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Semin Neurol 2023; 43(04): 506-517
DOI: 10.1055/s-0043-1771464
Review Article

Overview of the Gut–Brain Axis: From Gut to Brain and Back Again

Zoë Post
1   Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois
,
Richard A. Manfready
1   Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois
2   Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois
3   Departments of Physiology and Anatomy & Cell Biology, Rush University Medical Center, Chicago, Illinois
,
Ali Keshavarzian
1   Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois
2   Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois
3   Departments of Physiology and Anatomy & Cell Biology, Rush University Medical Center, Chicago, Illinois
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Abstract

The gut–brain axis refers to a bidirectional communication pathway linking the gastrointestinal system to the central nervous system. The hardware of this multifaceted pathway takes many forms, at once structural (neurons, microglia, intestinal epithelial cell barrier), chemical (neurotransmitters, enteroendocrine hormones, bacterial metabolites), and cellular (immune signaling, inflammatory pathways). The gut–brain axis is exquisitely influenced by our environment, diet, and behaviors. Here, we will describe recent progress in understanding the gut–brain axis in neurological disease, using Parkinson's disease as a guide. We will see that each component of the gut–brain axis is heavily mediated by intestinal microbiota and learn how gut–brain communication can go awry in microbial dysbiosis.

Keywords

gut–brain axis - microbiome–gut–brain axis - neuroendocrinology - neuroinflammation


Publication History

Article published online:
10 August 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Rutsch A, Kantsjö JB, Ronchi F. The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology. Front Immunol 2020; 11: 604179
    CrossrefPubMedGoogle Scholar
  • 2 Margolis KG, Cryan JF, Mayer EA. The microbiota-gut-brain axis: from motility to mood. Gastroenterology 2021; 160 (05) 1486-1501
    CrossrefPubMedGoogle Scholar
  • 3 Harrell CR, Jovicic N, Djonov V, Arsenijevic N, Volarevic V. Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases. Cells 2019; 8 (12) 1605
    CrossrefPubMedGoogle Scholar
  • 4 Manfready RA, Engen PA, Verhagen Metman L. et al. Attenuated postprandial GLP-1 response in Parkinson's disease. Front Neurosci 2021; 15: 660942
    CrossrefPubMedGoogle Scholar
  • 5 Fairbrass KM, Lovatt J, Barberio B, Yuan Y, Gracie DJ, Ford AC. Bidirectional brain-gut axis effects influence mood and prognosis in IBD: a systematic review and meta-analysis. Gut 2022; 71 (09) 1773-1780
    CrossrefPubMedGoogle Scholar
  • 6 Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R. Current understanding of the human microbiome. Nat Med 2018; 24 (04) 392-400
    CrossrefPubMedGoogle Scholar
  • 7 Kaelberer MM, Buchanan KL, Klein ME. et al. A gut-brain neural circuit for nutrient sensory transduction. Science 2018; 361 (6408) 1219
    CrossrefPubMedGoogle Scholar
  • 8 Payne SC, Furness JB, Burns O. et al. Anti-inflammatory effects of abdominal vagus nerve stimulation on experimental intestinal inflammation. Front Neurosci 2019; 13: 418
    CrossrefPubMedGoogle Scholar
  • 9 Caspani G, Kennedy S, Foster JA, Swann J. Gut microbial metabolites in depression: understanding the biochemical mechanisms. Microb Cell 2019; 6 (10) 454-481
    CrossrefPubMedGoogle Scholar
  • 10 Sampson TR, Debelius JW, Thron T. et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell 2016; 167 (06) 1469-1480.e12
    CrossrefPubMedGoogle Scholar
  • 11 Zheng P, Zeng B, Zhou C. et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Mol Psychiatry 2016; 21 (06) 786-796
    CrossrefPubMedGoogle Scholar
  • 12 Kelly JR, Borre Y, O' Brien C. et al. Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res 2016; 82: 109-118
    CrossrefPubMedGoogle Scholar
  • 13 Bougeard C, Picarel-Blanchot F, Schmid R, Campbell R, Buitelaar J. Prevalence of autism spectrum disorder and co-morbidities in children and adolescents: a systematic literature review. Front Psychiatry 2021; 12: 744709
    CrossrefPubMedGoogle Scholar
  • 14 Lin CH, Chen CC, Chiang HL. et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease. J Neuroinflammation 2019; 16 (01) 129
    CrossrefPubMedGoogle Scholar
  • 15 Keshavarzian A, Green SJ, Engen PA. et al. Colonic bacterial composition in Parkinson's disease. Mov Disord 2015; 30 (10) 1351-1360
    CrossrefPubMedGoogle Scholar
  • 16 Voigt RM, Forsyth CB, Green SJ, Engen PA, Keshavarzian A. Circadian rhythm and the gut microbiome. Int Rev Neurobiol 2016; 131: 193-205
    CrossrefPubMedGoogle Scholar
  • 17 Gruber J, Kennedy BK. Microbiome and longevity: gut microbes send signals to host mitochondria. Cell 2017; 169 (07) 1168-1169
    CrossrefPubMedGoogle Scholar
  • 18 Stilling RM, van de Wouw M, Clarke G, Stanton C, Dinan TG, Cryan JF. The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis?. Neurochem Int 2016; 99: 110-132
    CrossrefPubMedGoogle Scholar
  • 19 Li G, Lin J, Zhang C. et al. Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease. Gut Microbes 2021; 13 (01) 1968257
    CrossrefPubMedGoogle Scholar
  • 20 Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne) 2020; 11: 25
    CrossrefPubMedGoogle Scholar
  • 21 Valles-Colomer M, Falony G, Darzi Y. et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol 2019; 4 (04) 623-632
    CrossrefPubMedGoogle Scholar
  • 22 Manfready RA, Forsyth CB, Voigt RM, Hall DA, Goetz CG, Keshavarzian A. Gut-brain communication in Parkinson's disease: enteroendocrine regulation by GLP-1. Curr Neurol Neurosci Rep 2022; 22 (07) 335-342
    CrossrefPubMedGoogle Scholar
  • 23 Athauda D, Foltynie T. Insulin resistance and Parkinson's disease: a new target for disease modification?. Prog Neurobiol 2016; 145-146: 98-120
    CrossrefPubMedGoogle Scholar
  • 24 Heppner KM, Kirigiti M, Secher A. et al. Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and binding in the male nonhuman primate (Macaca mulatta) brain. Endocrinology 2015; 156 (01) 255-267
    CrossrefPubMedGoogle Scholar
  • 25 Bertilsson G, Patrone C, Zachrisson O. et al. Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson's disease. J Neurosci Res 2008; 86 (02) 326-338
    CrossrefPubMedGoogle Scholar
  • 26 Nuamnaichati N, Parichatikanond W, Mangmool S. Cardioprotective effects of glucagon-like peptide-1 (9–36) against oxidative injury in H9c2 cardiomyoblasts: Potential role of the PI3K/akt/NOS pathway. J Cardiovasc Pharmacol 2022; 79 (01) e50-e63
    CrossrefPubMedGoogle Scholar
  • 27 Athauda D, Foltynie T. Protective effects of the GLP-1 mimetic exendin-4 in Parkinson's disease. Neuropharmacology 2018; 136 (Pt B): 260-270
    CrossrefPubMedGoogle Scholar
  • 28 Athauda D, Maclagan K, Skene SS. et al. Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial. Lancet 2017; 390 (10103): 1664-1675
    CrossrefPubMedGoogle Scholar
  • 29 Caputi V, Giron MC. Microbiome-gut-brain axis and toll-like receptors in Parkinson's disease. Int J Mol Sci 2018; 19 (06) 1689
    CrossrefPubMedGoogle Scholar
  • 30 Forsyth CB, Shannon KM, Kordower JH. et al. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PLoS One 2011; 6 (12) e28032
    CrossrefPubMedGoogle Scholar
  • 31 Janeway Jr CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002; 20 (01) 197-216
    CrossrefPubMedGoogle Scholar
  • 32 Perez-Pardo P, Dodiya HB, Engen PA. et al. Role of TLR4 in the gut-brain axis in Parkinson's disease: a translational study from men to mice. Gut 2019; 68 (05) 829-843
    CrossrefPubMedGoogle Scholar
  • 33 Dutta G, Zhang P, Liu B. The lipopolysaccharide Parkinson's disease animal model: mechanistic studies and drug discovery. Fundam Clin Pharmacol 2008; 22 (05) 453-464
    CrossrefPubMedGoogle Scholar
  • 34 Abdel-Haq R, Schlachetzki JCM, Glass CK, Mazmanian SK. Microbiome-microglia connections via the gut-brain axis. J Exp Med 2019; 216 (01) 41-59
    CrossrefPubMedGoogle Scholar
  • 35 Noelker C, Morel L, Lescot T. et al. Toll like receptor 4 mediates cell death in a mouse MPTP model of Parkinson disease. Sci Rep 2013; 3 (01) 1393
    CrossrefPubMedGoogle Scholar
  • 36 Song L, Pei L, Yao S, Wu Y, Shang Y. NLRP3 inflammasome in neurological diseases, from functions to therapies. Front Cell Neurosci 2017; 11: 63
    CrossrefPubMedGoogle Scholar
  • 37 Gordon R, Albornoz EA, Christie DC. et al. Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice. Sci Transl Med 2018; 10 (465) eaah4066
    CrossrefPubMedGoogle Scholar
  • 38 Codolo G, Plotegher N, Pozzobon T. et al. Triggering of inflammasome by aggregated α-synuclein, an inflammatory response in synucleinopathies. PLoS One 2013; 8 (01) e55375
    CrossrefPubMedGoogle Scholar
  • 39 Elliott EI, Sutterwala FS. Initiation and perpetuation of NLRP3 inflammasome activation and assembly. Immunol Rev 2015; 265 (01) 35-52
    CrossrefPubMedGoogle Scholar
  • 40 Hanslik KL, Ulland TK. The role of microglia and the Nlrp3 inflammasome in Alzheimer's disease. Front Neurol 2020; 11: 570711
    CrossrefPubMedGoogle Scholar
  • 41 Cruz-Pereira JS, Rea K, Nolan YM, O'Leary OF, Dinan TG, Cryan JF. Depression's unholy trinity: dysregulated stress, immunity, and the microbiome. Annu Rev Psychol 2020; 71 (01) 49-78
    CrossrefPubMedGoogle Scholar
  • 42 Blume J, Douglas SD, Evans DL. Immune suppression and immune activation in depression. Brain Behav Immun 2011; 25 (02) 221-229
    CrossrefPubMedGoogle Scholar
  • 43 Lee CH, Giuliani F. The role of inflammation in depression and fatigue. Front Immunol 2019; 10: 1696
    CrossrefPubMedGoogle Scholar
  • 44 Foster JA, Baker GB, Dursun SM. The relationship between the gut microbiome-immune system-brain axis and major depressive disorder. Front Neurol 2021; 12: 721126
    CrossrefPubMedGoogle Scholar
  • 45 Mowat AM, Agace WW. Regional specialization within the intestinal immune system. Nat Rev Immunol 2014; 14 (10) 667-685
    CrossrefPubMedGoogle Scholar
  • 46 Agirman G, Yu KB, Hsiao EY. Signaling inflammation across the gut-brain axis. Science 2021; 374 (6571) 1087-1092
    CrossrefPubMedGoogle Scholar
  • 47 Louveau A, Smirnov I, Keyes TJ. et al. Structural and functional features of central nervous system lymphatic vessels. Nature 2015; 523 (7560) 337-341
    CrossrefPubMedGoogle Scholar
  • 48 Benakis C, Brea D, Caballero S. et al. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells. Nat Med 2016; 22 (05) 516-523
    CrossrefPubMedGoogle Scholar
  • 49 Schwartz K, Boles BR. Microbial amyloids – functions and interactions within the host. Curr Opin Microbiol 2013; 16 (01) 93-99
    CrossrefPubMedGoogle Scholar
  • 50 Yuki N, Susuki K, Koga M. et al. Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain-Barre syndrome. Proc Natl Acad Sci U S A 2004; 101 (31) 11404-11409
    CrossrefPubMedGoogle Scholar
  • 51 Abdel-Gadir A, Stephen-Victor E, Gerber GK. et al. Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy. Nat Med 2019; 25 (07) 1164-1174
    CrossrefPubMedGoogle Scholar
  • 52 Biton M, Haber AL, Rogel N. et al. T helper cell cytokines modulate intestinal stem cell renewal and differentiation. Cell 2018; 175 (05) 1307-1320.e22
    CrossrefPubMedGoogle Scholar
  • 53 Traxinger BR, Richert-Spuhler LE, Lund JM. Mucosal tissue regulatory T cells are integral in balancing immunity and tolerance at portals of antigen entry. Mucosal Immunol 2022; 15 (03) 398-407
    CrossrefPubMedGoogle Scholar
  • 54 Jamwal DR, Laubitz D, Harrison CA. et al. Intestinal epithelial expression of MHCII determines severity of chemical, T-cell–induced, and infectious colitis in mice. Gastroenterology 2020; 159 (04) 1342-1356.e6
    CrossrefPubMedGoogle Scholar
  • 55 Lui PP, Cho I, Ali N. Tissue regulatory T cells. Immunology 2020; 161 (01) 4-17
    CrossrefPubMedGoogle Scholar
  • 56 Hegazy AN, West NR, Stubbington MJT. et al; Oxford IBD Cohort Investigators. Circulating and tissue-resident CD4+ T cells with reactivity to intestinal microbiota are abundant in healthy individuals and function is altered during inflammation. Gastroenterology 2017; 153 (05) 1320-1337.e16
    CrossrefPubMedGoogle Scholar
  • 57 Smith PM, Howitt MR, Panikov N. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013; 341 (6145) 569-573
    CrossrefPubMedGoogle Scholar
  • 58 Campbell C, McKenney PT, Konstantinovsky D. et al. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature 2020; 581 (7809) 475-479
    CrossrefPubMedGoogle Scholar
  • 59 Ito M, Komai K, Mise-Omata S. et al. Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. Nature 2019; 565 (7738) 246-250
    CrossrefPubMedGoogle Scholar
  • 60 Choi J, Kim BR, Akuzum B, Chang L, Lee JY, Kwon HK. TREGking from gut to brain: the control of regulatory T cells along the gut-brain axis. Front Immunol 2022; 13: 916066
    CrossrefPubMedGoogle Scholar
  • 61 Jena PK, Sheng L, Di Lucente J, Jin LW, Maezawa I, Wan YY. Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet-induced systemic inflammation, microglial activation, and reduced neuroplasticity. FASEB J 2018; 32 (05) 2866-2877
    CrossrefPubMedGoogle Scholar
  • 62 Baloni P, Funk CC, Yan J. et al; Alzheimer's Disease Metabolomics Consortium. Metabolic network analysis reveals altered bile acid synthesis and metabolism in Alzheimer's disease. Cell Rep Med 2020; 1 (08) 100138
    CrossrefPubMedGoogle Scholar
  • 63 Berginer VM, Salen G, Shefer S. Long-term treatment of cerebrotendinous xanthomatosis with chenodeoxycholic acid. N Engl J Med 1984; 311 (26) 1649-1652
    CrossrefPubMedGoogle Scholar
  • 64 Yanovsky Y, Schubring SR, Yao Q. et al. Waking action of ursodeoxycholic acid (UDCA) involves histamine and GABAA receptor block. PLoS One 2012; 7 (08) e42512
    CrossrefPubMedGoogle Scholar
  • 65 Poole DP, Godfrey C, Cattaruzza F. et al. Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system. Neurogastroenterol Motil 2010; 22 (07) 814-825 , e227–e228
    CrossrefPubMedGoogle Scholar
  • 66 Latorre R, Sternini C, De Giorgio R, Greenwood-Van Meerveld B. Enteroendocrine cells: a review of their role in brain-gut communication. Neurogastroenterol Motil 2016; 28 (05) 620-630
    CrossrefPubMedGoogle Scholar
  • 67 Hölscher C. Central effects of GLP-1: new opportunities for treatments of neurodegenerative diseases. J Endocrinol 2014; 221 (01) T31-T41
    CrossrefPubMedGoogle Scholar
  • 68 Cryan JF, O'Riordan KJ, Cowan CSM. et al. The microbiota-gut-brain axis. Physiol Rev 2019; 99 (04) 1877-2013
    CrossrefPubMedGoogle Scholar
  • 69 Terry N, Margolis KG. Serotonergic mechanisms regulating the GI tract: Experimental evidence and therapeutic relevance. In: Gastrointestinal Pharmacology. Vol 239. Switzerland: Springer International Publishing AG; 2017: 319-342
    Google Scholar
  • 70 Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry 2017; 4 (05) 409-418
    CrossrefPubMedGoogle Scholar
  • 71 Aaldijk E, Vermeiren Y. The role of serotonin within the microbiota-gut-brain axis in the development of Alzheimer's disease: a narrative review. Ageing Res Rev 2022; 75: 101556
    CrossrefPubMedGoogle Scholar
  • 72 Cross AJ, Crow TJ, Ferrier IN, Johnson JA, Bloom SR, Corsellis JAN. Serotonin receptor changes in dementia of the Alzheimer type. J Neurochem 1984; 43 (06) 1574-1581
    CrossrefPubMedGoogle Scholar
  • 73 Sheline YI, Snider BJ, Beer JC. et al. Effect of escitalopram dose and treatment duration on CSF Aβ levels in healthy older adults: a controlled clinical trial. Neurology 2020; 95 (19) e2658-e2665
    CrossrefPubMedGoogle Scholar
  • 74 Kessing LV, Søndergård L, Forman JL, Andersen PK. Antidepressants and dementia. J Affect Disord 2009; 117 (1-2): 24-29
    CrossrefPubMedGoogle Scholar
  • 75 Alboni S, van Dijk RM, Poggini S. et al. Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment. Mol Psychiatry 2017; 22 (04) 635
    CrossrefPubMedGoogle Scholar
  • 76 McVey Neufeld KA, Bienenstock J, Bharwani A. et al. Oral selective serotonin reuptake inhibitors activate vagus nerve dependent gut-brain signalling. Sci Rep 2019; 9 (01) 14290-11
    CrossrefPubMedGoogle Scholar
  • 77 Reigstad CS, Salmonson CE, Rainey III JF. et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 2015; 29 (04) 1395-1403
    CrossrefPubMedGoogle Scholar
  • 78 Clarke G, McKernan DP, Gaszner G, Quigley EM, Cryan JF, Dinan TG. A distinct profile of tryptophan metabolism along the kynurenine pathway downstream of toll-like receptor activation in irritable bowel syndrome. Front Pharmacol 2012; 3: 90
    CrossrefPubMedGoogle Scholar
  • 79 Hartstra AV, Schüppel V, Imangaliyev S. et al. Infusion of donor feces affects the gut-brain axis in humans with metabolic syndrome. Mol Metab 2020; 42: 101076
    CrossrefPubMedGoogle Scholar
  • 80 Zhu F, Guo R, Wang W. et al. Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice. Mol Psychiatry 2020; 25 (11) 2905-2918
    CrossrefPubMedGoogle Scholar
  • 81 Yano JM, Yu K, Donaldson GP. et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 2015; 161 (02) 264-276
    CrossrefPubMedGoogle Scholar
  • 82 Noristani HN, Verkhratsky A, Rodríguez JJ. High tryptophan diet reduces CA1 intraneuronal β-amyloid in the triple transgenic mouse model of Alzheimer's disease. Aging Cell 2012; 11 (05) 810-822
    CrossrefPubMedGoogle Scholar
  • 83 Jackson A, Forsyth CB, Shaikh M. et al. Diet in Parkinson's disease: critical role for the microbiome. Front Neurol 2019; 10: 1245
    CrossrefPubMedGoogle Scholar
  • 84 Hatcher JM, Pennell KD, Miller GW. Parkinson's disease and pesticides: a toxicological perspective. Trends Pharmacol Sci 2008; 29 (06) 322-329
    CrossrefPubMedGoogle Scholar
  • 85 Tanner CM, Kamel F, Ross GW. et al. Rotenone, paraquat, and Parkinson's disease. Environ Health Perspect 2011; 119 (06) 866-872
    CrossrefPubMedGoogle Scholar
  • 86 Salminen A, Ojala J, Kaarniranta K, Kauppinen A. Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases. Cell Mol Life Sci 2012; 69 (18) 2999-3013
    CrossrefPubMedGoogle Scholar
  • 87 Cicchetti F, Drouin-Ouellet J, Gross RE. Environmental toxins and Parkinson's disease: what have we learned from pesticide-induced animal models?. Trends Pharmacol Sci 2009; 30 (09) 475-483
    CrossrefPubMedGoogle Scholar
  • 88 Więckowska-Gacek A, Mietelska-Porowska A, Wydrych M, Wojda U. Western diet as a trigger of Alzheimer's disease: from metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration. Ageing Res Rev 2021; 70: 101397
    CrossrefPubMedGoogle Scholar
  • 89 Makki K, Deehan EC, Walter J, Bäckhed F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe 2018; 23 (06) 705-715
    CrossrefPubMedGoogle Scholar
  • 90 Maraki MI, Yannakoulia M, Stamelou M. et al. Mediterranean diet adherence is related to reduced probability of prodromal Parkinson's disease. Mov Disord 2019; 34 (01) 48-57
    CrossrefPubMedGoogle Scholar
  • 91 Gao X, Cassidy A, Schwarzschild MA, Rimm EB, Ascherio A. Habitual intake of dietary flavonoids and risk of Parkinson disease. 2012 Accessed June 20, 2023 at: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41247278
    PubMedGoogle Scholar
  • 92 Alcalay RN, Gu Y, Mejia-Santana H, Cote L, Marder KS, Scarmeas N. The association between Mediterranean diet adherence and Parkinson's disease. Mov Disord 2012; 27 (06) 771-774
    CrossrefPubMedGoogle Scholar
  • 93 Hoyles L, Snelling T, Umlai UK. et al. Microbiome–host systems interactions: Protective effects of propionate upon the blood–brain barrier. 2018 Accessed June 20, 2023 at: http://hdl.handle.net/10044/1/57884
    PubMedGoogle Scholar
  • 94 van de Wouw M, Boehme M, Lyte JM. et al. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations. J Physiol 2018; 596 (20) 4923-4944
    CrossrefPubMedGoogle Scholar
  • 95 Christ A, Günther P, Lauterbach MAR. et al. Western diet triggers NLRP3-dependent innate immune reprogramming. Cell 2018; 172 (1-2): 162-175.e14
    CrossrefPubMedGoogle Scholar
  • 96 Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci 2015; 7: 52
    CrossrefPubMedGoogle Scholar
  • 97 Tőzsér J, Benkő S. Natural compounds as regulators of NLRP3 inflammasome-mediated IL-1β production. Mediators Inflamm 2016; 2016: 5460302-5460316
    CrossrefPubMedGoogle Scholar
  • 98 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 (09) 1007-1014
    CrossrefPubMedGoogle Scholar
  • 99 Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab 2014; 19 (02) 181-192
    CrossrefPubMedGoogle Scholar
  • 100 Maswood N, Young J, Tilmont E. et al. Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease. Proc Natl Acad Sci U S A 2004; 101 (52) 18171-18176
    CrossrefPubMedGoogle Scholar
  • 101 Youm YH, Nguyen KY, Grant RW. et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med 2015; 21 (03) 263-269
    CrossrefPubMedGoogle Scholar
  • 102 Youm YH, Grant RW, McCabe LR. et al. Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging. Cell Metab 2013; 18 (04) 519-532
    CrossrefPubMedGoogle Scholar
  • 103 Fann DY, Santro T, Manzanero S. et al. Intermittent fasting attenuates inflammasome activity in ischemic stroke. Exp Neurol 2014; 257: 114-119
    CrossrefPubMedGoogle Scholar
  • 104 Moon M, Kim HG, Hwang L. et al. Neuroprotective effect of ghrelin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease by blocking microglial activation. Neurotox Res 2009; 15 (04) 332-347
    CrossrefPubMedGoogle Scholar
  • 105 Mason GM, Lokhandwala S, Riggins T, Spencer RMC. Sleep and human cognitive development. Sleep Med Rev 2021; 57: 101472
    CrossrefPubMedGoogle Scholar
  • 106 Sen P, Molinero-Perez A, O'Riordan KJ, McCafferty CP, O'Halloran KD, Cryan JF. Microbiota and sleep: awakening the gut feeling. Trends Mol Med 2021; 27 (10) 935-945
    CrossrefPubMedGoogle Scholar
  • 107 Pires GN, Bezerra AG, Tufik S, Andersen ML. Effects of acute sleep deprivation on state anxiety levels: a systematic review and meta-analysis. Sleep Med 2016; 24: 109-118
    CrossrefPubMedGoogle Scholar
  • 108 Koch CE, Leinweber B, Drengberg BC, Blaum C, Oster H. Interaction between circadian rhythms and stress. Neurobiol Stress 2016; 6 (C): 57-67
    CrossrefPubMedGoogle Scholar
  • 109 Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci 2015; 9: 392
    CrossrefPubMedGoogle Scholar
  • 110 Zanini MA, Castro J, Cunha GR. et al. Abnormalities in sleep patterns in individuals at risk for psychosis and bipolar disorder. Schizophr Res 2015; 169 (1-3): 262-267
    CrossrefPubMedGoogle Scholar
  • 111 Hyun MK, Baek Y, Lee S. Association between digestive symptoms and sleep disturbance: a cross-sectional community-based study. BMC Gastroenterol 2019; 19 (01) 34
    CrossrefPubMedGoogle Scholar
  • 112 Ogawa Y, Miyoshi C, Obana N. et al. Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice. Sci Rep 2020; 10 (01) 19554
    CrossrefPubMedGoogle Scholar
  • 113 Yu L, Han X, Cen S. et al. Beneficial effect of GABA-rich fermented milk on insomnia involving regulation of gut microbiota. Microbiol Res 2020; 233: 126409
    CrossrefPubMedGoogle Scholar
  • 114 Scheiermann C, Kunisaki Y, Frenette PS. Circadian control of the immune system. Nat Rev Immunol 2013; 13 (03) 190-198
    CrossrefPubMedGoogle Scholar
  • 115 Ruben MD, Wu G, Smith DF. et al. A database of tissue-specific rhythmically expressed human genes has potential applications in circadian medicine. Sci Transl Med 2018; 10 (458) eaat8806
    CrossrefPubMedGoogle Scholar
  • 116 Bishehsari F, Engen PA, Voigt RM. et al. Abnormal eating patterns cause circadian disruption and promote alcohol-associated colon carcinogenesis. Cell Mol Gastroenterol Hepatol 2020; 9 (02) 219-237
    CrossrefPubMedGoogle Scholar
  • 117 Forsyth CB, Shaikh M, Bishehsari F. et al. Alcohol feeding in mice promotes colonic hyperpermeability and changes in colonic organoid stem cell fate. Alcohol Clin Exp Res 2017; 41 (12) 2100-2113
    CrossrefPubMedGoogle Scholar
  • 118 Summa KC, Voigt RM, Forsyth CB. et al. Disruption of the circadian clock in mice increases intestinal permeability and promotes alcohol-induced hepatic pathology and inflammation. PLoS One 2013; 8 (06) e67102
    CrossrefPubMedGoogle Scholar
  • 119 Swanson GR, Gorenz A, Shaikh M. et al. Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking. Am J Physiol Gastrointest Liver Physiol 2016; 311 (01) G192-G201
    CrossrefPubMedGoogle Scholar
  • 120 Moravcová S, Pačesová D, Melkes B. et al. The day/night difference in the circadian clock's response to acute lipopolysaccharide and the rhythmic Stat3 expression in the rat suprachiasmatic nucleus. PLoS One 2018; 13 (09) e0199405
    CrossrefPubMedGoogle Scholar
  • 121 Videnovic A, Golombek D. Circadian and sleep disorders in Parkinson's disease. Exp Neurol 2013; 243: 45-56
    CrossrefPubMedGoogle Scholar
  • 122 Heintz-Buschart A, Pandey U, Wicke T. et al. The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder. Mov Disord 2018; 33 (01) 88-98
    CrossrefPubMedGoogle Scholar
  • 123 Moreno-Indias I, Torres M, Montserrat JM. et al. Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. Eur Respir J 2015; 45 (04) 1055-1065
    CrossrefPubMedGoogle Scholar
  • 124 Li Y, Zhang B, Zhou Y. et al. Gut microbiota changes and their relationship with inflammation in patients with acute and chronic insomnia. Nat Sci Sleep 2020; 12: 895-905
    CrossrefPubMedGoogle Scholar
  • 125 Zhang Y, Xie B, Chen X, Zhang J, Yuan S. A key role of gut microbiota-vagus nerve/spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration. Life Sci 2021; 265: 118736
    CrossrefPubMedGoogle Scholar
  • 126 Kaczmarek JL, Musaad SM, Holscher HD. Time of day and eating behaviors are associated with the composition and function of the human gastrointestinal microbiota. Am J Clin Nutr 2017; 106 (05) 1220-1231
    CrossrefPubMedGoogle Scholar
  • 127 Thompson RS, Vargas F, Dorrestein PC, Chichlowski M, Berg BM, Fleshner M. Dietary prebiotics alter novel microbial dependent fecal metabolites that improve sleep. Sci Rep 2020; 10 (01) 3848
    CrossrefPubMedGoogle Scholar
  • 128 Petrov ME, Whisner CM, McCormick D, Todd M, Reifsnider E. Sleep-wake patterns during infancy are associated with gut microbial community structure in toddlerhood (Abstract Supplement 0243). Sleep (Basel) 2019; 42 (01) A100
    CrossrefPubMedGoogle Scholar
  • 129 Lightman SL, Birnie MT, Conway-Campbell BL. Dynamics of ACTH and cortisol secretion and implications for disease. Endocr Rev 2020; 41 (03) 470-490
    CrossrefPubMedGoogle Scholar
  • 130 Gareau MG, Silva MA, Perdue MH. Pathophysiological mechanisms of stress-induced intestinal damage. Curr Mol Med 2008; 8 (04) 274-281
    CrossrefPubMedGoogle Scholar
  • 131 Dodiya HB, Forsyth CB, Voigt RM. et al. Chronic stress-induced gut dysfunction exacerbates Parkinson's disease phenotype and pathology in a rotenone-induced mouse model of Parkinson's disease. Neurobiol Dis 2020; 135: 104352
    CrossrefPubMedGoogle Scholar
  • 132 Braak H, Rüb U, Gai WP, Del Tredici K. Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna) 2003; 110 (05) 517-536
    CrossrefPubMedGoogle Scholar
  • 133 Dogra N, Mani RJ, Katare DP. The gut-brain axis: two ways signaling in Parkinson's disease. Cell Mol Neurobiol 2022; 42 (02) 315-332
    CrossrefPubMedGoogle Scholar
  • 134 Holmqvist S, Chutna O, Bousset L. et al. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol 2014; 128 (06) 805-820
    CrossrefPubMedGoogle Scholar
  • 135 Rietdijk CD, Perez-Pardo P, Garssen J, van Wezel RJ, Kraneveld AD. Exploring Braak's hypothesis of Parkinson's disease. Front Neurol 2017; 8: 37
    CrossrefPubMedGoogle Scholar
  • 136 Svensson E, Horváth-Puhó E, Thomsen RW. et al. Vagotomy and subsequent risk of Parkinson's disease. Ann Neurol 2015; 78 (04) 522-529
    CrossrefPubMedGoogle Scholar
  • 137 Kelly LP, Carvey PM, Keshavarzian A. et al. Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson's disease. Mov Disord 2014; 29 (08) 999-1009
    CrossrefPubMedGoogle Scholar
  • 138 Liddle RA. Parkinson's disease from the gut. Brain Res 2018; 1693 (Pt B): 201-206
    CrossrefPubMedGoogle Scholar
  • 139 Shannon KM, Keshavarzian A, Mutlu E. et al. Alpha-synuclein in colonic submucosa in early untreated Parkinson's disease. Mov Disord 2012; 27 (06) 709-715
    CrossrefPubMedGoogle Scholar
  • 140 Shannon KM, Keshavarzian A, Dodiya HB, Jakate S, Kordower JH. Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Mov Disord 2012; 27 (06) 716-719
    CrossrefPubMedGoogle Scholar
  • 141 Knudsen K, Krogh K, Østergaard K, Borghammer P. Constipation in Parkinson's disease: subjective symptoms, objective markers, and new perspectives. Mov Disord 2017; 32 (01) 94-105
    CrossrefPubMedGoogle Scholar
  • 142 Fasano A, Visanji NP, Liu LWC, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol 2015; 14 (06) 625-639
    CrossrefPubMedGoogle Scholar
  • 143 Borghammer P, Van Den Berge N. Brain-first versus gut-first Parkinson's disease: a hypothesis. J Parkinsons Dis 2019; 9 (Suppl. 02) S281-S295
    CrossrefPubMedGoogle Scholar
  • 144 Guo M, Wang J, Zhao Y. et al. Microglial exosomes facilitate α-synuclein transmission in Parkinson's disease. Brain 2020; 143 (05) 1476-1497
    CrossrefPubMedGoogle Scholar
  • 145 Ding XB, Wang XX, Xia DH. et al. Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson's disease. Nat Med 2021; 27 (03) 411-418
    CrossrefPubMedGoogle Scholar
  • 146 Pal G, Ramirez V, Engen PA. et al. Deep nasal sinus cavity microbiota dysbiosis in Parkinson's disease. NPJ Parkinsons Dis 2021; 7 (01) 111
    CrossrefPubMedGoogle Scholar
  • 147 Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuroendocrinol Lett 2008; 29 (01) 117-124
    PubMedGoogle Scholar
  • 148 Manosso LM, Lin J, Carlessi AS. et al. Sex-related patterns of the gut-microbiota-brain axis in the neuropsychiatric conditions. Brain Res Bull 2021; 171: 196-208
    CrossrefPubMedGoogle Scholar
  • 149 Hao WZ, Li XJ, Zhang PW, Chen JX. A review of antibiotics, depression, and the gut microbiome. Psychiatry Res 2020; 284: 112691
    CrossrefPubMedGoogle Scholar
  • 150 Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: a systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev 2019; 102: 13-23
    CrossrefPubMedGoogle Scholar
  • 151 Castro-Nallar E, Bendall ML, Pérez-Losada M. et al. Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls. PeerJ 2015; 3: e1140
    CrossrefPubMedGoogle Scholar
  • 152 Golofast B, Vales K. The connection between microbiome and schizophrenia. Neurosci Biobehav Rev 2020; 108: 712-731
    CrossrefPubMedGoogle Scholar
  • 153 Zheng P, Zeng B, Liu M. et al. The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice. Sci Adv 2019; 5 (02) eaau8317
    CrossrefPubMedGoogle Scholar
  • 154 Fiorentino M, Sapone A, Senger S. et al. Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism 2016; 7 (01) 49
    CrossrefPubMedGoogle Scholar
  • 155 Asbjornsdottir B, Snorradottir H, Andresdottir E. et al. Zonulin-dependent intestinal permeability in children diagnosed with mental disorders: a systematic review and meta-analysis. Nutrients 2020; 12 (07) 1982
    CrossrefPubMedGoogle Scholar
  • 156 Alabdali A, Al-Ayadhi L, El-Ansary A. Association of social and cognitive impairment and biomarkers in autism spectrum disorders. J Neuroinflammation 2014; 11 (01) 4 DOI: 10.1186/1742-2094-11-4.
    CrossrefPubMedGoogle Scholar