Bağırsak Mikrobiyotasının Epigenetik ve Nutrigenetik Etkileşimi ve Longevity ile İlişkisinin İncelenmesi

Abstract

Bağırsak mikrobiyotası, yaşam tarzı, beslenme alışkanlıkları, çevresel faktörler ve genetik etmenlerle şekillenen dinamik bir sistemdir. Mikrobiyota tarafından üretilen metabolitlerin epigenetik düzenleyicilerle etkileşimi; inflamatuar yanıtların düzenlenmesi, gen ekspresyonunun kontrolü ve bilişsel fonksiyonların korunması gibi yaşlanma sürecini etkileyen çeşitli fizyolojik mekanizmalarda rol oynar. Son yıllarda yapılan araştırmalar, DNA metilasyonu, histon modifikasyonları ve mikroRNA’lar gibi epigenetik mekanizmaların uzun ömürlülük ile ilişkisini ortaya koyarken; nutrigenetik yaklaşımlar, bireyin genetik yapısına uygun olarak planlanan beslenme modellerinin mikrobiyota bileşimi ve fonksiyonları üzerinde belirleyici etkiler oluşturabileceğini göstermektedir. Bununla birlikte, mikrobiyota bileşimi bireyler arasında genetik çeşitlilik, yaşam tarzı ve çevresel maruziyetler gibi birçok faktöre bağlı olarak önemli ölçüde farklılık gösterebilir. Bu nedenle, tek bir beslenme modelinin tüm bireyler için aynı etkiyi göstermesi beklenemez; bunun yerine, genetik yapı, epigenetik profil ve mikrobiyal kompozisyon temel alınarak geliştirilen kişiye özgü beslenme stratejilerine ihtiyaç duyulmaktadır. Bu doğrultuda, özellikle mikrobiyotayı hedef alan Akdeniz diyeti gibi beslenme yaklaşımları ile polifenol açısından zengin biyoaktif bileşiklerin ve probiyotik-prebiyotik takviyelerin yaşlanma üzerindeki etkilerinin daha fazla klinik çalışma ile desteklenmesi gerekmektedir. Bu derlemede, bağırsak mikrobiyotası ile epigenetik ve nutrigenetik mekanizmalar arasındaki etkileşimlerin sağlıklı yaşlanma üzerindeki etkileri; diyet modelleri (Akdeniz, Batı tarzı, vegan/vejetaryen), polifenoller, probiyotikler, prebiyotikler, kısa zincirli yağ asidi üretimi, epigenetik saat ile ilişkisi, vitamin-mineral etkileşimleri ve yüz yaş üzeri bireylerin mikrobiyal profilleri üzerinden güncel bilimsel veriler doğrultusunda ele alınmıştır.

Keywords

• Epigenetik
• longevity
• mikrobiyota
• nutrigenetik

Epigenetic and Nutrigenetic Interactions of Intestinal Microbiota and Their Relationship With Longevity

Abstract

The gut microbiota is a dynamic system shaped by lifestyle, dietary habits, environmental factors and genetic factors. The interaction of metabolites produced by the microbiota with epigenetic regulators plays a role in many physiological processes such as control of inflammatory responses, epigenetic regulation of gene expression and protection of cognitive functions by affecting the aging process. While recent studies have revealed the relationship between longevity and epigenetic mechanisms such as DNA methylation, histone modifications and microRNAs and longevity, nutrigenetic approaches show that nutritional models planned in accordance with the genetic makeup of the individual can have decisive effects on microbiota composition and functions. However, the composition of the microbiota can differ significantly between individuals depending on many factors such as genetic diversity, lifestyle and environmental exposures. Therefore, a single nutritional model cannot be expected to have the same effect for all individuals; instead, individualized nutritional strategies based on genetic makeup, epigenetic profile and microbial composition are needed. In this direction, nutritional approaches such as the Mediterranean diet, which specifically targets the microbiota, and the effects of polyphenol-rich bioactive compounds and probiotic-prebiotic supplements on aging need to be supported by more clinical studies. In this review, the effects of interactions between gut microbiota and epigenetic and nutrigenetic mechanisms on healthy aging are discussed in line with current scientific data on dietary patterns (Mediterranean, Western-style, vegan/vegetarian), polyphenols, probiotics, prebiotics, SCFA production, relationship with the epigenetic clock, vitamin-mineral interactions and microbial profiles of individuals over 100 years of age.

Keywords

• Epigenetic
• longevity
• microbiota
• nutrigenetic

References

1. Guo J, Huang X, Dou L, Yan M, Shen T, Tang W, et al. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Signal Transduct Target Ther. 2022 Dec 16;7(1):391.
2. DeJong EN, Surette MG, Bowdish DME. The Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence. Cell Host Microbe. 2020 Aug;28(2):180–9.
3. Dong C, Miao Y, Zhao R, Yang M, Guo A, Xue Z, et al. Single‐Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring. Adv Sci (Weinh).. 2022 Dec;9(36):e2204849.
4. Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C, et al. Microbiota in health and diseases. Signal Transduct Target Ther. 2022 Apr 23;7(1):135.
5. Berg G, Rybakova D, Fischer D, Cernava T, Vergès MCC, Charles T, et al. Microbiome definition re-visited: old concepts and new challenges. Microbiome. 2020 Dec 30;8(1):103.
6. Ferenc K, Sokal-Dembowska A, Helma K, Motyka E, Jarmakiewicz-Czaja S, Filip R. Modulation of the Gut Microbiota by Nutrition and Its Relationship to Epigenetics. Int J Mol Sci. 2024 Jan 19;25(2):1228.
7. He Y, Chen Y, Yao L, Wang J, Sha X, Wang Y. The Inflamm-Aging Model Identifies Key Risk Factors in Atherosclerosis. Front Genet. 2022 May 30;13:865827.
8. Caldarelli M, Rio P, Marrone A, Giambra V, Gasbarrini A, Gambassi G, et al. Inflammaging: The Next Challenge—Exploring the Role of Gut Microbiota, Environmental Factors, and Sex Differences. Biomedicines. 2024 Aug 1;12(8):1716.

9. Ullah H, Arbab S, Tian Y, Liu CQ, Chen Y, Qijie L, et al. The gut microbiota-brain axis in neurological disorder. Front Neurosci. 2023 Aug 4;17:1225875.
10. Liberale L, Badimon L, Montecucco F, Lüscher TF, Libby P, Camici GG. Inflammation, Aging, and Cardiovascular Disease. J Am Coll Cardiol. 2022 Mar;79(8):837-47.
11. Jiang B, Dong YN, Xiong Y, Jiang CX, Ping J, Wu Q, et al. Global research trends in inflammaging from 2005 to 2024: a bibliometric analysis. Front Aging. 2025 Apr 10;6:1554186.
12. García-Domínguez M. Pathological and Inflammatory Consequences of Aging. Biomolecules. 2025 Mar 12;15(3):404.
13. Khan R, Di Gesù CM, Lee J, McCullough LD. The contribution of age-related changes in the gut-brain axis to neurological disorders. Gut Microbes. 2024 Jan-Dec;16(1):2302801.
14. Badal VD, Vaccariello ED, Murray ER, Yu KE, Knight R, Jeste D V., et al. The Gut Microbiome, Aging, and Longevity: A Systematic Review. Nutrients. 2020 Dec 7;12(12):3759.
15. Jing Y, Wang Q, Bai F, Li Z, Li Y, Liu W, et al. Role of microbiota-gut-brain axis in natural aging-related alterations in behavior. Front Neurosci. 2024 Apr 18;18:1362239.
16. Vesnina A, Prosekov A, Atuchin V, Minina V, Ponasenko A. Tackling Atherosclerosis via Selected Nutrition. Int J Mol Sci. 2022 Jul 26;23(15):8233.
17. Gomaa EZ. Human gut microbiota/microbiome in health and diseases: a review. Antonie Van Leeuwenhoek. 2020 Dec 2;113(12):2019–40.
18. Langsetmo L, Johnson A, Demmer RT, Fino N, Orwoll ES, Ensrud KE, et al. The Association between Objectively Measured Physical Activity and the Gut Microbiome among Older Community Dwelling Men. J Nutr Health Aging. 2019 Jun;23(6):538–46.
19. Ghosh TS, Shanahan F, O’Toole PW. The gut microbiome as a modulator of healthy ageing. Nat Rev Gastroenterol Hepatol. 2022 Sep 25;19(9):565–84.
20. Bana B, Cabreiro F. The Microbiome and Aging. Annu Rev Genet. 2019 Dec 3;53(1):239–61.
21. Spychala MS, Venna VR, Jandzinski M, Doran SJ, Durgan DJ, Ganesh BP, et al. Age‐related changes in the gut microbiota influence systemic inflammation and stroke outcome. Ann Neurol. 2018 Jul 18;84(1):23–36.
22. Carías Domínguez AM, de Jesús Rosa Salazar D, Stefanolo JP, Cruz Serrano MC, Casas IC, Zuluaga Peña JR. Intestinal Dysbiosis: Exploring Definition, Associated Symptoms, and Perspectives for a Comprehensive Understanding — a Scoping Review. Probiotics Antimicrob Proteins. 2025 Feb 5;17(1):440–9.
23. Yamamura R, Inoue KY, Nishino K, Yamasaki S. Intestinal and fecal pH in human health. Front Microbiomes. 2023 Jul 26;2:1192316.
24. Van Hul M, Cani PD, Petitfils C, De Vos WM, Tilg H, El-Omar EM. What defines a healthy gut microbiome? Gut. 2024 Nov;73(11):1893–908.
25. Cӑtoi AF, Corina A, Katsiki N, Vodnar DC, Andreicuț AD, Stoian AP, et al. Gut microbiota and aging-A focus on centenarians. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2020 Jul;1866(7):165765.
26. Coman V, Vodnar DC. Gut microbiota and old age: Modulating factors and interventions for healthy longevity. Exp Gerontol. 2020 Nov;141:111095.
27. Allum F, Grundberg E. Capturing functional epigenomes for insight into metabolic diseases. Mol Metab. 2020 Aug;38:100936.
28. Galow AM, Peleg S. How to Slow down the Ticking Clock: Age-Associated Epigenetic Alterations and Related Interventions to Extend Life Span. Cells. 2022 Jan 29;11(3):468.
29. Armstrong NJ, Mather KA, Thalamuthu A, Wright MJ, Trollor JN, Ames D, et al. Aging, exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks. Epigenomics. 2017 May 4;9(5):689–700.
30. Conole ELS, Robertson JA, Smith HM, Cox SR, Marioni RE. Epigenetic clocks and DNA methylation biomarkers of brain health and disease. Nat Rev Neurol. 2025 Aug;21(8):411-21.
31. Fuentealba M, Rouch L, Guyonnet S, Lemaitre JM, de Souto Barreto P, Vellas B, et al. A blood-based epigenetic clock for intrinsic capacity predicts mortality and is associated with clinical, immunological and lifestyle factors. Nat Aging. 2025 Jul;5(7):1207-16.
32. Gutman D, Rivkin E, Fadida A, Sharvit L, Hermush V, Rubin E, et al. Exceptionally Long-Lived Individuals (ELLI) Demonstrate Slower Aging Rate Calculated by DNA Methylation Clocks as Possible Modulators for Healthy Longevity. Int J Mol Sci. 2020 Jan 17;21(2):615.
33. Field AE, Robertson NA, Wang T, Havas A, Ideker T, Adams PD. DNA Methylation Clocks in Aging: Categories, Causes, and Consequences. Mol Cell. 2018 Sep;71(6):882–95.
34. Mostafavi Abdolmaleky H, Zhou JR. Gut Microbiota Dysbiosis, Oxidative Stress, Inflammation, and Epigenetic Alterations in Metabolic Diseases. Antioxidants. 2024 Aug 14;13(8):985.
35. Nohesara S, Abdolmaleky HM, Zhou JR, Thiagalingam S. Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies. Genes (Basel). 2023 Dec 14;14(12):2217.
36. Kolodziejczyk AA, Zheng D, Elinav E. Diet–microbiota interactions and personalized nutrition. Nat Rev Microbiol. 2019 Dec 20;17(12):742–53.
37. Reva K, Laranjinha J, Rocha BS. Epigenetic Modifications Induced by the Gut Microbiota May Result from What We Eat: Should We Talk about Precision Diet in Health and Disease? Metabolites. 2023 Mar 2;13(3):375.
38. O’Riordan KJ, Collins MK, Moloney GM, Knox EG, Aburto MR, Fülling C, et al. Short chain fatty acids: Microbial metabolites for gut-brain axis signalling. Mol Cell Endocrinol. 2022 Apr;546:111572.
39. Wang J, Zhu N, Su X, Gao Y, Yang R. Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis. Cells. 2023 Mar 2;12(5):793.
40. Salazar N, Arboleya S, Fernández-Navarro T, de los Reyes-Gavilán CG, Gonzalez S, Gueimonde M. Age-Associated Changes in Gut Microbiota and Dietary Components Related with the Immune System in Adulthood and Old Age: A Cross-Sectional Study. Nutrients. 2019 Jul 31;11(8):1765.
41. Strasser B, Wolters M, Weyh C, Krüger K, Ticinesi A. The Effects of Lifestyle and Diet on Gut Microbiota Composition, Inflammation and Muscle Performance in Our Aging Society. Nutrients. 2021 Jun 15;13(6):2045.
42. Vesnina A, Prosekov A, Kozlova O, Atuchin V. Genes and Eating Preferences, Their Roles in Personalized Nutrition. Genes (Basel). 2020 Mar 27;11(4):357.
43. Abdullah MMH, Jones PJH, Eck PK. Nutrigenetics of cholesterol metabolism: observational and dietary intervention studies in the postgenomic era. Nutr Rev. 2015 Aug;73(8):523–43.
44. Mehrdad M, Doaei S, Gholamalizadeh M, Fardaei M, Fararouei M, Eftekhari MH. Association of FTO rs9939609 polymorphism with serum leptin, insulin, adiponectin, and lipid profile in overweight adults. Adipocyte. 2020 Jan 1;9(1):51–6.
45. del Bosque-Plata L, Martínez-Martínez E, Espinoza-Camacho MÁ, Gragnoli C. The Role of TCF7L2 in Type 2 Diabetes. Diabetes. 2021 Jun 1;70(6):1220–8.
46. Lou L, Wang J, Wang J. Genetic associations between Transcription Factor 7 Like 2 rs7903146 polymorphism and type 2 diabetes mellitus: a meta-analysis of 115,809 subjects. Diabetol Metab Syndr. 2019 Dec 5;11(1):56.
47. Wang F, Zheng J, Cheng J, Zou H, Li M, Deng B, et al. Personalized nutrition: A review of genotype-based nutritional supplementation. Front Nutr. 2022 Sep 9;9:992986.
48. Bonetti G, Medori MC, Dhuli K, Macchia A, Donato K, Cristoni S, et al. Nutrigenomics: SNPs correlated to detoxification, antioxidant capacity and longevity. Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):209-213.
49. Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I, et al. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr. 2018 Feb 9;57(1):1–24.
50. Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota–gut–brain communication. Nat Rev Gastroenterol Hepatol. 2019 Aug 23;16(8):461–78.
51. Campaniello D, Corbo MR, Sinigaglia M, Speranza B, Racioppo A, Altieri C, et al. How Diet and Physical Activity Modulate Gut Microbiota: Evidence, and Perspectives. Nutrients. 2022 Jun 14;14(12):2456.
52. Bakke D, Sun J. Ancient Nuclear Receptor VDR With New Functions: Microbiome and Inflammation. Inflamm Bowel Dis. 2018 May 18;24(6):1149–54.
53. Battistini C, Ballan R, Herkenhoff ME, Saad SMI, Sun J. Vitamin D Modulates Intestinal Microbiota in Inflammatory Bowel Diseases. Int J Mol Sci. 2020 Dec 31;22(1):362.
54. Scarpellini E, Balsiger LM, Maurizi V, Rinninella E, Gasbarrini A, Giostra N, et al. Zinc and gut microbiota in health and gastrointestinal disease under the COVID‐19 suggestion. BioFactors. 2022 Mar 26;48(2):294–306.
55. Bielik V, Kolisek M. Bioaccessibility and Bioavailability of Minerals in Relation to a Healthy Gut Microbiome. Int J Mol Sci. 2021 Jun 24;22(13):6803.
56. Reed S, Knez M, Uzan A, Stangoulis JCR, Glahn RP, Koren O, et al. Alterations in the Gut ( Gallus gallus ) Microbiota Following the Consumption of Zinc Biofortified Wheat ( Triticum aestivum )-Based Diet. J Agric Food Chem. 2018 Jun 27;66(25):6291–9.
57. Reed S, Neuman H, Moscovich S, Glahn R, Koren O, Tako E. Chronic Zinc Deficiency Alters Chick Gut Microbiota Composition and Function. Nutrients. 2015 Nov 27;7(12):9768–84.
58. Knezevic J, Starchl C, Tmava Berisha A, Amrein K. Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function? Nutrients. 2020 Jun 12;12(6):1769.
59. Sauer AK, Grabrucker AM. Zinc Deficiency During Pregnancy Leads to Altered Microbiome and Elevated Inflammatory Markers in Mice. Front Neurosci. 2019 Nov 29;13:1295.
60. Dinu LD, Avram I, Pelinescu DR, Vamanu E. Mineral-Enriched Postbiotics: A New Perspective for Microbial Therapy to Prevent and Treat Gut Dysbiosis. Biomedicines. 2022 Sep 25;10(10):2392.
61. Piskin E, Cianciosi D, Gulec S, Tomas M, Capanoglu E. Iron Absorption: Factors, Limitations, and Improvement Methods. ACS Omega. 2022 Jun 21;7(24):20441–56.
62. Mu Q, Chen L, Gao X, Shen S, Sheng W, Min J, et al. The role of iron homeostasis in remodeling immune function and regulating inflammatory disease. Sci Bull (Beijing). 2021 Sep;66(17):1806–16.
63. Aleksandrova K, Romero-Mosquera B, Hernandez V. Diet, Gut Microbiome and Epigenetics: Emerging Links with Inflammatory Bowel Diseases and Prospects for Management and Prevention. Nutrients. 2017 Aug 30;9(9):962.
64. Davis C, Bryan J, Hodgson J, Murphy K. Definition of the Mediterranean Diet; A Literature Review. Nutrients. 2015 Nov 5;7(11):9139–53.
65. Rojo-López MI, Bermúdez-López M, Castro E, Farràs C, Torres G, Pamplona R, et al. Mediterranean Diet Is a Predictor of Progression of Subclinical Atherosclerosis in a Mediterranean Population: The ILERVAS Prospective Cohort Study. Nutrients. 2024 Oct 24;16(21):3607.
66. Perrone P, D’Angelo S. Gut Microbiota Modulation Through Mediterranean Diet Foods: Implications for Human Health. Nutrients. 2025 Mar 8;17(6):948.
67. Ghosh TS, Rampelli S, Jeffery IB, Santoro A, Neto M, Capri M, et al. Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut. 2020 Jul;69(7):1218–28.
68. Martinez KB, Leone V, Chang EB. Western diets, gut dysbiosis, and metabolic diseases: Are they linked? Gut Microbes. 2017 Mar 4;8(2):130–42.
69. Malesza IJ, Malesza M, Walkowiak J, Mussin N, Walkowiak D, Aringazina R, et al. High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review. Cells. 2021 Nov 14;10(11):3164.
70. Zinöcker M, Lindseth I. The Western Diet–Microbiome-Host Interaction and Its Role in Metabolic Disease. Nutrients. 2018 Mar 17;10(3):365.
71. Tomova A, Bukovsky I, Rembert E, Yonas W, Alwarith J, Barnard ND, Kahleova H. The Effects of Vegetarian and Vegan Diets on Gut Microbiota. Front Nutr. 2019 Apr 17;6:47.
72. Losasso C, Eckert EM, Mastrorilli E, Villiger J, Mancin M, Patuzzi I, et al. Assessing the Influence of Vegan, Vegetarian and Omnivore Oriented Westernized Dietary Styles on Human Gut Microbiota: A Cross Sectional Study. Front Microbiol. 2018 Mar 5;9:317.
73. Gyriki D, Nikolaidis CG, Bezirtzoglou E, Voidarou C, Stavropoulou E, Tsigalou C. The gut microbiota and aging: interactions, implications, and interventions. Front Aging. 2025 May 14;6:1452917.
74. Shen X, Tilves C, Kim H, Tanaka T, Spira AP, Chia CW, et al. Plant-based diets and the gut microbiome: findings from the Baltimore Longitudinal Study of Aging. Am J Clin Nutr. 2024 Mar;119(3):628–38.
75. Dwaraka VB, Aronica L, Carreras-Gallo N, Robinson JL, Hennings T, Carter MM, et al. Unveiling the epigenetic impact of vegan vs. omnivorous diets on aging: insights from the Twins Nutrition Study (TwiNS). BMC Med. 2024 Jul 29;22(1):301.
76. Sidhu SRK, Kok CW, Kunasegaran T, Ramadas A. Effect of Plant-Based Diets on Gut Microbiota: A Systematic Review of Interventional Studies. Nutrients. 2023 Mar 21;15(6):1510.
77. Plamada D, Vodnar DC. Polyphenols—Gut Microbiota Interrelationship: A Transition to a New Generation of Prebiotics. Nutrients. 2021 Dec 28;14(1):137.
78. Gamage E, Orr R, Travica N, Lane MM, Dissanayaka T, Kim JH, et al. Polyphenols as novel interventions for depression: Exploring the efficacy, mechanisms of action, and implications for future research. Neurosci Biobehav Rev. 2023 Aug;151:105225.
79. Wu W, Mi Y, Meng Q, Li N, Li W, Wang P, et al. Natural polyphenols as novel interventions for aging and age-related diseases: Exploring efficacy, mechanisms of action and implications for future research. Chin Herb Med. 2025 Apr;17(2):279–91.
80. Ma G, Chen Y. Polyphenol supplementation benefits human health via gut microbiota: A systematic review via meta-analysis. J Funct Foods. 2020 Mar;66:103829.
81. Sung MM, Byrne NJ, Robertson IM, Kim TT, Samokhvalov V, Levasseur J, et al. Resveratrol improves exercise performance and skeletal muscle oxidative capacity in heart failure. American Journal of Physiology-Heart and Circulatory Physiology. 2017 Apr 1;312(4):H842–53.
82. Zhao L, Zhang Q, Ma W, Tian F, Shen H, Zhou M. A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota. Food Funct. 2017;8(12):4644–56.
83. Qiu Y, Yang J, Wang L, Yang X, Gao K, Zhu C, et al. Dietary resveratrol attenuation of intestinal inflammation and oxidative damage is linked to the alteration of gut microbiota and butyrate in piglets challenged with deoxynivalenol. J Anim Sci Biotechnol. 2021 Dec 16;12(1):71.
84. Wang P, Li D, Ke W, Liang D, Hu X, Chen F. Resveratrol-induced gut microbiota reduces obesity in high-fat diet-fed mice. Int J Obes. 2020 Jan 4;44(1):213–25.
85. Chaplin A, Carpéné C, Mercader J. Resveratrol, Metabolic Syndrome, and Gut Microbiota. Nutrients. 2018 Nov 3;10(11):1651.
86. Li B, Yan Y, Zhang T, Xu H, Wu X, Yao G, et al. Quercetin reshapes gut microbiota homeostasis and modulates brain metabolic profile to regulate depression-like behaviors induced by CUMS in rats. Front Pharmacol. 2024 Mar 26;15:1362464.
87. Khairudin MAS, Mhd Jalil AM, Hussin N. Effects of Polyphenols in Tea (Camellia sinensis sp.) on the Modulation of Gut Microbiota in Human Trials and Animal Studies. Gastroenterol Insights. 2021 May 6;12(2):202–16.
88. Wang X, Liu Y, Wu Z, Zhang P, Zhang X. Tea Polyphenols: A Natural Antioxidant Regulates Gut Flora to Protect the Intestinal Mucosa and Prevent Chronic Diseases. Antioxidants. 2022 Jan 28;11(2):253.
89. Jung ES, Park J il, Park H, Holzapfel W, Hwang JS, Lee CH. Seven-day Green Tea Supplementation Revamps Gut Microbiome and Caecum/Skin Metabolome in Mice from Stress. Sci Rep. 2019 Dec 5;9(1):18418.
90. Boyajian JL, Ghebretatios M, Schaly S, Islam P, Prakash S. Microbiome and Human Aging: Probiotic and Prebiotic Potentials in Longevity, Skin Health and Cellular Senescence. Nutrients. 2021 Dec 18;13(12):4550.
91. Shi R, Ye J, Fan H, Hu X, Wu X, Wang D, et al. Lactobacillus plantarum LLY-606 Supplementation Ameliorates the Cognitive Impairment of Natural Aging in Mice: The Potential Role of Gut Microbiota Homeostasis. J Agric Food Chem. 2024 Feb 28;72(8):4049–62.
92. Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep. 2017 Oct 19;7(1):13537.
93. Kishimoto S, Nono M, Makizaki Y, Tanaka Y, Ohno H, Nishida E, et al. Lactobacillus paracasei subsp. paracasei 2004 improves health and lifespan in Caenorhabditis elegans. Sci Rep. 2024 May 7;14(1):10453.
94. Kumaree KK, Prasanth MI, Sivamaruthi BS, Kesika P, Tencomnao T, Chaiyasut C, et al. Lactobacillus paracasei HII01 enhances lifespan and promotes neuroprotection in Caenorhabditis elegans. Sci Rep. 2023 Oct 4;13(1):16707.
95. Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, et al. Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features. Cell. 2018 Sep;174(6):1388-1405.e21.
96. 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 Mar 4;10(2):210–5.
97. Kong F, Hua Y, Zeng B, Ning R, Li Y, Zhao J. Gut microbiota signatures of longevity. Current Biology. 2016 Sep;26(18):R832–3.
98. Kennedy JM, De Silva A, Walton GE, Gibson GR. A review on the use of prebiotics in ulcerative colitis. Trends Microbiol. 2024 May;32(5):507–15.
99. Arnold JW, Roach J, Fabela S, Moorfield E, Ding S, Blue E, et al. Correction to: The pleiotropic effects of prebiotic galacto-oligosaccharides on the aging gut. Microbiome. 2021 Dec 26;9(1):56.
100. Tosti V, Bertozzi B, Fontana L. Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms. The Journals of Gerontology: Series A. 2018 Mar 2;73(3):318–26.
101. Ruiz-Ruiz S, Sanchez-Carrillo S, Ciordia S, Mena MC, Méndez-García C, Rojo D, et al. Functional microbiome deficits associated with ageing: Chronological age threshold. Aging Cell. 2020 Jan;19(1):e13063.