Gut Microbial Dysbiosis in the Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Case-Control Studies

Published:August 28, 2019DOI:



      Irritable bowel syndrome (IBS) is the most common functional digestive condition in the industrialized world. The gut microbiota plays a key role in disease pathogenesis.


      A systematic review and meta-analysis on case–control studies was conducted to determine whether there is gut microbial dysbiosis in participants with IBS in comparison with healthy controls and, if so, whether the dysbiosis pattern differs among IBS subtypes and geographic regions.


      This review was conducted and reported according to the MOOSE (Meta-Analysis of Observational Studies in Epidemiology) 2000 and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 guidelines. Research articles published up to May 9, 2018 were identified through MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (Cochrane Library),, EMBASE, and Web of Science. Study quality was assessed using the Newcastle-Ottawa Scale. Case–control studies of participants with IBS who had undergone quantitative gut microbial stool analysis were included. The primary exposure measure of interest is log10 bacterial counts per gram of stool. Meta-analyses were performed to estimate the mean difference (MD) in gut microbiota between participants with IBS and healthy controls using the random-effects model with inverse variance in Revman 5.3 and R 3.5.1. Publication bias was assessed with funnel plots and Egger’s test. Between-study heterogeneity was analyzed using Higgins I2 statistic with 95% CIs.


      There were 6,333 unique articles identified; 52 qualified for full-text screening. Of these, 23 studies were included for analysis (n=1,340 participants from North America, Europe, and Asia). Overall, the studies were moderate in quality. Comparing participants with IBS to healthy controls, lower fecal Lactobacillus (MD= –0.57 log10 colony-forming unit [CFU]/g; P<0.01) and Bifidobacterium (MD= –1.04 log10CFU/g; P<0.01), higher Escherichia coli (MD=0.60 log10CFU/g; P<0.01), and marginally higher Enterobacter (MD=0.74 log10CFU/g; P=0.05). No difference was found between participants with IBS and healthy controls in fecal Bacteroides and Enterococcus (P=0.18 and 0.68, respectively). Publication bias was not observed except in Bifidobacterium (P=0.015). Subgroup analyses on participants with diarrhea-predominant and constipation-predominant IBS showed consistent results with the primary results. A subgroup analysis of Chinese studies was consistent with the primary results, except for fecal Bacteroides, which was increased in participants with IBS vs healthy controls (MD=0.29; 95% CI 0.13 to 0.46; P<0.01). Although substantial heterogeneity was detected (I2>75%) in most comparisons, the direction of the effect estimates is relatively consistent across studies.


      IBS is characterized by gut microbial dysbiosis. Prospective, large-scale studies are needed to delineate how gut microbial profiles can be used to guide targeted therapies in this challenging patient population.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the Academy of Nutrition and Dietetics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ford A.C.
        • Moayyedi P.
        • Chey W.D.
        • et al.
        American College of Gastroenterology monograph on management of irritable bowel syndrome.
        Am J Gastroenterol. 2018; 113: 1-18
        • Canavan C.
        • West J.
        • Card T.
        The epidemiology of irritable bowel syndrome.
        Clin Epidemiol. 2014; 6: 71-80
        • El-Salhy M.
        Irritable bowel syndrome: Diagnosis and pathogenesis.
        World J Gastroenterol. 2012; 18: 5151-5163
        • Simren M.
        • Palsson O.S.
        • Whitehead W.E.
        Update on Rome IV Criteria for colorectal disorders: Implications for clinical practice.
        Curr Gastroenterol Rep. 2017; 19: 15
        • Makker J.
        • Chilimuri S.
        • Bella J.N.
        Genetic epidemiology of irritable bowel syndrome.
        World J Gastroenterol. 2015; 21: 11353-11361
        • Powell N.
        • Walker M.M.
        • Talley N.J.
        The mucosal immune system: Master regulator of bidirectional gut-brain communications.
        Nat Rev Gastroenterol Hepatol. 2017; 14: 143-159
        • Pellissier S.
        • Bonaz B.
        The place of stress and emotions in the irritable bowel syndrome.
        Vitam Hormon. 2017; 103: 327-354
        • Deiteren A.
        • de Wit A.
        • van der Linden L.
        • De Man J.G.
        • Pelckmans P.A.
        • De Winter B.Y.
        Irritable bowel syndrome and visceral hypersensitivity: Risk factors and pathophysiological mechanisms.
        Acta Gastroenterol Belg. 2016; 79: 29-38
        • Quigley E.M.
        Disturbances of motility and visceral hypersensitivity in irritable bowel syndrome: Biological markers or epiphenomenon.
        Gastroenterol Clin North Am. 2005; 34 (vi): 221-233
        • Mullin G.E.
        • Shepherd S.J.
        • Chander Roland B.
        • Ireton-Jones C.
        • Matarese L.E.
        Irritable bowel syndrome: Contemporary nutrition management strategies.
        JPEN. 2014; 38: 781-799
        • Sundin J.
        • Ohman L.
        • Simren M.
        Understanding the gut microbiota in inflammatory and functional gastrointestinal diseases.
        Psychosom Med. 2017; 79: 857-867
        • Moloney R.D.
        • Johnson A.C.
        • O'Mahony S.M.
        • Dinan T.G.
        • Greenwood-Van Meerveld B.
        • Cryan J.F.
        Stress and the microbiota-gut-brain axis in visceral parelevance to irritable bowel syndrome.
        CNS Neurosci Ther. 2016; 22: 102-117
        • Gonzalez-Castro A.M.
        • Martinez C.
        • Salvo-Romero E.
        • et al.
        Mucosal pathobiology and molecular signature of epithelial barrier dysfunction in the small intestine in irritable bowel syndrome.
        J Gastroenterol Hepatol. 2017; 32: 53-63
        • Menees S.
        • Chey W.
        The gut microbiome and irritable bowel syndrome.
        F1000Res. 2018; 7
        • Rea K.
        • O'Mahony S.M.
        • Dinan T.G.
        • Cryan J.F.
        The role of the gastrointestinal microbiota in visceral pain.
        Handb Exp Pharmacol. 2017; 239: 269-287
        • Fukui H.
        Increased intestinal permeability and decreased barrier function: Does it really influence the risk of inflammation?.
        Inflamm Intest Dis. 2016; 1: 135-145
        • Ohman L.
        • Simren M.
        Pathogenesis of IBS: Role of inflammation, immunity and neuroimmune interactions.
        Nat Rev Gastroenterol Hepatol. 2010; 7: 163-173
        • Shi N.
        • Li N.
        • Duan X.
        • Niu H.
        Interaction between the gut microbiome and mucosal immune system.
        Mil Med Res. 2017; 4: 14
        • Donnachie E.
        • Schneider A.
        • Mehring M.
        • Enck P.
        Incidence of irritable bowel syndrome and chronic fatigue following GI infection: A population-level study using routinely collected claims data.
        Gut. 2018; 67: 1078-1086
        • Moser G.
        • Fournier C.
        • Peter J.
        Intestinal microbiome-gut-brain axis and irritable bowel syndrome.
        Wien Med Wochenschr. 2018; 168: 62-66
        • Halvorson H.A.
        • Schlett C.D.
        • Riddle M.S.
        Postinfectious irritable bowel syndrome—A meta-analysis.
        Am J Gastroenterol. 2006; 101 (quiz 1942): 1894-1899
        • Chen B.
        • Kim J.J.
        • Zhang Y.
        • Du L.
        • Dai N.
        Prevalence and predictors of small intestinal bacterial overgrowth in irritable bowel syndrome: A systematic review and meta-analysis.
        J Gastroenterol. 2018; 53: 807-818
        • Li J.
        • Zhu W.
        • Liu W.
        • Wu Y.
        • Wu B.
        Rifaximin for irritable bowel syndrome: A meta-analysis of randomized placebo-controlled trials.
        Medicine (Baltimore). 2016; 95e2534
        • Ford A.C.
        • Quigley E.M.
        • Lacy B.E.
        • et al.
        Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: Systematic review and meta-analysis.
        Am J Gastroenterol. 2014; 109 (; quiz 1546, 1562): 1547-1561
        • Zhang Y.
        • Li L.
        • Guo C.
        • et al.
        Effects of probiotic type, dose and treatment duration on irritable bowel syndrome diagnosed by Rome III criteria: A meta-analysis.
        BMC Gastroenterol. 2016; 16: 62
        • Valentin N.
        • Camilleri M.
        • Carlson P.
        • et al.
        Potential mechanisms of effects of serum-derived bovine immunoglobulin/protein isolate therapy in patients with diarrhea-predominant irritable bowel syndrome.
        Physiol Rep. 2017; 5
        • El-Salhy M.
        • Mazzawi T.
        Fecal microbiota transplantation for managing irritable bowel syndrome.
        Expert Rev Gastroenterol Hepatol. 2018; 12: 439-445
        • Jernberg C.
        • Lofmark S.
        • Edlund C.
        • Jansson J.K.
        Long-term ecological impacts of antibiotic administration on the human intestinal microbiota.
        ISME J. 2007; 1: 56-66
        • Mullin G.
        • Nanavati J.
        • Singh R.
        • Alammar N.
        • Salem A.
        • Shinohara T.
        Gut microbiome influence on the outcome of irritable bowel syndrome: A systematic review and meta-analysis. PROSPERO 2017 CRD42017070613.
        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration.
        PLoS Med. 2009; 6e1000100
        • Stroup D.F.
        • Berlin J.A.
        • Morton S.C.
        • et al.
        Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group.
        JAMA. 2000; 283: 2008-2012
        • Stang A.
        Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.
        Eur J Epidemiol. 2010; 25: 603-605
        • DerSimonian R.
        • Laird N.
        Meta-analysis in clinical trials.
        Control Clin Trials. 1986; 7: 177-188
        • Higgins J.P.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Stat Med. 2002; 21: 1539-1558
        • Ioannidis J.P.
        • Patsopoulos N.A.
        • Evangelou E.
        Uncertainty in heterogeneity estimates in meta-analyses.
        BMJ. 2007; 335: 914-916
      1. Higgins J.P.T. Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011 (Updated March 2011Accessed June 16, 2019)
        • Sterne J.A.
        • Sutton A.J.
        • Ioannidis J.P.
        • et al.
        Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials.
        BMJ. 2011; 343: d4002
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • Minder C.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Kicinski M.
        • Springate D.A.
        • Kontopantelis E.
        Publication bias in meta-analyses from the Cochrane Database of Systematic Reviews.
        Stat Med. 2015; 34: 2781-2793
      2. Review Manager [computer program]. Version 5.3.5. The Nordic Cochrane Center: The Cochrane Collaboration, Copenhagen2014
      3. R: A Language and Environment for Statistical Computing [computer program]. R Foundation for Statistical Computing, Vienna, Austria2017
        • Zhang L.
        Significance of intestinal tract normal bacteria flora quantitative analysis of IBS sufferers.
        Chin Med Guides. 2008; 5: 94-96
        • Zhang L.
        • Gu F.
        • Bai P.
        Analysis of targeted gut microbiota inpatients with irritable bowel syndrome using 16 s rDNA qPCR.
        Shandong Med J. 2009; 49: 51-52
        • Durban A.
        • Abellan J.J.
        • Jimenez-Hernandez N.
        • et al.
        Structural alterations of faecal and mucosa-associated bacterial communities in irritable bowel syndrome.
        Environ Microbiol Rep. 2012; 4: 242-247
        • Hua C.
        • Cao H.
        Changes of the intestinal microflora in children with irritable bowel syndrome by SYBR green 1 real time fluorescent quantitative PCR method.
        Med Pharm J Chin Peoples Liberation Army. 2014; 26: 93-96
        • Sheikh Sajjadieh M.R.
        • Kuznetsova L.V.
        • Bojenko V.B.
        Dysbiosis in Ukrainian children with irritable bowel syndrome affected by natural radiation.
        Iran J Pediatr. 2012; 22: 364-368
        • Botschuijver S.
        • Roeselers G.
        • Levin E.
        • et al.
        Intestinal fungal dysbiosis is associated with visceral hypersensitivity in patients with irritable bowel syndrome and rats.
        Gastroenterology. 2017; 153: 1026-1039
        • Carroll I.M.
        • Chang Y.H.
        • Park J.
        • Sartor R.B.
        • Ringel Y.
        Luminal and mucosal-associated intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome.
        Gut Pathog. 2010; 2: 19
        • Carroll I.M.
        • Ringel-Kulka T.
        • Keku T.O.
        • et al.
        Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome.
        Am J Physiol Gastrointest Liver Physiol. 2011; 301: G799-G807
        • Chassard C.
        • Dapoigny M.
        • Scott K.P.
        • et al.
        Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome.
        Aliment Pharmacol Ther. 2012; 35: 828-838
        • Cui S.
        • Hu Y.
        Multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study.
        Int J Clin Exp Med. 2012; 5: 238-244
        • Duboc H.
        • Rainteau D.
        • Rajca S.
        • et al.
        Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome.
        Neurogastroenterol Motil. 2012; 24 (e246-517): 513-520
        • Malinen E.
        • Rinttila T.
        • Kajander K.
        • et al.
        Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR.
        Am J Gastroenterol. 2005; 100: 373-382
        • Mättö J.
        • Maunuksela L.
        • Kajander K.
        • et al.
        Composition and temporal stability of gastrointestinal microbiota in irritable bowel syndrome—A longitudinal study in IBS and control subjects.
        FEMS Immunol Med Microbiol. 2005; 43: 213-222
        • Noor S.O.
        • Ridgway K.
        • Scovell L.
        • et al.
        Ulcerative colitis and irritable bowel patients exhibit distinct abnormalities of the gut microbiota.
        BMC Gastroenterol. 2010; 10: 134
        • Si J.M.
        • Yu Y.C.
        • Fan Y.J.
        • Chen S.J.
        Intestinal microecology and quality of life in irritable bowel syndrome patients.
        World J Gastroenterol. 2004; 10: 1802-1805
        • Tana C.
        • Umesaki Y.
        • Imaoka A.
        • Handa T.
        • Kanazawa M.
        • Fukudo S.
        Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome.
        Neurogastroenterol Motil. 2010; 22 (e114-515): 512-519
        • Li X.
        • Wang Q.
        • Chu Y.
        Analysis of patients with intestinal target bacteria diarrhea type irritable bowel syndrome.
        Acta Univ. 2014; 49: 633-638
        • Chen F.
        • Zhang F.M.
        Study on the intestinal flora status of patients with different subtypes of irritable bowel syndrome.
        Jiangxi Med J. 2014; 49: 1459-1461
        • Wang X.M.
        Changes of intestinal flora and mast cells in patients with irritable bowel syndrome and ulcerative colitis.
        Guangdong Med J. 2015; 36: 756-758
        • Hu L.Y.
        • Wang Q.M.
        • Jiang B.Y.
        Alteration and significance ofintestinal microbiota in patients with irritable bowel syndrome.
        Univ Med Anhui. 2012; 47: 86-89
        • Zhuang Y.H.
        • Yang C.H.
        • Yang X.D.
        Study on the microecologicalchanges and curetive effects of irritable bowel syndrome by Chinese drug “Shenqu.
        Chin J Microecol. 2005; 17: 41
        • Lopetuso L.R.
        • Petito V.
        • Graziani C.
        • et al.
        Gut microbiota in health, diverticular disease, irritable bowel syndrome, and inflammatory bowel diseases: Time for microbial marker of gastrointestinal disorders.
        Dig Dis. 2018; 36: 56-65
        • Zhuang X.
        • Xiong L.
        • Li L.
        • Li M.
        • Chen M.
        Alterations of gut microbiota in patients with irritable bowel syndrome: A systematic review and meta-analysis.
        J Gastroenterol Hepatol. 2017; 32: 28-38
        • Julian P.T.H.
        • Sally G.
        Cochrane Handbook for Systematic Reviews of Interventions.
        John Wiley & Sons, Chichester, West Sussex/Hoboken NJ2008
        • Takeshima N.
        • Sozu T.
        • Tajika A.
        • Ogawa Y.
        • Hayasaka Y.
        • Furukawa T.A.
        Which is more generalizable, powerful and interpretable in meta-analyses, mean difference or standardized mean difference?.
        BMC Med Res Methodol. 2014; 14: 30
        • Yu Y.C.
        • Si J.M.
        • Fan Y.J.
        Control study on the microecology in irritable bowel syndrome.
        Chin J Digest. 2004; 24: 427-428
        • Zhang D.R.
        • Xu X.
        Intestinal flora changesin patients with irritable bowel syndrome after ingestion of Clostridium butyicum preparation.
        Chin J Microecol. 1999; 11: 164-166
        • Li J.
        • Zhu R.
        • Wan P.
        Analysis of the gut microbiota and treatment of 63 cases of patients with irritable bowel syndrome.
        J Chin Physician. 2003; S1: 92-93
        • Wu G.D.
        • Chen J.
        • Hoffmann C.
        • et al.
        Linking long-term dietary patterns with gut microbial enterotypes.
        Science. 2011; 334: 105-108
        • Yatsunenko T.
        • Rey F.E.
        • Manary M.J.
        • et al.
        Human gut microbiome viewed across age and geography.
        Nature. 2012; 486: 222-227
        • Hempel S.
        • Miles J.N.
        • Booth M.J.
        • Wang Z.
        • Morton S.C.
        • Shekelle P.G.
        Risk of bias: A simulation study of power to detect study-level moderator effects in meta-analysis.
        Syst Rev. 2013; 2: 107
        • Liu H.N.
        • Wu H.
        • Chen Y.Z.
        • Chen Y.J.
        • Shen X.Z.
        • Liu T.T.
        Altered molecular signature of intestinal microbiota in irritable bowel syndrome patients compared with healthy controls: A systematic review and meta-analysis.
        Dig Liver Dis. 2017; 49: 331-337
        • Shukla R.
        • Ghoshal U.
        • Dhole T.N.
        • Ghoshal U.C.
        Fecal microbiota in patients with irritable bowel syndrome compared with healthy controls using real-time polymerase chain reaction: An evidence of dysbiosis.
        Digest Dis Sci. 2015; 60: 2953-2962
        • Rinttila T.
        • Kassinen A.
        • Malinen E.
        • Krogius L.
        • Palva A.
        Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR.
        J Appl Microbiol. 2004; 97: 1166-1177
        • Gerritzen A.
        • Wittke J.W.
        • Wolff D.
        Rapid and sensitive detection of Shiga toxin-producing Escherichia coli directly from stool samples by real-time PCR in comparison to culture, enzyme immunoassay and Vero cell cytotoxicity assay.
        Clin Lab. 2011; 57: 993-998
        • Kontopantelis E.
        • Springate D.A.
        • Reeves D.
        A re-analysis of the Cochrane Library data: The dangers of unobserved heterogeneity in meta-analyses.
        PLoS One. 2013; 8e69930
        • Huedo-Medina T.B.
        • Sanchez-Meca J.
        • Marin-Martinez F.
        • Botella J.
        Assessing heterogeneity in meta-analysis: Q statistic or I2 index?.
        Psychol Methods. 2006; 11: 193-206
        • Kassinen A.
        • Krogius-Kurikka L.
        • Makivuokko H.
        • et al.
        The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects.
        Gastroenterology. 2007; 133: 24-33
        • Saulnier D.M.
        • Riehle K.
        • Mistretta T.A.
        • et al.
        Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome.
        Gastroenterology. 2011; 141: 1782-1791
        • Rajilic-Stojanovic M.
        • Biagi E.
        • Heilig H.G.
        • et al.
        Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome.
        Gastroenterology. 2011; 141: 1792-1801
        • Jalanka-Tuovinen J.
        • Salojarvi J.
        • Salonen A.
        • et al.
        Faecal microbiota composition and host-microbe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome.
        Gut. 2014; 63: 1737-1745
        • Jeffery I.B.
        • O'Toole P.W.
        • Ohman L.
        • et al.
        An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota.
        Gut. 2012; 61: 997-1006
        • Pittayanon R.
        • Lau J.T.
        • Yuan Y.
        • et al.
        Gut microbiota in patients with irritable bowel syndrome—A systematic review.
        Gastroenterology. 2019 Mar 30; (pii: S0016-5085(19)34649-9. [Epub ahead of print])
        • Rangel I.
        • Sundin J.
        • Fuentes S.
        • Repsilber D.
        • de Vos W.M.
        • Brummer R.J.
        The relationship between faecal-associated and mucosal-associated microbiota in irritable bowel syndrome patients and healthy subjects.
        Aliment Pharmacol Ther. 2015; 42: 1211-1221
        • Eckburg P.B.
        • Bik E.M.
        • Bernstein C.N.
        • et al.
        Diversity of the human intestinal microbial flora.
        Science. 2005; 308: 1635-1638
        • Maharshak N.
        • Ringel Y.
        • Katibian D.
        • et al.
        Fecal and mucosa-associated intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome.
        Digest Dis Sci. 2018; 63: 1890-1899
        • Keita A.V.
        • Soderholm J.D.
        Mucosal permeability and mast cells as targets for functional gastrointestinal disorders.
        Curr Opin Pharmacol. 2018; 43: 66-71
        • Damodharan K.
        • Palaniyandi S.A.
        • Yang S.H.
        • Suh J.W.
        In vitro probiotic characterization of Lactobacillus strains from fermented radish and their anti-adherence activity against enteric pathogens.
        Can J Microbiol. 2015; 61: 837-850
        • Pusceddu M.M.
        • Gareau M.G.
        Visceral pain: Gut microbiota, a new hope?.
        J Biomed Sci. 2018; 25: 73
        • Ford A.C.
        • Harris L.A.
        • Lacy B.E.
        • Quigley E.M.M.
        • Moayyedi P.
        Systematic review with meta-analysis: The efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome.
        Aliment Pharmacol Ther. 2018; 48: 1044-1060
        • Ringel-Kulka T.
        • Goldsmith J.R.
        • Carroll I.M.
        • et al.
        Lactobacillus acidophilus NCFM affects colonic mucosal opioid receptor expression in patients with functional abdominal pain—A randomised clinical study.
        Aliment Pharmacol Ther. 2014; 40: 200-207
        • de Weerth C.
        Do bacteria shape our development? Crosstalk between intestinal microbiota and HPA axis.
        Neurosci Biobehav Rev. 2017; 83: 458-471
        • Yousefi B.
        • Eslami M.
        • Ghasemian A.
        • Kokhaei P.
        • Salek Farrokhi A.
        • Darabi N.
        Probiotics importance and their immunomodulatory properties.
        J Cell Physiol. 2019; 234: 8008-8018
        • Cao Y.N.
        • Feng L.J.
        • Wang B.M.
        • et al.
        Lactobacillus acidophilus and Bifidobacterium longum supernatants upregulate the serotonin transporter expression in intestinal epithelial cells.
        Saudi J Gastroenterol. 2018; 24: 59-66
        • Singh R.
        • Salem A.
        • Nanavati J.
        • Mullin G.E.
        The role of diet in the treatment of irritable bowel syndrome: A systematic review.
        Gastroenterol Clin North Am. 2018; 47: 107-137
        • Schumann D.
        • Klose P.
        • Lauche R.
        • Dobos G.
        • Langhorst J.
        • Cramer H.
        Low fermentable, oligo-, di-, mono-saccharides and polyol diet in the treatment of irritable bowel syndrome: A systematic review and meta-analysis.
        Nutrition. 2018; 45: 24-31
        • Staudacher H.M.
        • Irving P.M.
        • Lomer M.C.
        • Whelan K.
        Mechanisms and efficacy of dietary FODMAP restriction in IBS.
        Nat Rev Gastroenterol Hepatol. 2014; 11: 256-266
        • Staudacher H.M.
        • Lomer M.C.
        • Anderson J.L.
        • et al.
        Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome.
        J Nutr. 2012; 142: 1510-1518
        • Staudacher H.M.
        • Lomer M.C.E.
        • Farquharson F.M.
        • et al.
        A diet low in FODMAPs reduces symptoms in patients with irritable bowel syndrome and a probiotic restores Bifidobacterium species: A randomized controlled trial.
        Gastroenterology. 2017; 153: 936-947
        • McIntosh K.
        • Reed D.E.
        • Schneider T.
        • et al.
        FODMAPs alter symptoms and the metabolome of patients with IBS: A randomised controlled trial.
        Gut. 2017; 66: 1241-1251
        • Chumpitazi B.P.
        • Cope J.L.
        • Hollister E.B.
        • et al.
        Randomised clinical trial: Gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome.
        Aliment Pharmacol Ther. 2015; 42: 418-427
        • Parkes G.C.
        • Rayment N.B.
        • Hudspith B.N.
        • et al.
        Distinct microbial populations exist in the mucosa-associated microbiota of sub-groups of irritable bowel syndrome.
        Neurogastroenterol Motil. 2012; 24: 31-39
        • Russell D.A.
        • Ross R.P.
        • Fitzgerald G.F.
        • Stanton C.
        Metabolic activities and probiotic potential of bifidobacteria.
        Int J Food Microbiol. 2011; 149: 88-105
        • Sloan T.J.
        • Jalanka J.
        • Major G.A.D.
        • et al.
        A low FODMAP diet is associated with changes in the microbiota and reduction in breath hydrogen but not colonic volume in healthy subjects.
        PLoS One. 2018; 13e0201410
        • Tuohy K.M.
        • Conterno L.
        • Gasperotti M.
        • Viola R.
        Up-regulating the human intestinal microbiome using whole plant foods, polyphenols, and/or fiber.
        J Agric Food Chem. 2012; 60: 8776-8782
        • Connolly M.L.
        • Tuohy K.M.
        • Lovegrove J.A.
        Wholegrain oat-based cereals have prebiotic potential and low glycaemic index.
        Br J Nutr. 2012; 108: 2198-2206
        • Staudacher H.M.
        • Whelan K.
        Altered gastrointestinal microbiota in irritable bowel syndrome and its modification by diet: Probiotics, prebiotics and the low FODMAP diet.
        Proc Nutr Soc. 2016; 75: 306-318
        • Valeur J.
        • Smastuen M.C.
        • Knudsen T.
        • Lied G.A.
        • Roseth A.G.
        Exploring gut microbiota composition as an indicator of clinical response to dietary FODMAP restriction in patients with irritable bowel syndrome.
        Digest Dis Sci. 2018; 63: 429-436
        • Bennet S.M.P.
        • Bohn L.
        • Storsrud S.
        • et al.
        Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs.
        Gut. 2018; 67: 872-881


      L. Wang is a PhD student and a Cochrane methodologist, The Johns Hopkins School of Public Health, Baltimore, MD


      N. Alammar is a gastroenterology Fellow, Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, and an assistant professor of medicine, King Saud University, Riyadh, Saudi Arabia.


      R. Singh is a medical resident Department of Internal Medicine, Sinai Hospital of Baltimore, MD.


      R. Chaudhary is an internal medicine hospitalist, Department of Internal Medicine, Sinai Hospital of Baltimore, MD.


      J. Nanavati is a clinical informationist, Welch Medical Library, The Johns Hopkins University School of Medicine, Baltimore, MD.


      Y. Song is a visiting scholar, Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD.


      G. E. Mullin is an associate professor, Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD.