PDF herunterladen
Erfahrungsheilkunde 2019; 68(05): 270-277
DOI: 10.1055/a-1008-7780
Wissen
© MVS Medizinverlage Stuttgart GmbH & Co. KG Stuttgart · New York

Veränderungen der Darm-Gehirn-Achse beim Reizdarmsyndrom – Ein Update

Stephanie Gladys Kühne
,
Andreas Stengel
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
17. Oktober 2019 (online)

    Lizenzen und Reprints

Zusammenfassung

Das Reizdarmsyndrom (RDS) ist eine der häufigsten funktionellen Störungen. Hierbei sind gastrointestinale Symptome wie abdominelle Schmerzen, Diarrhoe oder Obstipation nicht ausreichend organopathologisch erklärbar. Dennoch wurden beim RDS verschiedene Veränderungen im Bereich der Darm-Gehirn-Achse beschrieben, welche pathogenetische, aber auch therapeutische Relevanz haben können. Der vorliegende Artikel soll ein Update zum aktuellen Forschungsstand der Veränderungen der Darm-Gehirn-Achse und potenzieller dort ansetzender Therapieoptionen beim RDS geben.

Abstract

Irritable bowel syndrome (IBS) is one of the most common functional disorders. Gastrointestinal symptoms such as abdominal pain, diarrhea and constipation are not sufficiently explained by organopathological alterations. Nonetheless, several alterations of the gut-brain axis have been described in IBS patients which might play a role in the pathogenesis but also in the therapy of the disease. The current article will give an update on the state-of-knowledge on alterations of the gut-brain axis in IBS and respective potential treatment targets.

Schlüsselwörter

Darm-Gehirn-Achse - Mikrobiom - Psychosomatik - Reizdarmsyndrom - somatoform

Key words

Brain-gut axis - irritable bowel syndrome - microbiome - psychosomatic - somatoform
 

  • Literatur

  • 1 Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features and rome IV. Gastroenterology. 2016 doi:10.1053/j.gastro.2016.02.032
    PubMedGoogle Scholar
  • 2 Lacy BE, Mearin F, Chang L. et al. Bowel disorders. Gastroenterology 2016; 150: 1393-1407
    CrossrefPubMedGoogle Scholar
  • 3 Van Oudenhove L, Levy RL, Crowell MD. et al. Biopsychosocial aspects of functional gastrointestinal disorders: how central and environmental processes contribute to the development and expression of functional gastrointestinal disorders. Gastroenterology 2016; 150: 1355-1367
    CrossrefPubMedGoogle Scholar
  • 4 Palsson OS, Whitehead WE, van Tilburg MA. et al. Rome IV diagnostic questionnaires and tables for investigators and clinicians. Gastroenterology. 2016 doi:10.1053/j.gastro.2016.02.014
    PubMedGoogle Scholar
  • 5 Carabotti M, Scirocco A, Maselli MA. et al. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol 2015; 28: 203-209
    PubMedGoogle Scholar
  • 6 Zhu X, Han Y, Du J. et al. Microbiota-gut-brain axis and the central nervous system. Oncotarget 2017; 8: 53829-53838
    CrossrefPubMedGoogle Scholar
  • 7 Bonaz B, Bazin T, Pellissier S. The vagus nerve at the interface of the microbiota-gut-brain axis. Front Neurosci 2018; 12: 49 doi:10.3389/fnins.2018.00049
    CrossrefPubMedGoogle Scholar
  • 8 Appleton J. The gut-brain axis: influence of microbiota on mood and mental health. Integrative Medicine (Encinitas, Calif) 2018; 17: 28-32
    PubMedGoogle Scholar
  • 9 Stengel A, Taché Y. Gut-brain neuroendocrine signaling under conditions of stress-focus on food intake-regulatory mediators. Front Endocrinol (Lausanne) 2018; 9: 498 doi:10.3389/fendo.2018.00498
    CrossrefPubMedGoogle Scholar
  • 10 Boeckxstaens G, Camilleri M, Sifrim D. et al. Fundamentals of neurogastroenterology: physiology/motility – sensation. Gastroenterology. 2016 doi:10.1053/j.gastro.2016.02.030
    PubMedGoogle Scholar
  • 11 Yang B, Wei J, Ju P. et al. Effects of regulating intestinal microbiota on anxiety symptoms: A systematic review. General Psychiatry 2019; 32: e100056 doi:10.1136/gpsych-2019–100056
    CrossrefPubMedGoogle Scholar
  • 12 Mandal A, Prabhavalkar KS, Bhatt LK. Gastrointestinal hormones in regulation of memory. Peptides 2018; 102: 16-25
    CrossrefPubMedGoogle Scholar
  • 13 Russo R, Cristiano C, Avagliano C. et al. Gut-brain axis: role of lipids in the regulation of inflammation, pain and CNS diseases. Curr Med Chem 2018; 25: 3930-3952
    CrossrefPubMedGoogle Scholar
  • 14 Heym N, Heasman BC, Hunter K. et al. The role of microbiota and inflammation in self-judgement and empathy: implications for understanding the brain-gut-microbiome axis in depression. Psychopharmacol (Berl). 2019 doi:10.1007/s00213–019–05230–2
    PubMedGoogle Scholar
  • 15 Lach G, Schellekens H, Dinan TG. et al. Anxiety, depression, and the microbiome: A role for gut peptides. Neurotherapeutics 2018; 15: 36-59
    CrossrefPubMedGoogle Scholar
  • 16 Luca M, Di Mauro M, Di Mauro M. et al. Gut microbiota in alzheimer’s disease, depression, and type 2 diabetes mellitus: the role of oxidative stress. Oxidative medicine and cellular longevity 2019; 2019: 4730539 doi:10.1155/2019/4730539
    PubMedGoogle Scholar
  • 17 Raskov H, Burcharth J, Pommergaard HC. et al. Irritable bowel syndrome, the microbiota and the gut-brain axis. Gut Microbes 2016; 7: 365-383
    CrossrefPubMedGoogle Scholar
  • 18 Midenfjord I, Polster A, Sjovall H. et al. Anxiety and depression in irritable bowel syndrome: Exploring the interaction with other symptoms and pathophysiology using multivariate analyses. Neurogastroenterol Motil. 2019 doi:10.1111/nmo.13619: e13619
    PubMedGoogle Scholar
  • 19 Zamani M, Alizadeh-Tabari S, Zamani V. Systematic review with meta-analysis: the prevalence of anxiety and depression in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2019 doi:10.1111/apt.15325
    PubMedGoogle Scholar
  • 20 Shariati A, Fallah F, Pormohammad A. et al. The possible role of bacteria, viruses, and parasites in initiation and exacerbation of irritable bowel syndrome. J Cellular Physiol 2019; 234: 8550-8569
    CrossrefPubMedGoogle Scholar
  • 21 Lee YY, Annamalai C, Rao SSC. Post-infectious irritable bowel syndrome. Current Gastroenterol Reports 2017; 19: 56 doi:10.1007/s11894–017–0595–4
    PubMedGoogle Scholar
  • 22 Saito YA, Petersen GM, Larson JJ. et al. Familial aggregation of irritable bowel syndrome: A family case-control study. Am J Gastroenterol 2010; 105: 833-841
    CrossrefPubMedGoogle Scholar
  • 23 Makker J, Chilimuri S, Bella JN. Genetic epidemiology of irritable bowel syndrome. World J Gastroenterol 2015; 21: 11353-11361
    CrossrefPubMedGoogle Scholar
  • 24 Beyder A, Mazzone A, Strege PR. et al. Loss-of-function of the voltage-gated sodium channel NaV1. 5 (channelopathies) in patients with irritable bowel syndrome. Gastroenterol 2014; 146: 1659-1668
    CrossrefPubMedGoogle Scholar
  • 25 Gulewitsch MD, Weimer K, Enck P. et al. Stress reactivity in childhood functional abdominal pain or irritable bowel syndrome. Eur J Pain (London, England) 2017; 21: 166-177
    CrossrefPubMedGoogle Scholar
  • 26 Sibelli A, Chalder T, Everitt H. et al. A systematic review with meta-analysis of the role of anxiety and depression in irritable bowel syndrome onset. Psychol Med 2016; 46: 3065-3080
    CrossrefPubMedGoogle Scholar
  • 27 Martínez C, González-Castro A, Vicario M. et al. Cellular and molecular basis of intestinal barrier dysfunction in the irritable bowel syndrome. Gut and Liver 2012; 6: 305
    CrossrefPubMedGoogle Scholar
  • 28 Ford AC, Lacy BE, Talley NJ. Irritable bowel syndrome. NEJM 2017; 376: 2566-2578
    CrossrefPubMedGoogle Scholar
  • 29 Witt ST, Bednarska O, Keita AV. et al. Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome. NeuroImage Clinical 2019; 21: 101602 doi:10.1016/j.nicl.2018.11.012
    CrossrefPubMedGoogle Scholar
  • 30 Chey WY, Jin HO, Lee MH. et al. Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am J Gastroenterol 2001; 96: 1499-1506
    CrossrefPubMedGoogle Scholar
  • 31 Bassotti G, Chistolini F, Marinozzi G. et al. Abnormal colonic propagated activity in patients with slow transit constipation and constipation-predominant irritable bowel syndrome. Digestion 2003; 68: 178-183
    CrossrefPubMedGoogle Scholar
  • 32 Yu Y-C, Li J, Zhang M. et al. Resveratrol improves brain-gut axis by regulation of 5-HT-dependent signaling in the rat model of irritable bowel syndrome. Front Cell Neurosci 2019; 13: 30-30
    CrossrefPubMedGoogle Scholar
  • 33 Lin M, Chen L, Xiao Y. et al. Activation of cannabinoid 2 receptor relieves colonic hypermotility in a rat model of irritable bowel syndrome. Neurogastroenterol Motil 2019; 31: e13555 doi:10.1111/nmo.13555
    CrossrefPubMedGoogle Scholar
  • 34 Sinagra E, Morreale GC, Mohammadian G. et al. New therapeutic perspectives in irritable bowel syndrome: targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond. World J Gastroenterol 2017; 23: 6593-6627
    CrossrefPubMedGoogle Scholar
  • 35 Ohman L, Lindmark AC, Isaksson S. et al. B-cell activation in patients with irritable bowel syndrome (IBS). Neurogastroenterology and Motility 2009; 21: 644-650
    PubMedGoogle Scholar
  • 36 Ohman L, Isaksson S, Lindmark AC. et al. T-cell activation in patients with irritable bowel syndrome. Am J Gastroenterol 2009; 104: 1205-1212
    CrossrefPubMedGoogle Scholar
  • 37 Yang J, Shang B, Shi H. et al. The role of toll-like receptor 4 and mast cell in the ameliorating effect of electroacupuncture on visceral hypersensitivity in rats. Neurogastroenterol Motil 2019; 31: e13583 doi:10.1111/nmo.13583
    CrossrefPubMedGoogle Scholar
  • 38 Holzer P, Farzi A. Neuropeptides and the microbiota-gut-brain axis. Adv Exp Med Biol 2014; 817: 195-219
    Google Scholar
  • 39 He X, Cui LH, Wang XH. et al. Modulation of inflammation by toll-like receptor 4/nuclear factor-kappa B in diarrhea-predominant irritable bowel syndrome. Oncotarget 2017; 8: 113957-113965
    CrossrefPubMedGoogle Scholar
  • 40 Barbara G, Cremon C, Carini G. et al. The immune system in irritable bowel syndrome. J Neurogastroenterol Motil 2011; 17: 349-359
    CrossrefPubMedGoogle Scholar
  • 41 Nozu T, Miyagishi S, Nozu R. et al. Pioglitazone improves visceral sensation and colonic permeability in a rat model of irritable bowel syndrome. J Pharmacol Sci 2019; 139: 46-49
    CrossrefPubMedGoogle Scholar
  • 42 Dunlop SP, Jenkins D, Neal KR. et al. Randomized, double-blind, placebo-controlled trial of prednisolone in post-infectious irritable bowel syndrome. Aliment Pharmacol Ther 2003; 18: 77-84
    CrossrefPubMedGoogle Scholar
  • 43 Barbara G, Cremon C, Annese V. et al. Randomised controlled trial of mesalazine in IBS. Gut 2016; 65: 82-90
    CrossrefPubMedGoogle Scholar
  • 44 Leighton MP, Lam C, Mehta S. et al. Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): Study protocol for a randomised controlled trial. Trials 2013; 14: 10
    CrossrefPubMedGoogle Scholar
  • 45 Labus JS, Osadchiy V, Hsiao EY. et al. Evidence for an association of gut microbial clostridia with brain functional connectivity and gastrointestinal sensorimotor function in patients with irritable bowel syndrome, based on tripartite network analysis. Microbiome 2019; 7: 45 doi:10.1186/s40168–019–0656-z
    CrossrefPubMedGoogle Scholar
  • 46 Duan R, Zhu S, Wang B. et al. Alterations of gut microbiota in patients with irritable bowel syndrome based on 16 S rRNA-targeted sequencing: a systematic review. Clin Transl Gastroenterol 2019; 10: e00012 doi:10.14309/ctg.0000000000000012
    CrossrefPubMedGoogle Scholar
  • 47 Yano JM, Yu K, Donaldson GP. et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 2015; 161: 264-276
    CrossrefPubMedGoogle Scholar
  • 48 Labus JS, Hollister EB, Jacobs J. et al. Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome. Microbiome 2017; 5: 49 doi:10.1186/s40168–017–0260-z
    CrossrefPubMedGoogle Scholar
  • 49 Leprun PMB, Clarke G. The gut microbiome and pharmacology: a prescription for therapeutic targeting of the gut–brain axis. Curr Opin Pharmacol 2019; 49: 17-23
    CrossrefPubMedGoogle Scholar
  • 50 Hungin APS, Mitchell CR, Whorwell P. et al. Systematic review: probiotics in the management of lower gastrointestinal symptoms – an updated evidence-based international consensus. Aliment Pharmacol Ther 2018; 47: 1054-1070
    CrossrefPubMedGoogle Scholar
  • 51 Zhang F, Zhang T, Zhu H. et al. Evolution of fecal microbiota transplantation in methodology and ethical issues. Curr Opin Pharmacol 2019; 49: 11-16
    CrossrefPubMedGoogle Scholar
  • 52 Halkjær SI, Christensen AH, Lo BZS. et al. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: Results from a randomised, double-blind placebo-controlled study. Gut 2018; 67: 2107-2115
    CrossrefPubMedGoogle Scholar
  • 53 Pimentel M, Lembo A, Chey WD. et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. NEJM 2011; 364: 22-32
    CrossrefPubMedGoogle Scholar
  • 54 Cash BD, Pimentel M, Rao SSC. et al. Repeat treatment with rifaximin improves irritable bowel syndrome-related quality of life: a secondary analysis of a randomized, double-blind, placebo-controlled trial. Ther Adv Gastroenterol 2017; 10: 689-699
    CrossrefPubMedGoogle Scholar
  • 55 Fodor AA, Pimentel M, Chey WD. et al. Rifaximin is associated with modest, transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea-predominant irritable bowel syndrome. Gut Microbes 2019; 10: 22-33
    CrossrefPubMedGoogle Scholar
  • 56 Peter J, Fournier C, Keip B. et al. Intestinal microbiome in irritable bowel syndrome before and after gut-directed hypnotherapy. Int J Mol Sci 2018; 19 doi:10.3390/ijms19113619
    PubMedGoogle Scholar
  • 57 Saito Y, Zimmerman J, Harmsen WS. et al. Irritable bowel syndrome aggregates strongly in families: a family-based case-control study. Neurogastroenterol Motil 2008; 20: 790-797
    CrossrefPubMedGoogle Scholar
  • 58 Kilpatrick LA, Labus JS, Coveleskie K. et al. The HTR3A polymorphism c. –42C > T is associated with amygdala responsiveness in patients with irritable bowel syndrome. Gastroenterology 2011; 140: 1943-1951
    CrossrefPubMedGoogle Scholar
  • 59 Gazouli M, Wouters MM, Kapur-Pojskic L. et al. Lessons learned – resolving the enigma of genetic factors in IBS. Nat Rev Gastroenterol Hepatol 2016; 13: 77-87
    Google Scholar
  • 60 Nash DT, Nash SD. Ranolazine for chronic stable angina. Lancet 2008; 372: 1335-1341
    CrossrefPubMedGoogle Scholar
  • 61 Mukhtar K, Nawaz H, Abid S. Functional gastrointestinal disorders and gut-brain axis: what does the future hold?. World J Gastroenterol 2019; 25: 552-566
    CrossrefPubMedGoogle Scholar
  • 62 Baj A, Moro E, Bistoletti M. et al. Glutamatergic signaling along the microbiota-gut-brain axis. Int J Mol Sci 2019; 20 doi:10.3390/ijms20061482
    PubMedGoogle Scholar
  • 63 Bonaz B, Sinniger V, Pellissier S. The vagus nerve in the neuro-immune axis: implications in the pathology of the gastrointestinal tract. Front Immunol 2017; 8: 1452-1452
    CrossrefPubMedGoogle Scholar
  • 64 Pellissier S, Dantzer C, Mondillon L. et al. Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in crohn’s disease and irritable bowel syndrome. Plos One 2014; 9: e105328 doi:10.1371/journal.pone.0105328
    CrossrefPubMedGoogle Scholar
  • 65 Bonaz B, Sinniger V, Pellissier S. Vagal tone: effects on sensitivity, motility, and inflammation. Neurogastroenterol Motil 2016; 28: 455-462
    CrossrefPubMedGoogle Scholar
  • 66 Frokjaer JB, Bergmann S, Brock C. et al. Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity. Neurogastroenterol Motil 2016; 28: 592-598
    CrossrefPubMedGoogle Scholar
  • 67 Zheng Y, Yu T, Tang Y. et al. Efficacy and safety of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Plos One 2017; 12: e0172846 doi:10.1371/journal.pone.0172846
    CrossrefPubMedGoogle Scholar
  • 68 Icenhour A, Witt ST, Elsenbruch S. et al. Brain functional connectivity is associated with visceral sensitivity in women with Irritable Bowel Syndrome. NeuroImage Clinical 2017; 15: 449-457
    CrossrefPubMedGoogle Scholar
  • 69 Josefsson A, Rosendahl A, Jerlstad P. et al. Visceral sensitivity remains stable over time in patients with irritable bowel syndrome, but with individual fluctuations. Neurogastroenterol Motil 2019; 31: e13603 doi:10.1111/nmo.13603
    PubMedGoogle Scholar
  • 70 Hong JY, Naliboff B, Labus JS. et al. Altered brain responses in subjects with irritable bowel syndrome during cued and uncued pain expectation. Neurogastroenterol Motil 2016; 28: 127-138
    CrossrefPubMedGoogle Scholar
  • 71 Nan J, Yang W, Meng P. et al. Changes of the postcentral cortex in irritable bowel syndrome patients. Brain Imaging Behav. 2019 doi:10.1007/s11682–019–00087–7
    PubMedGoogle Scholar
  • 72 Van den Houte K, Carbone F, Pannemans J. et al. Prevalence and impact of self-reported irritable bowel symptoms in the general population. United European Gastroenterol J 2019; 7: 307-315
    CrossrefPubMedGoogle Scholar
  • 73 Goebel-Stengel M, Stengel A. Die Rolle der Darm-Gehirn-Achse in der Pathophysiologie des Reizdarmsyndroms. zkm 2016; 8 (05) 48-53
    PubMedGoogle Scholar
  • 74 Whorwell PJ, Prior A, Faragher EB. Controlled trial of hypnotherapy in the treatment of severe refractory irritable-bowel syndrome. Lancet 1984; 2: 1232-1234
    PubMedGoogle Scholar
  • 75 Gonsalkorale WM. Gut-directed hypnotherapy: the Manchester approach for treatment of irritable bowel syndrome. Int J Clin Exp Hypn 2006; 54: 27-50
    CrossrefPubMedGoogle Scholar
  • 76 Peters SL, Muir JG, Gibson PR. Review article: gut-directed hypnotherapy in the management of irritable bowel syndrome and inflammatory bowel disease. Aliment Pharmacol Ther 2015; 41: 1104-1115
    CrossrefPubMedGoogle Scholar