;26(6):884–896.e5. 10.1016/j.cmet.2017.09.024[PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
6. Flachsbart F, Dose J, Gentschew L, et al. : Identification and characterization of two functional variants in the human longevity gene FOXO3. Nat Commun. 2017;8(1):2063. 10.1038/s41467-017-02183-y[PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
7. Ermolaeva MA, Segref A, Dakhovnik A, et al. : DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance. Nature. 2013;501(7467):416–20. 10.1038/nature12452[PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
8. Libert S, Zwiener J, Chu X, et al. : Regulation of Drosophila life span by olfaction and food-derived odors. Science. 2007;315(5815):1133–7. 10.1126/science.1136610 [PubMed] [CrossRef] [Google Scholar]F1000 Recommendation
9. LIU RK, WALFORD RL: Increased Growth and Life-span with Lowered Ambient Temperature in the Annual Fish, Cynolebias adloffi. Nature. 1966;212:1277–8. 10.1038/2121277a0 [CrossRef] [Google Scholar]
10. Weindruch R, Walford RL, Fligiel S, et al. : The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J Nutr. 1986;116(4):641–54. 10.1093/jn/116.4.641 [PubMed] [CrossRef] [Google Scholar]
11. Semova I, Carten JD, Stombaugh J, et al. : Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish. Cell Host Microbe. 2012;12(3):277–88. 10.1016/j.chom.2012.08.003[PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
12. Bates JM, Mittge E, Kuhlman J, et al. : Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev Biol. 2006;297(2):374–86. 10.1016/j.ydbio.2006.05.006 [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
13. Sommer F, Bäckhed F: The gut microbiota–masters of host development and physiology. Nat Rev Microbiol. 2013;11(4):227–38. 10.1038/nrmicro2974 [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
14. Thaiss CA, Levy M, Korem T, et al. : Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations. Cell. 2016;167(6):1495–1510.e12. 10.1016/j.cell.2016.11.003 [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
15. Geva-Zatorsky N, Sefik E, Kua L, et al. : Mining the Human Gut Microbiota for Immunomodulatory Organisms. Cell. 2017;168(5):928–943.e11. 10.1016/j.cell.2017.01.022 [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
16. Kootte RS, Levin E, Salojärvi J, et al. : Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition. Cell Metab.2017;26(4):611–619.e6. 10.1016/j.cmet.2017.09.008 [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
17. Ottman N, Smidt H, de Vos WM, et al. : The function of our microbiota: who is out there and what do they do? Front Cell Infect Microbiol. 2012;2:104. 10.3389/fcimb.2012.00104 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
18. Yatsunenko T, Rey FE, Manary MJ, et al. : Human gut microbiome viewed across age and geography.Nature. 2012;486(7402):222–7. 10.1038/nature11053 [PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
19. Qin J, Li R, Raes J, et al. : A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65. 10.1038/nature08821 [PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
20. O’Toole PW, Jeffery IB: Gut microbiota and aging. Science. 2015;350(6265):1214–5. 10.1126/science.aac8469 [PubMed] [CrossRef] [Google Scholar]
21. Ridaura VK, Faith JJ, Rey FE, et al. : Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214. 10.1126/science.1241214 [PMC free article][PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
22. Lee CH, Steiner T, Petrof EO, et al. : Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA. 2016;315(2):142–9. 10.1001/jama.2015.18098 [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
23. Matsumoto M, Kurihara S, Kibe R, et al. : Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on upregulation of gut bacterial polyamine production. PLoS One. 2011;6(8):e23652. 10.1371/journal.pone.0023652 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
24. Biagi E, Franceschi C, Rampelli S, et al. : Gut Microbiota and Extreme Longevity. Curr Biol.2016;26(11):1480–5. 10.1016/j.cub.2016.04.016 [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
25. Biagi E, Nylund L, Candela M, et al. : Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One. 2010;5(5):e10667. 10.1371/journal.pone.0010667[PMC free article] [PubMed] [CrossRef] [Google Scholar]
26. Langille MG, Meehan CJ, Koenig JE, et al. : Microbial shifts in the aging mouse gut. Microbiome.2014;2(1):50. 10.1186/s40168-014-0050-9 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
27. Lee SG, Kaya A, Avanesov AS, et al. : Age-associated molecular changes are deleterious and may modulate life span through diet. Sci Adv. 2017;3(2):e1601833. 10.1126/sciadv.1601833 [PMC free article][PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
28. Guo L, Karpac J, Tran SL, et al. : PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell. 2014;156(1–2):109–22. 10.1016/j.cell.2013.12.018 [PMC free article][PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
29. Han B, Sivaramakrishnan P, Lin CJ, et al. : Microbial Genetic Composition Tunes Host Longevity.Cell. 2017;169(7):1249–1262.e13. 10.1016/j.cell.2017.05.036 [PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
30. Sánchez-Blanco A, Rodríguez-Matellán A, González-Paramás A, et al. : Dietary and microbiome factors determine longevity in Caenorhabditis elegans. Aging (Albany NY). 2016;8(7):1513–39. 10.18632/aging.101008 [PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
31. Hu C, Brunet A: The African turquoise killifish: A research organism to study vertebrate aging and diapause. Aging Cell. 2018;17(3):e12757. 10.1111/acel.12757 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
32. Kim Y, Nam HG, Valenzano DR: The short-lived African turquoise killifish: an emerging experimental model for ageing. Dis Model Mech. 2016;9(2):115–29. 10.1242/dmm.023226 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
33. Smith P, Willemsen D, Popkes M, et al. : Regulation of life span by the gut microbiota in the short-lived African turquoise killifish. eLlife. 2017; pii: e27014. 10.7554/eLife.27014 [PMC free article][PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
34. Cellerino A, Valenzano DR, Reichard M: From the bush to the bench: the annual Nothobranchiusfishes as a new model system in biology. Biol Rev Camb Philos Soc. 2016;91(2):511–33. 10.1111/brv.12183 [PubMed] [CrossRef] [Google Scholar]
35. Fraumene C, Manghina V, Cadoni E, et al. : Caloric restriction promotes rapid expansion and long-lasting increase of Lactobacillus in the rat fecal microbiota. Gut Microbes. 2018;9(2):104–14. 10.1080/19490976.2017.1371894 [PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
36. Zhang C, Li S, Yang L, et al. : Structural modulation of gut microbiota in life-long calorie-restricted mice. Nat Commun. 2013;4: 2163. 10.1038/ncomms3163 [PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
37. Yan J, Herzog JW, Tsang K, et al. : Gut microbiota induce IGF-1 and promote bone formation and growth. Proc Natl Acad Sci U S A. 2016;113(47):E7554–E7563. 10.1073/pnas.1607235113[PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
38. Nastasi C, Candela M, Bonefeld CM, et al. : The effect of short-chain fatty acids on human monocyte-derived dendritic cells. Sci Rep. 2015;5: 16148. 10.1038/srep16148 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
39. Ciarlo E, Heinonen T, Herderschee J, et al. : Impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo. Sci Rep. 2016;6: 37944. 10.1038/srep37944 [PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
40. Edwards C, Canfield J, Copes N, et al. : D-beta-hydroxybutyrate extends lifespan in C. elegans. Aging (Albany NY). 2014;6(8):621–44. 10.18632/aging.100683 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
41. Arpaia N, Campbell C, Fan X, et al. : Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451–5. 10.1038/nature12726 [PMC free article][PubMed] [CrossRef] [Google Scholar]
42. Johnson SC, Rabinovitch PS, Kaeberlein M: mTOR is a key modulator of ageing and age-related disease. Nature. 2013;493(7432):338–45. 10.1038/nature11861 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
43. Bitto A, Ito TK, Pineda VV, et al. : Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. eLife. 2016;5: pii: e16351. 10.7554/eLife.16351 [PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
44. Franceschi C, Campisi J: Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69 Suppl 1:S4–9. 10.1093/gerona/glu057 [PubMed] [CrossRef] [Google Scholar]
45. Gálvez EJC, Iljazovic A, Gronow A, et al. : Shaping of Intestinal Microbiota in Nlrp6- and Rag2-Deficient Mice Depends on Community Structure. Cell Rep. 2017;21(13):3914–26. 10.1016/j.celrep.2017.12.027 [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
46. Wrzosek L, Miquel S, Noordine ML, et al. : Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent. BMC Biol. 2013;11:61. 10.1186/1741-7007-11-61[PMC free article] [PubMed] [CrossRef] [Google Scholar]
47. Rosshart SP, Vassallo BG, Angeletti D, et al. : Wild Mouse Gut Microbiota Promotes Host Fitness and Improves Disease Resistance. Cell. 2017;171(5):1015–1028.e13. 10.1016/j.cell.2017.09.016 [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
48. Hand TW, Dos Santos LM, Bouladoux N, et al. : Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science. 2012;337(6101):1553–6. 10.1126/science.1220961[PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
49. Manfredo Vieira S, Hiltensperger M, Kumar V, et al. : Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science. 2018;359(6380):1156–61. 10.1126/science.aar7201[PMC free article] [PubMed] [CrossRef] [Google Scholar] F1000 Recommendation
50. Garud NR, Good BH, Hallatschek O, et al. : Evolutionary dynamics of bacteria in the gut microbiome within and across hosts. 2017. 10.1101/210955 [CrossRef] [Google Scholar] F1000 Recommendation


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