PDF herunterladen
CC BY 4.0 · Arq Neuropsiquiatr 2023; 81(07): 670-684
DOI: 10.1055/s-0043-1767818
View and Review

The brain-gut-microbiota axis in the treatment of neurologic and psychiatric disorders

O eixo microbiota-intestino-cérebro no tratamento de desordens neurológicas e psiquiátricas
Maria Fernanda Naufel 
1   Universidade Federal de São Paulo, Departamento de Fisiologia, São Paulo SP, Brazil.
,
Giselle de Martin Truzzi 
2   Universidade Federal de São Paulo, Departamento de Psicobiologia, São Paulo SP, Brazil.
,
Caroline Marcantonio Ferreira 
3   Universidade Federal de São Paulo, Departamento de Ciências Farmacêuticas, São Paulo SP, Brazil.
,
Fernando Morgadinho Santos Coelho 
2   Universidade Federal de São Paulo, Departamento de Psicobiologia, São Paulo SP, Brazil.
4   Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brazil.
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

Abstract

The human gut microbiota is a complex ecosystem made of trillions of microorganisms. The composition can be affected by diet, metabolism, age, geography, stress, seasons, temperature, sleep, and medications. The increasing evidence about the existence of a close and bi-directional correlation between the gut microbiota and the brain indicates that intestinal imbalance may play a vital role in the development, function, and disorders of the central nervous system. The mechanisms of interaction between the gut-microbiota on neuronal activity are widely discussed. Several potential pathways are involved with the brain-gut-microbiota axis, including the vagus nerve, endocrine, immune, and biochemical pathways. Gut dysbiosis has been linked to neurological disorders in different ways that involve activation of the hypothalamic-pituitary-adrenal axis, imbalance in neurotransmitter release, systemic inflammation, and increase in the permeability of the intestinal and the blood-brain barrier. Mental and neurological diseases have become more prevalent during the coronavirus disease 2019pandemic and are an essential issue in public health globally. Understanding the importance of diagnosing, preventing, and treating dysbiosis is critical because gut microbial imbalance is a significant risk factor for these disorders. This review summarizes evidence demonstrating the influence of gut dysbiosis on mental and neurological disorders.

Resumo

A microbiota intestinal humana é um ecossistema complexo feito de trilhões de microrganismos, cuja composição pode ser afetada pela dieta, pelo metabolismo, pela idade, geografia, pelo estresse, pelas estações do ano, pela temperatura, pelo sono e por medicamentos. A crescente evidência sobre a existência de uma correlação estreita e bidirecional entre a microbiota intestinal e o cérebro indica que o desequilíbrio intestinal pode desempenhar um papel vital no desenvolvimento, na função e nos distúrbios do sistema nervoso central. Os mecanismos de interação entre a microbiota intestinal e a atividade neuronal são amplamente discutidos. Várias vias potenciais estão envolvidas com o eixo microbiota-intestino-cérebro, incluindo o nervo vago e as vias endócrinas, imunes e bioquímicas. A disbiose intestinal tem sido associada a distúrbios neurológicos de diferentes maneiras que envolvem a ativação do eixo hipotálamo-hipófise-adrenal, o desequilíbrio na liberação de neurotransmissores, a inflamação sistêmica e o aumento da permeabilidade das barreiras intestinal e hematoencefálica. As doenças mentais e neurológicas tornaram-se mais prevalentes durante a pandemia de coronavirus disease 2019 e são uma questão global essencial na saúde pública. Compreender a importância de diagnosticar, prevenir e tratar a disbiose é fundamental porque o desequilíbrio microbiano intestinal é um fator de risco significativo para esses distúrbios. Esta revisão resume as evidências que demonstram a influência da disbiose intestinal em distúrbios mentais e neurológicos.

Keywords

Gastrointestinal Microbiome - Dysbiosis - Central Nervous System - Therapeutics

Palavras-chave

Microbioma Gastrointestinal - Disbiose - Sistema Nervoso Central - Terapêutica

Authors' Contributions

MFN, GMT, CMF, FMC: research idea and study design, drafting or revision of manuscript, and data acquisition and interpretation.


Support

The present work was supported by the Hospital São Paulo and the Department of Neurology and Neurosurgery of Universidade Federal de São Paulo, Brazil.




Publikationsverlauf

Eingereicht: 13. Oktober 2022

Angenommen: 04. Dezember 2022

Artikel online veröffentlicht:
04. Juli 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Eckburg PB, Bik EM, Bernstein CN. et al. Diversity of the human intestinal microbial flora. Science 2005; 308 (5728): 1635-1638
    CrossrefPubMedSuche in Google Scholar
  • 2 Integrative HMPRNC. Integrative HMP (iHMP) Research Network Consortium. The Integrative Human Microbiome Project. Nature 2019; 569 (7758): 641-648
    CrossrefPubMedSuche in Google Scholar
  • 3 Toor D, Wsson MK, Kumar P. et al. Dysbiosis Disrupts Gut Immune Homeostasis and Promotes Gastric Diseases. Int J Mol Sci 2019; 20 (10) 20
    CrossrefPubMedSuche in Google Scholar
  • 4 Bravo JA, Forsythe P, Chew MV. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 2011; 108 (38) 16050-16055
    CrossrefPubMedSuche in Google Scholar
  • 5 Allen AP, Hutch W, Borre YE. et al. Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Transl Psychiatry 2016; 6 (11) e939
    CrossrefPubMedSuche in Google Scholar
  • 6 Houser MC, Tansey MG. The gut-brain axis: is intestinal inflammation a silent driver of Parkinson's disease pathogenesis?. NPJ Parkinsons Dis 2017; 3: 3
    CrossrefPubMedSuche in Google Scholar
  • 7 Frost G, Sleeth ML, Sahuri-Arisoylu M. et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun 2014; 5: 3611
    CrossrefPubMedSuche in Google Scholar
  • 8 Tang Q, Jin G, Wang G. et al. Current Sampling Methods for Gut Microbiota: A Call for More Precise Devices. Front Cell Infect Microbiol 2020; 10: 151
    CrossrefPubMedSuche in Google Scholar
  • 9 Wei S, Bahl MI, Baunwall SMD, Hvas CL, Licht TR. Determining Gut Microbial Dysbiosis: a Review of Applied Indexes for Assessment of Intestinal Microbiota Imbalances. Appl Environ Microbiol 2021; 87 (11) 87
    Suche in Google Scholar
  • 10 Brüssow H. Problems with the concept of gut microbiota dysbiosis. Microb Biotechnol 2020; 13 (02) 423-434
    CrossrefPubMedSuche in Google Scholar
  • 11 Horiuchi Y, Kimura R, Kato N. et al. Evolutional study on acetylcholine expression. Life Sci 2003; 72 (15) 1745-1756
    CrossrefPubMedSuche in Google Scholar
  • 12 Cattaneo A, Cattane N, Galluzzi S. et al; INDIA-FBP Group. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging 2017; 49: 60-68
    CrossrefPubMedSuche in Google Scholar
  • 13 Chen Y, Xu J, Chen Y. Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients 2021; 13 (06) 13
    CrossrefPubMedSuche in Google Scholar
  • 14 Cummings J, Aisen P, Apostolova LG, Atri A, Salloway S, Weiner M. Aducanumab: Appropriate Use Recommendations. J Prev Alzheimers Dis 2021; 8 (04) 398-410
    CrossrefPubMedSuche in Google Scholar
  • 15 de Rijke TJ, Doting MHE, van Hemert S. et al. A Systematic Review on the Effects of Different Types of Probiotics in Animal Alzheimer's Disease Studies. Front Psychiatry 2022; 13: 879491
    CrossrefPubMedSuche in Google Scholar
  • 16 Cirstea MS, Sundvick K, Golz E. et al. The Gut Mycobiome in Parkinson's Disease. J Parkinsons Dis 2021; 11 (01) 153-158
    CrossrefPubMedSuche in Google Scholar
  • 17 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
    CrossrefPubMedSuche in Google Scholar
  • 18 Lorente-Picón M, Laguna A. New Avenues for Parkinson's Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota. Biomolecules 2021; 11 (03) 11
    CrossrefPubMedSuche in Google Scholar
  • 19 Palacios N, Hannoun A, Flahive J. et al. Effect of Levodopa Initiation on the Gut Microbiota in Parkinson's Disease. Front Neurol 2021; 12: 574529
    CrossrefPubMedSuche in Google Scholar
  • 20 Xue LJ, Yang XZ, Tong Q. et al. Fecal microbiota transplantation therapy for Parkinson's disease: A preliminary study. Medicine (Baltimore) 2020; 99 (35) e22035
    CrossrefPubMedSuche in Google Scholar
  • 21 Jangi S, Gandhi R, Cox LM. et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun 2016; 7: 12015
    CrossrefPubMedSuche in Google Scholar
  • 22 Adamczyk-Sowa M, Medrek A, Madej P, Michlicka W, Dobrakowski P. Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology?. J Immunol Res 2017; 2017: 7904821
    CrossrefPubMedSuche in Google Scholar
  • 23 Schepici G, Silvestro S, Bramanti P, Mazzon E. The Gut Microbiota in Multiple Sclerosis: An Overview of Clinical Trials. Cell Transplant 2019; 28 (12) 1507-1527
    CrossrefPubMedSuche in Google Scholar
  • 24 Dahlin M, Prast-Nielsen S. The gut microbiome and epilepsy. EBioMedicine 2019; 44: 741-746
    CrossrefPubMedSuche in Google Scholar
  • 25 Ceccarani C, Viganò I, Ottaviano E. et al. Is Gut Microbiota a Key Player in Epilepsy Onset? A Longitudinal Study in Drug-Naive Children. Front Cell Infect Microbiol 2021; 11: 749509
    CrossrefPubMedSuche in Google Scholar
  • 26 International Classification of Sleep Disorders – Third edition (ICSD-3). 3rd ed.. American Academy of Sleep Medicine; 2014
    Suche in Google Scholar
  • 27 Veasey SC, Rosen IM. Obstructive Sleep Apnea in Adults. N Engl J Med 2019; 380 (15) 1442-1449
    CrossrefPubMedSuche in Google Scholar
  • 28 Badran M, Mashaqi S, Gozal D. The gut microbiome as a target for adjuvant therapy in obstructive sleep apnea. Expert Opin Ther Targets 2020; 24 (12) 1263-1282
    CrossrefPubMedSuche in Google Scholar
  • 29 Valentini F, Evangelisti M, Arpinelli M. et al. Gut microbiota composition in children with obstructive sleep apnoea syndrome: a pilot study. Sleep Med 2020; 76: 140-147
    CrossrefPubMedSuche in Google Scholar
  • 30 Durgan DJ. Obstructive Sleep Apnea-Induced Hypertension: Role of the Gut Microbiota. Curr Hypertens Rep 2017; 19 (04) 35
    CrossrefPubMedSuche in Google Scholar
  • 31 Liew SC, Aung T. Sleep deprivation and its association with diseases- a review. Sleep Med 2021; 77: 192-204
    CrossrefPubMedSuche in Google Scholar
  • 32 Reynolds AC, Paterson JL, Ferguson SA, Stanley D, Wright Jr KP, Dawson D. The shift work and health research agenda: Considering changes in gut microbiota as a pathway linking shift work, sleep loss and circadian misalignment, and metabolic disease. Sleep Med Rev 2017; 34: 3-9
    CrossrefPubMedSuche in Google Scholar
  • 33 Wang Z, Chen WH, Li SX. et al. Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation. Mol Psychiatry 2021; 26 (11) 6277-6292
    CrossrefPubMedSuche in Google Scholar
  • 34 Karl JP, Hatch AM, Arcidiacono SM. et al. Effects of Psychological, Environmental and Physical Stressors on the Gut Microbiota. Front Microbiol 2018; 9: 2013
    CrossrefPubMedSuche in Google Scholar
  • 35 Smith RP, Easson C, Lyle SM. et al. Gut microbiome diversity is associated with sleep physiology in humans. PLoS One 2019; 14 (10) e0222394
    CrossrefPubMedSuche in Google Scholar
  • 36 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
    CrossrefPubMedSuche in Google Scholar
  • 37 Park YS, Kim SH, Park JW. et al. Melatonin in the colon modulates intestinal microbiota in response to stress and sleep deprivation. Intest Res 2020; 18 (03) 325-336
    CrossrefPubMedSuche in Google Scholar
  • 38 Hernández-García J, Navas-Carrillo D, Orenes-Piñero E. Alterations of circadian rhythms and their impact on obesity, metabolic syndrome and cardiovascular diseases. Crit Rev Food Sci Nutr 2020; 60 (06) 1038-1047
    CrossrefPubMedSuche in Google Scholar
  • 39 Voigt RM, Forsyth CB, Green SJ, Engen PA, Keshavarzian A. Circadian Rhythm and the Gut Microbiome. Int Rev Neurobiol 2016; 131: 193-205
    CrossrefPubMedSuche in Google Scholar
  • 40 Parekh PJ, Oldfield IV EC, Johnson DA. The Effects of Sleep on the Commensal Microbiota: Eyes Wide Open?. J Clin Gastroenterol 2018; 52 (03) 204-209
    CrossrefPubMedSuche in Google Scholar
  • 41 Anderson JR, Carroll I, Azcarate-Peril MA. et al. A preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adults. Sleep Med 2017; 38: 104-107
    CrossrefPubMedSuche in Google Scholar
  • 42 Hua X, Zhu J, Yang T. et al. The Gut Microbiota and Associated Metabolites Are Altered in Sleep Disorder of Children With Autism Spectrum Disorders. Front Psychiatry 2020; 11: 855
    CrossrefPubMedSuche in Google Scholar
  • 43 Lecomte A, Barateau L, Pereira P. et al. Gut microbiota composition is associated with narcolepsy type 1. Neurol Neuroimmunol Neuroinflamm 2020; 7 (06) 7
    CrossrefPubMedSuche in Google Scholar
  • 44 Wagner-Skacel J, Dalkner N, Moerkl S. et al. Sleep and Microbiome in Psychiatric Diseases. Nutrients 2020; 12 (08) 12
    CrossrefPubMedSuche in Google Scholar
  • 45 Organization WH. Depression and Other Common Mental Disorders Global Health Estimates. World Health Organization; 2017
    Suche in Google Scholar
  • 46 Canet-Juric L, Andrés ML, Del Valle M. et al. A Longitudinal Study on the Emotional Impact Cause by the COVID-19 Pandemic Quarantine on General Population. Front Psychol 2020; 11: 565688
    CrossrefPubMedSuche in Google Scholar
  • 47 Bet PM, Hugtenburg JG, Penninx BW, Hoogendijk WJ. Side effects of antidepressants during long-term use in a naturalistic setting. Eur Neuropsychopharmacol 2013; 23 (11) 1443-1451
    CrossrefPubMedSuche in Google Scholar
  • 48 Bowers HM, Williams SJ, Geraghty AWA. et al. Helping people discontinue long-term antidepressants: views of health professionals in UK primary care. BMJ Open 2019; 9 (07) e027837
    CrossrefPubMedSuche in Google Scholar
  • 49 Dinan TG, Cryan JF. Brain-Gut-Microbiota Axis and Mental Health. Psychosom Med 2017; 79 (08) 920-926
    CrossrefPubMedSuche in Google Scholar
  • 50 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
    CrossrefPubMedSuche in Google Scholar
  • 51 Suganya K, Koo BS. Gut-Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions. Int J Mol Sci 2020; 21 (20) 21
    CrossrefPubMedSuche in Google Scholar
  • 52 Misiak B, Łoniewski I, Marlicz W. et al. The HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota?. Prog Neuropsychopharmacol Biol Psychiatry 2020; 102: 109951
    CrossrefPubMedSuche in Google Scholar
  • 53 Waclawiková B, El Aidy S. Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression. Pharmaceuticals (Basel) 2018; 11 (03) 11
    CrossrefPubMedSuche in Google Scholar
  • 54 Kim DY, Camilleri M. Serotonin: a mediator of the brain-gut connection. Am J Gastroenterol 2000; 95 (10) 2698-2709
    CrossrefPubMedSuche in Google Scholar
  • 55 Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res 2018; 1693 (Pt B): 128-133
    CrossrefPubMedSuche in Google Scholar
  • 56 Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?. Gastroenterology 2002; 122 (04) 1140-1156
    CrossrefPubMedSuche in Google Scholar
  • 57 Faravelli C, Lo Sauro C, Godini L. et al. Childhood stressful events, HPA axis and anxiety disorders. World J Psychiatry 2012; 2 (01) 13-25
    CrossrefPubMedSuche in Google Scholar
  • 58 Huo R, Zeng B, Zeng L. et al. Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis. Front Cell Infect Microbiol 2017; 7: 489
    CrossrefPubMedSuche in Google Scholar
  • 59 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
    CrossrefPubMedSuche in Google Scholar
  • 60 Huang F, Wu X. Brain Neurotransmitter Modulation by Gut Microbiota in Anxiety and Depression. Front Cell Dev Biol 2021; 9: 649103
    CrossrefPubMedSuche in Google Scholar
  • 61 Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol 2004; 70 (11) 6459-6465
    CrossrefPubMedSuche in Google Scholar
  • 62 Iglesias-Vázquez L, Van Ginkel Riba G, Arija V, Canals J. Composition of Gut Microbiota in Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Nutrients 2020; 12 (03) 12
    CrossrefPubMedSuche in Google Scholar
  • 63 Socała K, Doboszewska U, Szopa A. et al. The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders. Pharmacol Res 2021; 172: 105840
    CrossrefPubMedSuche in Google Scholar
  • 64 Bhadra R, Cobb DA, Weiss LM, Khan IA. Psychiatric disorders in toxoplasma seropositive patients–the CD8 connection. Schizophr Bull 2013; 39 (03) 485-489
    CrossrefPubMedSuche in Google Scholar
  • 65 Kim YK, Shin C. The Microbiota-Gut-Brain Axis in Neuropsychiatric Disorders: Pathophysiological Mechanisms and Novel Treatments. Curr Neuropharmacol 2018; 16 (05) 559-573
    CrossrefPubMedSuche in Google Scholar
  • 66 Painold A, Mörkl S, Kashofer K. et al. A step ahead: Exploring the gut microbiota in inpatients with bipolar disorder during a depressive episode. Bipolar Disord 2019; 21 (01) 40-49
    CrossrefPubMedSuche in Google Scholar
  • 67 Yolken R, Adamos M, Katsafanas E. et al. Individuals hospitalized with acute mania have increased exposure to antimicrobial medications. Bipolar Disord 2016; 18 (05) 404-409
    CrossrefPubMedSuche in Google Scholar
  • 68 Parkin K, Christophersen CT, Verhasselt V, Cooper MN, Martino D. Risk Factors for Gut Dysbiosis in Early Life. Microorganisms 2021; 9 (10) 9
    CrossrefPubMedSuche in Google Scholar
  • 69 Mörkl S, Butler MI, Holl A, Cryan JF, Dinan TG. Probiotics and the Microbiota-Gut-Brain Axis: Focus on Psychiatry. Curr Nutr Rep 2020; 9 (03) 171-182
    CrossrefPubMedSuche in Google Scholar
  • 70 Bousquet M, Calon F, Cicchetti F. Impact of ω-3 fatty acids in Parkinson's disease. Ageing Res Rev 2011; 10 (04) 453-463
    CrossrefPubMedSuche in Google Scholar
  • 71 Modi SR, Collins JJ, Relman DA. Antibiotics and the gut microbiota. J Clin Invest 2014; 124 (10) 4212-4218
    CrossrefPubMedSuche in Google Scholar
  • 72 Cankaya S, Cankaya B, Kilic U, Kilic E, Yulug B. The therapeutic role of minocycline in Parkinson's disease. Drugs Context 2019; 8: 212553
    CrossrefPubMedSuche in Google Scholar
  • 73 Tait C, Sayuk GS. The Brain-Gut-Microbiotal Axis: A framework for understanding functional GI illness and their therapeutic interventions. Eur J Intern Med 2021; 84: 1-9
    CrossrefPubMedSuche in Google Scholar
  • 74 Long-Smith C, O'Riordan KJ, Clarke G, Stanton C, Dinan TG, Cryan JF. Microbiota-Gut-Brain Axis: New Therapeutic Opportunities. Annu Rev Pharmacol Toxicol 2020; 60: 477-502
    CrossrefPubMedSuche in Google Scholar
  • 75 Tamtaji OR, Taghizadeh M, Daneshvar Kakhaki R. et al. Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trial. Clin Nutr 2019; 38 (03) 1031-1035
    CrossrefPubMedSuche in Google Scholar
  • 76 Agahi A, Hamidi GA, Daneshvar R. et al. Does Severity of Alzheimer's Disease Contribute to Its Responsiveness to Modifying Gut Microbiota? A Double Blind Clinical Trial. Front Neurol 2018; 9: 662
    CrossrefPubMedSuche in Google Scholar
  • 77 Barichella M, Pacchetti C, Bolliri C. et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT. Neurology 2016; 87 (12) 1274-1280
    CrossrefPubMedSuche in Google Scholar
  • 78 Rahimlou M, Nematollahi S, Husain D, Banaei-Jahromi N, Majdinasab N, Hosseini SA. Probiotic supplementation and systemic inflammation in relapsing-remitting multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Front Neurosci 2022; 16: 901846
    CrossrefPubMedSuche in Google Scholar
  • 79 Kouchaki E, Tamtaji OR, Salami M. et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr 2017; 36 (05) 1245-1249
    CrossrefPubMedSuche in Google Scholar
  • 80 Lee HJ, Hong JK, Kim JK. et al. Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients 2021; 13 (08) 13
    CrossrefPubMedSuche in Google Scholar
  • 81 Ho YT, Tsai YC, Kuo TBJ, Yang CCH. Effects of Lactobacillus plantarum PS128 on Depressive Symptoms and Sleep Quality in Self-Reported Insomniacs: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial. Nutrients 2021; 13 (08) 13
    CrossrefPubMedSuche in Google Scholar
  • 82 Kazemi A, Noorbala AA, Azam K, Eskandari MH, Djafarian K. Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial. Clin Nutr 2019; 38 (02) 522-528
    CrossrefPubMedSuche in Google Scholar
  • 83 Sanchez M, Darimont C, Panahi S. et al. Effects of a Diet-Based Weight-Reducing Program with Probiotic Supplementation on Satiety Efficiency, Eating Behaviour Traits, and Psychosocial Behaviours in Obese Individuals. Nutrients 2017; 9 (03) 9
    CrossrefPubMedSuche in Google Scholar
  • 84 Qin Q, Liu H, Yang Y. et al. Probiotic Supplement Preparation Relieves Test Anxiety by Regulating Intestinal Microbiota in College Students. Dis Markers 2021; 2021: 5597401
    PubMedSuche in Google Scholar
  • 85 Slykerman RF, Hood F, Wickens K. et al; Probiotic in Pregnancy Study Group. Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial. EBioMedicine 2017; 24: 159-165
    CrossrefPubMedSuche in Google Scholar
  • 86 Shaaban SY, El Gendy YG, Mehanna NS. et al. The role of probiotics in children with autism spectrum disorder: A prospective, open-label study. Nutr Neurosci 2018; 21 (09) 676-681
    CrossrefPubMedSuche in Google Scholar
  • 87 Santocchi E, Guiducci L, Prosperi M. et al. Effects of Probiotic Supplementation on Gastrointestinal, Sensory and Core Symptoms in Autism Spectrum Disorders: A Randomized Controlled Trial. Front Psychiatry 2020; 11: 550593
    CrossrefPubMedSuche in Google Scholar
  • 88 Ghaderi A, Banafshe HR, Mirhosseini N. et al. Clinical and metabolic response to vitamin D plus probiotic in schizophrenia patients. BMC Psychiatry 2019; 19 (01) 77
    CrossrefPubMedSuche in Google Scholar
  • 89 Tomasik J, Yolken RH, Bahn S, Dickerson FB. Immunomodulatory Effects of Probiotic Supplementation in Schizophrenia Patients: A Randomized, Placebo-Controlled Trial. Biomark Insights 2015; 10: 47-54
    CrossrefPubMedSuche in Google Scholar
  • 90 Reininghaus EZ, Wetzlmair LC, Fellendorf FT. et al. The Impact of Probiotic Supplements on Cognitive Parameters in Euthymic Individuals with Bipolar Disorder: A Pilot Study. Neuropsychobiology 2018; •••: 1-8
    Suche in Google Scholar
  • 91 Del Toro-Barbosa M, Hurtado-Romero A, Garcia-Amezquita LE, García-Cayuela T. Psychobiotics: Mechanisms of Action, Evaluation Methods and Effectiveness in Applications with Food Products. Nutrients 2020; 12 (12) 12
    CrossrefPubMedSuche in Google Scholar
  • 92 Pedrolli DB, Ribeiro NV, Squizato PN, de Jesus VN, Cozetto DA. Team AQA Unesp at iGEM 2017. Engineering Microbial Living Therapeutics: The Synthetic Biology Toolbox. Trends Biotechnol 2019; 37 (01) 100-115
    CrossrefPubMedSuche in Google Scholar
  • 93 Riglar DT, Silver PA. Engineering bacteria for diagnostic and therapeutic applications. Nat Rev Microbiol 2018; 16 (04) 214-225
    CrossrefPubMedSuche in Google Scholar
  • 94 Zhu F, Tu H, Chen T. The Microbiota-Gut-Brain Axis in Depression: The Potential Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect. Nutrients 2022; 14 (10) 14
    CrossrefPubMedSuche in Google Scholar
  • 95 Xiao L, Yan J, Yang T. et al. Fecal Microbiome Transplantation from Children with Autism Spectrum Disorder Modulates Tryptophan and Serotonergic Synapse Metabolism and Induces Altered Behaviors in Germ-Free Mice. mSystems 2021; 6 (02) 6
    CrossrefPubMedSuche in Google Scholar