Skip to main content
SpringerLink
Log in

Gut Microbiota and Microbiota-Related Metabolites as Possible Biomarkers of Cognitive Aging

  • Chapter
  • First Online:
Reviews on Biomarker Studies in Aging and Anti-Aging Research

Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 1178))

Abstract

Gut microbiota composition and functionality can influence the pathophysiology of age-related cognitive impairment and dementia, according to a large number of animal studies. The translation of this concept to humans is still uncertain, due to the relatively low number of clinical studies focused on fecal microbiota and large number of environmental factors that influence the microbiota composition. However, the fecal microbiota composition of older patients with dementia is deeply different from that of healthy active controls, conditioning a different metabolic profile. The possible use of fecal microbiota-related parameters and microbiota-derived metabolites as biomarkers of cognitive performance and dementia is critically reviewed in this paper, focusing on the most promising areas of research for the future.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 189.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Schmidt TSB, Raes J, Bork P (2018) The human gut microbiome: from association to modulation. Cell 172(6):1198–1215

    Article  CAS  PubMed  Google Scholar 

  2. Gentile CL, Weir TL (2018) The gut microbiota at the intersection of diet and human health. Science 362:776–780

    Article  CAS  PubMed  Google Scholar 

  3. Ticinesi A, Nouvenne A, Tana C, Prati B, Cerundolo N, Miraglia C et al (2018) The impact of intestinal microbiota on bio-medical research: definitions, techniques and physiology of a “new frontier”. Acta Biomed 89(9S):52–59

    PubMed  Google Scholar 

  4. Milosevic I, Vujovic A, Barac A, Djelic M, Korac M, Radovanovic Spurnic A et al (2019) Gut-liver axis, gut microbiota, and its modulation in the management of liver disease: a review of the literature. Int J Mol Sci 20(2):395. pii: E395. https://doi.org/10.3390/ijms20020395

    Article  CAS  PubMed Central  Google Scholar 

  5. Cosola C, Rocchetti MT, Sabatino A, Fiaccadori E, Di Iorio BR, Gesualdo L (2019) Microbiota issue in CKD: how promising are gut-targeted approaches? J Nephrol 32(1):27–37

    Article  CAS  PubMed  Google Scholar 

  6. Ticinesi A, Milani C, Guerra A, Allegri F, Lauretani F, Nouvenne A et al (2018) Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers. Gut 67(12):2097–2106

    Article  CAS  PubMed  Google Scholar 

  7. Quach D, Britton RA (2017) Gut microbiota and bone health. Adv Exp Med Biol 1033:47–58

    Article  CAS  PubMed  Google Scholar 

  8. Ticinesi A, Lauretani F, Milani C, Nouvenne A, Tana C, Del Rio D et al (2017) Aging gut microbiota at the cross-road between nutrition, physical frailty, and sarcopenia: is there a gut-muscle axis? Nutrients 9(12):E1303. pii: E1303. https://doi.org/10.3390/nu9121303

    Article  CAS  PubMed  Google Scholar 

  9. Junges VM, Closs VE, Nogueira GM, Valle Gottlieb MG (2018) Crosstalk between gut microbiota and the central nervous system: a focus for Alzheimer’s disease. Curr Alzheimer Res 15:1–12.43

    Article  CAS  Google Scholar 

  10. Ticinesi A, Tana C, Nouvenne A, Prati B, Lauretani F, Meschi T (2018) Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review. Clin Interv Aging 13:1497–1511

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kowalski K, Mulak A (2019) Brain-gut-microbiota axis in Alzheimer’s disease. J Neurogastroenterol Motil 25(1):48–60

    Article  PubMed  PubMed Central  Google Scholar 

  12. Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C et al (2017) Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging 49:60–68

    Article  CAS  PubMed  Google Scholar 

  13. Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC et al (2017) Gut microbiome alterations in Alzheimer’s disease. Sci Rep 7(1):13537. https://doi.org/10.1038/s41598-017-13601-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Manderino L, Carroll I, Azcarate-Peril MA, Rochette A, Heinberg L, Peat C et al (2017) Preliminary evidence for an association between the composition of gut microbiome and cognitive function in neurologically-healthy older adults. J Int Neuropsychol Soc 23(8):700–705

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zhuang ZQ, Shen LL, Li WW, Fu X, Zeng F, Gui L et al (2018) Gut microbiota is altered in patients with Alzheimer’s disease. J Alzheimers Dis 63(4):1337–1346

    Article  CAS  PubMed  Google Scholar 

  16. Saji N, Niida S, Murotani K, Hisada T, Tsuduki T, Sugimoto T et al (2019) Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan. Sci Rep 9:1008. https://doi.org/10.1038/s41598-018-38218-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Desmedt O, Broers VJV, Zamariola G, Pachikian B, Delzenne N, Luminet O (2019) Effects of prebiotics on affect and cognition in human intervention studies. Nutr Rev 77(2):81–95

    Article  PubMed  Google Scholar 

  18. Leblhuber F, Steiner K, Schuetz B, Fuchs D, Gostner JM (2018) Probiotic supplementation in patients with Alzheimer’s dementia – An explorative intervention study. Curr Alzheimer Res 15:1106–1113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Tran TTT, Cousin FJ, Lynch DB, Menon R, Brulc J, Brown JRM et al (2019) Prebiotic supplementation in frail older people affects specific gut microbiota taxa but not global diversity. Microbiome 7:39. https://doi.org/10.1186/s40168-019-0654-1

    Article  PubMed  PubMed Central  Google Scholar 

  20. Agahi A, Hamidi GA, Daneshvar R, Hamdieh M, Soheili M, Alinaghipour A et al (2018) Does severity of Alzheimer’s disease contribute to its responsiveness to modifying gut microbiota? A double blind clinical trial. Front Neurol 9:662. https://doi.org/10.3389/fneur.2018.00662

    Article  PubMed  PubMed Central  Google Scholar 

  21. Inoue T, Kobayashi Y, Mori N, Sakagawa M, Xiao JZ, Moritani T et al (2018) Effect of combined bifidobacteria supplementation and resistance training on cognitive function, body composition and bowel habits of healthy elderly subjects. Benef Microbes 9(6):843–853

    Article  CAS  PubMed  Google Scholar 

  22. Ticinesi A, Lauretani F, Tana C, Nouvenne A, Ridolo E, Meschi T (2019) Exercise and immune system as modulators of intestinal microbiome: implications for the gut-muscle axis hypothesis. Exerc Immunol Rev 25:84–95

    PubMed  Google Scholar 

  23. Ticinesi A, Milani C, Lauretani F, Nouvenne A, Mancabelli L, Lugli GA et al (2017) Gut microbiota composition is associated with polypharmacy in elderly hospitalized patients. Sci Rep 7(1):11102. https://doi.org/10.1038/s41598-017-10734-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jackson MA, Verdi S, Maxan ME, Shin CM, Zierer J, Bowyer RCE et al (2018) Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nat Commun 9(1):2655. https://doi.org/10.1038/s41467-018-05184-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Davenport ER, Mizrahi-Mian O, Michelini K, Barreiro LB, Ober C, Gilad Y (2014) Seasonal variation in human gut microbiome composition. PLoS One 9(3):e90731. https://doi.org/10.1371/journal.pone.0090731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. O’Toole PW, Jeffery IB (2015) Gut microbiome and aging. Science 350(6265):1214–1215

    Article  CAS  PubMed  Google Scholar 

  27. Vandeputte D, Falony G, Vieiera-Silva S, Tito RY, Joossens M, Raes J (2016) Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut 65(1):57–62

    Article  CAS  PubMed  Google Scholar 

  28. Vandeputte D, Kathagen G, D’hoe K, Vieira-Silva S, Valles-Colomer M, Sabino J et al (2017) Quantitative microbiome profiling links gut community variation to microbial load. Nature 551(7681):507–511

    Article  CAS  PubMed  Google Scholar 

  29. Zhernakova A, Kurilshikov A, Bonder MJ, Tigchelaar EF, Schirmer M, Vatanen T et al (2016) Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352(6285):565–569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Falony G, Vandeputte D, Caenepeel C, Vieira-Silva S, Daryoush T, Vermeire S et al (2019) The human microbiome in health and disease: hype or hope. Acta Clin Belg 74(2):53–64

    Article  PubMed  Google Scholar 

  31. Ticinesi A, Tana C, Nouvenne A (2019) The intestinal microbiome and its relevance for functionality in older persons. Curr Opin Clin Nutr Metab Care 22(1):4–12

    Article  CAS  PubMed  Google Scholar 

  32. Mancuso C, Santangelo R (2018) Alzheimer’s disease and gut microbiota modifications: the long way between preclinical studies and clinical evidence. Pharm Res 129:329–336

    Article  CAS  Google Scholar 

  33. Lozupone M, La Montagna M, D’Urso F, Daniele A, Greco A, Seripa D et al (2019) The role of biomarkers in psychiatry. Adv Exp Med Biol 1118:135–162

    Article  PubMed  Google Scholar 

  34. Ruan Q, D’Onofrio G, Sancarlo D, Greco A, Lozupone M, Seripa D et al (2017) Emerging biomarkers and screening for cognitive frailty. Aging Clin Exp Res 29:1075–1086

    Article  PubMed  Google Scholar 

  35. Ventura M, Turroni F, Canchaya C, Vaughan EE, O’Toole PW, Van Sinderen D (2009) Microbial diversity in the human intestine and novel insights from metagenomics. Front Biosci 14:3214–3221

    Article  CAS  Google Scholar 

  36. Milani C, Hevia A, Foroni E, Duranti S, Turroni F, Lugli GA et al (2013) Assessing the fecal microbiota: an optimized ion torrent 16S rRNA gene-based analysis protocol. PLoS One 8(7):e68739. https://doi.org/10.1371/journal.pone.0068739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kim BR, Shin J, Guevarra RB, Lee JH, Kim DW, Seol KH et al (2017) Deciphering diversity indices for a better understanding of microbial communities. J Microbiol Biotechnol 27(12):2089–2093

    Article  PubMed  Google Scholar 

  38. Schloss PD, Handelsman J (2006) Introducing SONS, a tool for operational taxonomic unit-based comparisons of microbial community memberships and structures. Appl Environ Microbiol 75:7537–7541

    Article  CAS  Google Scholar 

  39. Ticinesi A, Milani C, Lauretani F, Nouvenne A, Tana C, Ventura M et al (2019) Gut microbiome in the elderly hospitalized patient: a marker of disease and prognosis? In: Faintuch J, Faintuch S (eds) Microbiome and metabolome in diagnosis, therapy, and other strategic applications. Associated Press, London, pp 287–296. isbn:978-0-12-815249-2

    Chapter  Google Scholar 

  40. Milani C, Ticinesi A, Gerritsen J, Nouvenne A, Lugli GA, Mancabelli L et al (2016) Gut microbiota composition and Clostridium difficile infection in hospitalized elderly individuals: a metagenomic study. Sci Rep 6:25945. https://doi.org/10.1038/srep2594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ianiro G, Tilg H, Gasbarrini A (2016) Antibiotics as deep modulators of gut microbiota: between good and evil. Gut 65(11):1906–1911

    Article  CAS  PubMed  Google Scholar 

  42. Perez-Cobas AE, Gosalbes MJ, Friedrichs A, Knecht H, Artacho A, Eismann K et al (2013) Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut 62(11):1591–1601

    Article  CAS  PubMed  Google Scholar 

  43. Zhan G, Yang N, Li S, Huang N, Fang X, Zhang J et al (2018) Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice. Aging 10(6):1257–1267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hoffman JD, Parikh I, Green SJ, Chlipala G, Mohney RP, Keaton M et al (2017) Age drives distortion of brain metabolic, vascular and cognitive functions, and the gut microbiome. Front Aging Neurosci 9:298. https://doi.org/10.3389/fnagi.2017.00298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fröhlich EE, Farzi A, Mayerhofer R, Reichmann F, Jačan A, Wagner B et al (2016) Cognitive impairment by antibiotic-induced gut dysbiosis: analysis of gut microbiota-brain communication. Brain Behav Immun 56:140–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Minter MR, Zhang C, Leone V, Ringus DL, Zhang X, Oyler-Castillo P et al (2016) Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease. Sci Rep 6:30028. https://doi.org/10.1038/srep30028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Minter MR, Hinterleitner R, Meisel M, Zhang C, Leone V, Zhang X et al (2017) Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE/PSΔE9 murine model of Alzheimer’s disease. Sci Rep 7:10411. https://doi.org/10.1038/s41598-017-11047-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Harach T, Marungruang N, Duthilleul N, Cheatham V, McCoy KD, Frisoni G et al (2017) Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci Rep 7:41802. https://doi.org/10.1038/srep41802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Bajaj JS, Fagan A, Sikaroodi M, White MB, Sterling RK, Gilles H et al (2017) Liver transplant modulates gut microbial dysbiosis and cognitive function in cirrhosis. Liver Transpl 23:907–914

    Article  PubMed  Google Scholar 

  50. Bajaj JS, Vargas HE, Reddy KR, Lai JC, O’Leary JG, Tandon P et al (2019) Association between intestinal microbiota collected at hospital admission and outcomes of patients with cirrhosis. Clin Gastroenterol Hepatol 17:756–765

    Article  PubMed  Google Scholar 

  51. Fernandez-Real JM, Serino M, Blasco G, Puig J, Daunis-i-Estadella J, Ricart W et al (2015) Gut microbiota interacts with brain microstructure and function. J Clin Endocrinol Metab 100(12):4505–4513

    Article  CAS  PubMed  Google Scholar 

  52. Zhang F, Yang J, Ji Y, Sun M, Shen J, Sun J et al (2019) Gut microbiota dysbiosis is not independently associated with neurocognitive impairment in people living with HIV. Front Microbiol 9:3352. https://doi.org/10.3389/fmicb.2018.03352

    Article  PubMed  PubMed Central  Google Scholar 

  53. Verdi S, Jackson MA, Beaumont M, Bowyer RCE, Bell JT, Spector TD et al (2018) An investigation into physical frailty as a link between the gut microbiome and cognitive health. Front Aging Neurosci 10:398. https://doi.org/10.3389/fnagi.2018.00398

    Article  PubMed  PubMed Central  Google Scholar 

  54. Araos R, Andreatos N, Ugalde J, Mitchell S, Mylonakis E, D’Agata EMC (2018) Fecal microbiome among nursing home residents with advanced dementia and Clostridium difficile. Dig Dis Sci 63(6):1525–1531

    Article  PubMed  PubMed Central  Google Scholar 

  55. Costea PI, Hildebrand F, Arumugam M, Bäckhed F, Blaser MJ, Bushman FD et al (2018) Enterotypes in the landscape of gut microbial community composition. Nat Microbiol 3(1):8–16

    Article  CAS  PubMed  Google Scholar 

  56. Mariat D, Firmesse O, Levenez F, Guimarȃes V, Sokol H, Doré J et al (2009) The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 9:123. https://doi.org/10.1186/1471-2180-9-123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Sze MA, Schloss PD (2016) Looking for a signal in the noise: revisiting obesity and the microbiome. mBio 7(4):e01018–e01016. https://doi.org/10.1128/mBio.01018-16

    Article  PubMed  PubMed Central  Google Scholar 

  58. Indiani CMDSP, Rizzardi KF, Castelo PM, Ferraz LFC, Darrieux M, Parisotto TM (2018) Childhood obesity and Firmicutes/Bacteroidetes ratio in the gut microbiota: a systematic review. Child Obes 14(8):501–509

    Article  PubMed  Google Scholar 

  59. Koliada A, Syzenko G, Moseiko V, Budovska L, Puchkov K, Perederiy V et al (2017) Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukranian population. BMC Microbiol 17(1):120. https://doi.org/10.1186/s12866-017-1027-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sanguinetti E, Collado MC, Marrachelli VG, Monleon D, Selma-Royo M, Pardo-Tendero MM et al (2018) Microbiome-metabolome signatures in mice genetically prone to develop dementia, fed a normal or fatty diet. Sci Rep 8:4907. https://doi.org/10.1038/s41598-018-23261-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Zhang P, Yu Y, Qin Y, Zhou Y, Tang R, Wang Q et al (2019) Alterations to the microbiota-colon-brain axis in high-fat-diet-induced obese mice compared to diet-resistant mice. J Nutr Biochem 65:54–65

    Article  CAS  PubMed  Google Scholar 

  62. Bäuerl C, Collado MC, Diaz Cuevas A, Viña J, Pérez Martìnez G (2018) Shifts in gut microbiota composition in APP/PSS1 transgenic mouse model of Alzheimer’s disease during lifespan. Lett Appl Microbiol 66(6):464–471

    Article  CAS  PubMed  Google Scholar 

  63. Bonfili L, Cecarini V, Berardi S, Scarpona S, Suchodolski JS, Nasuti C et al (2017) Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci Rep 7:2426. https://doi.org/10.1038/s41598-017-02587-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Shen L, Liu L, Ji HF (2017) Alzheimer’s disease histological and behavioral manifestations in transgenic mice correlate with specific gut microbiome state. J Alzheimers Dis 56(1):385–390

    Article  CAS  PubMed  Google Scholar 

  65. Tran TTT, Corsini S, Kellingray L, Hegarty C, Le Gall G, Narbad A et al (2019) APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer’s disease pathophysiology. FASEB J 33:8221–8231

    Article  PubMed  PubMed Central  Google Scholar 

  66. Blasco G, Moreno-Navarrete JM, Rivero M, Pérez-Brocal V, Garre-Olmo J, Puig J et al (2017) The gut metagenome changes in parallel to waist circumference, brain iron deposition, and cognitive function. J Clin Endocrinol Metab 102:2962–2973

    Article  PubMed  Google Scholar 

  67. Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S et al (2012) Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol 302:G168–G175

    Article  CAS  PubMed  Google Scholar 

  68. Bajaj JS, Ahluwalia V, Steinberg JL, Hobgood S, Boling PA, Godschalk M et al (2016) Elderly patients have an altered gut-brain axis regardless of the presence of cirrhosis. Sci Rep 6:38481. https://doi.org/10.1038/srep38481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bajaj JS, Fagan A, White MB, Wade JB, Hylemon PB, Heuman DM et al (2019) Specific gut and salivary microbiota patterns are linked with different cognitive testing strategies in minimal hepatic encephalopathy. Am J Gastroenterol 114:1080–1090

    Article  PubMed  PubMed Central  Google Scholar 

  70. Qian Y, Yang Y, Xu S, Wu C, Song Y, Qin N et al (2018) Alteration of the fecal microbiota in Chinese patients with Parkinson’s disease. Brain Behav Immun 70:194–202

    Article  PubMed  Google Scholar 

  71. Barichella M, Severgnini M, Cilia R, Cassani E, Bolliri C, Caronni S et al (2019) Unraveling gut microbiota in Parkinson’s disease and atypical parkinsonism. Mov Disord 34(3):396–405

    Article  PubMed  Google Scholar 

  72. Franceschi F, Ojetti V, Candelli M, Covino M, Cardone S, Potenza A et al (2019) Microbes and Alzheimer’s disease: lessons from H. pylori and GUT microbiota. Eur Rev Med Pharmacol Sci 23:426–430

    CAS  PubMed  Google Scholar 

  73. Alkasir R, Li J, Li X, Jin M, Zhu B (2017) Human gut microbiota: the links with dementia development. Protein Cell 8(2):90–102

    Article  CAS  PubMed  Google Scholar 

  74. Giau VV, Wu SY, Jamerlan A, An SSA, Kim SY, Hulme J (2018) Gut microbiota and their neuroinflammatory implications in Alzheimer’s disease. Nutrients 10:1765. https://doi.org/10.3390/nu10111765

    Article  CAS  PubMed Central  Google Scholar 

  75. Sanz Y, Romanì-Perez M, Benìtez-Pàez A, Portune KJ, Brigidi P, Rampelli S et al (2018) Towards microbiome-informed dietary recommendations for promoting metabolic and mental health: opinion papers of the MyNewGut project. Clin Nutr 37:2191–2197

    Article  PubMed  Google Scholar 

  76. Westfall S, Lomis N, Kahouli I, Dia SY, Singh SP, Prakash S (2017) Microbiome, probiotics and neurodegenerative diseases: deciphering the gut-brain axis. Cell Mol Life Sci 74:3769–3787

    Article  CAS  PubMed  Google Scholar 

  77. Friedland RP, Chapman MR (2017) The role of microbial amyloid in neurodegeneration. PLoS Pathog 13(12):e1006654. https://doi.org/10.1371/journal.ppat.1006654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Li S, Shao Y, Li K, HuangFu C, Wang W, Liu Z et al (2018) Vascular cognitive impairment and the gut microbiota. J Alzheimers Dis 63(4):1209–1222

    Article  PubMed  Google Scholar 

  79. Kiely A, Ferland G, Ouliass B, O’Toole PW, Purtill H, O’Connor EM (2018) Vitamin K status and inflammation are associated with cognition in older Irish adults. Nutr Neurosci 1–9

    Google Scholar 

  80. Quigley EMM (2016) Leaky gut – concept or clinical entity? Curr Opin Gastroenterol 32(2):74–79

    Article  PubMed  Google Scholar 

  81. Liebisch G, Ecker J, Roth S, Schweizer S, Öttl V, Schött HF et al (2019) Quantification of fecal short-chain fatty acids by liquid chromatography tandem mass spectrometry-investigation of pre-analytic stability. Biomol Ther 9(4):E121. https://doi.org/10.3390/biom9040121

    Article  CAS  Google Scholar 

  82. Belizário JE, Faintuch J, Garay-Malpartida M (2018) Gut microbiome dysbiosis and immunometabolism: new frontiers for treatment of metabolic diseases. Mediat Inflamm 2018:2037838–2037812. https://doi.org/10.1155/2018/2037838

    Article  CAS  Google Scholar 

  83. López P, Sánchez M, Perez-Cruz C, Velázquez-Villegas LA, Syeda T, Aguilar-López M et al (2018) Long-term genistein consumption modifies gut microbiota, improving glucose metabolism, metabolic endotoxinemia, and cognitive function in mice fed a high-fat diet. Mol Nutr Food Res 62:1800313

    Article  CAS  Google Scholar 

  84. Hayashi K, Hasegawa Y, Takemoto Y, Cao C, Takeya H, Komohara Y et al (2019) Continuous intracerebroventricular injection of Porphyromonas gingivalis lipopolysaccharide induces systemic organ dysfunction in a mouse model of Alzheimer’s disease. Exp Gerontol 120:1–5

    Article  CAS  PubMed  Google Scholar 

  85. Zhao Y, Cong L, Jaber V, Lukiw WJ (2017) Microbiome-derived lipopolysaccharide enriched in the perinuclear region of Alzheimer’s disease brain. Front Immunol 8:1064. https://doi.org/10.3389/fimmu.2017.01064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zhan X, Stamova B, Jin LW, DeCarli C, Phinney B, Sharp FR (2016) Gram-negative bacterial molecules associate with Alzheimer’s disease pathology. Neurology 87(22):2324–2332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhao Y, Jaber V, Lukiw WJ (2017) Secretory products of the human GI tract microbiome and their potential impact on Alzheimer’s disease (AD): detection of lipopolysaccharide (LPS) in AD hippocampus. Front Cell Infect Microbiol 7:318. https://doi.org/10.3389/fcimb.2017.00318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Andreadou E, Pantazaki AA, Daniilidou M, Tsolaki M (2017) Rhamnolipids, microbial virulence factors, in Alzheimer’s disease. J Alzheimers Dis 59(1):209–222

    Article  CAS  PubMed  Google Scholar 

  89. Zgoda-Pols JR, Chowdhury S, Wirth M, Milburn MV, Alexander DC, Alton KB (2011) Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: investigation of nicotinic acid receptor agonists. Toxicol Appl Pharmacol 255:48–56

    Article  CAS  PubMed  Google Scholar 

  90. Weber D, Oefner PJ, Hiergeist A, Koestler J, Gessner A, Weber M et al (2015) Low urinary indoxyl sulfate levels early after transplantation reflect a disrupted microbiome and are associated with poor outcome. Blood 126:1723–1728

    Article  CAS  PubMed  Google Scholar 

  91. Ramos-Chávez LA, Roldán-Roldán G, Garcia-Juárez B, González-Esquivel D, Pérez de la Cruz G, Pineda B et al (2018) Low serum tryptophan levels as an indicator of global cognitive performance in nondemented women over 50 years old. Oxidative Med Cell Longev 2018:8604718. https://doi.org/10.1155/2018/8604718

    Article  Google Scholar 

  92. Hafstad-Solvang SE, Nordrehaug JE, Tell GS, Nygård O, McCann A, Ueland PM et al (2019) The kynurenine pathway and cognitive performance in community-dwelling older adults. The Hordaland Health Study. Brain Behav Immun 75:155–162

    Article  CAS  Google Scholar 

  93. Castillo-Rodriguez E, Fernandez-Prado R, Esteras R, Perez-Gomez MV, Gracia-Iguacel C, Fernandez-Fernandez B et al (2018) Impact of altered intestinal microbiota on chronic kidney disease progression. Toxins (Basel) 10(7):E300. https://doi.org/10.3390/toxins10070300

    Article  CAS  Google Scholar 

  94. Lin YT, Wu PH, Lee HH, Mubanga M, Chen CS, Kuo MC et al (2019) Indole-3 acetic acid increased risk of impaired cognitive function in patients receiving hemodialysis. Neurotoxicology 73:85–91

    Article  CAS  PubMed  Google Scholar 

  95. Karu N, McKercher C, Nichols DS, Davies N, Shellie RA, Hilder EF et al (2016) Tryptophan metabolism, its relation to inflammation and stress markers and association with psychological and cognitive functioning: Tasmanian Chronic Kidney Disease pilot study. BMC Nephrol 17:171. https://doi.org/10.1186/s12882-016-0387-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Yeh YC, Huang MF, Liang SS, Hwang SJ, Tsai JC, Liu TL et al (2016) Indoxyl sulfate, not p-cresyl sulfate, is associated with cognitive impairment in early-stage chronic kidney disease. Neurotoxicology 53:148–152

    Article  CAS  PubMed  Google Scholar 

  97. Lin YT, Wu PH, Tsai YC, Hsu YL, Wang HY, Kuo MC et al (2019) Indoxyl sulfate induces apoptosis through oxidative stress and mitogen-activated protein kinase signalinig pathway inhibition in human astrocytes. J Clin Med 8(2):E191. https://doi.org/10.3390/jcm8020191

    Article  PubMed  Google Scholar 

  98. Paley EL, Merkulova-Rainon T, Faynboym A, Shestopalov VI, Aksenoff I (2018) Geographical distribution and diversity of gut microbial NADH-Ubiquinone oxidoreductase sequence associated with Alzheimer’s disease. J Alzheimers Dis 61:1531–1540

    Article  CAS  PubMed  Google Scholar 

  99. Canfora EE, Jocken JW, Blaak EE (2015) Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol 11(10):577–591

    Article  CAS  PubMed  Google Scholar 

  100. Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E (2017) Dysbiosis and the immune system. Nat Rev Immunol 17(4):219–232

    Article  CAS  PubMed  Google Scholar 

  101. Russo R, Cristiano C, Avagliano C, De Caro C, La Rana G, Mattace Raso G et al (2017) Gut-brain axis: role of lipids in the regulation of inflammation, pain and CNS diseases. Curr Med Chem 24:1–22

    Google Scholar 

  102. Stilling RM, van de Vouw M, Clarke G, Stanton C, Dinan TG, Cryan JF (2016) The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis? Neurochem Int 99:110–132

    Article  CAS  PubMed  Google Scholar 

  103. Romo-Araiza A, Gutiérrez-Salmeán G, Galván EJ, Hernández-Frausto M, Herrera-López G, Romo-Parra H et al (2018) Probiotics and prebiotics as a therapeutic strategy to improve memory in a model of middle-aged rats. Front Aging Neurosci 10:416. https://doi.org/10.3389/fnagi.2018.00416

    Article  PubMed  PubMed Central  Google Scholar 

  104. Liu J, Sun J, Wang F, Yu X, Ling Z, Li H et al (2015) Neuroprotective effects of Clostridium butyricum against vascular dementia in mice via metabolic butyrate. Biomed Res Int 2015:412946. https://doi.org/10.1155/2015/412946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Sun J, Wang F, Ling Z, Yu X, Chen W, Li H et al (2016) Clostridium butyricum attenuates cerebral ischemia/reperfusion injury in diabetic mice via modulation of gut microbiota. Brain Res 1642:180–188

    Article  CAS  PubMed  Google Scholar 

  106. Kobayashi Y, Sugahara H, Shimada K, Mitsuyama E, Kuhara T, Yasuoka A et al (2017) Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s diseases. Sci Rep 7:13510. https://doi.org/10.1038/s41598-017-13368-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Nguyen TTT, Fujimura Y, Mimura I, Fujii Y, Nguyen NL, Arakawa N et al (2018) Cultivable butyrate-producing bacteria of elderly Japanese diagnosed with Alzheimer’s disease. J Microbiol 56(10):760–771

    Article  CAS  PubMed  Google Scholar 

  108. Staley C, Weingarden AR, Khoruts A, Sadowsky MJ (2017) Interaction of gut microbiota with bile acid metabolism and its influence on diseases states. Appl Microbiol Biotechnol 101(7):47–64

    Article  CAS  PubMed  Google Scholar 

  109. Keene CD, Rodrigues CM, Eich T, Chhabra MS, Steer CJ, Low WC (2002) Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington’s disease. Proc Natl Acad Sci U S A 99(16):10671–10676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Nunes AF, Amaral JD, Lo AC, Fonseca MB, Viana RJ, Callaerts-Vegh Z et al (2012) TUDCA, a bile acid, attenuates amyloid precursor protein processing and amyloid-β deposition in APP/PS1 mice. Mol Neurobiol 45(3):440–454

    Article  CAS  PubMed  Google Scholar 

  111. Dionisio PA, Amaral JD, Ribeiro MF, Lo AC, D’Hooge R, Rodrigues CM (2015) Amyloid-β pathology is attenuated by tauroursodeoxycholic acid treatment in APP/PS1 mice after disease onset. Neurobiol Aging 36(1):228–240

    Article  CAS  PubMed  Google Scholar 

  112. Olzarán J, Gil-de-Gómez L, Rodríguez-Martín A, Valentí-Soler M, Frades-Payo B, Marín-Muñoz J et al (2015) A blood-based, 7-metabolite signature for early diagnosis of Alzheimer’s disease. J Alzheimers Dis 45(4):1157–1173

    Article  CAS  Google Scholar 

  113. Nho K, Kueider-Paisley A, MahmoudianDehkordi S, Arnold M, Risacher SL, Louie G et al (2019) Altered bile acid profile in mild cognitive impairment and Alzheimer’s disease: relationship to neuroimaging and CSF biomarkers. Alzheimers Dement 15:232–244

    Article  PubMed  Google Scholar 

  114. Li D, Ke Y, Zhan R, Liu C, Zhao M, Zeng A et al (2018) Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice. Aging Cell 10:e12768. https://doi.org/10.1111/acel.12768. [Epub ahead of print]

    Article  CAS  Google Scholar 

  115. Vogt NM, Romano KA, Darst BF, Engelman CD, Johnson SC, Carlsson CM et al (2018) The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease. Alzheimers Res Ther 10:124. https://doi.org/10.1186/s13195-018-0451-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Potì F, Santi D, Spaggiari G, Zimetti F, Zanotti I (2019) Polyphenol health effects on cardiovascular and neurodegenerative disorders: a review and meta-analysis. Int J Mol Sci 20:351. https://doi.org/10.3390/ijms20020351

    Article  CAS  PubMed Central  Google Scholar 

  117. Wang D, Ho L, Faith J, Ono K, Janle EM, Lachcik PJ et al (2015) Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer’s disease β-amyloid oligomerization. Mol Nutr Food Res 59:1025–1040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Frolinger T, Sims S, Smith C, Wang J, Cheng H, Faith J et al (2019) The gut microbiota composition affects dietary polyphenols-mediated cognitive resilience in mice by modulating the bioavailability of phenolic acids. Sci Rep 9:3546. https://doi.org/10.1038/s41598-019-39994-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Selma MV, González-Sarrías A, Salais-Salvadó J, Andrés-Lacueva C, Alasalvar C, Örem A et al (2018) The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: comparison between normoweight, overweight-obesity and metabolic syndrome. Clin Nutr 37(3):897–905

    Article  CAS  PubMed  Google Scholar 

  120. González-Sarrías A, García-Villalba R, Romo-Vaquero M, Alasalvar C, Örem A, Zafrilla P et al (2017) Clustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate: a randomized clinical trial. Mol Nutr Food Res 61(5):1600830. https://doi.org/10.1002/mnfr.201600830

    Article  CAS  Google Scholar 

  121. Gong Z, Huang J, Xu B, Ou Z, Zhang L, Lin X et al (2019) Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice. J Neuroinflammation 16(1):62. https://doi.org/10.1186/s12974-019-1450-3

    Article  PubMed  PubMed Central  Google Scholar 

  122. Fang EF, Hou Y, Palikaras K, Adriaanse BA, Kerr JS, Yang B et al (2019) Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nat Neurosci 22(3):401–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Bookheimer SY, Renner BA, Ekstrom A, Li Z, Henning SM, Brown JA et al (2013) Pomegranate juice augments memory and FMRI activity in middle-aged and older adults with mild memory complaints. Evid Based Complement Alternat Med 2013:946298. https://doi.org/10.1155/2013/946298

    Article  PubMed  PubMed Central  Google Scholar 

  124. Alisi L, Cao R, De Angelis C, Cafolla A, Caramia F, Cartocci G et al (2019) The relationship between vitamin K and cognition: a review of current evidence. Front Neurosci 10:239. https://doi.org/10.3389/fneur.2019.00239

    Article  Google Scholar 

  125. Mongkhon P, Naser AY, Fanning L, Tse G, Lau WCY, Wong ICK et al (2019) Oral anticoagulants and risk of dementia: a systematic review and meta-analysis of observational studies and randomized controlled trials. Neurosci Biobehav Rev 96:1–9

    Article  CAS  PubMed  Google Scholar 

  126. Tamadon-Nejad S, Ouliass B, Rochford J, Ferland G (2018) Vitamin K deficiency induced by warfarin is associated with cognitive and behavioral perturbations, and alterations in brain sphingolipids in rats. Front Aging Neurosci 10:213. https://doi.org/10.3389/fnagi.2018.00213

    Article  PubMed  PubMed Central  Google Scholar 

  127. Brangier A, Ferland G, Rolland Y, Gautier J, Féart C, Annweiler C (2018) Vitamin K antagonists and cognitive decline in older adults: a 24-month follow-up. Nutrients 10:666. https://doi.org/10.3390/nu10060666

    Article  CAS  PubMed Central  Google Scholar 

  128. LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, Ventura M (2013) Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol 24(2):160–168

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

All authors have no conflict of interest to declare. No funding is reported for this manuscript.

Author information

Authors and Affiliations

  1. Geriatric Rehabilitation Department, University-Hospital of Parma, Parma, Italy

    Andrea Ticinesi, Antonio Nouvenne, Claudio Tana, Beatrice Prati & Tiziana Meschi

  2. Microbiome Research Hub, University of Parma, Parma, Italy

    Andrea Ticinesi, Antonio Nouvenne & Tiziana Meschi

  3. Department of Medicine and Surgery, University of Parma, Parma, Italy

    Tiziana Meschi

Authors
  1. Andrea Ticinesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Nouvenne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claudio Tana
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beatrice Prati
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tiziana Meschi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Ticinesi .

Editor information

Editors and Affiliations

  1. Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil

    Paul C. Guest

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ticinesi, A., Nouvenne, A., Tana, C., Prati, B., Meschi, T. (2019). Gut Microbiota and Microbiota-Related Metabolites as Possible Biomarkers of Cognitive Aging. In: Guest, P. (eds) Reviews on Biomarker Studies in Aging and Anti-Aging Research. Advances in Experimental Medicine and Biology(), vol 1178. Springer, Cham. https://doi.org/10.1007/978-3-030-25650-0_8

Download citation

Publish with us

Policies and ethics

Search

Navigation