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The low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide, and polyol) diet is a beneficial therapeutic approach for patients with irritable bowel syndrome (IBS). However, how the low FODMAP diet works is still not completely understood. These mechanisms encompass not only traditionally known factors such as luminal distension induced by gas and water but also recent evidence on the role of FOMAPs in the modulation of visceral hypersensitivity, increases in intestinal permeability, the induction of microbiota changes, and the production of short-chain fatty acids (SCFAs), as well as metabolomics and alterations in motility. Although most of the supporting evidence is of low quality, recent trials have confirmed its effectiveness, even though the majority of the evidence pertains only to the restriction phase and its effectiveness in relieving abdominal bloating and pain. This review examines potential pathophysiological mechanisms and provides an overview of the existing evidence on the effectiveness of the low FODMAP diet across various IBS subtypes. Key considerations for its use include the challenges and disadvantages associated with its practical implementation, including the need for professional guidance, variations in individual responses, concerns related to microbiota, nutritional deficiencies, the development of constipation, the necessity of excluding an eating disorder before commencing the diet, and the scarcity of long-term data. Despite its recognized efficacy in symptom management, acknowledging these limitations becomes imperative for a nuanced comprehension of the role of a low FODMAP diet in managing IBS. By investigating its potential mechanisms and evidence across IBS subtypes and addressing emerging modulations alongside limitations, this review aims to serve as a valuable resource for healthcare practitioners, researchers, and patients navigating the intricate landscape of IBS.

The irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction. IBS is still associated with areas of uncertainties, especially regarding the optimal diagnostic work-up and the more appropriate management. Experts from 7 Italian Societies conducted a Delphi consensus with literature summary and voting process on 27 statements. Recommendations and quality of evidence were evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was defined as >80% agreement and reached for all statements. In terms of diagnosis, the consensus supports a positive diagnostic strategy with a symptom-based approach, including the psychological comorbidities assessment and the exclusion of alarm symptoms, together with the digital rectal examination, full blood count, C-reactive protein, serology for coeliac disease, and fecal calprotectin assessment. Colonoscopy should be recommended in patients with alarm features. Regarding treatment, the consensus strongly supports a dietary approach for patients with IBS, the use of soluble fiber, secretagogues, tricyclic antidepressants, psychologically directed therapies and, only in specific IBS subtypes, rifaximin. A conditional recommendation was achieved for probiotics, polyethylene glycol, antispasmodics, selective serotonin reuptake inhibitors and, only in specific IBS subtypes, 5-HT3 antagonists, 5-HT4 agonists, bile acid sequestrants., Competing Interests: Declaration of Competing Interest The following authors declare the following paid or unpaid consultancies, business interests or sources of honoraria payments for the past three years, and anything else which could potentially be viewed as a conflict of interest: GB: Aboca, AB Biotics, Agave, Alfa Sigma, AGPharma, Bayer, Bromatech, Cadigroup, Biocodex, Sanofy, GE Healthcare, Mayoly, Diadema, Sofar; CC: Sofar, Interalia Pharma, Schwabe Pharma; consultation fees from Alfa Sigma; MB: is consultant for GE Healthcare, Aboca, Diadema, Norgine, Alfasigma, SOFAR, Agave; MC: is consultant for Arena, RB, Takeda, Mayoly, Biocodex and Sanofi and is Co-Chief Investigator in a research grant funded by Sanofi; LF: is consultant for Alfasigma e Norgine; GM: served as an advisory board member for EG Pharma; received lecture grants from AlfaSigma, Bromatech, Echosens, Ferring and Schwabe Pharma. EVS, has served as speaker for Abbvie, AGPharma, Alfasigma, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Innovamedica, Malesci, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Unifarco; has served as consultant for Alfasigma, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Falk, Fresenius Kabi, Janssen, Merck & Co, Reckitt Benckiser, Regeneron, Sanofi, Shire, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; he received research support from Reckitt Benckiser, SILA, Sofar, Unifarco; AS: is clinical investigator for Janssen Biologics B.V., Eli Lilly Cork Limited and Novalac; consultant for Aboca, Abbott, Angelini e Novalac; was clinical investigator for Aboca and PAREXEL International. VS: Alfa Sigma, Bayer, Coloplast, GE Healthcare, Menarini, Norgine. All the other authors declared no conflicts of interest., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Nocebo effects occurring in patients receiving placebo frequently impact on adverse events reported in randomized controlled trials (RCTs) in irritable bowel syndrome (IBS). Therefore, we conducted a systematic review and meta-analysis to assess the proportion of patients randomized to placebo or active drug experiencing any adverse event in trials of licensed drugs for IBS with constipation (IBS-C) or diarrhea (IBS-D), and to estimate the risk of developing adverse events among patients randomized to placebo., Methods: We searched MEDLINE, EMBASE CLASSIC and EMBASE, and the Cochrane central register of controlled trials (through June 2021) to identify RCTs comparing licensed drugs with placebo in adults with IBS-C or IBS-D. We generated Forest plots of pooled adverse event rates in both active drug and placebo arms and pooled risk differences (RDs) with 95% confidence intervals (CIs)., Key Results: There were 21 RCTs of licensed drugs versus placebo in IBS-C (5953 patients placebo) and 17 in IBS-D (3854 patients placebo). Overall, 34.9% and 46.9% of placebo patients in IBS-C and IBS-D trials, respectively, developed at least one adverse event, with a statistically significantly higher risk of any adverse event and withdrawal due to an adverse event with active drug. In IBS-C and IBS-D trials, rates of each individual adverse event were generally higher with active drug. However, in IBS-C trials, only diarrhea or headache was significantly more common with active drug (RD 0.066 (95% CI 0.043-0.088) and RD 0.011 (95% CI 0.002-0.021), respectively), and in IBS-D trials only constipation, nausea, or abdominal pain (RD 0.096 (95% CI 0.054-0.138), 0.014 (95% CI 0.002-0.027), and 0.018 (95% CI 0.002-0.034), respectively)., Conclusions & Inferences: Patients with IBS randomized to placebo have a high risk of reporting adverse events, which might relate to both nocebo and non-nocebo factors. Although patients' expectations and psychosocial factors may be involved, further understanding of the mechanisms are important to control or optimize these effects in RCTs, as well as in clinical practice., (© 2021 John Wiley & Sons Ltd.)

Background & Aims: There are several licensed drugs for irritable bowel syndrome (IBS) that have proven efficacy in randomized controlled trials (RCTs), but placebo response rates are high. We conducted a systematic review and meta-analysis of licensed drugs to estimate magnitude of placebo response rate according to Food and Drug Administration (FDA)-recommended endpoints and to assess how this varies with stringency of the endpoint used to define response., Methods: We searched MEDLINE, EMBASE CLASSIC and EMBASE, and the Cochrane central register of controlled trials (through January 2021) to identify RCTs comparing licensed drugs with placebo in adult IBS patients. Studies assessed efficacy according to at least one of composite response, abdominal pain response, or stool response. Data were extracted as intention-to-treat analyses, with dropouts assumed to be treatment failures and pooled using a random-effects model., Results: There were 17 RCTs of licensed drugs versus placebo in IBS with constipation (4603 patients placebo) and 17 trials in IBS with diarrhea (3908 patients placebo). In IBS with constipation, according to FDA criteria, pooled composite, abdominal pain, and stool response rates with placebo over ≥6 of 12 weeks were 18.9%, 34.6%, and 30.1%, respectively. Evaluating response rates over ≥9 of 12 weeks led to placebo response rates of 4.3% for the composite endpoint, 24.5% for abdominal pain, and 7.7% for stool. In IBS with diarrhea, pooled placebo response rates according to FDA criteria were 16.2% for the composite endpoint, 40.2% for abdominal pain, and 16.2% for stool. Increasing the threshold used to define abdominal pain response from ≥30% improvement to ≥40% or ≥50% led to lower placebo response rates of 34.5% and 23.4%., Conclusions: Future RCTs should adhere to current FDA-recommended endpoints for IBS because these lead to lower placebo response rates. However, consideration should be given to further refining some of these to better differentiate between active drug and placebo., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Disorders of gut-brain interaction, such as irritable bowel syndrome (IBS) and functional dyspepsia (FD), frequently overlap, but the impact of this on the natural history is unknown. We examined this issue in a longitudinal follow-up study conducted in a large cohort of individuals., Methods: We collected complete demographic, symptom, mood, and psychological health data from 1374 adults who self-identified as having IBS. We applied the Rome IV criteria to examine what proportion met criteria for IBS and FD, as well as the degree of overlap between them. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, treatments commenced, and psychological health according to degree of overlap between IBS and FD., Results: Overall, 807 individuals met the Rome IV criteria for IBS at baseline and provided complete data. At study entry, overlap of FD occurred in 446 (55.3%) people who met Rome IV criteria for IBS. At 12 months, 451 (55.9%) individuals were successfully followed up. The proportion of individuals consulting their primary care physician (P = .001) or a gastroenterologist (P < .001) because of their IBS was significantly higher in those with overlap of IBS and FD, and the number of new IBS treatments commenced was significantly higher (P = .007). Those with overlap of IBS and FD reported significantly more severe IBS symptoms (P < .001), continuous abdominal pain, and that their IBS symptoms limited normal daily activities ≥50% of the time. Finally, those with overlap were more likely to report abnormal anxiety and depression scores at 12 months compared with those with IBS alone, and to have higher levels of somatization (P < .001 for all analyses)., Conclusions: The natural history of people with IBS with overlap FD defined according to Rome IV criteria is more severe than those with IBS alone. This has important implications for future treatment trials in IBS., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder, which follows a relapsing and remitting course. Little is known about how evolving definitions of IBS or treatment for the condition affect symptom stability. We conducted a 12-month longitudinal follow-up study of individuals who self-identified as having IBS to examine these issues., Methods: We collected demographic, gastrointestinal symptom, mood, and psychological health data at baseline, and gastrointestinal symptom data at 12 months, from adults who self-identified as having IBS, registered with 3 organizations providing services to people with IBS. We applied the Rome III and Rome IV criteria simultaneously at baseline and 12 months and subtyped participants according to predominant stool form or frequency. We examined stability of a diagnosis of IBS, and stability of IBS subtype, for the Rome IV and III criteria separately and examined the effect of commencing new therapy on fluctuation of symptoms., Results: Of 1,375 individuals recruited at baseline, 784 (57.0%) provided data at 12 months. Of these, 452 met the Rome IV criteria for IBS at baseline, of whom 133 (29.4%) fluctuated to another functional bowel disorder at 12 months. In the remaining 319 (70.6%) who still met the Rome IV criteria for IBS, IBS subtype changed in 101 (31.7%) subjects, with IBS with mixed bowel habit (IBS-M) the least stable. Commencing a new treatment for IBS did not affect symptom stability. Among 631 who met the Rome III criteria at baseline responding at 12 months, 104 (16.5%) fluctuated to another functional bowel disorder. In the 527 (83.5%) who still met the Rome III criteria for IBS, IBS subtype fluctuated in 129 (24.5%), with IBS-M the most stable subtype. Again, commencing a new treatment for IBS did not affect symptom stability., Discussion: Fluctuation between functional bowel disorders and predominant stool subtype is common in people with IBS and does not appear to be influenced solely by treatment. Rome IV IBS appears less stable than Rome III IBS., (Copyright © 2020 by The American College of Gastroenterology.)

Background: Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders, but community prevalence appears to vary widely between different countries. This variation might be due to the fact that previous cross-sectional surveys have neither applied uniform diagnostic criteria nor used identical methodology, rather than being due to true global variability. We aimed to determine the global prevalence of IBS., Methods: We did a systematic review and meta-analysis of data from all population-based studies using relatively uniform methodology and using only the most recent iterations of the Rome criteria (Rome III and IV). We searched MEDLINE, Embase, and Embase Classic (from Jan 1, 2006, to April 30, 2020) to identify cross-sectional surveys reporting the prevalence of IBS in adults (≥90% of participants aged ≥18 years) according to the Rome III or Rome IV criteria. We also hand-searched a selection of conference proceedings for relevant abstracts published between 2006 and 2019. We extracted prevalence data for all studies, according to the criteria used to define the presence of IBS. We did a meta-analysis to estimate pooled prevalence rates, according to study location and certain other characteristics (eg, sex and IBS subtype)., Findings: We identified 4143 citations, of which 184 studies appeared relevant. 57 of these studies were eligible, and represented 92 separate adult populations, comprising 423 362 participants. The pooled prevalence of IBS in 53 studies that used the Rome III criteria, from 38 countries and comprising 395 385 participants, was 9·2% (95% CI 7·6-10·8; I 2 =99·7%). By contrast, pooled IBS prevalence among six studies that used the Rome IV criteria, from 34 countries and comprising 82 476 individuals, was 3·8% (95% CI 3·1-4·5; I 2 =96·6%). IBS with mixed bowel habit (IBS-M) was the most common subtype with the Rome III criteria, reported by 33·8% (95% CI 27·8-40·0; I 2 =98·1%) of people fulfilling criteria for IBS (ie, 3·7% [2·6-4·9] of all included participants had IBS-M), but IBS with diarrhoea (IBS-D) was the most common subtype with the Rome IV criteria (reported by 31·5% [95% CI 23·2-40·5; I 2 =98·1% 61·6%] of people with IBS, corresponding to 1·4% [0·9-1·9] of all included participants having IBS-D). The prevalence of IBS was higher in women than in men (12·0% [95% CI 9·3-15·0] vs 8·6% [6·3-11·2]; odds ratio 1·46 [95% CI 1·33-1·59]). Prevalence varied substantially between individual countries, and this variability persisted even when the same diagnostic criteria were applied and identical methodology was used in studies., Interpretation: Even when uniform symptom-based criteria are applied, based on identical methodology, to define the presence of IBS, prevalence varies substantially between countries. Prevalence was substantially lower with the Rome IV criteria, suggesting that these more restrictive criteria might be less suitable than Rome III for population-based epidemiological surveys., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: We aimed to evaluate the prevalence of irritable bowel syndrome (IBS) in patients with typical reflux symptoms as distinguished into gastroesophageal reflux disease (GERD), hypersensitive esophagus (HE), and functional heartburn (FH) by means of endoscopy and multichannel intraluminal impedance (MII)-pH monitoring. The secondary aim was to detect pathophysiological and clinical differences between different sub-groups of patients with heartburn., Methods: Patients underwent a structured interview based on questionnaires for GERD, IBS, anxiety, and depression. Off-therapy upper-gastrointestinal (GI) endoscopy and 24 h MII-pH monitoring were performed in all cases. In patients with IBS, fecal calprotectin was measured and colonoscopy was scheduled for values >100 mg/kg to exclude organic disease. Multivariate logistic regression analysis was performed to identify independent risk factors for FH., Results: Of the 697 consecutive heartburn patients who entered the study, 454 (65%) had reflux-related heartburn (GERD+HE), whereas 243 (35%) had FH. IBS was found in 147/454 (33%) GERD/HE but in 187/243 (77%) FH patients (P<0.001). At multivariate analysis, IBS and anxiety were independent risk factors for FH in comparison with reflux-related heartburn (GERD+HE)., Conclusions: IBS overlaps more frequently with FH than with GERD and HE, suggesting common pathways and treatment. HE showed intermediate characteristic between GERD and FH.