1. Labat-Robert J, Robert L.Longevity and aging Role of free radicals and xanthine oxidase. A review.PatholBiol.

(2014)62:61–6. doi:10.1016/j.patbio.2014.02.009

2.Inatomi T,Otomaru K.Effffects ofheat-killed Enterococcus faecalis T-110 supplementation on gut immunity, gutflflora, and intestinal infection in naturally aged hamsters.PloS ONE.(2020)15:e0240773. doi: 10.1371/journal.pone.0240773

3.Tsukamoto H, Kouwaki T, Oshiumi H.Aging-associated extracellular vesicles contain immune regulatory microRNAsalleviating hyperinflflammatory state and immune dysfunction in theelderly.iScience. (2020) 23:101520. doi: 10.1016/j.isci.2020.101520

4.Giuffffrè M, Campigotto M,Campisciano G, Comar M, Crocè LS. A story of liver and gut microbes: how doesthe intestinal flflora affffect liver disease? a review of the literature. Am JPhysiol Gastrointest Liver Physiol. (2020) 318:G889–906. doi: 10.1152/ajpgi.00161.2019

5.Chen Y, Zhou J, Wang L. Role andmechanism of gut

microbiota in human disease. FrontCell Infect Microbiol. (2021)11:625913. doi: 10.3389/fcimb.2021.625913

6.Bezirtzoglou E, Stavropoulou E,Kantartzi K, Tsigalou C, Voidarou C,Mitropoulou G, et al. Maintaining digestivehealth in diabetes: the role of the gut microbiome and the challenge offunctional foods. Microorganisms. (2021)

3:9. doi:10.3390/microorganisms9030516

7.Shenghua P, Ziqin Z, Shuyu T,Huixia Z, Xianglu R, Jiao G. An integrated fecal microbiome and metabolome inthe aged mice reveal anti-aging effffects from the intestines and biochemicalmechanism of FuFang zhenshu TiaoZhi (FTZ).

Biomed Pharmacother. (2020)121:109421. doi:10.1016/j.biopha.2019.109421

8.Zhao D, Liu X, Zhao S, Li Z, QinX. 1H NMR-based fecal metabolomicsreveals changes in gastrointestinal functionof aging rats induced by d-galactose.Rejuvenation Res. (2020) 24:1–29. doi:10.1089/rej.2020.2352

9.Schlimme E, Martin D, Meisel H.Nucleosides and nucleotides: natural bioactive substances in milk andcolostrum. Br J Nutr. (2000) 84(Suppl.1):S59–68. doi: 10.1017/S0007114500002269

10.Carver JD, Allan Walker W. Therole of nucleotides in human nutrition.J Nutr Biochem.(1995)6:58–72.doi:10.1016/0955-2863(94)00019-I

11.Hess JR, Greenberg NA. The roleof nucleotides in the immune and gastrointestinal systems: potential clinicalapplications. Nutr Clin Pract.(2012) 27:281–94. doi: 10.1177/0884533611434933

12.George K. Grimble OMW.Nucleotides as immunomodulators

in clinical nutrition. Curr OpinClin Nutr Metab Care.

(2001)4:57–64. doi:10.1097/00075197-200101000-00011

13. Klein CJ. Nutrient requirementsfor preterm infant formulas.JNutr.(2002)132:1395S−549.doi:10.1093/jn/132.6.1395S

14.Carver JD. Advances innutritional modififications of infant formulas. Am J Clin Nutr. (2003)77:1550S−54. doi: 10.1093/ajcn/77.6.1550S

15. Slobodianik NH. Dietaryribonucleotides and health.Nutrition.(2003)19:68–9.doi:10.1016/S0899-9007(02)00951-6

16.Mountzouris KC, McCartney AL,Gibson GR. Intestinal microflflora of human infants and current trends for itsnutritional modulation. Br J Nutr. (2007)87:405–20. doi: 10.1079/BJN2002563

17.Sánchez-Pozo A, Gil A.Nucleotides as semiessential nutritional components.Br J Nutr. (2007)87:S135–37. doi: 10.1079/BJN 2001467

18.Lane AN, Fan TW. Regulation ofmammalian nucleotide metabolism and biosynthesis. Nucleic Acids Res. (2015)43:2466–85. doi: 10.1093/nar/gkv047

19.Boccaletto P, Machnicka MA, PurtaE, Piatkowski P, Baginski B, Wirecki TK, et al. MODOMICS: a database of RNAmodifification pathways.2017 update. Nucleic Acids Res. (2018) 46:D303–07. doi:10.1093/nar/gkx1030

20.Ding T, Song G, Liu X, Xu M, LiY. Nucleotides as optimal candidates for essential nutrients in livingorganisms: a review.J Funct Foods.(2021)82:104498.doi:10.1016/j.jffff.2021.104498

21.Ohkusa T, Ozaki Y, Sato C, MikuniK, Ikeda H. Long-term ingestion of lactosucrose increases Bififidobacterium spin human fecal flflora. Digestion.(1995) 56:415–20. doi: 10.1159/000201269

22. Carver JD, Saste M, Sosa R,Zaritt J, Kuchan M, Barness LA. The effffects of dietary nucleotides onintestinal blood flflow in preterm infants. Pediatr Res.(2002)52:425–9.doi:10.1203/00006450-200209000-00020

23.Segarra S, Miro G, Montoya A,Pardo-Marin L, Boque N, Ferrer L, et al. Randomized, allopurinol-controlledtrial of the effffects of dietary nucleotides and active hexose correlatedcompound in the treatment of canine leishmaniosis.VetParasitol.(2017)239:50–6.doi: 10.1016/j.vetpar.2017.04.014

24.Wei Z, Yi L, Xu W, Zhou H, ZhangY, Zhang W, et al. Effffects of dietary nucleotides on growth, non-specifificimmune response and disease resistance of sea cucumber Apostichopus japonicas.Fish Shellfifish Immunol. (2015) 47:1–6. doi: 10.1016/j.fsi.2015.08.017

25.Arnaud A, Fontana L, Angulo AJ,Gil A, Lopez-Pedrosa JM. Exogenous nucleosides alter the intracellularnucleotide pool in hepatic cell cultures.Implications in cell proliferation andfunction. Clin Nutr. (2003) 22:391–

9. doi:10.1016/S0261-5614(03)00037-2

26.Ortega A, Gil A, Sanchez-Pozo A.Exogenous nucleosides modulate expression and activity of transcription factorsin Caco-2 cells. J Nutr Biochem.(2011) 22:595–604. doi:10.1016/j.jnutbio.2010.05.003

27.Dong W,Wu Z, Xu L, Fang Y, Xu Y.Maternal supplementation of nucleotides improves the behavioral development ofprenatal ethanol-exposed mice. Cogn Affffect Behav Neurosci(2014)14:879–90.doi:10.3758/s13415-013-0218-y

28.Xu M, Liang R, Li Y, Wang J. Anti-fatigueeffffects of dietary nucleotides in mice.Food Nutr Res.(2017) 61:1334485. doi:10.1080/16546628.2017.1334485

29.Assoni AD,Amorim AB,Saleh MAD,TseMLP,Berto DA.Dietary

glutamine, glutamic acid andnucleotide supplementation accelerate carbon turnover (δ 13C) on stomach ofweaned piglets.Anim Nutr.(2017)3:225–31.doi:

10.1016/j.aninu.2017.04.006

30.Xie CY, Wang Q, Li G, Fan Z, WangH, Wu X. Dietary supplement with nucleotides in the form of uridinemonophosphate or uridine stimulate intestinal development and promotenucleotide transport in weaned piglets. J Sci Food Agric. (2019) 99:6108–13.doi: 10.1002/jsfa.9850

31.Hosokawa M, Kasai R, Higuchi K,Takeshita S, Shimizu K, Hamamoto H, et al.Grading score system: a method forevaluation of the degree of senescence

in Senescence Accelerated Mouse(SAM). Mech Ageing Dev. (1984) 26:91–102. doi: 10.1016/0047-6374(84)90168-4

32.Ding T, Li T, Li J.Identifification of natural product compounds as quorum sensing inhibitors inPseudomonas flfluorescens P07 through virtual screening.Bioorg Med Chem. (2018)26:4088–99. doi: 10.1016/j.bmc.2018.06.039

33.He F,Ouwehand AC, Isolauri E,Hosoda M, Benno Y, Salminen S.Difffferences in composition and mucosal adhesionof bififidobacteria isolated from healthy adults and healthy seniors. CurrMicrobiol. (2001) 43:351– 4. doi: 10.1007/s002840010315

34.Mancuso C, Santangelo R.Alzheimer’s disease and gut microbiota modififications:The long way betweenpreclinical studies and clinical evidence.Pharmacol Res. (2018)129:329–36.doi:10.1016/j.phrs.2017.12.009

35.Eckburg PB, Bik EM, Bernstein CN,Purdom E, Dethlefsen L, Sargent M, et al.Diversity of the human intestinalmicrobial flflora.Science.(2005)308:1635–8.doi: 10.1126/science.1110591

36.Parthasarathy G, Chen J, Chen X,Chia N, O’Connor HM, Wolf PG, et al. Relationship between microbiota of thecolonic mucosa vs feces and symptoms, colonic transit, and methane productionin female patients with chronic constipation.Gastroenterology.(2016)150:367–79.doi: 10.1053/j.gastro.2015.10.005

37.Cuomo P, Papaianni M, Sansone C,Iannelli A, Iannelli D, Medaglia C, et al. An in vitro model to investigate therole of Helicobacter pylori in type 2 diabetes,obesity, Alzheimer’s disease andcardiometabolic disease.Int J Mol Sci.(2020)8:21.doi:10.3390/ijms21218369

38.Zendehdel A,Roham M.Role ofhelicobacter pylori infection in the manifestation of old age-related diseases.Mol Genet Genomic Med.(2020)8:e1157.doi: 10.1002/mgg3.1157

39.Sibai M, Altuntas E, Yildirim B,Ozturk G, Yildirim S, Demircan T.Microbiome and longevity: high abundance oflongevity-linked Muribaculaceae in the gut of the long-living Rodent Spalaxleucodon.OMICS.(2020) 24:592–601.doi:10.1089/omi.2020.0116

40.Kim DH, Jin YH. Intestinalbacterial β-glucuronidase activity of patients with colon cancer. Arch PharmRes. (2001) 24:564–67. doi: 10.1007/BF02975166

41.Humblot C, Lhoste E, KnasmüllerS, Gloux K, Bruneau A, Bensaada M,et al. Protective effffects of Brusselssprouts, oligosaccharides and fermented milk towards2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced genotoxicity in the humanflflora associated

F344 rat: role of xenobioticmetabolising enzymes and intestinal microflflora. J Chromatogr B Analyt TechnolBiomed Life Sci.(2004) 802:231–7.doi: 10.1016/j.jchromb.2003.11.018

42.McKernan RM, Whiting PJ. Whitingwhich GABAA-receptor

subtypes really occur in the brain?Trends Neurosci.(1996)

19:139–43. doi:10.1016/S0166-2236(96)80023-3

43. Lanctôt KL, Herrmann N, MazzottaP, Khan LR, Ingber N. GABAergic function in Alzheimer’s disease: evidence fordysfunction and potential as a therapeutic target for the treatment of behaviouraland psychological symptoms of dementia. Can J Psychiatry.(2004)49:439–53. doi:10.1177/070674370404900705 44. Messaoudi M, Lalonde R, Violle N, Javelot H,Desor D, Nejdi A,et al. Assessment of psychotropic-like properties of aprobiotic formulation (Lactobacillus helveticus R0052 and Bififidobacterium

longum R0175) in rats and humansubjects. Br J Nutr. (2011)

105:755–64. doi:10.1017/S0007114510004319

45.Ohsawa K, Uchida N, Ohki K,Nakamura Y, Yokogoshi H. Lactobacillus helveticus-fermented milk improveslearning and memory in mice. Nutr Neurosci.(2015)18:232–40. doi:10.1179/1476830514Y.0000000122

46.Lehto SM, Niskanen L, Tolmunen T,Hintikka J, Viinamaki H, Heiskanen T, et al. Low serum HDL-cholesterol levelsare associated with long symptom duration in patients with major depressivedisorder. Psychiatry Clin Neurosci.

(2010) 64:279–83. doi:10.1111/j.1440-1819.2010.02079.x