Current Behavioral Neuroscience Reports

, Volume 5, Issue 1, pp 1–12 | Cite as

Inter-relationship of the Intestinal Microbiome, Diet, and Mental Health

Brain and Microbiome (R Heijtz, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Brain and Microbiome


Purpose of the Review

An unbalanced microbiota (dysbiosis) has been associated with or causative for a large array of human pathologies, including cognitive/emotional-related disorders. This review focuses on recent findings that address the restoration of a dysbiotic microbiota by dietary interventions with the main purpose of influencing brain function.

Recent Findings

Recent research strongly suggests a critical connection between dietary habits, cognitive performance, and microbiota, but a thorough study of this inter-relationship presents a significant challenge. Although gut microbiota composition may be altered by environmental variables, it is fairly stable during adulthood and old age, and the analysis of gut microbial composition is not enough to fully understand the impact of a nutritional intervention in the gut microbiota and its consequences on the brain. Novel findings suggest the need for including the analysis of the metabolome and specific biomarkers of the microbial metabolism for the understanding of the effect of nutritional interventions on brain function.


This review explores evidences pointing towards diet having a pivotal impact on the host’s development and progression of mental disorders through the regulation of microbiota composition and functionality. It is also discussed the role of key microbial metabolites as essential biomarkers to a better understanding of the complexity of the inter-relationship between microbiota, diet, and mental health.


Gut microbiota Mental health Dietary intervention Biomarker Metabolome 



This work was supported by a grant from Instituto de Salud Carlos III FEDER, (PI17/00223).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. 1.
    Sekirov I, Russell SL, Antunes LCM, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90:859–904.PubMedCrossRefGoogle Scholar
  2. 2.
    Nuriel-Ohayon M, Neuman H, Koren O. Microbial changes during pregnancy, birth, and infancy. Front Microbiol. 2016;7:1–13.CrossRefGoogle Scholar
  3. 3.
    Heijtz RD. Fetal, neonatal, and infant microbiome: perturbations and subsequent effects on brain development and behavior. Semin Fetal Neonatal Med. 2016;21:410–7.CrossRefGoogle Scholar
  4. 4.
    Zhernakova A, Kurilshikov A, Jan Bonder M, Tigchelaar EF, Schirmer M, Vatanen T, et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science. 2017;352:565–9.CrossRefGoogle Scholar
  5. 5.
    Falony G, Joossens M, Vieira-silva S, Wang J, Darzi Y, Faust K, et al. Population-level analysis of gut microbiome variation. Science. 2016;352:560–4.PubMedCrossRefGoogle Scholar
  6. 6.
    Kundu P, Blacher E, Elinav E, Pettersson S. Our gut microbiome: the evolving inner self. Cell. 2017;171:1481–93.PubMedCrossRefGoogle Scholar
  7. 7.
    Claesson MJ, Cusack S, O’Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci. 2011;108:4586–91.PubMedCrossRefGoogle Scholar
  8. 8.
    Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488:178–84.PubMedCrossRefGoogle Scholar
  9. 9.
    Kumar M, Babaei P, Ji B, Nielsen J. Human gut microbiota and healthy aging: recent developments and future prospective. Nutr Healthy Aging. 2016;4:3–16.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Saraswati S, Sitaraman R. Aging and the human gut microbiota-from correlation to causality. Front Microbiol. 2015;5:1–4.CrossRefGoogle Scholar
  11. 11.
    Santoro A, Ostan R, Candela M, Biagi E, Brigidi P, Capri M, et al. Gut microbiota changes in the extreme decades of human life: a focus on centenarians. Cell Mol Life Sci. 2018;75:129–48.PubMedCrossRefGoogle Scholar
  12. 12.
    Proctor C, Thiennimitr P, Chattipakorn N. Diet, gut microbiota and cognition. Metab Brain Dis. 2017;32:1–17.PubMedCrossRefGoogle Scholar
  13. 13.
    Vuong HE, Hsiao EY. Emerging roles for the gut microbiome in autism spectrum disorder. Biol Psychiatry. 2017;81:411–23.PubMedCrossRefGoogle Scholar
  14. 14.
    Hu X, Wang T, Jin F. Alzheimer’s disease and gut microbiota. Sci China Life Sci. 2016;59:1006–23.PubMedCrossRefGoogle Scholar
  15. 15.
    Parashar A, Udayabanu M. Parkinsonism and related disorders gut microbiota: implications in Parkinson’s disease. Park. Relat. Disord. 2017:1–7.Google Scholar
  16. 16.
    Lima-ojeda JM, Rupprecht R, Baghai TC. “ I am I and my bacterial circumstances”: linking gut and depression. Front Psychiatry. 2017;8:1–13.CrossRefGoogle Scholar
  17. 17.
    Carabotti M, Scirocco A, Antonietta M, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015;28:203–9.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Foster JA, Rinaman L, Cryan JF. Neurobiology of stress stress & the gut-brain axis: regulation by the microbiome. Neurobiol Stress. 2017:1–13.Google Scholar
  19. 19.
    Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG, et al. Minireview: gut microbiota: the neglected. Mol Endocrinol. 2014;28:1221–38.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Desbonnet L, Clarke G, Traplin A, O’Sullivan O, Crispie F, Moloney RD, et al. Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour. Brain Behav Immun. 2015;48:165–73.PubMedCrossRefGoogle Scholar
  21. 21.
    Fasano A, Visanji NP, Liu LWC, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol. 2015;14:625–39.PubMedCrossRefGoogle Scholar
  22. 22.
    McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014;133:872–83.PubMedCrossRefGoogle Scholar
  23. 23.
    Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu X-N, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004;558:263–75.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155:1451–63.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Bruce-Keller AJ, Salbaum JM, Berthoud HR. Harnessing gut microbes for mental health: getting from here to there. Biol Psychiatry. 2017:1–10.Google Scholar
  26. 26.
    Arentsen T, Qian Y, Gkotzis S, Femenia T, Wang T, Udekwu K, et al. The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior. Mol Psychiatry. 2017;22:257–66.PubMedCrossRefGoogle Scholar
  27. 27.
    Arentsen T, Khalid R, Qian Y, Diaz HR. Sex-dependent alterations in motor and anxiety-like behavior of aged bacterial peptidoglycan sensing molecule 2 knockout mice. Brain Behav Immun. 2018;67:345–54.PubMedCrossRefGoogle Scholar
  28. 28.
    Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, et al. The Alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One. 2010;5:e9505.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Kumar DK, Choi SH, Washicosky KJ, Eimer WA, Tucker S, Ghofrani J, et al. Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci. Transl. Med. 2016;8:340ra72.PubMedCrossRefGoogle Scholar
  30. 30.
    Sarkar A, Lehto SM, Harty S, Dinan TG, Cryan JF, Burnet PWJ. Psychobiotics and the manipulation of bacteria–gut–brain signals. Trends Neurosci. 2016;39:763–81.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Valls-Pedret C, Sala-Vila A, Serra-Mir M, Corella D, de la Torre R, Ángel Martínez-González M, et al. Mediterranean diet and age-related cognitive decline a randomized clinical trial. JAMA Intern Med. 2015;175:1094–103.PubMedCrossRefGoogle Scholar
  32. 32.
    Otaegui-Arrazola A, Amiano P, Elbusto A, Urdaneta E, Martínez-Lage P. Diet, cognition, and Alzheimer’s disease: food for thought. Eur J Nutr. 2014;53:1–23.PubMedCrossRefGoogle Scholar
  33. 33.
    Tussing-humphreys L, Lamar M, Blumenthal JA, Babyak M, Fantuzzi G, Blumstein L, et al. Building research in diet and cognition: the BRIDGE randomized controlled trial. Contemp Clin Trials. 2017;59:87–97.PubMedCrossRefGoogle Scholar
  34. 34.
    Backhed F. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Walker AW, Ince J, Duncan SH, Webster LM, Holtrop G, Ze X, et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 2011;5:220–30.PubMedCrossRefGoogle Scholar
  36. 36.
    Arumugam M, Raes J, Pelletier E, Le Paslier D, Batto J, Bertalan M, et al. Enterotypes of the human gut microbiome. Nature. 2013;473:174–80.CrossRefGoogle Scholar
  37. 37.
    Wu GD, Chen J, Hoffmann C, Bittinger K, Chen Y, Sue AK, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2012;334:105–8.CrossRefGoogle Scholar
  38. 38.
    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–63.PubMedCrossRefGoogle Scholar
  39. 39.
    Roager HM, Licht TR, Poulsen SK, Larsen TM, Bahl MI. Microbial enterotypes, inferred by the Prevotella-to-Bacteroides ratio, remained stable during a 6-month randomized controlled diet intervention with the new Nordic diet. Appl Environ Microbiol. 2014;80:1142–9.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Jeffery IB, Claesson MJ, O’Toole PW, Shanahan F. Categorization of the gut microbiota: enterotypes or gradients? Nat Rev Microbiol. 2012;10:591–2.PubMedCrossRefGoogle Scholar
  41. 41.
    Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2017;49:60–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Unger MM, Spiegel J, Dillmann K-U, Grundmann D, Philippeit H, Bürmann J, et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord. 2016;32:66–72.PubMedCrossRefGoogle Scholar
  43. 43.
    Wu GD, Compher C, Chen EZ, Smith SA, Shah RD, Bittinger K, et al. Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut. 2016;65:63–72.PubMedCrossRefGoogle Scholar
  44. 44.
    Ou J, Carbonero F, Zoetendal EG, DeLany JP, Wang M, Newton K, et al. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr. 2013;98:111–20.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci. 2010;107:14691–6.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Martínez I, Stegen JC, Maldonado-Gómez MX, Eren AM, Siba PM, Greenhill AR, et al. The gut microbiota of rural Papua new Guineans: composition, diversity patterns, and ecological processes. Cell Rep. 2015;11:527–38.PubMedCrossRefGoogle Scholar
  47. 47.
    Francis H, Stevenson R. The longer-term impacts of Western diet on human cognition and the brain. Appetite. 2013;63:119–28.PubMedCrossRefGoogle Scholar
  48. 48.
    Taylor MK, Sullivan DK, Swerdlow RH, Vidoni ED, Morris JK, Mahnken JD, et al. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults. Am J Clin Nutr. 2017;106:1463–70.PubMedCrossRefGoogle Scholar
  49. 49.
    Bruce-Keller AJ, Fernandez-Kim SO, Townsend RL, Kruger C, Carmouche R, Newman S, et al. Maternal obese-type gut microbiota differentially impact cognition, anxiety and compulsive behavior in male and female offspring in mice. PLoS One. 2017;12:1–20.CrossRefGoogle Scholar
  50. 50.
    Val-Laillet D, Besson M, Guérin S, Coquery N, Randuineau G, Kanzari A, et al. A maternal Western diet during gestation and lactation modifies offspring’s microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs. FASEB J. 2017;31:2037–49.PubMedCrossRefGoogle Scholar
  51. 51.
    Baym CL, Khan NA, Monti JM, Raine LB, Drollette ES, Moore RD, et al. Dietary lipids are differentially associated with hippocampal-dependent relational memory in prepubescent children. Am J Clin Nutr. 2014;99:1026–33.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Khan NA, Raine LB, Drollette ES, Scudder MR, Kramer AF, Hillman CH. Dietary fiber is positively associated with cognitive control among prepubertal children. J Nutr. 2015;145:143–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Bruce-Keller AJ, Keller JN, Morrison CD. Obesity and vulnerability of the CNS. Biochim Biophys Acta. 1792;2009:395–400.Google Scholar
  54. 54.
    Ronan L, Alexander-Bloch AF, Wagstyl K, Farooqi S, Brayne C, Tyler LK, et al. Obesity associated with increased brain age from midlife. Neurobiol Aging. 2016;47:63–70.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Prickett C, Brennan L, Stolwyk R. Examining the relationship between obesity and cognitive function: a systematic literature review. Obes Res Clin Pract. 2015;9:93–113.PubMedCrossRefGoogle Scholar
  56. 56.
    Bruce-Keller AJ, Salbaum JM, Luo M, Blanchard E, Taylor CM, Welsh DA, et al. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry. 2015;77:607–15.PubMedCrossRefGoogle Scholar
  57. 57.
    Tong TYN, Wareham NJ, Khaw K, Imamura F, Forouhi NG. Prospective association of the Mediterranean diet with cardiovascular disease incidence and mortality and its population impact in a non-Mediterranean population: the EPIC-Norfolk study. BMC Med. 2016;14:1–11.CrossRefGoogle Scholar
  58. 58.
    Gotsis E, Anagnostis P. Health benefits of the Mediterranean diet: an update of research over the last 5 years. Angiology. 2015;66:304–18.PubMedCrossRefGoogle Scholar
  59. 59.
    Huhn S, Masouleh SK, Stumvoll M, Villringer A. Components of a Mediterranean diet and their impact on cognitive functions in aging. Front Aging Neurosci. 2015;7:1–10.CrossRefGoogle Scholar
  60. 60.
    Frisardi V, Panza F, Seripa D, Imbimbo BP, Vendemiale G, Pilotto A, et al. Nutraceutical properties of mediterranean diet and cognitive decline: possible underlying mechanisms. J Alzheimers Dis. 2010;22:715–40.PubMedCrossRefGoogle Scholar
  61. 61.
    Wang X, Wang W, Li L, George P, Hyoung-gon L, Xiongwei Z. Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochem Biophys Acta. 1842;2015:1240–7.Google Scholar
  62. 62.
    Covas M-I, de la Torre R, Fito M. Virgin olive oil: a key food for cardiovascular risk protection. Br. J. Nutr. 2015;113(Suppl):S19–28.PubMedCrossRefGoogle Scholar
  63. 63.
    Zamora-Ros R, Serafini M, Estruch R, Lamuela-Raventós RM, Martínez-González MA, Salas-Salvadó J, et al. Mediterranean diet and non enzymatic antioxidant capacity in the PREDIMED study: evidence for a mechanism of antioxidant tuning. Nutr Metab Cardiovasc Dis. 2013;23:1167–74.PubMedCrossRefGoogle Scholar
  64. 64.
    Tomasello G, Mazzola M, Leone A, Sinagra E, Zummo G, Farina F, et al. Nutrition, oxidative stress and intestinal dysbiosis: influence of diet on gut microbiota in inflammatory bowel diseases. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016;160:461–6.PubMedGoogle Scholar
  65. 65.
    Mosele JI, Martín-Peláez S, Macià A, Farràs M, Valls RM, Catalán Ú, et al. Faecal microbial metabolism of olive oil phenolic compounds: in vitro and in vivo approaches. Mol Nutr Food Res. 2014;58:1809–19.PubMedCrossRefGoogle Scholar
  66. 66.
    Moreno-Indias I, Sánchez-Alcoholado L, Pérez-Martínez P, Andrés-Lacueva C, Cardona F, Tinahones F, et al. Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients. Food Funct. 2016;7:1775–87.PubMedCrossRefGoogle Scholar
  67. 67.
    Cueva C, Gil-Sánchez I, Ayuda-Durán B, González-Manzano S, González-Paramás AM, Santos-Buelga C, et al. An integrated view of the effects of wine polyphenols and their relevant metabolites on gut and host health. Molecules. 2017;22:1–15.CrossRefGoogle Scholar
  68. 68.
    Barroso E, Muñoz-González I, Jiménez E, Bartolomé B, Moreno-Arribas MV, Peláez C, et al. Phylogenetic profile of gut microbiota in healthy adults after moderate intake of red wine. Mol Nutr Food Res. 2016;0:1–9.Google Scholar
  69. 69.
    Dueñas M, Cueva C, Muñoz-González I, Jiménez-Girón A, Sánchez-Patán F, Santos-Buelga C, et al. Studies on modulation of gut microbiota by wine polyphenols: from isolated cultures to Omic approaches. Antioxidants. 2015;4:1–21.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Queipo-Ortuño MI. Influence of red wine polyphenols on the gut microbiota ecology. Am J Clin Nutr. 2012;95:1323–34.PubMedCrossRefGoogle Scholar
  71. 71.
    Gutiérrez-Díaz I, Fernández-Navarro T, Sánchez B, Margolles A, González S. Mediterranean diet and faecal microbiota: a transversal study. Food Funct. 2016;7:2347–56.PubMedCrossRefGoogle Scholar
  72. 72.
    Martín-Peláez S, Castañer O, Solà R, Motilva MJ, Castell M, Pérez-Cano FJ, et al. Influence of phenol-enriched olive oils on human intestinal immune function. Nutrients. 2016;8:1–14.CrossRefGoogle Scholar
  73. 73.
    Graf D, Di Cagno R, Fåk F, Flint HJ, Nyman M, Saarela M, et al. Contribution of diet to the composition of the human gut microbiota. Microb Ecol Health Dis. 2015;26:26164.PubMedGoogle Scholar
  74. 74.
    De Filippis F, Pellegrini N, Vannini L, Jeffery IB, La Storia A, Laghi L, et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. 2016;65:1812–21.PubMedCrossRefGoogle Scholar
  75. 75.
    Mitsou EK, Kakali A, Antonopoulou S, Mountzouris KC, Yannakoulia M, Panagiotakos DB, et al. Adherence to the Mediterranean diet is associated with the gut microbiota pattern and gastrointestinal characteristics in an adult population. Br J Nutr. 2017;117:1645–55.PubMedCrossRefGoogle Scholar
  76. 76.
    Shakersain B, Santoni G, Larsson SC, Faxén-Irving G, Fastbom J, Fratiglioni L, et al. Prudent diet may attenuate the adverse effects of Western diet on cognitive decline. Alzheimers Dement. 2016;12:100–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, Aggarwal NT. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement. 2015;11:1007–14.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20:145–55.PubMedCrossRefGoogle Scholar
  79. 79.
    Masi A, Quintana DS, Glozier N, Lloyd AR, Hickie IB, Guastella AJ. Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry. 2015;20:440–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Rubio-Perez JM, Morillas-Ruiz JM. A review: inflammatory process in Alzheimer’s disease. Role Cytokines Sci World J. 2012:1–15.Google Scholar
  81. 81.
    Prather AA, Vogelzangs N, Penninx BWJH. Sleep duration, insomnia, and markers of systemic inflammation: results from the Netherlands Study of Depression and Anxiety (NESDA). J Psychiatr Res. 2015;60:95–102.PubMedCrossRefGoogle Scholar
  82. 82.
    Lichtwark IT, Newnham ED, Robinson SR, Shepherd SJ, Hosking P, Gibson PR, et al. Cognitive impairment in coeliac disease improves on a gluten-free diet and correlates with histological and serological indices of disease severity. Aliment Pharmacol Ther. 2014;40:160–70.PubMedCrossRefGoogle Scholar
  83. 83.
    Caminero A, Nistal E, Herrán AR, Pérez-Andrés J, Ferrero MA, Vaquero Ayala L, et al. Differences in gluten metabolism among healthy volunteers, coeliac disease patients and first-degree relatives. Br J Nutr. 2015;114:1157–67.PubMedCrossRefGoogle Scholar
  84. 84.
    Bergman EN. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol Rev. 1990;70:567–90.PubMedCrossRefGoogle Scholar
  85. 85.
    MacFabe DF. Enteric short-chain fatty acids: microbial messengers of metabolism, mitochondria, and mind: implications in autism spectrum disorders. Microb Ecol Heal Dis. 2015;26:1–14.Google Scholar
  86. 86.
    Bourassa MW, Alim I, Bultman SJ, Ratan RR. Butyrate, neuroepigenetics and the gut microbiome: can a high fiber diet improve brain health? Neurosci Lett. 2016;625:56–63.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Soret R, Chevalier J, De Coppet P, Poupeau G, Derkinderen P, Segain JP, et al. Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats. Gastroenterology. 2010;138:1772–82.PubMedCrossRefGoogle Scholar
  88. 88.
    Borghi E, Borgo F, Severgnini M, Savini MN, Casiraghi MC, Vignoli A. Rett syndrome: a focus on gut microbiota. Int J Mol Sci. 2017;18:344–61.PubMedCentralCrossRefGoogle Scholar
  89. 89.
    Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J, et al. Altered gut microbiota in Rett syndrome. Microbiome. 2016;4:41–56.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud D-J, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54:2325–40.CrossRefGoogle Scholar
  91. 91.
    Wolever TMS, Josse RG, Leiter LA, Chiasson JL. Time of day and glucose tolerance status affect serum short-chain fatty acid concentrations in humans. Metabolism. 1997;46:805–11.PubMedCrossRefGoogle Scholar
  92. 92.
    Cho CE, Caudill MA. Trimethylamine-N-oxide: friend, foe, or simply caught in the cross-fire? Trends Endocrinol Metab. 2017;28:121–30.PubMedCrossRefGoogle Scholar
  93. 93.
    Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. Nat. Med. 2013;19:576–85.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Cho CE, Taesuwan S, Malysheva OV, Bender E, Tulchinsky NF, Yan J, et al. Trimethylamine N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: a randomized controlled trial. Mol Nutr Food Res. 2017;61Google Scholar
  95. 95.
    Tang WW, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575–84.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Tang WH, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116:448–55.PubMedCrossRefGoogle Scholar
  97. 97.
    Dambrova M, Latkovskis G, Kuka J, Strele I, Konrade I, Grinberga S, et al. Diabetes is associated with higher trimethylamine N-oxide plasma levels. Exp Clin Endocrinol Diabetes. 2016;124:251–6.PubMedCrossRefGoogle Scholar
  98. 98.
    Xu R, Wang Q, Li L. A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. BMC Genomics. 2015;16(Suppl 7):S4.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Xu R, Wang Q. Towards understanding brain-gut-microbiome connections in Alzheimer’s disease. BMC Syst Biol. 2016;10:63.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Grant WB. Trends in diet and Alzheimer’s disease during the nutrition transition in Japan and developing countries. J Alzheimers Dis. 2014;38:611–20.PubMedGoogle Scholar
  101. 101.
    Del Rio D, Zimetti F, Caffarra P, Tassotti M, Bernini F, Brighenti F, et al. The gut microbial metabolite trimethylamine-N-oxide is present in human cerebrospinal fluid. Nutrients. 2017;9:1053.PubMedCentralCrossRefGoogle Scholar
  102. 102.
    O’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.PubMedCrossRefGoogle Scholar
  103. 103.
    Maddison DC, Giorgini F. The kynurenine pathway and neurodegenerative disease. Semin Cell Dev Biol. 2015;40:134–41.PubMedCrossRefGoogle Scholar
  104. 104.
    Schwarcz R, Stone TW. The kynurenine pathway and the brain: challenges, controversies and promises. Neuropharmacology. 2017;112:237–47.PubMedCrossRefGoogle Scholar
  105. 105.
    Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology. 2017;112:399–412.PubMedCrossRefGoogle Scholar
  106. 106.
    Yu E, Ruiz-Canela M, Guasch-Ferré M, Zheng Y, Toledo E, Clish CB, et al. Increases in plasma tryptophan are inversely associated with incident cardiovascular disease in the Prevención con Dieta Mediterránea (PREDIMED) study. J Nutr. 2017;147:314–22.PubMedPubMedCentralGoogle Scholar
  107. 107.
    Gérard P. Metabolism of cholesterol and bile acids by the gut microbiota. PathoGenetics. 2013;3:14–24.Google Scholar
  108. 108.
    Ackerman HD, Gerhard GS. Bile acids in neurodegenerative disorders. Front Aging Neurosci. 2016;8:263.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Olazarán J, Gil-De-Gómez L, Rodríguez-Martín A, Valentí-Soler M, Frades-Payo B, Marín-Muñoz J, et al. A blood-based, 7-metabolite signature for the early diagnosis of Alzheimer’s disease. J Alzheimers Dis. 2015;45:1157–73.PubMedGoogle Scholar
  110. 110.
    Huppert T, Schmidt B, Beluk N, Sparto P. In older adults. Park Relat Disord. 2010;16:S25.CrossRefGoogle Scholar
  111. 111.
    Pan X, Elliott CT, McGuinness B, Passmore P, Kehoe PG, Hölscher C, et al. Metabolomic profiling of bile acids in clinical and experimental samples of Alzheimer’s disease. Meta. 2017;7:1–12.Google Scholar
  112. 112.
    Lo AC, Callaerts-Vegh Z, Nunes AF, Rodrigues CMP, D’Hooge R. Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice. Neurobiol Dis. 2013;50:21–9.PubMedCrossRefGoogle Scholar
  113. 113.
    Wilson A, McLean C, Kim RB. Trimethylamine-N-oxide. Curr Opin Lipidol. 2016;27:148–54.PubMedCrossRefGoogle Scholar
  114. 114.
    Yarchoan M, Xie SX, Kling MA, Toledo JB, Wolk DA, Lee EB, et al. Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias. Brain. 2012;135:3749–56.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Yiannakopoulou EC. Targeting oxidative stress response by green tea polyphenols: clinical implications. Free Radic Res. 2013;47:667–71.PubMedCrossRefGoogle Scholar
  116. 116.
    Marín L, Miguélez EM, Villar CJ, Lombó F. Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties. Biomed Res Int. 2015;2015Google Scholar
  117. 117.
    Cardona F, Andrés-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuño MI. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem. 2013;24:1415–22.PubMedCrossRefGoogle Scholar
  118. 118.
    Vetrani C, Rivellese AA, Annuzzi G, Adiels M, Borén J, Mattila I, et al. Metabolic transformations of dietary polyphenols: comparison between in vitro colonic and hepatic models and in vivo urinary metabolites. J Nutr Biochem. 2016;33:111–8.PubMedCrossRefGoogle Scholar
  119. 119.
    Vetrani C, Rivellese AA, Annuzzi G, Mattila I, Meudec E, Hyötyläinen T, et al. Phenolic metabolites as compliance biomarker for polyphenol intake in a randomized controlled human intervention. Food Res Int. 2014;63:233–8.CrossRefGoogle Scholar
  120. 120.
    Muñoz-González I, Jiménez-Girón A, Martín-Álvarez PJ, Bartolomé B, Moreno-Arribas MV. Profiling of microbial-derived phenolic metabolites in human feces after moderate red wine intake. J Agric Food Chem. 2013;61:9470–9.PubMedCrossRefGoogle Scholar
  121. 121.
    Brown NM, Galandi SL, Summer SS, Zhao X, Heubi JE, King EC, et al. S-(−)equol production is developmentally regulated and related to early diet composition. Nutr Res. 2014;34:401–9.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Etxeberria U, Fernández-Quintela A, Milagro FI, Aguirre L, Martínez JA, Portillo MP. Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition. J Agric Food Chem. 2013;61:9517–33.PubMedCrossRefGoogle Scholar
  123. 123.
    Cheng P-F, Chen J-J, Zhou X-Y, Ren Y-F, Huang W, Zhou J-J, et al. Do soy isoflavones improve cognitive function in postmenopausal women? A meta-analysis. Menopause. 2015;Google Scholar
  124. 124.
    Gleason CE, Fischer BL, Dowling NM, Setchell KDR, Atwood CS, Carlsson CM, et al. Cognitive effects of soy isoflavones in patients with Alzheimer’s disease. J Alzheimers Dis. 2015;22:198–206.Google Scholar
  125. 125.
    Wilkins HM, Mahnken JD, Welch P, Bothwell R, Koppel S, Jackson RL, et al. A mitochondrial biomarker-based study of S-Equol in Alzheimer’s disease subjects: results of a single-arm. Pilot Trial J Alzheimers Dis. 2017;59:291–300.PubMedGoogle Scholar
  126. 126.
    Etxeberria U, Arias N, Boqué N, Romo-Hualde A, Macarulla MT, Portillo MP, et al. Metabolic faecal fingerprinting of trans-resveratrol and quercetin following a high-fat sucrose dietary model using liquid chromatography coupled to high-resolution mass spectrometry. Food Funct. 2015;6:2758–67.PubMedCrossRefGoogle Scholar
  127. 127.
    Schantz M, Erk T, Richling E. Metabolism of green tea catechins by the human small intestine. Biotechnol J. 2010;5:1050–9.PubMedCrossRefGoogle Scholar
  128. 128.
    Pasinetti GM, Wang J, Ho L, Zhao W, Dubner L. Roles of resveratrol and other grape-derived polyphenols in Alzheimer’s disease prevention and treatment. Biochim. Biophys. Acta. 2015;1852:1202–8.PubMedCrossRefGoogle Scholar
  129. 129.
    Bode LM, Bunzel D, Huch M, Cho G-S, Ruhland D, Bunzel M, et al. In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. Am J Clin Nutr. 2013;97:295–309.PubMedCrossRefGoogle Scholar
  130. 130.
    Chen ML, Yi L, Zhang Y, Zhou X, Ran L, Yang J, et al. Resveratrol attenuates trimethylamine-N-oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via remodeling of the gut microbiota. MBio. 2016;7:e02210–5.PubMedPubMedCentralGoogle Scholar
  131. 131.
    De la Torre R, De Sola S, Pons M, Duchon A, de Lagran MM, Farré M, et al. Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in down syndrome mouse models and in humans. Mol Nutr Food Res. 2014;58:278–88.PubMedCrossRefGoogle Scholar
  132. 132.
    Xu PX, Wang SW, Yu XL, Su YJ, Wang T, Zhou WW, et al. Rutin improves spatial memory in Alzheimer’s disease transgenic mice by reducing Aβ oligomer level and attenuating oxidative stress and neuroinflammation. Behav Brain Res. 2014;264:173–80.PubMedCrossRefGoogle Scholar
  133. 133.
    Sabogal-Guáqueta AM, Muñoz-Manco JI, Ramírez-Pineda JR, Lamprea-Rodriguez M, Osorio E, Cardona-Gómez GP. The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology. 2015;93:134–45.PubMedCrossRefGoogle Scholar
  134. 134.
    Subash S, Braidy N, Essa MM, Zayana A-B, Ragini V, Al-Adawi S, et al. Long-term (15 mo) dietary supplementation with pomegranates from Oman attenuates cognitive and behavioral deficits in a transgenic mice model of Alzheimer’s disease. Nutrition. 2015;31:223–9.PubMedCrossRefGoogle Scholar
  135. 135.
    Burton-Freeman BM, Sandhu AK, Edirisinghe I. Red raspberries and their bioactive polyphenols: cardiometabolic and neuronal health links. Adv Nutr. 2016;7:44–65.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Integrative Pharmacology and Systems Neurosciences Research Group, IMIMBarcelonaSpain
  2. 2.Autonomous University of BarcelonaBellaterraSpain
  3. 3.Department of Experimental and Health SciencesUniversitat Pompeu FabraBarcelonaSpain
  4. 4.Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN)Instituto Salud Carlos IIIMadridSpain

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