geroprobПроблемы геронаукиProblems of Geroscience2949-47452949-4753АНО «ОСО ИТЕМ»10.37586/2949-4745-3-2024-154-160geroprob-70Research ArticleОбзорыReviewsКишечный микробиом как ключевой фактор в старении: механизмы и последствия для здоровьяThe gut microbiome as a central player in aging: mechanisms and health outcomeshttps://orcid.org/0009-0009-0858-2053МельницкаяА. А.MelnitskaiaA. A.

Мельницкая Александра Андреевна, врач-гериатр, младший научный сотрудник лаборатории биомаркеров старения

Москва

Melnitskaia Aleksandra A., MD, geriatrician, Junior Researcher, Laboratory of Biomarkers of Aging

Moscow

alexandrazhur@gmail.comhttps://orcid.org/0000-0002-2028-3939МачехинаЛ. В.MatchekhinaL. V.

Мачехина Любовь Викторовна, канд. мед. наук, заведующая лабораторией биомаркеров старения

Москва

Machekhina Lubov V., MD, PhD, Head of the Laboratory of Biomarkers of Aging

Moscow

machehina_lv@rgnkc.ruhttps://orcid.org/0000-0002-3544-5347ИльющенкоА. К.IlyushchenkoA. K.

Ильющенко Анна Константиновна, врач-терапевт, младший научный сотрудник лаборатории биомаркеров старения

Москва

Ilyushchenko Anna K., MD, internist

Moscow

Ilyushchenko_ak@rgnkc.ruhttps://orcid.org/0000-0002-3657-0676СтражескоИ. Д.StrazheskoI. D.

Стражеско Ирина Дмитриевна, д-р мед. наук, заместитель директора по трансляционной медицине ; ведущий научный сотрудник  отдела возраст-ассоциированных заболеваний медицинского научно-образовательного центра МГУ им. М.В. Ломоносова

Москва

Strazhesko Irina D., MD, PhD, Deputy Director for Translational Medicine,  Leading Researcher at the Department of Age-Related Diseases, Medical Scientific and Educational Center of Lomonosov Moscow State University

Moscow

ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России (Пироговский Университет), ОСП «Российский геронтологический научно-клинический центр»РоссияRussian Gerontology Research and Clinical Centre, Pirogov Russian National Research Medical UniversityRussian Federation20242009202403154160Copyright © Мельницкая А.А., Мачехина Л.В., Ильющенко А.К., Стражеско И.Д., 20242024Мельницкая А.А., Мачехина Л.В., Ильющенко А.К., Стражеско И.Д.Melnitskaia A.A., Matchekhina L.V., Ilyushchenko A.K., Strazhesko I.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.geronauka.com/jour/article/view/70

В статье обсуждаются механизмы влияния кишечного микробиома на старение человека и связанные с ним заболевания. Авторы рассматривают изменения в составе микробиоты с возрастом и их влияние на воспаление, иммунный ответ и проницаемость кишечного барьера. Особое внимание уделено патогенетическим взаимосвязям между кишечной микробиотой и развитием сердечно-сосудистых, метаболических и нейродегенеративных заболеваний. Отмечается роль дисбаланса в микробиоме — дисбиоза — как одного из ключевых механизмов ускорения процессов старения. В обзоре представлен комплексный анализ современных исследований, демонстрирующих влияние микробных метаболитов на системы организма через оси «кишечник — мозг», «кишечник — сердечно-сосудистая система» и «кишечник — эндокринная система».

The article explores the mechanisms by which the gut microbiome influences human aging and associated diseases. The authors examine age-related changes in the composition of the microbiota and their effects on inflammation, immune response, and intestinal barrier permeability. Special attention is given to the pathogenic interactions between the gut microbiota and the development of cardiovascular, metabolic, and neurodegenerative diseases. The role of microbiome imbalance, known as dysbiosis, is highlighted as one of the key mechanisms accelerating the aging process. The review provides a comprehensive analysis of recent studies that demonstrate the impact of microbial metabolites on various body systems through the «gut-brain,» «gut-cardiovascular,» and «gut-endocrine» axes.

кишечная микробиотастарениедисбиозинфламэйджингнейродегенеративные заболеваниясердечно-сосудистые заболеванияметаболические заболеванияgut microbiotaagingdysbiosisinflammagingneurodegenerative diseasescardiovascular diseasesmetabolic diseasesРабота выполнена в рамках программы «Приоритет 2030».This work was carried out with financial support from the Priority 2030 programme.ReferencesWorld Health Organization. Ageing and health. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/ageingand-health. Published October 4, 2021. (дата обращения: 28.08.2024)World Health Organization. Ageing and health. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/ageing-and-health. Published October 4, 2021. (дата обращения: 28.08.2024)López-Otín C., Blasco M.A., Partridge L., Serrano M., Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023;186(2):243- 278. doi: 10.1016/j.cell.2022.11.001López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023;186(2):243-278. doi:10.1016/j.cell.2022.11.001Schmauck-Medina T., Molière A., Lautrup S., et al. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging (Albany NY). 2022;14(16):6829-6839. doi: 10.18632/aging.204248Schmauck-Medina T, Molière A, Lautrup S, et al. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging (Albany NY). 2022;14(16):6829-6839. doi:10.18632/aging.204248Thursby E., Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823-1836. Published 2017 May 16. doi: 10.1042/BCJ20160510Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823-1836. Published 2017 May 16. doi:10.1042/BCJ20160510Li Y., Tian X., Luo J., Bao T., Wang S., Wu X. Molecular mechanisms of aging and anti-aging strategies. Cell Commun Signal. 2024;22(1):285. Published 2024 May 24. doi: 10.1186/s12964-024-01663-1Li Y, Tian X, Luo J, Bao T, Wang S, Wu X. Molecular mechanisms of aging and anti-aging strategies. Cell Commun Signal. 2024;22(1):285. Published 2024 May 24. doi:10.1186/s12964-024-01663-1Ling Z., Liu X., Cheng Y., Yan X., Wu S. Gut microbiota and aging. Crit Rev Food Sci Nutr. 2022;62(13):3509-3534. doi: 10.1080/10408398.2020.1867054Ling Z, Liu X, Cheng Y, Yan X, Wu S. Gut microbiota and aging. Crit Rev Food Sci Nutr. 2022;62(13):3509-3534. doi:10.1080/10408398.2020.1867054Ghosh T.S., Das M., Jeffery I.B., O'Toole P.W. Adjusting for age improves identification of gut microbiome alterations in multiple diseases. Elife. 2020;9:e50240. Published 2020 Mar 11. doi: 10.7554/eLife.50240Ghosh TS, Das M, Jeffery IB, O'Toole PW. Adjusting for age improves identification of gut microbiome alterations in multiple diseases. Elife. 2020;9:e50240. Published 2020 Mar 11. doi:10.7554/eLife.50240Naspolini N.F., Schüroff P.A., Figueiredo M.J., et al. The Gut Microbiome in the First One Thousand Days of Neurodevelopment: A Systematic Review from the Microbiome Perspective. Microorganisms. 2024;12(3):424. Published 2024 Feb 20. doi: 10.3390/microorganisms12030424Naspolini NF, Schüroff PA, Figueiredo MJ, et al. The Gut Microbiome in the First One Thousand Days of Neurodevelopment: A Systematic Review from the Microbiome Perspective. Microorganisms. 2024;12(3):424. Published 2024 Feb 20. doi:10.3390/microorganisms12030424Rodríguez J.M., Murphy K., Stanton C., et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050. Published 2015 Feb 2. doi: 10.3402/mehd.v26.26050Rodríguez JM, Murphy K, Stanton C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050. Published 2015 Feb 2. doi:10.3402/mehd.v26.26050Li H., Wang J., Wu L. et al. The impacts of delivery mode on infant’s oral microflora. Sci Rep 8, 11938 (2018). doi: 10.1038/s41598-018-30397-7Li, H., Wang, J., Wu, L. et al. The impacts of delivery mode on infant’s oral microflora. Sci Rep 8, 11938 (2018). https://doi.org/10.1038/s41598-018-30397-7Martino C., Dilmore A.H., Burcham Z.M. et al. Microbiota succession throughout life from the cradle to the grave. Nat Rev Microbiol 20, 707-720 (2022). doi: 10.1038/s41579-022-00768-zMartino, C., Dilmore, A.H., Burcham, Z.M. et al. Microbiota succession throughout life from the cradle to the grave. Nat Rev Microbiol 20, 707–720 (2022). https://doi.org/10.1038/s41579-022-00768-zDi Vincenzo F., Del Gaudio A., Petito V., Lopetuso L.R., Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med. 2024;19(2):275- 293. doi: 10.1007/s11739-023-03374-wDi Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR, Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med. 2024;19(2):275-293. doi:10.1007/s11739-023-03374-wWeiss G.A., Hennet T. Mechanisms and consequences of intestinal dysbiosis. Cell Mol Life Sci. 2017;74(16):2959-2977. doi: 10.1007/s00018-017-2509-xWeiss GA, Hennet T. Mechanisms and consequences of intestinal dysbiosis. Cell Mol Life Sci. 2017;74(16):2959-2977. doi:10.1007/s00018-017-2509-xBuford T.W. (Dis)Trust your gut: the gut microbiome in agerelated inflammation, health, and disease. Microbiome 5, 80 (2017). doi: 10.1186/s40168-017-0296-0Buford, T.W. (Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease. Microbiome 5, 80 (2017). ttps://doi.org/10.1186/s40168-017-0296-0de la Cuesta-Zuluaga J., Kelley S.T., Chen Y., et al. Age- and Sex-Dependent Patterns of Gut Microbial Diversity in Human Adults. mSystems. 2019;4(4):e00261-19. Published 2019 May 14. doi: 10.1128/mSystems.00261-19de la Cuesta-Zuluaga J, Kelley ST, Chen Y, et al. Age- and Sex-Dependent Patterns of Gut Microbial Diversity in Human Adults. mSystems. 2019;4(4):e00261-19. Published 2019 May 14. doi:10.1128/mSystems.00261-19Gadecka A., Bielak-Zmijewska A. Slowing Down Ageing: The Role of Nutrients and Microbiota in Modulation of the Epigenome. Nutrients. 2019;11(6):1251. Published 2019 Jun 1. doi: 10.3390/ nu11061251Gadecka A, Bielak-Zmijewska A. Slowing Down Ageing: The Role of Nutrients and Microbiota in Modulation of the Epigenome. Nutrients. 2019;11(6):1251. Published 2019 Jun 1. doi:10.3390/nu11061251DeJong E.N., Surette M.G., Bowdish D.M. The Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence. Cell Host Microbe. 2020;28(2):180-189. doi: 10.1016/j.chom.2020.07.013DeJong EN, Surette MG, Bowdish DME. The Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence. Cell Host Microbe. 2020;28(2):180-189. doi:10.1016/j.chom.2020.07.013Alsegiani A.S., Shah Z.A.. The influence of gut microbiota alteration onage-related neuroinflammation and cognitive decline. Neural Regen Res. 2022;17(11):2407-2412. doi: 10.4103/1673-5374.335837Alsegiani AS, Shah ZA. The influence of gut microbiota alteration on age-related neuroinflammation and cognitive decline. Neural Regen Res. 2022;17(11):2407-2412. doi:10.4103/1673-5374.335837Ziganshina E.E., Sharifullina D.M., Lozhkin A.P., Khayrullin R.N., Ignatyev I.M., Ziganshin A.M. Bacterial Communities Associated with Atherosclerotic Plaques from Russian Individuals with Atherosclerosis. PLoS One. 2016;11(10):e0164836. Published 2016 Oct 13. doi: 10.1371/journal.pone.0164836Ziganshina EE, Sharifullina DM, Lozhkin AP, Khayrullin RN, Ignatyev IM, Ziganshin AM. Bacterial Communities Associated with Atherosclerotic Plaques from Russian Individuals with Atherosclerosis. PLoS One. 2016;11(10):e0164836. Published 2016 Oct 13. doi:10.1371/journal.pone.0164836Battson M.L., Lee D.M., Weir T.L., Gentile C.L. The gut microbiota as a novel regulator of cardiovascular function and disease. J Nutr Biochem. 2018;56:1-15. doi: 10.1016/j.jnutbio.2017.12.010Battson ML, Lee DM, Weir TL, Gentile CL. The gut microbiota as a novel regulator of cardiovascular function and disease. J Nutr Biochem. 2018;56:1-15. doi:10.1016/j.jnutbio.2017.12.010Tang W.H., Wang Z., Fan Y., et al. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-Noxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014;64(18):1908-1914. doi: 10.1016/j.jacc.2014.02.617Tang WH, Wang Z, Fan Y, et al. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014;64(18):1908-1914. doi:10.1016/j.jacc.2014.02.617Kondo T., Kishi M., Fushimi T., Ugajin S., Kaga T. Vinegar intake reduces body weight, body fat mass, and serum triglyceride levels in obese Japanese subjects. Biosci Biotechnol Biochem. 2009;73(8):1837-1843. doi: 10.1271/bbb.90231Kondo T, Kishi M, Fushimi T, Ugajin S, Kaga T. Vinegar intake reduces body weight, body fat mass, and serum triglyceride levels in obese Japanese subjects. Biosci Biotechnol Biochem. 2009;73(8):1837-1843. doi:10.1271/bbb.90231Wang L., Zhu Q., Lu A., et al. Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro) renin receptor and intrarenal renin-angiotensin system. J Hypertens. 2017;35(9):1899-1908. doi: 10.1097/HJH.0000000000001378Wang L, Zhu Q, Lu A, et al. Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin-angiotensin system. J Hypertens. 2017;35(9):1899-1908. doi:10.1097/HJH.0000000000001378Roshanravan N., Mahdavi R., Alizadeh E., et al. Effect of Butyrate and Inulin Supplementation on Glycemic Status, Lipid Profile and Glucagon-Like Peptide 1 Level in Patients with Type 2 Diabetes: A Randomized Double-Blind, Placebo-Controlled Trial. Horm Metab Res. 2017;49(11):886-891. doi: 10.1055/s-0043-119089Roshanravan N, Mahdavi R, Alizadeh E, et al. Effect of Butyrate and Inulin Supplementation on Glycemic Status, Lipid Profile and Glucagon-Like Peptide 1 Level in Patients with Type 2 Diabetes: A Randomized Double-Blind, Placebo-Controlled Trial. Horm Metab Res. 2017;49(11):886-891. doi:10.1055/s-0043-119089Natarajan N., Hori D., Flavahan S., et al. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G proteincoupled receptor 41. Physiol Genomics. 2016;48(11):826-834. doi: 10.1152/physiolgenomics.00089.2016Natarajan N, Hori D, Flavahan S, et al. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiol Genomics. 2016;48(11):826-834. doi:10.1152/physiolgenomics.00089.2016Pluznick J. A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes. 2014;5(2):202-207. doi: 10.4161/gmic.27492Pluznick J. A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes. 2014;5(2):202-207. doi:10.4161/gmic.27492Laman J.D., Schoneveld A.H., Moll F.L., van Meurs M., Pasterkamp G. Significance of peptidoglycan, a proinflammatory bacterial antigen in atherosclerotic arteries and its association with vulnerable plaques. Am J Cardiol. 2002;90(2):119-123. doi: 10.1016/s0002-9149(02)02432-3Laman JD, Schoneveld AH, Moll FL, van Meurs M, Pasterkamp G. Significance of peptidoglycan, a proinflammatory bacterial antigen in atherosclerotic arteries and its association with vulnerable plaques. Am J Cardiol. 2002;90(2):119-123. doi:10.1016/s0002-9149(02)02432-3Jie Z., Xia H., Zhong S.L., et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017;8(1):845. Published 2017 Oct 10. doi: 10.1038/s41467-017-00900-1Jie Z, Xia H, Zhong SL, et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017;8(1):845. Published 2017 Oct 10. doi:10.1038/s41467-017-00900-1Amabebe E., Robert F.O., Agbalalah T., Orubu E.S. Microbial dysbiosis-induced obesity: role of gut microbiota in homoeostasis of energy metabolism. Br J Nutr. 2020;123(10):1127-1137. doi: 10.1017/S0007114520000380Jie Z, Xia H, Zhong SL, et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017;8(1):845. Published 2017 Oct 10. doi:10.1038/s41467-017-00900-1Upadhyaya S., Banerjee G. Type 2 diabetes and gut microbiome: at the intersection of known and unknown. Gut Microbes. 2015;6(2):85- 92. doi: 10.1080/19490976.2015.1024918Amabebe E, Robert FO, Agbalalah T, Orubu ESF. Microbial dysbiosis-induced obesity: role of gut microbiota in homoeostasis of energy metabolism. Br J Nutr. 2020;123(10):1127-1137. doi:10.1017/S0007114520000380Harsch I.A., Konturek P.C. The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into «Old» Diseases. Med Sci (Basel). 2018;6(2):32. Published 2018 Apr 17. doi: 10.3390/medsci6020032Upadhyaya S, Banerjee G. Type 2 diabetes and gut microbiome: at the intersection of known and unknown. Gut Microbes. 2015;6(2):85-92. doi:10.1080/19490976.2015.1024918Wu J., Yang K., Fan H., Wei M., Xiong Q. Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus. Front Endocrinol (Lausanne). 2023;14:1114424. Published 2023 May 9. doi: 10.3389/fendo.2023.1114424Harsch IA, Konturek PC. The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into "Old" Diseases. Med Sci (Basel). 2018;6(2):32. Published 2018 Apr 17. doi:10.3390/medsci6020032de Vos W.M., Tilg H., Van Hul M., Cani P.D. Gut microbiome and health: mechanistic insights. Gut. 2022;71(5):1020-1032. doi: 10.1136/gutjnl-2021-326789Wu J, Yang K, Fan H, Wei M, Xiong Q. Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus. Front Endocrinol (Lausanne). 2023;14:1114424. Published 2023 May 9. doi:10.3389/fendo.2023.1114424Allegretti J.R., Kassam Z., Mullish B.H., et al. Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients. Clin Gastroenterol Hepatol. 2020;18(4):855-863.e2. doi: 10.1016/j.cgh.2019.07.006de Vos WM, Tilg H, Van Hul M, Cani PD. Gut microbiome and health: mechanistic insights. Gut. 2022;71(5):1020-1032. doi:10.1136/gutjnl-2021-326789Rhodes J.M.. The role of Escherichia coli in inflammatory bowel disease. Gut. 2007;56(5):610-612. doi: 10.1136/gut.2006.111872Allegretti JR, Kassam Z, Mullish BH, et al. Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients. Clin Gastroenterol Hepatol. 2020;18(4):855-863.e2. doi:10.1016/j.cgh.2019.07.006Zhang J., Hoedt E.C., Liu Q., et al. Elucidation of Proteus mirabilis as a Key Bacterium in Crohn's Disease Inflammation. Gastroenterology. 2021;160(1):317-330.e11. doi: 10.1053/j.gastro.2020.09.036Rhodes JM. The role of Escherichia coli in inflammatory bowel disease. Gut. 2007;56(5):610-612. doi:10.1136/gut.2006.111872Pai C.S., Wang C.Y., Hung W.W., et al. Interrelationship of Gut Microbiota, Obesity, Body Composition and Insulin Resistance in Asians with Type 2 Diabetes Mellitus. J Pers Med. 2022;12(4):617. Published 2022 Apr 11. doi: 10.3390/jpm12040617Zhang J, Hoedt EC, Liu Q, et al. Elucidation of Proteus mirabilis as a Key Bacterium in Crohn's Disease Inflammation. Gastroenterology. 2021;160(1):317-330.e11. doi:10.1053/j.gastro.2020.09.036Pedersen H.K., Gudmundsdottir V., Nielsen H.B., et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016;535(7612):376-381. doi: 10.1038/nature18646Pai CS, Wang CY, Hung WW, et al. Interrelationship of Gut Microbiota, Obesity, Body Composition and Insulin Resistance in Asians with Type 2 Diabetes Mellitus. J Pers Med. 2022;12(4):617. Published 2022 Apr 11. doi:10.3390/jpm12040617Xu Z., Jiang W., Huang W., Lin Y., Chan F.K., Ng S.C. Gut microbiota in patients with obesity and metabolic disorders — a systematic review. Genes Nutr. 2022;17(1):2. Published 2022 Jan 29. doi: 10.1186/s12263-021-00703-6Pedersen HK, Gudmundsdottir V, Nielsen HB, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016;535(7612):376-381. doi:10.1038/nature18646Thingholm L.B., Rühlemann M.C., Koch M., et al. Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition. Cell Host Microbe. 2019;26(2):252-264.e10. doi: 10.1016/j.chom.2019.07.004Duvallet 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. Published 2017 Dec 5. doi:10.1038/s41467-017-01973-8Duvallet C., Gibbons S.M., Gurry T., Irizarry R.A., Alm E.J.. Meta-analysis of gut microbiome studies identifies disease-specific and shared responses. Nat Commun. 2017;8(1):1784. Published 2017 Dec 5. doi: 10.1038/s41467-017-01973-8Xu Z, Jiang W, Huang W, Lin Y, Chan FKL, Ng SC. Gut microbiota in patients with obesity and metabolic disorders - a systematic review. Genes Nutr. 2022;17(1):2. Published 2022 Jan 29. doi:10.1186/s12263-021-00703-6Bisanz J.E., Upadhyay V., Turnbaugh J.A., Ly K., Turnbaugh P.J. Meta-Analysis Reveals Reproducible Gut Microbiome Alterations in Response to a High-Fat Diet. Cell Host Microbe. 2019;26(2):265- 272.e4. doi: 10.1016/j.chom.2019.06.013Bisanz JE, Upadhyay V, Turnbaugh JA, Ly K, Turnbaugh PJ. Meta-Analysis Reveals Reproducible Gut Microbiome Alterations in Response to a High-Fat Diet. Cell Host Microbe. 2019;26(2):265-272.e4. doi:10.1016/j.chom.2019.06.013O'Mahony S.M., Clarke G., Borre Y.E., Dinan T.G., Cryan J.F. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res. 2015;277:32-48. doi: 10.1016/j.bbr.2014.07.027Thingholm LB, Rühlemann MC, Koch M, et al. Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition. Cell Host Microbe. 2019;26(2):252-264.e10. doi:10.1016/j.chom.2019.07.004Dinan T.G., Cryan J.F. Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. J Physiol. 2017;595(2):489-503. doi: 10.1113/JP273106Dinan TG, Cryan JF. Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. J Physiol. 2017;595(2):489-503. doi:10.1113/JP273106Kennedy P.J., Cryan J.F., Dinan T.G., Clarke G. Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology. 2017;112(Pt B):399-412. doi: 10.1016/j.neuropharm.2016.07.002O'Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res. 2015;277:32-48. doi:10.1016/j.bbr.2014.07.027Lin L., Zhang J. Role of intestinal microbiota and metabolites on gut homeostasis and human diseases. BMC Immunol 18, 2 (2017). doi: 10.1186/s12865-016-0187-3Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology. 2017;112(Pt B):399-412. doi:10.1016/j.neuropharm.2016.07.002Rowland I., Gibson G., Heinken A. et al. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr 57, 1–24 (2018). doi: 10.1007/s00394-017-1445-8Lin, L., Zhang, J. Role of intestinal microbiota and metabolites on gut homeostasis and human diseases. BMC Immunol 18, 2 (2017). https://doi.org/10.1186/s12865-016-0187-3Wendeln A.C., Degenhardt K., Kaurani L., et al. Innate immune memory in the brain shapes neurological disease hallmarks. Nature. 2018;556(7701):332-338. doi: 10.1038/s41586-018-0023-4Rowland, I., Gibson, G., Heinken, A. et al. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr 57, 1–24 (2018). https://doi.org/10.1007/s00394-017-1445-8Philip Mani A., Balasubramanian B., Mali L.A., Joseph K.S., Meyyazhagan A., Pappuswamy M., Joseph B.V. The Role of the Gut Microbiota in Neurodegenerative Diseases. Microbiology Research. 2024; 15(2):489-507. https://doi.org/10.3390/microbiolres15020033Latorre R, Sternini C, De Giorgio R, Greenwood-Van Meerveld B. Enteroendocrine cells: a review of their role in brain-gut communication. Neurogastroenterol Motil. 2016;28(5):620-630. doi:10.1111/nmo.12754Vogt N.M., Romano K.A., Darst B.F., et al. The gut microbiotaderived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease. Alz Res Therapy 10, 124 (2018). doi: 0.1186/s13195-018-0451-2Bravo JA, Forsythe P, Chew MV, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011;108(38):16050-16055. doi:10.1073/pnas.1102999108Del Rio D., Zimetti F., Caffarra P., Tassotti M., Bernini F., Brighenti F., Zini A., Zanotti I. The Gut Microbial Metabolite Trimethylamine-N-Oxide Is Present in Human Cerebrospinal Fluid. Nutrients. 2017; 9(10):1053. doi: 10.3390/nu9101053Wendeln AC, Degenhardt K, Kaurani L, et al. Innate immune memory in the brain shapes neurological disease hallmarks. Nature. 2018;556(7701):332-338. doi:10.1038/s41586-018-0023-4Qiao C.M., Quan W., Zhou Y., et al. Orally Induced High Serum Level of Trimethylamine N-oxide Worsened Glial Reaction and Neuroinflammation on MPTP-Induced Acute Parkinson's Disease Model Mice. Mol Neurobiol. 2023;60(9):5137-5154. doi: 10.1007/s12035-023-03392-xPhilip Mani A, Balasubramanian B, Mali LA, Joseph KS, Meyyazhagan A, Pappuswamy M, Joseph BV. The Role of the Gut Microbiota in Neurodegenerative Diseases. Microbiology Research. 2024; 15(2):489-507. https://doi.org/10.3390/microbiolres15020033Zhang Y., Jian W. Signal Pathways and Intestinal Flora through Trimethylamine N-oxide in Alzheimer's Disease. Curr Protein Pept Sci. 2023;24(9):721-736. doi: 10.2174/1389203724666230717125406Vogt, N.M., Romano, K.A., Darst, B.F. et al. The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease. Alz Res Therapy 10, 124 (2018). https://doi.org/10.1186/s13195-018-0451-2Gao K., Mu C.L., Farzi A., Zhu W.Y. Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain. Adv Nutr. 2020;11(3):709- 723. doi: 10.1093/advances/nmz127Del Rio D, Zimetti F, Caffarra P, Tassotti M, Bernini F, Brighenti F, Zini A, Zanotti I. The Gut Microbial Metabolite Trimethylamine-N-Oxide Is Present in Human Cerebrospinal Fluid. Nutrients. 2017; 9(10):1053. https://doi.org/10.3390/nu9101053Braidy N., Grant R., Adams S., et al. Mechanism for Quinolinic Acid Cytotoxicity in Human Astrocytes and Neurons. Neurotox Res 16, 77–86 (2009). doi: 10.1007/s12640-009-9051-zQiao CM, Quan W, Zhou Y, et al. Orally Induced High Serum Level of Trimethylamine N-oxide Worsened Glial Reaction and Neuroinflammation on MPTP-Induced Acute Parkinson's Disease Model Mice. Mol Neurobiol. 2023;60(9):5137-5154. doi:10.1007/s12035-023-03392-xTanaka M., Török N., Tóth F., Szabó Á., Vécsei L. Co-Players in Chronic Pain: Neuroinflammation and the Tryptophan-Kynurenine Metabolic Pathway. Biomedicines. 2021; 9(8):897. doi: 10.3390/biomedicines9080897Zhang Y, Jian W. Signal Pathways and Intestinal Flora through Trimethylamine N-oxide in Alzheimer's Disease. Curr Protein Pept Sci. 2023;24(9):721-736. doi:10.2174/1389203724666230717125406Kowalski K., Mulak A. Brain-Gut-Microbiota Axis in Alzheimer's Disease. J Neurogastroenterol Motil. 2019;25(1):48-60. doi: 10.5056/jnm18087Gao K, Mu CL, Farzi A, Zhu WY. Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain. Adv Nutr. 2020;11(3):709-723. doi:10.1093/advances/nmz127Tan A.H., Lim S.Y., Lang A.E. The microbiome-gut-brain axis in Parkinson disease — from basic research to the clinic. Nat Rev Neurol. 2022;18(8):476-495. doi: 10.1038/s41582-022-00681-2Braidy, N., Grant, R., Adams, S. et al. Mechanism for Quinolinic Acid Cytotoxicity in Human Astrocytes and Neurons. Neurotox Res 16, 77–86 (2009). https://doi.org/10.1007/s12640-009-9051-zWang Q., Luo Y., Ray Chaudhuri K., Reynolds R., Tan E.K., Pettersson S. The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options. Brain. 2021;144(9):2571- 2593. doi: 10.1093/brain/awab156Tanaka M, Török N, Tóth F, Szabó Á, Vécsei L. Co-Players in Chronic Pain: Neuroinflammation and the Tryptophan-Kynurenine Metabolic Pathway. Biomedicines. 2021; 9(8):897. https://doi.org/10.3390/biomedicines9080897Kowalski K, Mulak A. Brain-Gut-Microbiota Axis in Alzheimer's Disease. J Neurogastroenterol Motil. 2019;25(1):48-60. doi:10.5056/jnm18087Kowalski K, Mulak A. Brain-Gut-Microbiota Axis in Alzheimer's Disease. J Neurogastroenterol Motil. 2019;25(1):48-60. doi:10.5056/jnm18087Tan AH, Lim SY, Lang AE. The microbiome-gut-brain axis in Parkinson disease - from basic research to the clinic. Nat Rev Neurol. 2022;18(8):476-495. doi:10.1038/s41582-022-00681-2Tan AH, Lim SY, Lang AE. The microbiome-gut-brain axis in Parkinson disease - from basic research to the clinic. Nat Rev Neurol. 2022;18(8):476-495. doi:10.1038/s41582-022-00681-2Wang Q, Luo Y, Ray Chaudhuri K, Reynolds R, Tan EK, Pettersson S. The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options. Brain. 2021;144(9):2571-2593. doi:10.1093/brain/awab156Wang Q, Luo Y, Ray Chaudhuri K, Reynolds R, Tan EK, Pettersson S. The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options. Brain. 2021;144(9):2571-2593. doi:10.1093/brain/awab156

The authors declare that there are no conflicts of interest present.