Mikrobiota und Reizdarmsyndrom – eine kritische Bestandsaufnahme

Zusammenfassung

Dieses narrative Review beleuchtet kritisch die Rolle der Darmmikrobiota bei funktionellen Störungen vom Typ Reizdarmsyndrom. Ausgehend von Veränderungen der Zusammensetzung und Vielfalt der Mikrobiota, wie sie oft in korrelativen Studien gefunden wurden, stellt es kritische Fragen nach Ursache/Wirkung, nach Spezifität und Sensitivität der Befunde im Vergleich zu anderen Erkrankungen und nach den klinisch-wissenschaftlichen Möglichkeiten, die Mikrobiota zu verändern. Dabei werden Prä-, Pro- und Antibiotika ebenso diskutiert wie der Einfluss von Ernährung und der Austausch durch fäkalen Mikrobiom-Transfer (FMT). Für das Reizdarmsyndrom haben sich bislang die wenigsten Strategien als erfolgreiche Therapieansätze erwiesen. Dies kann zum einen an der Heterogenität des Krankheitsbildes selbst liegen, zum anderen an nach wie vor unklaren Konzepten der mikrobiellen Forschung, z. B. dem Begriff der Dysbiose, oder an methodischen Differenzen der molekulargenetischen Forschung, die in den publizierten Arbeiten nicht sichtbar werden. Künftige Studien sollten sich auf die Identifizierung der Faktoren konzentrieren, die das Ansprechen auf solche Behandlungsarten erklären und vorhersagen können.

Abstract

This narrative review critically explores the role of the gut microbiota in functional bowel disorders of IBS-type. Starting with changes in the microbiota composition and diversity, as they have been often found in correlative IBS studies, it raises the question of cause and consequence, of sensitivity and specificity of findings in comparison to other diseases, and of the scientific and clinical options to manipulate the microbiota. This includes a discussion of pre- and probiotics and antibiotics as well as the role of nutrition and the microbiota exchange with fecal microbiota transfer (FMT). For IBS, most of these strategies have not been found to be successful therapies. This may be due to the heterogeneity of the disease itself, but eventually also due to the concepts of microbiological research, e. g., the term dysbiosis, or in methodological differences of the molecular-genetic research that are not visible in the published papers. Future studies should aim to identify those factors that may explain and predict the response to such therapies.

Schlüsselwörter

Mikrobiota - Mikrobiom - Dysbiose - Reizdarmsyndrom - Probiotika - Antibiotika - FODMAP - Stuhltransfer

Key words

microbiota - microbiome - dysbiosis - irritable bowel syndrome - probiotics - antibiotics - FODMAP - fecal microbiota transfer

• Literatur

• 1 Baquero F, Nombela C. The microbiome as a human organ. Clin Microbiol Infect 2012; 18 (Suppl. 04) 2-4
• 2 Rajilic-Stojanovic M, Jonkers DM, Salonen A. et al. Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena?. The American journal of gastroenterology 2015; 110: 278-287
• 3 Distrutti E, Monaldi L, Ricci P. et al. Gut microbiota role in irritable bowel syndrome: New therapeutic strategies. World journal of gastroenterology 2016; 22: 2219-2241
• 4 Lozupone CA, Stombaugh JI, Gordon JI. et al. Diversity, stability and resilience of the human gut microbiota. Nature 2012; 489: 220-230
• 5 Rajilic-Stojanovic M, Biagi E, Heilig HG. et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011; 141: 1792-1801
• 6 Simrén M, Barbara G, Flint HJ. et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut 2013; 62: 159-176
• 7 Aguilera M, Vergara P, Martinez V. Stress and antibiotics alter luminal and wall-adhered microbiota and enhance the local expression of visceral sensory-related systems in mice. Neurogastroenterology and motility 2013; 25: e515-e529
• 8 Ivanov II, de Frutos RL, Manel N. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell host & microbe 2008; 4: 337-349
• 9 Mayer EA, Savidge T, Shulman RJ. Brain-gut microbiome interactions and functional bowel disorders. Gastroenterology 2014; 146: 1500-1512
• 10 Bar F, Von Koschitzky H, Roblick U. et al. Cell-free supernatants of Escherichia coli Nissle 1917 modulate human colonic motility: evidence from an in vitro organ bath study. Neurogastroenterology and motility 2009; 21: 559-566, e16-7
• 11 Aguilera M, Cerda-Cuellar M, Martinez V. Antibiotic-induced dysbiosis alters host-bacterial interactions and leads to colonic sensory and motor changes in mice. Gut microbes 2015; 6: 10-23
• 12 Perez-Burgos A, Wang B, Mao YK. et al. Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents. American journal of physiology Gastrointestinal and liver physiology 2013; 304: G211-G220
• 13 Tillisch K, Labus J, Kilpatrick L. et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 2013; 144: 1394-1401, 401 e1-4
• 14 Fond G, Loundou A, Hamdani N. et al. Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis. European archives of psychiatry and clinical neuroscience 2014; 264: 651-660
• 15 Casen C, Vebo HC, Sekelja M. et al. Deviations in human gut microbiota: a novel diagnostic test for determining dysbiosis in patients with IBS or IBD. Alimentary pharmacology & therapeutics 2015; 42: 71-83
• 16 David LA, Maurice CF, Carmody RN. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014; 505: 559-563
• 17 Power SE, O'Toole PW, Stanton C. et al. Intestinal microbiota, diet and health. The British journal of nutrition 2014; 111: 387-402
• 18 Hayes P, Corish C, O'Mahony E. et al. A dietary survey of patients with irritable bowel syndrome. Journal of human nutrition and dietetics 2014; 27 (Suppl. 02) 36-47
• 19 Sood R, Gracie DJ, Law GR. et al. Systematic review with meta-analysis: the accuracy of diagnosing irritable bowel syndrome with symptoms, biomarkers and/or psychological markers. Alimentary pharmacology & therapeutics 2015; 42: 491-503
• 20 Zimmer J, Lange B, Frick JS. et al. A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. European journal of clinical nutrition 2012; 66: 53-60
• 21 Dey N, Wagner VE, Blanton LV. et al. Regulators of gut motility revealed by a gnotobiotic model of diet-microbiome interactions related to travel. Cell 2015; 163: 95-107
• 22 Riddle MS, Connor BA. The Traveling Microbiome. Curr Infect Dis Rep 2016; 18: 29
• 23 Turnbaugh PJ, Ley RE, Mahowald MA. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444: 1027-1031
• 24 Ley RE, Backhed F, Turnbaugh P. et al. Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences of the United States of America 2005; 102: 11070-11075
• 25 Ley RE, Turnbaugh PJ, Klein S. et al. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444: 1022-1023
• 26 Sze MA, Schloss PD. Looking for a Signal in the Noise: Revisiting Obesity and the Microbiome. mBio 2016 7 (4)
• 27 Zheng P, Zeng B, Zhou C. et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Molecular psychiatry 2016; 21: 786-796
• 28 Jiang H, Ling Z, Zhang Y. et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain, behavior, and immunity 2015; 48: 186-194
• 29 Rajilic-Stojanovic M, de Vos WM. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS microbiology reviews 2014; 38: 996-1047
• 30 Lloyd-Price J, Mahurkar A, Rahnavard G. et al. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature 2017; 550: 61-66
• 31 Crouzet L, Gaultier E, Del'Homme C. et al. The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota. Neurogastroenterol Motil 2013; 25: e272-e282
• 32 Brandt LJ, Borody TJ, Campbell J. Endoscopic fecal microbiota transplantation: “first-line” treatment for severe clostridium difficile infection?. Journal of clinical gastroenterology 2011; 45: 655-657
• 33 Eiseman B, Silen W, Bascom GS. et al. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 1958; 44: 854-859
• 34 Schwan A, Sjolin S, Trottestam U. et al. Relapsing Clostridium difficile enterocolitis cured by rectal infusion of normal faeces. Scandinavian journal of infectious diseases 1984; 16: 211-215
• 35 Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet (London, England) 1989; 1: 1156-1160
• 36 Borody TJ, Warren EF, Leis SM. et al. Bacteriotherapy using fecal flora: toying with human motions. Journal of clinical gastroenterology 2004; 38: 475-483
• 37 Zhang F, Luo W, Shi Y. et al. Should we standardize the 1700-year-old fecal microbiota transplantation?. The American journal of gastroenterology 2012; 107: 1755
• 38 Lehrer S. Duodenal infusion of feces for recurrent Clostridium difficile. The New England journal of medicine 2013; 368: 2144
• 39 Zhou M, Peng YJ, Chen Y. et al. Assessment of microbiome changes after rumen transfaunation: implications on improving feed efficiency in beef cattle. Microbiome 2018; 6: 62
• 40 DePeters EJ, George LW. Rumen transfaunation. Immunol Lett 2014; 162: 69-76
• 41 Imdad A, Nicholson MR, Tanner-Smith EE. et al. Fecal transplantation for treatment of inflammatory bowel disease. The Cochrane database of systematic reviews 2018; 11: CD012774
• 42 Johnsen PH, Hilpusch F, Cavanagh JP. et al. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. The lancet Gastroenterology & hepatology 2018; 3: 17-24
• 43 Ding C, Fan W, Gu L. et al. Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation: results from a prospective study with long-term follow-up. Gastroenterol Rep (Oxf) 2018; 6: 101-107
• 44 Khanna S. Microbiota Replacement Therapies: Innovation in Gastrointestinal Care. Clinical pharmacology and therapeutics 2018; 103: 102-111
• 45 Evrensel A, Ceylan ME. Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders. Clin Psychopharmacol Neurosci 2016; 14: 231-237
• 46 Lai CY, Sung J, Cheng F. et al. Systematic review with meta-analysis: review of donor features, procedures and outcomes in 168 clinical studies of faecal microbiota transplantation. Alimentary pharmacology & therapeutics 2019; 49: 354-363
• 47 Pritchard SE, Marciani L, Garsed KC. et al. Fasting and postprandial volumes of the undisturbed colon: normal values and changes in diarrhea-predominant irritable bowel syndrome measured using serial MRI. Neurogastroenterol Motil 2014; 26: 124-130
• 48 Tuck CJ, Muir JG, Barrett JS. et al. Fermentable oligosaccharides, disaccharides, monosaccharides and polyols: role in irritable bowel syndrome. Expert review of gastroenterology & hepatology 2014; 8: 819-834
• 49 Tap J, Derrien M, Tornblom H. et al. Identification of an Intestinal Microbiota Signature Associated With Severity of Irritable Bowel Syndrome. Gastroenterology 2017; 152: 111-123
• 50 Altobelli E, Del Negro V, Angeletti PM. et al. Low-FODMAP Diet Improves Irritable Bowel Syndrome Symptoms: A Meta-Analysis. Nutrients 2017 9 (9)
• 51 Marsh A, Eslick EM, Eslick GD. Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis. European journal of nutrition 2016; 55: 897-906
• 52 Dionne J, Ford AC, Yuan Y. et al. A Systematic Review and Meta-Analysis Evaluating the Efficacy of a Gluten-Free Diet and a Low FODMAPs Diet in Treating Symptoms of Irritable Bowel Syndrome. The American journal of gastroenterology 2018; 113: 1290-1300
• 53 Varju P, Farkas N, Hegyi P. et al. Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies. PloS one 2017; 12: e0182942
• 54 Eswaran SL, Chey WD, Han-Markey T. et al. A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D. The American journal of gastroenterology 2016; 111: 1824-1832
• 55 Bohn L, Storsrud S, Liljebo T. et al. Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel Syndrome as Well as Traditional Dietary Advice: A Randomized Controlled Trial. Gastroenterology 2015; 149: 1399-1407 e2
• 56 Huaman JW, Mego M, Manichanh C. et al. Effects of Prebiotics vs a Diet Low in Fodmaps in Patients with Functional Gut Disorder. Gastroenterology 2018; 155: 1004-1007
• 57 Elsenbruch S, Enck P. Placebo effects and their determinants in gastrointestinal disorders. Nature reviews Gastroenterology & hepatology 2015; 12: 472-485
• 58 Ford AC, Talley NJ, Spiegel BM. et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. Bmj 2008; 337: a2313
• 59 Enck P, Junne F, Klosterhalfen S. et al. Therapy options in irritable bowel syndrome. European journal of gastroenterology & hepatology 2010; 22: 1402-1411
• 60 Pedersen N, Andersen NN, Vegh Z. et al. Ehealth: low FODMAP diet vs Lactobacillus rhamnosus GG in irritable bowel syndrome. World journal of gastroenterology 2014; 20: 16215-16226
• 61 Peters SL, Yao CK, Philpott H. et al. Randomised clinical trial: the efficacy of gut-directed hypnotherapy is similar to that of the low FODMAP diet for the treatment of irritable bowel syndrome. Alimentary pharmacology & therapeutics 2016; 44: 447-459
• 62 Schumann D, Langhorst J, Dobos G. et al. Randomised clinical trial: yoga vs. a low-FODMAP diet in patients with irritable bowel syndrome. Alimentary pharmacology & therapeutics 2018; 47: 203-211
• 63 Pourmand H, Keshteli AH, Saneei P. et al. Adherence to a Low FODMAP Diet in Relation to Symptoms of Irritable Bowel Syndrome in Iranian Adults. Digestive diseases and sciences 2018; 63: 1261-1269
• 64 Wilder-Smith CH, Olesen SS, Materna A. et al. Predictors of response to a low-FODMAP diet in patients with functional gastrointestinal disorders and lactose or fructose intolerance. Alimentary pharmacology & therapeutics 2017; 45: 1094-1106
• 65 McIntosh K, Reed DE, Schneider T. et al. FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial. Gut 2017; 66: 1241-1251
• 66 Manichanh C, Eck A, Varela E. et al. Anal gas evacuation and colonic microbiota in patients with flatulence: effect of diet. Gut 2014; 63: 401-408
• 67 Bajor A, Tornblom H, Rudling M. et al. Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS. Gut 2015; 64: 84-92
• 68 Mitchell H, Porter J, Gibson PR. et al. Review article: implementation of a diet low in FODMAPs for patients with irritable bowel syndrome-directions for future research. Alimentary pharmacology & therapeutics 2019; 49: 124-139
• 69 Krogsgaard LR, Lyngesen M, Bytzer P. Systematic review: quality of trials on the symptomatic effects of the low FODMAP diet for irritable bowel syndrome. Alimentary pharmacology & therapeutics 2017; 45: 1506-1513
• 70 Reese I, Schäfer C, Kleine-Tebbe J. et al. Non-celiac gluten/wheat sensitivity (NCGS) – a currently undefined disorder without validated diagnostic criteria and of unknown prevalence. Allergo Journal International 2018; 27: 147-151
• 71 Ford AC, Harris LA, Lacy BE. et al. Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. Alimentary pharmacology & therapeutics 2018; 48: 1044-1060
• 72 Ford AC, Quigley EM, Lacy BE. et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. The American journal of gastroenterology 2014; 109: 1547-1561
• 73 McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World journal of gastroenterology 2008; 14: 2650-2661
• 74 Nikfar S, Rahimi R, Rahimi F. et al. Efficacy of probiotics in irritable bowel syndrome: a meta-analysis of randomized, controlled trials. Diseases of the colon and rectum 2008; 51: 1775-1780
• 75 Moayyedi P, Ford AC, Talley NJ. et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 2010; 59: 325-332
• 76 Brenner DM, Moeller MJ, Chey WD. et al. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. The American journal of gastroenterology 2009; 104: 1033-1049
• 77 Hoveyda N, Heneghan C, Mahtani KR. et al. A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome. BMC gastroenterology 2009; 9: 15
• 78 Ritchie ML, Romanuk TN. A meta-analysis of probiotic efficacy for gastrointestinal diseases. PloS one 2012; 7: e34938
• 79 Didari T, Mozaffari S, Nikfar S. et al. Effectiveness of probiotics in irritable bowel syndrome: Updated systematic review with meta-analysis. World journal of gastroenterology 2015; 21: 3072-3084
• 80 Mazurak N, Broelz E, Storr M. et al. Probiotic Therapy of the Irritable Bowel Syndrome: Why Is the Evidence Still Poor and What Can Be Done About It?. Journal of neurogastroenterology and motility 2015; 21: 471-485
• 81 Enck P. Not more, but less studies are warranted-If you take your meta-analysis seriously. Neurogastroenterology and motility 2019; 31: e13473
• 82 Connell M, Shin A, James-Stevenson T. et al. Systematic review and meta-analysis: Efficacy of patented probiotic, VSL#3, in irritable bowel syndrome. Neurogastroenterology and motility 2018; 30: e13427
• 83 Kim HJ, Camilleri M, McKinzie S. et al. A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome. Alimentary pharmacology & therapeutics 2003; 17: 895-904
• 84 Kim HJ, Vazquez Roque MI, Camilleri M. et al. A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterology and motility 2005; 17: 687-696
• 85 Michail S, Kenche H. Gut microbiota is not modified by Randomized, Double-blind, Placebo-controlled Trial of VSL#3 in Diarrhea-predominant Irritable Bowel Syndrome. Probiotics and antimicrobial proteins 2011; 3: 1-7
• 86 Wong RK, Yang C, Song GH. et al. Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double-blinded placebo study. Digestive diseases and sciences 2015; 60: 186-194
• 87 Staudacher HM, Lomer MCE, Farquharson FM. et al. Diet Low in FODMAPs Reduces Symptoms in Patients with Irritable Bowel Syndrome and Probiotic Restores Bifidobacterium Species: a Randomized Controlled Trial. Gastroenterology 2017; 153: 936-947
• 88 Cani PD, de Vos WM. Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila. Frontiers in microbiology 2017; 8: 1765
• 89 Pyleris E, Giamarellos-Bourboulis EJ, Tzivras D. et al. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Digestive diseases and sciences 2012; 57: 1321-1329
• 90 Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. The American journal of gastroenterology 2000; 95: 3503-3506
• 91 Spiegel BM. Questioning the bacterial overgrowth hypothesis of irritable bowel syndrome: an epidemiologic and evolutionary perspective. Clinical gastroenterology and hepatology 2011; 9: 461-469
• 92 Aziz I, Tornblom H, Simren M. Small intestinal bacterial overgrowth as a cause for irritable bowel syndrome: guilty or not guilty?. Current opinion in gastroenterology 2017; 33: 196-202
• 93 Nayak AK, Karnad DR, Abraham P. et al. Metronidazole relieves symptoms in irritable bowel syndrome: the confusion with so-called “chronic amebiasis”. Indian journal of gastroenterology 1997; 16: 137-139
• 94 Villarreal AA, Aberger FJ, Benrud R. et al. Use of broad-spectrum antibiotics and the development of irritable bowel syndrome. WMJ 2012; 111: 17-20
• 95 Chaudhary NA, Truelove SC. The irritable colon syndrome. A study of the clinical features, predisposing causes, and prognosis in 130 cases. The Quarterly journal of medicine 1962; 31: 307-322
• 96 Thabane M, Kottachchi DT, Marshall JK. Systematic review and meta-analysis: The incidence and prognosis of post-infectious irritable bowel syndrome. Alimentary pharmacology & therapeutics 2007; 26: 535-544
• 97 Futagami S, Itoh T, Sakamoto C. Systematic review with meta-analysis: post-infectious functional dyspepsia. Alimentary pharmacology & therapeutics 2015; 41: 177-188
• 98 Schwille-Kiuntke J, Frick JS, Zanger P. et al. Post-infectious irritable bowel syndrome--a review of the literature. Zeitschrift fur Gastroenterologie 2011; 49: 997-1003
• 99 Schwille-Kiuntke J, Mazurak N, Enck P. Systematic review with meta-analysis: post-infectious irritable bowel syndrome after travellers’ diarrhoea. Alimentary pharmacology & therapeutics 2015; 41: 1029-1037
• 100 Card T, Enck P, Barbara G. et al. Post-infectious IBS: Defining its clinical features and prognosis using an internet-based survey. United European gastroenterology journal 2018; 6: 1245-1253
• 101 Lowe B, Andresen V, Fraedrich K. et al. Psychological outcome, fatigue, and quality of life after infection with shiga toxin-producing Escherichia coli O104. Clinical gastroenterology and hepatology 2014; 12: 1848-1855
• 102 Andresen V, Lowe B, Broicher W. et al. Post-infectious irritable bowel syndrome (PI-IBS) after infection with Shiga-like toxin-producing Escherichia coli (STEC) O104:H4: A cohort study with prospective follow-up. United European gastroenterology journal 2016; 4: 121-131
• 103 Donnachie E, Schneider A, Mehring M. et al. Incidence of irritable bowel syndrome and chronic fatigue following GI infection: a population-levelstudy using routinely collected claims data. Gut 2018; 67: 1078-1086
• 104 Enck P, Mazurak N. The “Biology-First” Hypothesis: Functional disorders may begin and end with biology-A scoping review. Neurogastroenterology and motility 2018; 30: e13394
• 105 Kruis W, Chrubasik S, Boehm S. et al. A double-blind placebo-controlled trial to study therapeutic effects of probiotic Escherichia coli Nissle 1917 in subgroups of patients with irritable bowel syndrome. International journal of colorectal disease 2012; 27: 467-474
• 106 Bruzzese E, Fedele MC, Bruzzese D. et al. Randomised clinical trial: a Lactobacillus GG and micronutrient-containing mixture is effective in reducing nosocomial infections in children, vs. placebo. Alimentary pharmacology & therapeutics 2016; 44: 568-575
• 107 Gatta L, Scarpignato C. Systematic review with meta-analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Alimentary pharmacology & therapeutics 2017; 45: 604-616
• 108 Ng QX, Ho CYX, Shin D. et al. A meta-analysis of the use of rifaximin to prevent travellers’ diarrhoea. J Travel Med 2017; 24
• 109 Festa V, Spila Alegiani S, Chiesara F. et al. Retrospective comparison of long-term ten-day/month rifaximin or mesalazine in prevention of relapse in acute diverticulitis. European review for medical and pharmacological sciences 2017; 21: 1397-1404
• 110 Tan VP, Liu KS, Lam FY. et al. Randomised clinical trial: rifaximin versus placebo for the treatment of functional dyspepsia. Alimentary pharmacology & therapeutics 2017; 45: 767-776
• 111 Abdel-Razik A, Mousa N, Shabana W. et al. Rifaximin in nonalcoholic fatty liver disease: hit multiple targets with a single shot. European journal of gastroenterology & hepatology 2018; 30: 1237-1246
• 112 Pimentel M. Review article: potential mechanisms of action of rifaximin in the management of irritable bowel syndrome with diarrhoea. Alimentary pharmacology & therapeutics 2016; 43 (Suppl. 01) 37-49
• 113 Pimentel M, Cash BD, Lembo A. et al. Repeat Rifaximin for Irritable Bowel Syndrome: No Clinically Significant Changes in Stool Microbial Antibiotic Sensitivity. Digestive diseases and sciences 2017; 62: 2455-2463
• 114 Kimer N, Pedersen JS, Tavenier J. et al. Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis; A randomized trial. Journal of gastroenterology and hepatology 2018; 33: 307-314
• 115 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 2018; 10: 22-33
• 116 Zeber-Lubecka N, Kulecka M, Ambrozkiewicz F. et al. Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome. Gut microbes 2016; 7: 397-413
• 117 Weber D, Oefner PJ, Dettmer K. et al. Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation. Bone Marrow Transplant 2016; 51: 1087-1092
• 118 Acosta A, Camilleri M, Shin A. et al. Effects of Rifaximin on Transit, Permeability, Fecal Microbiome, and Organic Acid Excretion in Irritable Bowel Syndrome. Clinical and translational gastroenterology 2016; 7: e173
• 119 Soldi S, Vasileiadis S, Uggeri F. et al. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach. Clinical and experimental gastroenterology 2015; 8: 309-325
• 120 DuPont HL. Introduction: understanding mechanisms of the actions of rifaximin in selected gastrointestinal diseases. Alimentary pharmacology & therapeutics 2016; 43 (Suppl. 01) 1-2
• 121 Ponziani FR, Zocco MA, D'Aversa F. et al. Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation. World journal of gastroenterology 2017; 23: 4491-4499
• 122 Ly D, De Lisi LE. Can antibiotics cause a psychosis?: Case report and review of the literature. Schizophrenia research 2017; 189: 204-207
• 123 Chae JH, Miller BJ. Beyond Urinary Tract Infections (UTIs) and Delirium: A Systematic Review of UTIs and Neuropsychiatric Disorders. Journal of psychiatric practice 2015; 21: 402-411
• 124 Lurie I, Yang YX, Haynes K. et al. Antibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control study. The Journal of clinical psychiatry 2015; 76: 1522-1528
• 125 Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review. Annals of general psychiatry 2017; 16: 14
• 126 Foster J, Reis DJ, Ilardi SS. et al. The anxiolytic effect of probiotics: A systematic review and meta-analysis of the clinical and preclinical literature. PloS one 2018; 13: e0199041
• 127 Wang H, Braun C, Enck P. Effects of Rifaximin on Central Responses to Social Stress-a Pilot Experiment. Neurotherapeutics 2018; 15: 807-818
• 128 Wang H, Lee IS, Braun C. et al. Effect of probiotics on central nervous system functions in animals and humans – a systematic review. Journal of neurogastroenterology and motility 2016; 22: 589-605
• 129 Wang H, Braun C, Murphy E. et al. Bifidobacterium longum 1714TM strain modulates brain activity of healthy volunteers during social stress. American journal of gastroenterology 2019 (in press)
• 130 Huang R, Wang K, Hu J. Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2016 8 (8)
• 131 Shaaban SY, El Gendy YG, Mehanna NS. et al. The role of probiotics in children with autism spectrum disorder: A prospective, open-label study. Nutritional neuroscience 2018; 21: 676-681
• 132 Kurokawa S, Kishimoto T, Mizuno S. et al. The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study. Journal of affective disorders 2018; 235: 506-512
• 133 Zoller C, Maroof P, Weik U. et al. No effect of social exclusion on salivary cortisol secretion in women in a randomized controlled study. Psychoneuroendocrinology 2010; 35: 1294-1298
• 134 Halkjaer 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
• 135 Jalanka J, Salonen A, Salojarvi J. et al. Effects of bowel cleansing on the intestinal microbiota. Gut 2015; 64: 1562-1568
• 136 Drago L, Toscano M, De Grandi R. et al. Persisting changes of intestinal microbiota after bowel lavage and colonoscopy. European journal of gastroenterology & hepatology 2016; 28: 532-537
• 137 Bingel U. Placebo Competence Team. Avoiding nocebo effects to optimize treatment outcome. Jama 2014; 312: 693-694
• 138 Enck P. Primum non nocere: is faecal microbiota transplantation doing harm to patients with IBS?. Gut 2019 (in press)
• 139 Enck P, Mazurak N. Dysbiosis in functional bowel disorders. Ann Nutr Metab 2018; 72: 296-306