Cellular and Molecular Life Sciences

, Volume 74, Issue 20, pp 3769–3787 | Cite as

Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis

  • Susan Westfall
  • Nikita Lomis
  • Imen Kahouli
  • Si Yuan Dia
  • Surya Pratap Singh
  • Satya PrakashEmail author


The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastrointestinal tract communicates with the central nervous system through the gut–brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecular communication network that link systemic imbalances with the development of neurodegeneration including insulin regulation, fat metabolism, oxidative markers and immune signaling. Age is a common factor in the development of neurodegenerative disease and probiotics prevent many harmful effects of aging such as decreased neurotransmitter levels, chronic inflammation, oxidative stress and apoptosis—all factors that are proven aggravators of neurodegenerative disease. Indeed patients with Parkinson’s and Alzheimer’s diseases have a high rate of gastrointestinal comorbidities and it has be proposed by some the management of the gut microbiota may prevent or alleviate the symptoms of these chronic diseases.


Gut microbiota Probiotics Gut-brain-axis Neurodegeneration Oxidative stress Short-chain fatty acids 


Author contributions

This review was conceptualized and written by SW with supporting sections written and edited by NL and SYD. Advisement and manuscript suggestions were provided by SPS and SP.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest or competing financial interests.


  1. 1.
    Burokas A, Moloney RD, Dinan TG, Cryan JF (2015) Microbiota regulation of the mammalian gut–brain axis. Adv Appl Microbiol 91:1–62. doi: 10.1016/bs.aambs.2015.02.001 PubMedCrossRefGoogle Scholar
  2. 2.
    Forsythe P, Bienenstock J, Kunze WA (2014) Vagal pathways for microbiome–brain–gut axis communication. Microbial endocrinology: the microbiota–gut–brain axis in health and disease. Springer, New York, pp 115–133Google Scholar
  3. 3.
    Bauer KC, Huus KE, Finlay BB (2016) Microbes and the mind: emerging hallmarks of the gut microbiota–brain axis. Cell Microbiol 18:632–644. doi: 10.1111/cmi.12585 PubMedCrossRefGoogle Scholar
  4. 4.
    Noble EE, Hsu TM, Kanoski SE (2017) Gut to brain dysbiosis: mechanisms linking western diet consumption, the microbiome, and cognitive impairment. Front Behav Neurosci 11:9. doi: 10.3389/fnbeh.2017.00009 PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Mulak A, Bonaz B (2015) Brain–gut–microbiota axis in Parkinson’s disease. WJG 21:10609–10620. doi: 10.3748/wjg.v21.i37.10609 PubMedGoogle Scholar
  6. 6.
    Friedland RP (2015) Mechanisms of molecular mimicry involving the microbiota in neurodegeneration. J Alzheimers Dis 45:349–362. doi: 10.3233/JAD-142841 PubMedGoogle Scholar
  7. 7.
    Qin J, Li R, Raes J et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65. doi: 10.1038/nature08821 PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Rajilic-Stojanovic M, Smidt H, de Vos WM (2007) Diversity of the human gastrointestinal tract microbiota revisited. Environ Microbiol 9:2125–2136. doi: 10.1111/j.1462-2920.2007.01369.x PubMedCrossRefGoogle Scholar
  9. 9.
    The Human Microbiome Project Consortium (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207–214. doi: 10.1038/nature11234 PubMedCentralCrossRefGoogle Scholar
  10. 10.
    Mandal RS, Saha S, Das S (2015) Metagenomic surveys of gut microbiota. Genom Proteom Bioinform 13:148–158. doi: 10.1016/j.gpb.2015.02.005 CrossRefGoogle Scholar
  11. 11.
    Everard A, Cani PD (2014) Gut microbiota and GLP-1. Rev Endocr Metab Disord 15:189–196. doi: 10.1007/s11154-014-9288-6 PubMedCrossRefGoogle Scholar
  12. 12.
    Burns AJ (2005) Migration of neural crest-derived enteric nervous system precursor cells to and within the gastrointestinal tract. Int J Dev Biol 49:143–150. doi: 10.1387/ijdb.041935ab PubMedCrossRefGoogle Scholar
  13. 13.
    O’Mahony SM, Clarke G, Borre YE et al (2014) Serotonin, tryptophan metabolism and the brain–gut–microbiome axis. Behav Brain Res. doi: 10.1016/j.bbr.2014.07.027 PubMedGoogle Scholar
  14. 14.
    Ochoa-Reparaz J, Mielcarz DW, Begum-Haque S, Kasper LH (2011) Gut, bugs, and brain: role of commensal bacteria in the control of central nervous system disease. Ann Neurol 69:240–247. doi: 10.1002/ana.22344 PubMedCrossRefGoogle Scholar
  15. 15.
    Luczynski P, McVey Neufeld K-A, Oriach CS et al (2016) Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior. Int J Neuropsychopharmacol 19(8):234–248. doi: 10.1093/ijnp/pyw020 CrossRefGoogle Scholar
  16. 16.
    Houlden A, Goldrick M, Brough D et al (2016) Brain injury induces specific changes in the caecal microbiota of mice via altered autonomic activity and mucoprotein production. Brain Behav Immun 57:10–20. doi: 10.1016/j.bbi.2016.04.003 PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Catanzaro R, Anzalone MG, Calabrese F et al (2014) The gut microbiota and its correlations with the central nervous system disorders. Panminerva Med 57(3):127–143PubMedGoogle Scholar
  18. 18.
    Dinan TG, Cryan JF (2017) Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. J Physiol 595:489–503. doi: 10.1113/JP273106 PubMedCrossRefGoogle Scholar
  19. 19.
    Kohler CA, Maes M, Slyepchenko A et al (2016) The gut–brain axis, including the microbiome, leaky gut and bacterial translocation: mechanisms and pathophysiological role in Alzheimer’s disease. Curr Pharm Des 22:6152–6166PubMedCrossRefGoogle Scholar
  20. 20.
    Jyothi HJ, Vidyadhara DJ, Mahadevan A et al (2015) Aging causes morphological alterations in astrocytes and microglia in human substantia nigra pars compacta. Neurobiol Aging 36:3321–3333. doi: 10.1016/j.neurobiolaging.2015.08.024 PubMedCrossRefGoogle Scholar
  21. 21.
    Erny D, Hrabe de Angelis AL, Jaitin D et al (2015) Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 18:965–977. doi: 10.1038/nn.4030 PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Sampson TR, Debelius JW, Thron T et al (2016) Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167(1469–1480):e12. doi: 10.1016/j.cell.2016.11.018 Google Scholar
  23. 23.
    Alam MZ, Alam Q, Kamal MA et al (2014) A possible link of gut microbiota alteration in type 2 diabetes and Alzheimer’s disease pathogenicity: an update. CNS Neurol Disord Drug Targets 13:383–390PubMedCrossRefGoogle Scholar
  24. 24.
    Naseer MI, Bibi F, Alqahtani MH et al (2014) Role of gut microbiota in obesity, type 2 diabetes and Alzheimer’s disease. CNS Neurol Disord Drug Targets 13:305–311PubMedCrossRefGoogle Scholar
  25. 25.
    Bekkering P, Jafri I, van Overveld FJ, Rijkers GT (2013) The intricate association between gut microbiota and development of type 1, type 2 and type 3 diabetes. Expert Rev Clin Immunol 9:1031–1041. doi: 10.1586/1744666X.2013.848793 PubMedCrossRefGoogle Scholar
  26. 26.
    Rao M, Gershon MD (2016) The bowel and beyond: the enteric nervous system in neurological disorders. Nat Rev Gastroenterol Hepatol 13:517–528. doi: 10.1038/nrgastro.2016.107 PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Baltazar MT, Dinis-Oliveira RJ, de Lourdes Bastos M et al (2014) Pesticides exposure as etiological factors of Parkinson’s disease and other neurodegenerative diseases—a mechanistic approach. Toxicol Lett 230:85–103. doi: 10.1016/j.toxlet.2014.01.039 PubMedCrossRefGoogle Scholar
  28. 28.
    Virmani A, Pinto L, Binienda Z, Ali S (2013) Food, nutrigenomics, and neurodegeneration–neuroprotection by what you eat! Mol Neurobiol 48:353–362. doi: 10.1007/s12035-013-8498-3 PubMedCrossRefGoogle Scholar
  29. 29.
    Ley RE, Hamady M, Lozupone C et al (2008) Evolution of mammals and their gut microbes. Science 320:1647–1651. doi: 10.1126/science.1155725 PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Goldman JG, Postuma R (2014) Premotor and nonmotor features of Parkinson’s disease. Curr Opin Neurol 27:434–441. doi: 10.1097/WCO.0000000000000112 PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13. doi: 10.1042/BJ20081386 PubMedCrossRefGoogle Scholar
  32. 32.
    Mitsuma T, Odajima H, Momiyama Z et al (2008) Enhancement of gene expression by a peptide p(CHWPR) produced by Bifidobacterium lactis BB-12. Microbiol Immunol 52:144–155. doi: 10.1111/j.1348-0421.2008.00022.x PubMedCrossRefGoogle Scholar
  33. 33.
    Wang X, Michaelis EK (2010) Selective neuronal vulnerability to oxidative stress in the brain. Front Aging Neurosci 2:12. doi: 10.3389/fnagi.2010.00012 PubMedPubMedCentralGoogle Scholar
  34. 34.
    Zhu X, Raina AK, Lee H-G et al (2004) Oxidative stress signalling in Alzheimer’s disease. Brain Res 1000:32–39PubMedCrossRefGoogle Scholar
  35. 35.
    Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S4–S9. doi: 10.1093/gerona/glu057 PubMedCrossRefGoogle Scholar
  36. 36.
    Biagi E, Nylund L, Candela M et al (2010) Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One 5:e10667. doi: 10.1371/journal.pone.0010667 PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Steen E, Terry BM, Rivera EJ et al (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease—is this type 3 diabetes? J Alzheimers Dis 7:63–80PubMedCrossRefGoogle Scholar
  38. 38.
    Cheng J, Palva AM, de Vos WM, Satokari R (2013) Contribution of the intestinal microbiota to human health: from birth to 100 years of age. In: Dobrindt U, Hacker JH, Svanborg C (eds) Between pathogenicity and commensalism. Springer, Berlin, pp 323–346Google Scholar
  39. 39.
    Claesson MJ, Cusack S, O’Sullivan O et al (2011) Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci USA 108(Suppl 1):4586–4591. doi: 10.1073/pnas.1000097107 PubMedCrossRefGoogle Scholar
  40. 40.
    Cassani E, Barichella M, Cancello R et al (2015) Increased urinary indoxyl sulfate (indican): new insights into gut dysbiosis in Parkinson’s disease. Parkinsonism Relat Disord 21:389–393. doi: 10.1016/j.parkreldis.2015.02.004 PubMedCrossRefGoogle Scholar
  41. 41.
    Scheperjans F, Aho V, Pereira PAB et al (2014) Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 30(3):350–358. doi: 10.1002/mds.26069 PubMedCrossRefGoogle Scholar
  42. 42.
    Keshavarzian A, Green SJ, Engen PA et al (2015) Colonic bacterial composition in Parkinson’s disease. Mov Disord 30:1351–1360. doi: 10.1002/mds.26307 PubMedCrossRefGoogle Scholar
  43. 43.
    Shannon KM, Keshavarzian A, Dodiya HB et al (2012) Is alpha-synuclein in the colon a biomarker for premotor Parkinson’s disease? Evidence from 3 cases. Mov Disord 27:716–719. doi: 10.1002/mds.25020 PubMedCrossRefGoogle Scholar
  44. 44.
    Unger MM, Spiegel J, Dillmann K-U et al (2016) Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord 32:66–72. doi: 10.1016/j.parkreldis.2016.08.019 PubMedCrossRefGoogle Scholar
  45. 45.
    Kidd SK, Schneider JS (2010) Protection of dopaminergic cells from MPP+-mediated toxicity by histone deacetylase inhibition. Brain Res 1354:172–178. doi: 10.1016/j.brainres.2010.07.041 PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Wu X, Chen PS, Dallas S et al (2008) Histone deacetylase inhibitors up-regulate astrocyte GDNF and BDNF gene transcription and protect dopaminergic neurons. Int J Neuropsychopharmacol 11:1123–1134. doi: 10.1017/S1461145708009024 PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Guseo A (2012) The Parkinson puzzle. Orv Hetil 153:2060–2069. doi: 10.1556/OH.2012.29461 PubMedCrossRefGoogle Scholar
  48. 48.
    Smith PD, Smythies LE, Shen R et al (2011) Intestinal macrophages and response to microbial encroachment. Mucosal Immunol 4:31–42. doi: 10.1038/mi.2010.66 PubMedCrossRefGoogle Scholar
  49. 49.
    Faden AI, Loane DJ (2015) Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation? Neurotherapeutics 12:143–150. doi: 10.1007/s13311-014-0319-5 PubMedCrossRefGoogle Scholar
  50. 50.
    Vivekanantham S, Shah S, Dewji R et al (2015) Neuroinflammation in Parkinson’s disease: role in neurodegeneration and tissue repair. Int J Neurosci 125:717–725. doi: 10.3109/00207454.2014.982795 PubMedCrossRefGoogle Scholar
  51. 51.
    Clarke G, Stilling RM, Kennedy PJ et al (2014) Minireview: gut microbiota: the neglected endocrine organ. Mol Endocrinol 28:1221–1238. doi: 10.1210/me.2014-1108 PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Mancuso C, Santangelo R (2014) Ferulic acid: pharmacological and toxicological aspects. Food Chem Toxicol 65:185–195. doi: 10.1016/j.fct.2013.12.024 PubMedCrossRefGoogle Scholar
  53. 53.
    Trombino S, Cassano R, Ferrarelli T et al (2013) Trans-ferulic acid-based solid lipid nanoparticles and their antioxidant effect in rat brain microsomes. Colloids Surf B Biointerfaces 109:273–279. doi: 10.1016/j.colsurfb.2013.04.005 PubMedCrossRefGoogle Scholar
  54. 54.
    Hu C-T, Wu J-R, Cheng C-C et al (2011) Reactive oxygen species-mediated PKC and integrin signaling promotes tumor progression of human hepatoma HepG2. Clin Exp Metastasis 28:851–863. doi: 10.1007/s10585-011-9416-6 PubMedCrossRefGoogle Scholar
  55. 55.
    Yabe T, Hirahara H, Harada N et al (2010) Ferulic acid induces neural progenitor cell proliferation in vitro and in vivo. Neuroscience 165:515–524. doi: 10.1016/j.neuroscience.2009.10.023 PubMedCrossRefGoogle Scholar
  56. 56.
    Yu L, Zhang Y, Liao M et al (2011) Neurogenesis-enhancing effect of sodium ferulate and its role in repair following stress-induced neuronal damage. WJNS 1(2):9–18. doi: 10.4236/wjns.2011.12002 CrossRefGoogle Scholar
  57. 57.
    Tomaro-Duchesneau C, Saha S, Malhotra M et al (2012) Probiotic ferulic acid esterase active Lactobacillus fermentum NCIMB 5221 APA microcapsules for oral delivery: preparation and in vitro characterization. Pharmaceuticals (Basel) 5:236–248. doi: 10.3390/ph5020236 CrossRefGoogle Scholar
  58. 58.
    Szwajgier D, Dmowska K (2010) Novel ferulic acid esterases from Bifidobacterium sp. produced on selected synthetic and natural carbon sources. Acta Sci Pol Technol Aliment 9:305–318Google Scholar
  59. 59.
    Bhathena J, Martoni C, Kulamarva A et al (2009) Orally delivered microencapsulated live probiotic formulation lowers serum lipids in hypercholesterolemic hamsters. J Med Food 12:310–319. doi: 10.1089/jmf.2008.0166 PubMedCrossRefGoogle Scholar
  60. 60.
    Durairajan SSK, Yuan Q, Xie L et al (2008) Salvianolic acid B inhibits Abeta fibril formation and disaggregates preformed fibrils and protects against Abeta-induced cytotoxicty. Neurochem Int 52:741–750. doi: 10.1016/j.neuint.2007.09.006 PubMedCrossRefGoogle Scholar
  61. 61.
    Mori T, Koyama N, Guillot-Sestier M-V et al (2013) Ferulic acid is a nutraceutical β-secretase modulator that improves behavioral impairment and Alzheimer-like pathology in transgenic mice. PLoS One 8:e55774. doi: 10.1371/journal.pone.0055774 PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Yan J-J, Jung J-S, Kim T-K et al (2013) Protective effects of ferulic acid in amyloid precursor protein plus presenilin-1 transgenic mouse model of Alzheimer disease. Biol Pharm Bull 36:140–143PubMedCrossRefGoogle Scholar
  63. 63.
    Zhang L, Wang H, Wang T et al (2015) Ferulic acid ameliorates nerve injury induced by cerebral ischemia in rats. Exp Ther Med 9:972–976PubMedCrossRefGoogle Scholar
  64. 64.
    Srinivasan M, Sudheer AR, Menon VP (2007) Ferulic acid: therapeutic potential through its antioxidant property. J Clin Biochem Nutr 40:92–100. doi: 10.3164/jcbn.40.92 PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Cheng C-Y, Tang N-Y, Kao S-T, Hsieh C-L (2016) Ferulic acid administered at various time points protects against cerebral infarction by activating p38 MAPK/p90RSK/CREB/Bcl-2 anti-apoptotic signaling in the subacute phase of cerebral ischemia–reperfusion injury in rats. PLoS One 11:e0155748PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Sung J-H, Gim S-A, Koh P-O (2014) Ferulic acid attenuates the cerebral ischemic injury-induced decrease in peroxiredoxin-2 and thioredoxin expression. Neurosci Lett 566:88–92. doi: 10.1016/j.neulet.2014.02.040 PubMedCrossRefGoogle Scholar
  67. 67.
    Patenaude A, Murthy MRV, Mirault M-E (2005) Emerging roles of thioredoxin cycle enzymes in the central nervous system. Cell Mol Life Sci 62:1063–1080. doi: 10.1007/s00018-005-4541-5 PubMedCrossRefGoogle Scholar
  68. 68.
    Gan Y, Ji X, Hu X et al (2012) Transgenic overexpression of peroxiredoxin-2 attenuates ischemic neuronal injury via suppression of a redox-sensitive pro-death signaling pathway. Antioxid Redox Signal 17:719–732. doi: 10.1089/ars.2011.4298 PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Saitoh M, Nishitoh H, Fujii M et al (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 17:2596–2606. doi: 10.1093/emboj/17.9.2596 PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Ma YH, Su N, Chao XD et al (2012) Thioredoxin-1 attenuates post-ischemic neuronal apoptosis via reducing oxidative/nitrative stress. Neurochem Int 60:475–483. doi: 10.1016/j.neuint.2012.01.029 PubMedCrossRefGoogle Scholar
  71. 71.
    Gim S-A, Sung J-H, Shah F-A et al (2013) Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model. Lab Anim Res 29:63. doi: 10.5625/lar.2013.29.2.63 PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Gao C, Holscher C, Liu Y, Li L (2012) GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease. Rev Neurosci 23:1–11CrossRefGoogle Scholar
  73. 73.
    Yoshimura T, Kawano Y, Arimura N et al (2005) GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 120:137–149. doi: 10.1016/j.cell.2004.11.012 PubMedCrossRefGoogle Scholar
  74. 74.
    Gu Y, Hamajima N, Ihara Y (2000) Neurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522. Biochemistry 39:4267–4275PubMedCrossRefGoogle Scholar
  75. 75.
    Petratos S, Li Q-X, George AJ et al (2008) The beta-amyloid protein of Alzheimer’s disease increases neuronal CRMP-2 phosphorylation by a Rho-GTP mechanism. Brain 131:90–108. doi: 10.1093/brain/awm260 PubMedCrossRefGoogle Scholar
  76. 76.
    Soutar MPM, Thornhill P, Cole AR, Sutherland C (2009) Increased CRMP2 phosphorylation is observed in Alzheimer’s disease; does this tell us anything about disease development? Curr Alzheimer Res 6:269–278PubMedCrossRefGoogle Scholar
  77. 77.
    Verbeke KA, Boobis AR, Chiodini A et al (2015) Towards microbial fermentation metabolites as markers for health benefits of prebiotics. Nutr Res Rev 28:42–66. doi: 10.1017/S0954422415000037 PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Tagliabue A, Elli M (2013) The role of gut microbiota in human obesity: recent findings and future perspectives. Nutr Metab Cardiovasc Dis 23:160–168. doi: 10.1016/j.numecd.2012.09.002 PubMedCrossRefGoogle Scholar
  79. 79.
    Kasubuchi M, Hasegawa S, Hiramatsu T et al (2015) Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients 7:2839–2849. doi: 10.3390/nu7042839 PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    den Besten G, van Eunen K, Groen AK et al (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54:2325–2340. doi: 10.1194/jlr.R036012 CrossRefGoogle Scholar
  81. 81.
    Gao Z, Yin J, Zhang J et al (2009) Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58:1509–1517. doi: 10.2337/db08-1637 PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Fushimi T, Suruga K, Oshima Y et al (2006) Dietary acetic acid reduces serum cholesterol and triacylglycerols in rats fed a cholesterol-rich diet. Br J Nutr 95:916–924PubMedCrossRefGoogle Scholar
  83. 83.
    Todesco T, Rao AV, Bosello O, Jenkins DJ (1991) Propionate lowers blood glucose and alters lipid metabolism in healthy subjects. Am J Clin Nutr 54:860–865PubMedGoogle Scholar
  84. 84.
    Saad MJA, Santos A, Prada PO (2016) Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology (Bethesda) 31:283–293. doi: 10.1152/physiol.00041.2015 Google Scholar
  85. 85.
    Soldavini J, Kaunitz JD (2013) Pathobiology and potential therapeutic value of intestinal short-chain fatty acids in gut inflammation and obesity. Dig Dis Sci 58:2756–2766. doi: 10.1007/s10620-013-2744-4 PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Brahe LK, Astrup A, Larsen LH (2013) Is butyrate the link between diet, intestinal microbiota and obesity-related metabolic diseases? Obes Rev 14:950–959. doi: 10.1111/obr.12068 PubMedCrossRefGoogle Scholar
  87. 87.
    De Vadder F, Kovatcheva-Datchary P, Goncalves D et al (2014) Microbiota-generated metabolites promote metabolic benefits via gut–brain neural circuits. Cell 156:84–96. doi: 10.1016/j.cell.2013.12.016 PubMedCrossRefGoogle Scholar
  88. 88.
    Delaere F, Duchampt A, Mounien L et al (2012) The role of sodium-coupled glucose co-transporter 3 in the satiety effect of portal glucose sensing. Mol Metab 2:47–53PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Lacassagne O, Kessler JP (2000) Cellular and subcellular distribution of the amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2 in the rat dorsal vagal complex. Neuroscience 99:557–563PubMedCrossRefGoogle Scholar
  90. 90.
    Greene JG (2014) Causes and consequences of degeneration of the dorsal motor nucleus of the vagus nerve in Parkinson’s disease. Antioxid Redox Signal 21:649–667. doi: 10.1089/ars.2014.5859 PubMedCrossRefGoogle Scholar
  91. 91.
    Lal S, Kirkup AJ, Brunsden AM et al (2001) Vagal afferent responses to fatty acids of different chain length in the rat. AJP: Gastrointest Liver Physiol 281:G907–G915Google Scholar
  92. 92.
    Sjogren MJC, Hellstrom PTO, Jonsson MAG et al (2002) Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer’s disease: a pilot study. J Clin Psychiatry 63:972–980PubMedCrossRefGoogle Scholar
  93. 93.
    Merrill CA, Jonsson MAG, Minthon L et al (2006) Vagus nerve stimulation in patients with Alzheimer’s disease: additional follow-up results of a pilot study through 1 year. J Clin Psychiatry 67:1171–1178PubMedCrossRefGoogle Scholar
  94. 94.
    Vijay N, Morris ME (2014) Role of monocarboxylate transporters in drug delivery to the brain. Curr Pharm Des 20:1487–1498PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Braniste V, Al-Asmakh M, Kowal C et al (2014) The gut microbiota influences blood–brain barrier permeability in mice. Sci Transl Med 6:263ra158. doi: 10.1126/scitranslmed.3009759 PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Brown AJ, Goldsworthy SM, Barnes AA et al (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278:11312–11319PubMedCrossRefGoogle Scholar
  97. 97.
    Beharry AW, Sandesara PB, Roberts BM et al (2014) HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy. J Cell Sci 127:1441–1453. doi: 10.1242/jcs.136390 PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Martins R, Lithgow GJ, Link W (2016) Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell 15:196–207. doi: 10.1111/acel.12427 PubMedCrossRefGoogle Scholar
  99. 99.
    Pino E, Amamoto R, Zheng L et al (2014) FOXO3 determines the accumulation of alpha-synuclein and controls the fate of dopaminergic neurons in the substantia nigra. Hum Mol Genet 23:1435–1452. doi: 10.1093/hmg/ddt530 PubMedCrossRefGoogle Scholar
  100. 100.
    Xu P, Das M, Reilly J, Davis RJ (2011) JNK regulates FoxO-dependent autophagy in neurons. Genes Dev 25:310–322. doi: 10.1101/gad.1984311 PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Bahia PK, Pugh V, Hoyland K et al (2012) Neuroprotective effects of phenolic antioxidant tBHQ associate with inhibition of FoxO3a nuclear translocation and activity. J Neurochem 123:182–191. doi: 10.1111/j.1471-4159.2012.07877.x PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Edwards C, Canfield J, Copes N et al (2014) D-beta-hydroxybutyrate extends lifespan in C. elegans. Aging (Albany NY) 6:621–644. doi: 10.18632/aging.100683 CrossRefGoogle Scholar
  103. 103.
    Zhang M, Poplawski M, Yen K et al (2009) Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling. PLoS Biol 7:e1000245. doi: 10.1371/journal.pbio.1000245 PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Cohen E, Bieschke J, Perciavalle RM et al (2006) Opposing activities protect against age-onset proteotoxicity. Science 313:1604–1610. doi: 10.1126/science.1124646 PubMedCrossRefGoogle Scholar
  105. 105.
    Koh H, Kim H, Kim MJ et al (2012) Silent information regulator 2 (Sir2) and Forkhead box O (FOXO) complement mitochondrial dysfunction and dopaminergic neuron loss in Drosophila PTEN-induced kinase 1 (PINK1) null mutant. J Biol Chem 287:12750–12758. doi: 10.1074/jbc.M111.337907 PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Nankova BB, Agarwal R, MacFabe DF, La Gamma EF (2014) Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells—possible relevance to autism spectrum disorders. PLoS One 9:e103740PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Bourassa MW, Alim I, Bultman SJ, Ratan RR (2016) Butyrate, neuroepigenetics and the gut microbiome: can a high fiber diet improve brain health? Neurosci Lett 625:56–63. doi: 10.1016/j.neulet.2016.02.009 PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Reigstad CS, Salmonson CE, Rainey JF et al (2015) Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 29:1395–1403. doi: 10.1096/fj.14-259598 PubMedCrossRefGoogle Scholar
  109. 109.
    Fukumoto S, Tatewaki M, Yamada T et al (2003) Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am J Physiol Regul Integr Comp Physiol 284:R1269–R1276PubMedCrossRefGoogle Scholar
  110. 110.
    Gershon MD (2013) 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes 20:14–21. doi: 10.1097/MED.0b013e32835bc703 PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    DeCastro M, Nankova BB, Shah P et al (2005) Short chain fatty acids regulate tyrosine hydroxylase gene expression through a cAMP-dependent signaling pathway. Brain Res Mol Brain Res 142:28–38. doi: 10.1016/j.molbrainres.2005.09.002 PubMedCrossRefGoogle Scholar
  112. 112.
    Govindarajan N, Agis-Balboa RC, Walter J et al (2011) Sodium butyrate improves memory function in an Alzheimer’s disease mouse model when administered at an advanced stage of disease progression. J Alzheimers Dis 26:187–197. doi: 10.3233/JAD-2011-110080 PubMedGoogle Scholar
  113. 113.
    del Rio R, Noubade R, Saligrama N et al (2012) Histamine H4 receptor optimizes T regulatory cell frequency and facilitates anti-inflammatory responses within the central nervous system. J Immunol 188:541–547. doi: 10.4049/jimmunol.1101498 PubMedCrossRefGoogle Scholar
  114. 114.
    Naddafi F, Mirshafiey A (2013) The neglected role of histamine in Alzheimer’s disease. Am J Alzheimers Dis Other Demen 28:327–336. doi: 10.1177/1533317513488925 PubMedCrossRefGoogle Scholar
  115. 115.
    Dong H, Zhang W, Zeng X et al (2014) Histamine induces upregulated expression of histamine receptors and increases release of inflammatory mediators from microglia. Mol Neurobiol 49:1487–1500. doi: 10.1007/s12035-014-8697-6 PubMedCrossRefGoogle Scholar
  116. 116.
    Schneider E, Rolli-Derkinderen M, Arock M, Dy M (2002) Trends in histamine research: new functions during immune responses and hematopoiesis. Trends Immunol 23:255–263PubMedCrossRefGoogle Scholar
  117. 117.
    Morgan RK, McAllister B, Cross L et al (2007) Histamine 4 receptor activation induces recruitment of FoxP3+ T cells and inhibits allergic asthma in a murine model. J Immunol 178:8081–8089PubMedCrossRefGoogle Scholar
  118. 118.
    Landete JM, de las Rivas B, Marcobal A, Munoz R (2008) Updated molecular knowledge about histamine biosynthesis by bacteria. Crit Rev Food Sci Nutr 48:697–714. doi: 10.1080/10408390701639041 PubMedCrossRefGoogle Scholar
  119. 119.
    Thomas CM, Hong T, van Pijkeren JP et al (2012) Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One 7:e31951PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Alvarez XA, Franco A, Fernandez-Novoa L, Cacabelos R (1996) Blood levels of histamine, IL-1 beta, and TNF-alpha in patients with mild to moderate Alzheimer disease. Mol Chem Neuropathol 29:237–252. doi: 10.1007/BF02815005 PubMedCrossRefGoogle Scholar
  121. 121.
    Stasiak A, Mussur M, Unzeta M et al (2011) The central histamine level in rat model of vascular dementia. J Physiol Pharmacol 62:549–558PubMedGoogle Scholar
  122. 122.
    Chen L, Xing T, Wang M et al (2011) Local infusion of ghrelin enhanced hippocampal synaptic plasticity and spatial memory through activation of phosphoinositide 3-kinase in the dentate gyrus of adult rats. Eur J Neurosci 33:266–275. doi: 10.1111/j.1460-9568.2010.07491.x PubMedCrossRefGoogle Scholar
  123. 123.
    Gahete MD, Cordoba-Chacon J, Kineman RD et al (2011) Role of ghrelin system in neuroprotection and cognitive functions: implications in Alzheimer’s disease. Peptides 32:2225–2228. doi: 10.1016/j.peptides.2011.09.019 PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Steinert RE, Feinle-Bisset C, Asarian L et al (2017) Ghrelin, CCK, GLP-1, and PYY(3-36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB. Physiol Rev 97:411–463. doi: 10.1152/physrev.00031.2014 PubMedCrossRefGoogle Scholar
  125. 125.
    Guan XM, Yu H, Palyha OC et al (1997) Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res 48:23–29PubMedCrossRefGoogle Scholar
  126. 126.
    Bauer PV, Hamr SC, Duca FA (2016) Regulation of energy balance by a gut–brain axis and involvement of the gut microbiota. Cell Mol Life Sci 73:737–755. doi: 10.1007/s00018-015-2083-z PubMedCrossRefGoogle Scholar
  127. 127.
    Fallucca F, Porrata C, Fallucca S, Pianesi M (2014) Influence of diet on gut microbiota, inflammation and type 2 diabetes mellitus. First experience with macrobiotic Ma-Pi 2 diet. Diabetes Metab Res Rev 30(Suppl 1):48–54. doi: 10.1002/dmrr.2518 PubMedCrossRefGoogle Scholar
  128. 128.
    Queipo-Ortuno MI, Seoane LM, Murri M et al (2013) Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels. PLoS One 8:e65465PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Dos Santos VV, Rodrigues ALS, De Lima TC et al (2013) Ghrelin as a neuroprotective and palliative agent in Alzheime’s and Parkinson’s disease. Curr Pharm Des 19:6773–6790PubMedCrossRefGoogle Scholar
  130. 130.
    Liu Y, Chen L, Xu X et al (2009) Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia/reperfusion and upregulate uncoupling protein-2. BMC Physiol 9:17. doi: 10.1186/1472-6793-9-17 PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Moon M, Choi JG, Nam DW et al (2011) Ghrelin ameliorates cognitive dysfunction and neurodegeneration in intrahippocampal amyloid-beta1-42 oligomer-injected mice. J Alzheimers Dis 23:147–159. doi: 10.3233/JAD-2010-101263 PubMedGoogle Scholar
  132. 132.
    Andrews ZB, Erion D, Beiler R et al (2009) Ghrelin promotes and protects nigrostriatal dopamine function via a UCP2-dependent mitochondrial mechanism. J Neurosci 29:14057–14065. doi: 10.1523/JNEUROSCI.3890-09.2009 PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Bayliss JA, Lemus M, Santos VV et al (2016) Acylated but not des-acyl ghrelin is neuroprotective in an MPTP mouse model of Parkinson’s disease. J Neurochem 137:460–471. doi: 10.1111/jnc.13576 PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Schwarcz R, Bruno JP, Muchowski PJ, Wu H-Q (2012) Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci 13:465–477. doi: 10.1038/nrn3257 PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Ruddick JP, Evans AK, Nutt DJ et al (2006) Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med 8:1–27. doi: 10.1017/S1462399406000068 PubMedCrossRefGoogle Scholar
  136. 136.
    Desbonnet L, Garrett L, Clarke G et al (2008) The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res 43:164–174. doi: 10.1016/j.jpsychires.2008.03.009 PubMedCrossRefGoogle Scholar
  137. 137.
    Braidy N, Grant R, Adams S et al (2009) Mechanism for quinolinic acid cytotoxicity in human astrocytes and neurons. Neurotox Res 16:77–86. doi: 10.1007/s12640-009-9051-z PubMedCrossRefGoogle Scholar
  138. 138.
    Vamos E, Pardutz A, Klivenyi P et al (2009) The role of kynurenines in disorders of the central nervous system: possibilities for neuroprotection. J Neurol Sci 283:21–27. doi: 10.1016/j.jnd.2009.02.326 PubMedCrossRefGoogle Scholar
  139. 139.
    Guillemin GJ, Williams KR, Smith DG et al (2003) Quinolinic acid in the pathogenesis of Alzheimer’s disease. Adv Exp Med Biol 527:167–176PubMedCrossRefGoogle Scholar
  140. 140.
    Widner B, Leblhuber F, Walli J et al (2000) Tryptophan degradation and immune activation in Alzheimer’s disease. J Neural Transm 107:343–353PubMedCrossRefGoogle Scholar
  141. 141.
    Clarke G, Grenham S, Scully P et al (2013) The microbiome–gut–brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18:666–673. doi: 10.1038/mp.2012.77 PubMedCrossRefGoogle Scholar
  142. 142.
    Wikoff WR, Anfora AT, Liu J et al (2009) Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 106:3698–3703. doi: 10.1073/pnas.0812874106 PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Freewan M, Rees MD, Plaza TSS et al (2013) Human indoleamine 2,3-dioxygenase is a catalyst of physiological heme peroxidase reactions: implications for the inhibition of dioxygenase activity by hydrogen peroxide. J Biol Chem 288:1548–1567. doi: 10.1074/jbc.M112.410993 PubMedCrossRefGoogle Scholar
  144. 144.
    Tomas MSJ, Claudia Otero M, Ocana V, Elena Nader-Macias M (2004) Production of antimicrobial substances by lactic acid bacteria I: determination of hydrogen peroxide. Methods Mol Biol 268:337–346. doi: 10.1385/1-59259-766-1:337 PubMedGoogle Scholar
  145. 145.
    Rahman A, Ting K, Cullen KM et al (2009) The excitotoxin quinolinic acid induces tau phosphorylation in human neurons. PLoS One 4:e6344. doi: 10.1371/journal.pone.0006344 PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Guillemin GJ, Brew BJ, Noonan CE et al (2005) Indoleamine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer’s disease hippocampus. Neuropathol Appl Neurobiol 31:395–404. doi: 10.1111/j.1365-2990.2005.00655.x PubMedCrossRefGoogle Scholar
  147. 147.
    Yamada A, Akimoto H, Kagawa S et al (2009) Proinflammatory cytokine interferon-gamma increases induction of indoleamine 2,3-dioxygenase in monocytic cells primed with amyloid beta peptide 1–42: implications for the pathogenesis of Alzheimer’s disease. J Neurochem 110:791–800. doi: 10.1111/j.1471-4159.2009.06175.x PubMedCrossRefGoogle Scholar
  148. 148.
    Giorgini F, Guidetti P, Nguyen Q et al (2005) A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease. Nat Genet 37:526–531. doi: 10.1038/ng1542 PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Forsythe P, Kunze WA, Bienenstock J (2012) On communication between gut microbes and the brain. Curr Opin Gastroenterol 28:557–562. doi: 10.1097/MOG.0b013e3283572ffa PubMedCrossRefGoogle Scholar
  150. 150.
    Lyte M (2014) Microbial endocrinology: host–microbiota neuroendocrine interactions influencing brain and behavior. Gut Microbes 5:381–389. doi: 10.4161/gmic.28682 PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Barrett E, Ross RP, O’Toole PW et al (2012) gamma-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113:411–417. doi: 10.1111/j.1365-2672.2012.05344.x PubMedCrossRefGoogle Scholar
  152. 152.
    Sun J, Ling Z, Wang F et al (2016) Clostridium butyricum pretreatment attenuates cerebral ischemia/reperfusion injury in mice via anti-oxidation and anti-apoptosis. Neurosci Lett 613:30–35. doi: 10.1016/j.neulet.2015.12.047 PubMedCrossRefGoogle Scholar
  153. 153.
    Ait-Belgnaoui A, Colom A, Braniste V et al (2014) Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol Motil 26:510–520. doi: 10.1111/nmo.12295 PubMedCrossRefGoogle Scholar
  154. 154.
    Ezendam J, de Klerk A, Gremmer ER, van Loveren H (2008) Effects of Bifidobacterium animalis administered during lactation on allergic and autoimmune responses in rodents. Clin Exp Immunol 154:424–431. doi: 10.1111/j.1365-2249.2008.03788.x PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Ochoa-Reparaz J, Mielcarz DW, Wang Y et al (2010) A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol 3:487–495. doi: 10.1038/mi.2010.29 PubMedCrossRefGoogle Scholar
  156. 156.
    Kobayashi T, Kato I, Nanno M et al (2010) Oral administration of probiotic bacteria, Lactobacillus casei and Bifidobacterium breve, does not exacerbate neurological symptoms in experimental autoimmune encephalomyelitis. Immunopharmacol Immunotoxicol 32:116–124. doi: 10.3109/08923970903200716 PubMedCrossRefGoogle Scholar
  157. 157.
    Kobayashi T, Suzuki T, Kaji R et al (2012) Probiotic upregulation of peripheral IL-17 responses does not exacerbate neurological symptoms in experimental autoimmune encephalomyelitis mouse models. Immunopharmacol Immunotoxicol 34:423–433. doi: 10.3109/08923973.2010.617755 PubMedCrossRefGoogle Scholar
  158. 158.
    Kwon H-K, Kim G-C, Kim Y et al (2013) Amelioration of experimental autoimmune encephalomyelitis by probiotic mixture is mediated by a shift in T helper cell immune response. Clin Immunol 146:217–227. doi: 10.1016/j.clim.2013.01.001 PubMedCrossRefGoogle Scholar
  159. 159.
    Lavasani S, Dzhambazov B, Nouri M et al (2010) A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One 5:e9009. doi: 10.1371/journal.pone.0009009 PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Ohland CL, Kish L, Bell H et al (2013) Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinology 38:1738–1747. doi: 10.1016/j.psyneuen.2013.02.008 PubMedCrossRefGoogle Scholar
  161. 161.
    Davari S, Talaei SA, Alaei H, Salami M (2013) Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome–gut–brain axis. Neuroscience 240:287–296. doi: 10.1016/j.neuroscience.2013.02.055 PubMedCrossRefGoogle Scholar
  162. 162.
    Gareau MG, Wine E, Rodrigues DM et al (2011) Bacterial infection causes stress-induced memory dysfunction in mice. Gut 60:307–317. doi: 10.1136/gut.2009.202515 PubMedCrossRefGoogle Scholar
  163. 163.
    Rao AV, Bested AC, Beaulne TM et al (2009) A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog 1:6. doi: 10.1186/1757-4749-1-6 PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Yan MH, Wang X, Zhu X (2013) Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radic Biol Med 62:90–101. doi: 10.1016/j.freeradbiomed.2012.11.014 PubMedCrossRefGoogle Scholar
  165. 165.
    Distrutti E, O’Reilly J-A, McDonald C et al (2014) Modulation of intestinal microbiota by the probiotic VSL#3 resets brain gene expression and ameliorates the age-related deficit in LTP. PLoS One 9:e106503PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Girard S-A, Bah TM, Kaloustian S et al (2009) Lactobacillus helveticus and Bifidobacterium longum taken in combination reduce the apoptosis propensity in the limbic system after myocardial infarction in a rat model. Br J Nutr 102:1420–1425. doi: 10.1017/S0007114509990766 PubMedCrossRefGoogle Scholar
  167. 167.
    Liu J, Sun J, Wang F et al (2015) Neuroprotective effects of Clostridium butyricum against vascular dementia in mice via metabolic butyrate. Biomed Res Int 2015:412946. doi: 10.1155/2015/412946 PubMedPubMedCentralGoogle Scholar
  168. 168.
    O’Sullivan E, Barrett E, Grenham S et al (2011) BDNF expression in the hippocampus of maternally separated rats: does Bifidobacterium breve 6330 alter BDNF levels? Benef Microbes 2:199–207. doi: 10.3920/BM2011.0015 PubMedCrossRefGoogle Scholar
  169. 169.
    Bercik P, Park AJ, Sinclair D et al (2011) The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut–brain communication. Neurogastroenterol Motil 23:1132–1139. doi: 10.1111/j.1365-2982.2011.01796.x PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Le TK, Hosaka T, Le TT et al (2014) Oral administration of Bifidobacterium spp. improves insulin resistance, induces adiponectin, and prevents inflammatory adipokine expressions. Biomed Res Int 35:303–310CrossRefGoogle Scholar
  171. 171.
    Bomhof MR, Saha DC, Reid DT et al (2014) Combined effects of oligofructose and Bifidobacterium animalis on gut microbiota and glycemia in obese rats. Obesity (Silver Spring) 22:763–771. doi: 10.1002/oby.20632 CrossRefGoogle Scholar
  172. 172.
    Hoarau C, Martin L, Faugaret D et al (2008) Supernatant from bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells. PLoS One 3:e2753. doi: 10.1371/journal.pone.0002753 PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Chang C-Y, Ke D-S, Chen J-Y (2009) Essential fatty acids and human brain. Acta Neurol Taiwan 18:231–241PubMedGoogle Scholar
  174. 174.
    Wall R, Marques TM, O’Sullivan O et al (2012) Contrasting effects of Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 on the composition of murine brain fatty acids and gut microbiota. Am J Clin Nutr 95:1278–1287. doi: 10.3945/ajcn.111.026435 PubMedCrossRefGoogle Scholar
  175. 175.
    McCarthy J, O’Mahony L, O’Callaghan L et al (2003) Double blind, placebo controlled trial of two probiotic strains in interleukin 10 knockout mice and mechanistic link with cytokine balance. Gut 52:975–980PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Rodes L, Khan A, Paul A et al (2013) Effect of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharides and inflammatory cytokines: an in vitro study using a human colonic microbiota model. J Microbiol Biotechnol 23:518–526PubMedCrossRefGoogle Scholar
  177. 177.
    Sudo N, Chida Y, Aiba Y et al (2004) Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. J Physiol 558:263–275. doi: 10.1113/jphysiol.2004.063388 PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Stone TW, Stoy N, Darlington LG (2013) An expanding range of targets for kynurenine metabolites of tryptophan. Trends Pharmacol Sci 34:136–143. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  179. 179.
    Mao Y-K, Kasper DL, Wang B et al (2013) Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons. Nat Commun 4:1465. doi: 10.1038/ncomms2478 PubMedCrossRefGoogle Scholar
  180. 180.
    Kuley E, Ozogul F, Ozogul Y, Akyol I (2011) The function of lactic acid bacteria and brine solutions on biogenic amine formation by foodborne pathogens in trout fillets. Food Chem 129:1211–1216. doi: 10.1016/j.foodchem.2011.05.113 PubMedCrossRefGoogle Scholar
  181. 181.
    Lin Q (2013) Submerged fermentation of Lactobacillus rhamnosus YS9 for gamma-aminobutyric acid (GABA) production. Braz J Microbiol 44:183–187PubMedPubMedCentralCrossRefGoogle Scholar
  182. 182.
    Stanaszek PM, Snell JF, O’Neill JJ (1977) Isolation, extraction, and measurement of acetylcholine from Lactobacillus plantarum. Appl Environ Microbiol 34:237–239PubMedPubMedCentralGoogle Scholar
  183. 183.
    Sobko T, Huang L, Midtvedt T et al (2006) Generation of NO by probiotic bacteria in the gastrointestinal tract. Free Radic Biol Med 41:985–991. doi: 10.1016/j.freeradbiomed.2006.06.020 PubMedCrossRefGoogle Scholar
  184. 184.
    Bajaj JS, Heuman DM, Hylemon PB et al (2014) Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis. Aliment Pharmacol Ther 39:1113–1125. doi: 10.1111/apt.12695 PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Fetissov SO, Hamze Sinno M, Coeffier M et al (2008) Autoantibodies against appetite-regulating peptide hormones and neuropeptides: putative modulation by gut microflora. Nutrition 24:348–359. doi: 10.1016/j.nut.2007.12.006 PubMedCrossRefGoogle Scholar
  186. 186.
    Konstantinov SR, Smidt H, de Vos WM et al (2008) S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc Natl Acad Sci USA 105:19474–19479. doi: 10.1073/pnas.0810305105 PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Amdekar S, Singh V, Kumar A et al (2013) Lactobacillus casei and Lactobacillus acidophilus regulate inflammatory pathway and improve antioxidant status in collagen-induced arthritic rats. J Interferon Cytokine Res 33:1–8. doi: 10.1089/jir.2012.0034 PubMedCrossRefGoogle Scholar
  188. 188.
    Bravo JA, Julio-Pieper M, Forsythe P et al (2012) Communication between gastrointestinal bacteria and the nervous system. Curr Opin Pharmacol 12:667–672. doi: 10.1016/j.coph.2012.09.010 PubMedCrossRefGoogle Scholar
  189. 189.
    Bhathena J, Duchesneau CT (2012) Effect of orally administered microencapsulated FA-producing L. fermentum on markers of metabolic syndrome: an in vivo analysis. J Diabetes. doi: 10.4172/2155-6156.S2-009 Google Scholar
  190. 190.
    Tomaro-Duchesneau C, Saha S, Malhotra M et al (2012) Lactobacillus fermentum NCIMB 5221 has a greater ferulic acid production compared to other ferulic acid esterase producing Lactobacilli. Int J Probiotics Prebiotics 7(1):23–32Google Scholar
  191. 191.
    Grompone G, Martorell P, Llopis S et al (2012) Anti-inflammatory Lactobacillus rhamnosus CNCM I-3690 strain protects against oxidative stress and increases lifespan in Caenorhabditis elegans. PLoS One 7:e52493PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Yan F, Cao H, Cover TL et al (2007) Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology 132:562–575. doi: 10.1053/j.gastro.2006.11.022 PubMedCrossRefGoogle Scholar
  193. 193.
    Sanchez B, Urdaci MC, Margolles A (2010) Extracellular proteins secreted by probiotic bacteria as mediators of effects that promote mucosa–bacteria interactions. Microbiology 156:3232–3242. doi: 10.1099/mic.0.044057-0 PubMedCrossRefGoogle Scholar
  194. 194.
    Claes IJJ, Lebeer S, Shen C et al (2010) Impact of lipoteichoic acid modification on the performance of the probiotic Lactobacillus rhamnosus GG in experimental colitis. Clin Exp Immunol 162:306–314. doi: 10.1111/j.1365-2249.2010.04228.x PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Sagar S, Morgan ME, Chen S et al (2014) Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma. Respir Res 15:46. doi: 10.1186/1465-9921-15-46 PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Ushakova G, Fed’kiv O, Prykhod’ko O et al (2009) The effect of long-term lactobacilli (lactic acid bacteria) enteral treatment on the central nervous system of growing rats. J Nutr Biochem 20:677–684. doi: 10.1016/j.jnutbio.2008.06.010 PubMedCrossRefGoogle Scholar
  197. 197.
    Pereira DIA, McCartney AL, Gibson GR (2003) An in vitro study of the probiotic potential of a bile-salt-hydrolyzing Lactobacillus fermentum strain, and determination of its cholesterol-lowering properties. Appl Environ Microbiol 69:4743–4752PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Duary RK, Bhausaheb MA, Batish VK, Grover S (2012) Anti-inflammatory and immunomodulatory efficacy of indigenous probiotic Lactobacillus plantarum Lp91 in colitis mouse model. Mol Biol Rep 39:4765–4775. doi: 10.1007/s11033-011-1269-1 PubMedCrossRefGoogle Scholar
  199. 199.
    Tsavkelova EA, Botvinko IV, Kudrin VS, Oleskin AV (2000) Detection of neurotransmitter amines in microorganisms with the use of high-performance liquid chromatography. Dokl Biochem 372:115–117PubMedGoogle Scholar
  200. 200.
    Chen Z, Guo L, Zhang Y et al (2014) Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity. J Clin Invest 124:3391–3406. doi: 10.1172/JCI72517 PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Shishov VA, Kirovskaia TA, Kudrin VS, Oleskin AV (2009) Amine neuromediators, their precursors, and oxidation products in the culture of Escherichia coli K-12. Prikl Biokhim Mikrobiol 45:550–554PubMedGoogle Scholar
  202. 202.
    Pryde S, Duncan S, Hold G et al (2002) The microbiology of butyrate formation in the human colon. FEMS Microbiol Lett 217:133–139PubMedCrossRefGoogle Scholar
  203. 203.
    Macfarlane S, Macfarlane GT (2003) Regulation of short-chain fatty acid production. Proc Nutr Soc 62:67–72PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  • Susan Westfall
    • 1
  • Nikita Lomis
    • 1
    • 2
  • Imen Kahouli
    • 1
    • 2
  • Si Yuan Dia
    • 1
  • Surya Pratap Singh
    • 3
  • Satya Prakash
    • 1
    • 2
    Email author
  1. 1.Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of MedicineMcGill UniversityMontrealCanada
  2. 2.Department of Experimental Medicine, Faculty of MedicineMcGill UniversityMontrealCanada
  3. 3.Department of BiochemistryBanaras Hindu UniversityVaranasiIndia

Personalised recommendations