Abstract
Aging is a complex phenomenon, driven by tangled interactions between biotic and environmental factors. In recent decades, mounting scientific evidence has laid the gut microbiome at the core of many age-related changes, including susceptibility to cardiometabolic diseases and immune system dysregulation. The gut microbiome undergoes considerable compositional and functional changes across the lifespan, and aging-related processes may be responsible for – and due to – its alteration in elderhood. In people who achieved successful aging (i.e., centenarians and semi-supercentenarians), peculiar microbial signatures have been detected, hinting the ability of the gut microbiome to adapt to aging-related stresses, improving overall host health. This book chapter aims to describe the gut microbiome in aging and successful aging, focusing on its close relationship with onset and progression or vice versa protection from aging-related diseases, especially cardiometabolic ones. Finally, readers will find a broad description of microbiota-derived metabolites affecting health status during aging, on the thin ice that is the fragile microbiota-host homeostasis in the last stages of life.
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References
Adnan S, Nelson JW, Ajami NJ, Venna VR, Petrosino JF, Bryan RM Jr, Durgan DJ. Alterations in the gut microbiota can elicit hypertension in rats. Physiol Genomics. 2017;49(2):96–104. https://doi.org/10.1152/physiolgenomics.00081.2016. Epub 2016 Dec 23. PMID: 28011881; PMCID: PMC5336599.
Barone M, D’Amico F, Rampelli S, Brigidi P, Turroni S. Age-related diseases, therapies and gut microbiome: a new frontier for healthy aging. Mech Ageing Dev. 2022;206:111711. https://doi.org/10.1016/j.mad.2022.111711. Epub 2022 Jul 20.
Benakis C, Poon C, Lane D, Brea D, Sita G, Moore J, Murphy M, Racchumi G, Iadecola C, Anrather J. Distinct commensal bacterial signature in the gut is associated with acute and long-term protection from ischemic stroke. Stroke. 2020;51(6):1844–54. https://doi.org/10.1161/STROKEAHA.120.029262. Epub 2020 May 14. PMID: 32404038; PMCID: PMC7810258.
Biagi E, Franceschi C, Rampelli S, Severgnini M, Ostan R, Turroni S, Consolandi C, Quercia S, Scurti M, Monti D, Capri M, Brigidi P, Candela M. Gut microbiota and extreme longevity. Curr Biol. 2016;26(11):1480–5. https://doi.org/10.1016/j.cub.2016.04.016. Epub 2016 May 12.
Brinkmann V, et al. The aryl hydrocarbon receptor (AhR) in the aging process: another puzzling role for this highly conserved transcription factor. Front Physiol. 2020;10:1561. https://doi.org/10.3389/fphys.2019.01561.
Candela M, Biagi E, Soverini M, Consolandi C, Quercia S, Severgnini M, Peano C, Turroni S, Rampelli S, Pozzilli P, Pianesi M, Fallucca F, Brigidi P. Modulation of gut microbiota dysbioses in type 2 diabetic patients by macrobiotic Ma-Pi 2 diet. Br J Nutr. 2016;116(1):80–93. https://doi.org/10.1017/S0007114516001045. Epub 2016 May 6. PMID: 27151248; PMCID: PMC4894062.
Crapser J, Ritzel R, Verma R, Venna VR, Liu F, Chauhan A, Koellhoffer E, Patel A, Ricker A, Maas K, Graf J, McCullough LD. Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice. Aging (Albany NY). 2016;8(5):1049–63. https://doi.org/10.18632/aging.100952. PMID: 27115295; PMCID: PMC4931853.
D’Amico F, Perrone AM, Rampelli S, Coluccelli S, Barone M, Ravegnini G, Fabbrini M, Brigidi P, De Iaco P, Turroni S. Gut microbiota dynamics during chemotherapy in epithelial ovarian cancer patients are related to therapeutic outcome. Cancers (Basel). 2021;13(16):3999. https://doi.org/10.3390/cancers13163999. PMID: 34439153; PMCID: PMC8393652.
Docimo G, Cangiano A, Romano RM, Pignatelli MF, Offi C, Paglionico VA, Galdiero M, Donnarumma G, Nigro V, Esposito D, Rotondi M, Candela G, Pasquali D. The human microbiota in endocrinology: implications for pathophysiology, treatment, and prognosis in thyroid diseases. Front Endocrinol (Lausanne). 2020;11:586529. https://doi.org/10.3389/fendo.2020.586529. PMID: 33343507; PMCID: PMC7746874.
Duvallet C, Gibbons SM, Gurry T, Irizarry RA, Alm EJ. Meta-analysis of gut microbiome studies identifies disease-specific and shared responses. Nat Commun. 2017;8(1):1784. https://doi.org/10.1038/s41467-017-01973-8. PMID: 29209090; PMCID: PMC5716994.
EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T, Castenmiller J, De Henauw S, Hirsch-Ernst KI, Maciuk A, Mangelsdorf I, McArdle HJ, Naska A, Pelaez C, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Cubadda F, Frenzel T, Heinonen M, Marchelli R, Neuhäuser-Berthold M, Poulsen M, Prieto Maradona M, Schlatter JR, van Loveren H, Ackerl R, Knutsen HK. Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to regulation (EU) 2015/2283. EFSA J. 2021;19(9):e06780. https://doi.org/10.2903/j.efsa.2021.6780. PMID: 34484452; PMCID: PMC8409316.
Fabbrini M, et al. Polyphenol and tannin nutraceuticals and their metabolites: how the human gut microbiota influences their properties. Biomol Ther. 2022;12(7):875. https://doi.org/10.3390/biom12070875.
Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54. https://doi.org/10.1111/j.1749-6632.2000.tb06651.x. PMID: 10911963.
Gupta H, Min BH, Ganesan R, Gebru YA, Sharma SP, Park E, Won SM, Jeong JJ, Lee SB, Cha MG, Kwon GH, Jeong MK, Hyun JY, Eom JA, Park HJ, Yoon SJ, Choi MR, Kim DJ, Suk KT. Gut microbiome in non-alcoholic fatty liver disease: from mechanisms to therapeutic role. Biomedicine. 2022;10(3):550. https://doi.org/10.3390/biomedicines10030550. PMID: 35327352; PMCID: PMC8945462.
Gurung M, Li Z, You H, Rodrigues R, Jump DB, Morgun A, Shulzhenko N. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020;51:102590. https://doi.org/10.1016/j.ebiom.2019.11.051. Epub 2020 Jan 3. PMID: 31901868; PMCID: PMC6948163.
Han M, Wang N, Han W, Ban M, Sun T, Xu J. Gut microbes in gynecologic cancers: causes or biomarkers and therapeutic potential. Front Oncol. 2022;12:902695. https://doi.org/10.3389/fonc.2022.902695. PMID: 35912194; PMCID: PMC9326394.
Hasavci D, Blank T. Age-dependent effects of gut microbiota metabolites on brain resident macrophages. Front Cell Neurosci. 2022. https://www.frontiersin.org/articles/10.3389/fncel.2022.944526
He S, Li H, Yu Z, Zhang F, Liang S, Liu H, Chen H, Lü M. The gut microbiome and sex hormone-related diseases. Front Microbiol. 2021;12:711137. https://doi.org/10.3389/fmicb.2021.711137. PMID: 34650525; PMCID: PMC8506209.
Hobby GP, Karaduta O, Dusio GF, Singh M, Zybailov BL, Arthur JM. Chronic kidney disease and the gut microbiome. Am J Physiol Renal Physiol. 2019;316(6):F1211–7. https://doi.org/10.1152/ajprenal.00298.2018. Epub 2019 Mar 13. PMID: 30864840; PMCID: PMC6620595.
Hoyles L, Pontifex MG, Rodriguez-Ramiro I, Anis-Alavi MA, Jelane KS, Snelling T, Solito E, Fonseca S, Carvalho AL, Carding SR, Müller M, Glen RC, Vauzour D, McArthur S. Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Microbiome. 2021;9(1):235. https://doi.org/10.1186/s40168-021-01181-z. PMID: 34836554; PMCID: PMC8626999.
Jie Z, Xia H, Zhong SL, Feng Q, Li S, Liang S, Zhong H, Liu Z, Gao Y, Zhao H, Zhang D, Su Z, Fang Z, Lan Z, Li J, Xiao L, Li J, Li R, Li X, Li F, Ren H, Huang Y, Peng Y, Li G, Wen B, Dong B, Chen JY, Geng QS, Zhang ZW, Yang H, Wang J, Wang J, Zhang X, Madsen L, Brix S, Ning G, Xu X, Liu X, Hou Y, Jia H, He K, Kristiansen K. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017;8(1):845. https://doi.org/10.1038/s41467-017-00900-1. PMID: 29018189; PMCID: PMC5635030.
Kashtanova DA, Klimenko NS, Strazhesko ID, Starikova EV, Glushchenko OE, Gudkov DA, Tkacheva ON. A cross-sectional study of the gut microbiota composition in Moscow long-livers. Microorganisms. 2020;8(8):1162. https://doi.org/10.3390/microorganisms8081162. PMID: 32751673; PMCID: PMC7463576.
Khan A, Ding Z, Ishaq M, Bacha AS, Khan I, Hanif A, Li W, Guo X. Understanding the effects of gut microbiota dysbiosis on nonalcoholic fatty liver disease and the possible probiotics role: recent updates. Int J Biol Sci. 2021;17(3):818–33. https://doi.org/10.7150/ijbs.56214. PMID: 33767591; PMCID: PMC7975705.
Kong F, Deng F, Li Y, Zhao J. Identification of gut microbiome signatures associated with longevity provides a promising modulation target for healthy aging. Gut Microbes. 2019;10(2):210–5. https://doi.org/10.1080/19490976.2018.1494102. Epub 2018 Aug 24. PMID: 30142010; PMCID: PMC6546316.
Koren O, Spor A, Felin J, Fåk F, Stombaugh J, Tremaroli V, Behre CJ, Knight R, Fagerberg B, Ley RE, Bäckhed F. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A. 2011;108 Suppl 1(Suppl 1):4592–8. https://doi.org/10.1073/pnas.1011383107. Epub 2010 Oct 11. PMID: 20937873; PMCID: PMC3063583.
Kundu P, Blacher E, Elinav E, Pettersson S. Our gut microbiome: the evolving inner self. Cell. 2017;171(7):1481–93. https://doi.org/10.1016/j.cell.2017.11.024.
Li WZ, Stirling K, Yang JJ, Zhang L. Gut microbiota and diabetes: from correlation to causality and mechanism. World J Diabetes. 2020;11(7):293–308. https://doi.org/10.4239/wjd.v11.i7.293. PMID: 32843932; PMCID: PMC7415231.
Liu J, Tan Y, Cheng H, Zhang D, Feng W, Peng C. Functions of gut microbiota metabolites, current status and future perspectives. Aging Dis. 2022;13(4):1106–26. https://doi.org/10.14336/AD.2022.0104.
Luan Z, Sun G, Huang Y, Yang Y, Yang R, Li C, Wang T, Tan D, Qi S, Jun C, Wang C, Wang S, Zhao Y, Jing Y. Metagenomics study reveals changes in gut microbiota in centenarians: a cohort study of Hainan centenarians. Front Microbiol. 2020;11:1474. https://doi.org/10.3389/fmicb.2020.01474. PMID: 32714309; PMCID: PMC7343713.
Odamaki T, Kato K, Sugahara H, Hashikura N, Takahashi S, Xiao JZ, Abe F, Osawa R. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol. 2016;16:90. https://doi.org/10.1186/s12866-016-0708-5. PMID: 27220822; PMCID: PMC4879732.
Palmu J, Salosensaari A, Havulinna AS, Cheng S, Inouye M, Jain M, Salido RA, Sanders K, Brennan C, Humphrey GC, Sanders JG, Vartiainen E, Laatikainen T, Jousilahti P, Salomaa V, Knight R, Lahti L, Niiranen TJ. Association between the gut microbiota and blood pressure in a population cohort of 6953 individuals. J Am Heart Assoc. 2020;9:e016641. https://doi.org/10.1161/JAHA.120.016641.
Park SH, Kim KA, Ahn YT, Jeong JJ, Huh CS, Kim DH. Comparative analysis of gut microbiota in elderly people of urbanized towns and longevity villages. BMC Microbiol. 2015;15:49. https://doi.org/10.1186/s12866-015-0386-8. PMID: 25887483; PMCID: PMC4345030.
Peh A, O’Donnell JA, Broughton BRS, Marques FZ. Gut microbiota and their metabolites in stroke: a double-edged sword. Stroke. 2022;53(5):1788–801. https://doi.org/10.1161/STROKEAHA.121.036800. Epub 2022 Feb 9.
Perridon BW, et al. The role of hydrogen sulfide in aging and age-related pathologies. Aging. 2016;8(10):2264–89. https://doi.org/10.18632/aging.101026.
Pluznick J. A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes. 2014;5:202–7. https://doi.org/10.4161/gmic.27492.
Rampelli S, et al. Shotgun metagenomics of human gut microbiota up to extreme longevity and the increasing role of xenobiotics degradation. SSRN Electron J. 2020:1–9. https://doi.org/10.2139/ssrn.3419082.
Régnier M, Van Hul M, Knauf C, Cani PD. Gut microbiome, endocrine control of gut barrier function and metabolic diseases. J Endocrinol. 2021;248(2):R67–82. https://doi.org/10.1530/JOE-20-0473.
Rocha DM, Caldas AP, Oliveira LL, Bressan J, Hermsdorff HH. Saturated fatty acids trigger TLR4-mediated inflammatory response. Atherosclerosis. 2016;244:211–5. https://doi.org/10.1016/j.atherosclerosis.2015.11.015. Epub 2015 Dec 2.
Sagar NA, Tarafdar S, Agarwal S, Tarafdar A, Sharma S. Polyamines: functions, metabolism, and role in human disease management. Med Sci. 2021;9(2):44. https://doi.org/10.3390/medsci9020044.
Santoro A, Bientinesi E, Monti D. Immunosenescence and inflammaging in the aging process: age-related diseases or longevity? Ageing Res Rev. 2021;71:101422. https://doi.org/10.1016/j.arr.2021.101422. Epub 2021 Aug 13.
Sato Y, Atarashi K, Plichta DR, Arai Y, Sasajima S, Kearney SM, Suda W, Takeshita K, Sasaki T, Okamoto S, Skelly AN, Okamura Y, Vlamakis H, Li Y, Tanoue T, Takei H, Nittono H, Narushima S, Irie J, Itoh H, Moriya K, Sugiura Y, Suematsu M, Moritoki N, Shibata S, Littman DR, Fischbach MA, Uwamino Y, Inoue T, Honda A, Hattori M, Murai T, Xavier RJ, Hirose N, Honda K. Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians. Nature. 2021;599(7885):458–64. https://doi.org/10.1038/s41586-021-03832-5. Epub 2021 Jul 29.
Shirvani Rad S, Nikkhah A, Orvatinia M, Ejtahed HS, Sarhangi N, Jamaldini SH, Khodayari N, Aghaei Meybodi HR, Hasanzad M. Gut microbiota: a perspective of precision medicine in endocrine disorders. J Diabetes Metab Disord. 2020;19(2):1827–34. https://doi.org/10.1007/s40200-020-00593-2. PMID: 33520863; PMCID: PMC7843755.
Silveira-Nunes G, Durso DF, Alves de Oliveira LR Jr, Cunha EHM, Maioli TU, Vieira AT, Speziali E, Correa-Oliveira R, Martins-Filho OA, Teixeira-Carvalho A, Franceschi C, Rampelli S, Turroni S, Brigidi P, Faria AMC. Hypertension is associated with intestinal microbiota dysbiosis and inflammation in a Brazilian population. Front Pharmacol. 2020;11:258. https://doi.org/10.3389/fphar.2020.00258.
Spychala MS, Venna VR, Jandzinski M, Doran SJ, Durgan DJ, Ganesh BP, Ajami NJ, Putluri N, Graf J, Bryan RM, McCullough LD. Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome. Ann Neurol. 2018;84(1):23–36. https://doi.org/10.1002/ana.25250. Epub 2018 Jul 18. PMID: 29733457; PMCID: PMC6119509.
Stanley D, Mason LJ, Mackin KE, Srikhanta YN, Lyras D, Prakash MD, Nurgali K, Venegas A, Hill MD, Moore RJ, Wong CH. Translocation and dissemination of commensal bacteria in post-stroke infection. Nat Med. 2016;22(11):1277–84. https://doi.org/10.1038/nm.4194. Epub 2016 Oct 3.
Tavella T, Rampelli S, Guidarelli G, Bazzocchi A, Gasperini C, Pujos-Guillot E, Comte B, Barone M, Biagi E, Candela M, Nicoletti C, Kadi F, Battista G, Salvioli S, O’Toole PW, Franceschi C, Brigidi P, Turroni S, Santoro A. Elevated gut microbiome abundance of Christensenellaceae, Porphyromonadaceae and Rikenellaceae is associated with reduced visceral adipose tissue and healthier metabolic profile in Italian elderly. Gut Microbes. 2021;13(1):1–19. https://doi.org/10.1080/19490976.2021.1880221. PMID: 33557667; PMCID: PMC7889099.
Tuikhar N, Keisam S, Labala RK, Imrat, Ramakrishnan P, Arunkumar MC, Ahmed G, Biagi E, Jeyaram K. Comparative analysis of the gut microbiota in centenarians and young adults shows a common signature across genotypically non-related populations. Mech Ageing Dev. 2019;179:23–35. https://doi.org/10.1016/j.mad.2019.02.001. Epub 2019 Feb 6.
Turroni S, Brigidi P, Cavalli A, Candela M. Microbiota-host transgenomic metabolism, bioactive molecules from the inside. J Med Chem. 2018;61(1):47–61. https://doi.org/10.1021/acs.jmedchem.7b00244. Epub 2017 Aug 3.
Vujkovic-Cvijin I, Sklar J, Jiang L, Natarajan L, Knight R, Belkaid Y. Host variables confound gut microbiota studies of human disease. Nature. 2020;587(7834):448–54. https://doi.org/10.1038/s41586-020-2881-9. Epub 2020 Nov 4. PMID: 33149306; PMCID: PMC7677204.
Wehedy E, Shatat IF, Al Khodor S. The human microbiome in chronic kidney disease: a double-edged sword. Front Med (Lausanne). 2022;8:790783. https://doi.org/10.3389/fmed.2021.790783. PMID: 35111779; PMCID: PMC8801809.
Wilmanski T, Diener C, Rappaport N, Patwardhan S, Wiedrick J, Lapidus J, Earls JC, Zimmer A, Glusman G, Robinson M, Yurkovich JT, Kado DM, Cauley JA, Zmuda J, Lane NE, Magis AT, Lovejoy JC, Hood L, Gibbons SM, Orwoll ES, Price ND. Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nat Metab. 2021;3(2):274–86. https://doi.org/10.1038/s42255-021-00348-0. Epub 2021 Feb 18. Erratum in: Nat Metab. 2021;3(4):586. PMID: 33619379; PMCID: PMC8169080.
Xia GH, You C, Gao XX, Zeng XL, Zhu JJ, Xu KY, Tan CH, Xu RT, Wu QH, Zhou HW, He Y, Yin J. Stroke Dysbiosis Index (SDI) in gut microbiome are associated with brain injury and prognosis of stroke. Front Neurol. 2019;10:397. https://doi.org/10.3389/fneur.2019.00397. PMID: 31068891; PMCID: PMC6491752.
Zhou Y, Hu G, Wang MC. Host and microbiota metabolic signals in aging and longevity. Nat Chem Biol. 2021;17:1027–36. https://doi.org/10.1038/s41589-021-00837-z.
Zhou Z, Sun B, Yu D, Zhu C. Gut microbiota: an important player in type 2 diabetes mellitus. Front Cell Infect Microbiol. 2022;12:834485. https://doi.org/10.3389/fcimb.2022.834485. PMID: 35242721; PMCID: PMC8886906.
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D’Amico, F., Fabbrini, M., Barone, M., Brigidi, P., Turroni, S. (2024). Aging and Gut Dysbiosis. In: Federici, M., Menghini, R. (eds) Gut Microbiome, Microbial Metabolites and Cardiometabolic Risk. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-031-35064-1_16
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