Relationship between Markers of Gut Barrier Function and Erythrocyte Membrane PUFAs in Diarrhea-Predominant IBS Patients Undergoing a Low-FODMAP Diet.

Many patients with irritable bowel syndrome (IBS) have a compromised intestinal barrier associated with low-grade inflammation. Polyunsaturated fatty acids (PUFAs) are potential mediators of inflammation: omega-6 PUFAs are pro-inflammatory, while omega-3 PUFAs are antioxidant and anti-inflammatory. Zonulin is a potential biomarker for small intestinal permeability (s-IP). This study investigated the relationship between PUFAs and gastrointestinal (GI) barrier integrity in IBS patients with predominant diarrhea (IBS-D). We evaluated GI barrier function indicators in the urine and bloodstream and erythrocyte membrane PUFA composition in 38 IBS-D patients (5 men, 33 women, 44.11 ± 1.64 years), categorized at baseline by fecal zonulin levels into high (≥107 ng/mL, H-FZ) and normal (<107 ng/mL N-FZ) groups. Evaluations were conducted prior to and following a 12-week diet low in FODMAPs (LFD). At baseline, H-FZ patients had s-IP significantly higher than the reference value, lower n-3 PUFAs levels, and higher n-6/n-3 PUFAs and arachidonic acid (AA) to eicosapentaenoic acid (EPA) ratios than N-FZ. After LFD, H-FZ patients showed significant increases in n-3 PUFAs levels; decreases in n-6 PUFAs, n-6/n-3 PUFAs and AA/EPA ratios; and improved s-IP. The n-6/n-3 PUFAs ratio positively correlated with fecal zonulin levels in all subjects. These findings highlight the relationship between PUFAs and the intestinal barrier, suggesting their role in IBS-D pathophysiology and confirming the positive effects of LFD in managing IBS-D.

Lactiplantibacillus plantarum Regulates Intestinal Physiology and Enteric Neurons in IBS through Microbial Tryptophan Metabolites.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by visceral pain and gut dysmotility. However, the specific mechanisms by which Lactobacillus strains relieve IBS remain unclear. Here, we screened Lactobacillus strains from traditional Chinese fermented foods with potential IBS-alleviating properties through in vitro and in vivo experiments. We demonstrated that Lactiplantibacillus plantarum D266 (Lp D266) administration effectively modulates intestinal peristalsis, enteric neurons, visceral hypersensitivity, colonic inflammation, gut barrier function, and mast cell activation. Additionally, Lp D266 shapes gut microbiota and enhances tryptophan (Trp) metabolism, thus activating the aryl hydrocarbon receptor (AhR) and subsequently enhancing IL-22 production to maintain gut homeostasis. Mechanistically, Lp D266 potentially modulates colonic physiology and enteric neurons by microbial tryptophan metabolites. Further, our study indicates that combining Lp D266 with Trp synergistically ameliorates IBS symptoms. Together, our experiments identify the therapeutic efficacy of tryptophan-catabolizing Lp D266 in regulating gut physiology and enteric neurons, providing new insights into the development of probiotic-mediated nutritional intervention for IBS management.

Probiotics in Functional Gastrointestinal Disorders.

The most frequent functional gastrointestinal disorders (FGID) in children include infantile colic, constipation, functional abdominal pain (FAP), and irritable bowel syndrome (IBS). Unfortunately, treatment options for FGID in children are limited, therefore many dietary interventions have been evaluated, including probiotics. This chapter summarizes currently available evidence and recommendations for probiotic use in the treatment of frequent FGIDs in children. The strongest evidence exists for the use of Limosilactobacillus (L.) reuteri DSM 17938 and Bifidobacterium animalis subsp. lactis BB-12 for the treatment of infantile colic in breastfed infants. Limited but yet encouraging evidence exists for Lacticaseibacillus rhamnosus GG (LGG) for the treatment of IBS and L. reuteri DSM 17938 for FAP.

Changes in Fecal Short-Chain Fatty Acids in IBS Patients and Effects of Different Interventions: A Systematic Review and Meta-Analysis.

CONTEXT: Short-chain fatty acids (SCFAs) have been reported to be associated with the pathogenesis of irritable bowel syndrome (IBS), but the results are conflicting. OBJECTIVE: Here, a systematic review of case-control studies detecting fecal SCFAs in IBS patients compared with healthy controls (HCs) and self-controlled studies or randomized controlled trials (RCTs) investigating fecal SCFA alterations after interventions were identified from several databases. DATA SOURCES: A systematic search of databases (PubMed, Web of Science, and Embase) identified 21 studies published before 24 February 2023. Data extractions: Three independent reviewers completed the relevant data extraction. DATA ANALYSIS: It was found that the fecal propionate concentration in IBS patients was significantly higher than that in HCs, while the acetate proportion was significantly lower. Low-FODMAP diets significantly reduced the fecal propionate concentration in the IBS patients while fecal microbiota transplantation and probiotic administration did not significantly change the fecal propionate concentration or acetate proportion. CONCLUSIONS: The results suggested that the fecal propionate concentration and acetate proportion could be used as biomarkers for IBS diagnosis. A low-FODMAP diet intervention could potentially serve as a treatment for IBS while FMT and probiotic administration need more robust trials.

Challenges of recruitment processes to a randomized dietary trial in irritable bowel syndrome.

Background: Irritable bowel syndrome (IBS) is common with a global prevalence of 4%. Dietary regimes with a low content of fermentable oligo-, di-, and monosaccharides and polyol (FODMAP) or a starch- and sucrose-reduced diet (SSRD) have proven to be efficient. The aim of the present study was to describe the recruitment process for a randomized dietary trial with low FODMAP or SSRD for 4 weeks with a follow-up period of 5 months. The results of the dietary trial itself are not included in this paper but will be presented in another publication. Methods: The County of Skåne, with 1,41 million inhabitants, was used as a base to perform a dietary trial in which IBS patients, age 18-70 years, were randomized to either low FODMAP or SSRD for 4 weeks. The estimated number of IBS patients in the actual age span was approximately 32,000. The trial was announced through lectures, letters to all primary healthcare centers (n=203), social media (two campaigns), and invitations to IBS patients identified in medical records (n=744). Results: Three referrals arrived from the healthcare system, 17 patients contacted the investigators in person after receiving information from their healthcare center, and four patients contacted the investigators after recommendations from friends. Of these, 14 were enrolled in the study. From social media, 218 names were delivered, of which 93 fulfilled the study criteria and were willing to participate when contacted by the investigators (42.7%). Of the 3587 identified IBS patients in medical records in close proximity to the hospital, 744 were randomly contacted. Forty-eight patients (6.5 %) were willing to be included in the study. Thus, 155 patients with IBS were included in this study. Conclusions: The inclusion rate for dietary intervention was very low considering the large population informed about the study. Announcements on social media seem to be the best way to recruit patients for intervention. Trial registration: NCT05192603, 29/11/2021, ClinicalTrials.gov. The PRS URL is https://register.clinicaltrials.gov.

Is the Mediterranean Low Fodmap Diet Effective in Managing Irritable Bowel Syndrome Symptoms and Gut Microbiota? An Innovative Research Protocol.

INTRODUCTION: Irritable bowel syndrome (IBS) symptoms can be effectively managed with the low FODMAP diet. However, its efficacy in reducing inflammation is not yet proven. On the contrary, the Mediterranean diet has anti-inflammatory properties with proven efficacy in treating chronic low-grade inflammation-related diseases. AIM: To publicly share our protocol evaluating the efficacy of the Mediterranean low-FODMAP (MED-LFD) versus NICE recommendations (British National Institute for Health and Care Excellence) diet in managing IBS symptoms and quality of life. MATERIALS AND METHODS: Participants meeting the Rome IV criteria will be randomly assigned to MED-LFD or NICE recommendations and they will be followed for six months. Efficacy, symptom relief, quality of life and mental health will be assessed using validated questionnaires. In addition, fecal samples will be analyzed to assess gut microbiota, and to measure branched and short-chain fatty acids, and volatile organic compounds (metabolic byproducts from bacteria). Expected results and discussion: By publicly sharing this clinical study protocol, we aim to improve research quality in the field of IBS management by allowing for peer review feedback, preventing data manipulation, reducing redundant research efforts, mitigating publication bias, and empowering patient decision-making. We expect that this protocol will show that MED-LFD can effectively alleviate IBS symptoms and it will provide pathophysiology insights on its efficacy. The new dietary pattern that combines the LFD and the MED approaches allows for the observation of the synergistic action of both diets, with the MED's anti-inflammatory and prebiotic properties enhancing the effects of the LFD while minimizing its limitations. Identifier in Clinical Trials: NCT03997708.

A diet low in fermentable oligo-, di-, monosaccharides and polyols improves abdominal and overall symptoms in persons with all subtypes of irritable bowel syndrome.

BACKGROUND: A diet low in fermentable oligo-, di-, monosaccharides and polyols (LFD) improves symptoms in patients with irritable bowel syndrome (IBS). Previous studies have focused on patients with IBS and diarrhea (IBS-D). It is unclear whether LFD is effective for IBS with constipation (IBS-C) or IBS with mixed bowel habits (IBS-M). This open-label, real-world study evaluates the relative effectiveness of the LFD among IBS subtypes. METHODS: This study analyzes data from a service that provides low-FODMAP meals to individuals with IBS. Participants met with a registered dietitian and completed the IBS symptom severity survey (IBS-SSS) before and after undergoing a 2-4-week period of FODMAP restriction. The primary endpoint was the proportion of participants with ≥50-point decrease in IBS-SSS between the three IBS subtypes. KEY RESULTS: After FODMAP restriction, 90% of participants with IBS-D, 75% with IBS-C, and 84% with IBS-M met the primary endpoint (p = 0.045). Similar improvement was seen for a 100-point decrease, but the difference between IBS subtypes was not significant (p = 0.46). After FODMAP restriction, all groups had statistically significant improvement in total IBS-SSS as well as individual symptom categories. Improvement in IBS-SSS subcategories was similar among the groups except for the categories of bloating severity (IBS-M had greatest improvement) and bowel movement satisfaction (IBS-C had less improvement). CONCLUSION & INFERENCES: Though the proportion of responders was highest for IBS-D and lowest for IBS-C, the LFD led to robust improvement in overall symptoms in all IBS subtypes. Key individual symptoms also showed significant improvements in all IBS subtypes.

Current and future pharmacotherapies for the management of constipation-predominant irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder affecting 9-23% of the world's population, with a higher prevalence among women. IBS is a complex disorder influenced by psychosocial, physiological, and genetic factors, exacerbated by stress. AREAS COVERED: Research confirms that the most common subtype of IBS is IBS-C. Therefore, new therapies are being developed to speed up bowel movement and reduce constipation, with drugs such as linaclotide, plecanatide, lubiprostone, or tegaserod available to reduce IBS-C symptoms. In addition, patients' condition is improved by foods rich in fiber and low in FODMAP and the use of biotics. EXPERT OPINION: The topic is of great importance due to the growing number of patients suffering from IBS-C and its significant impact on quality of life. Current clinical trials of new therapeutic options are not too successful, and it seems that one of the plausible treatment options could be the multi-drug cocktail with some, or perhaps even all its ingredients emerging from drug re-purposing. Another important path that needs to be explored further in IBS-C patients is the adjustment of dietary habits and/or introduction of dietary or nutritional intervention.

Dietetic Management of Irritable Bowel Syndrome: A National Survey of Dietary Approaches and Decision-making Factors.

BACKGROUND AND AIMS: There has been a growing emphasis on dietary therapies for irritable bowel syndrome (IBS). Furthermore, there has been an evolving evidence base for the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, gluten-free diet (GFD), and lactose-free diet. This study examines the dietary approaches employed and the factors influencing dietetic decision-making for IBS interventions. METHODS: Participants, including registered dietitians and nutritionists, were recruited from diverse healthcare settings at the point of registration for the 4th Sheffield National Dietetic Gastroenterology Symposium, 2023. A 15-question online survey investigated the practices of dietitians and nutritionists in managing IBS patients, covering dietary approaches, decision-making factors, and patient education. The evidence base for different dietary interventions was provided and a follow-up survey assessed symposium attendees, views on current IBS dietary practices. RESULTS: Out of 731 respondents, primarily registered dietitians (93%) and females (93%), 54% spent 10-50% of clinic time on IBS. Respondents noted that a GFD (34%), low lactose (32%), and traditional dietary advice (TDA) (18%) were the most frequently used dietary interventions that patients try before seeking professional advice. Delegates were asked to rank their dietary intervention preferences pre- and post-meeting (after the evidence base had been presented): TDA pre-meeting 75% versus post-meeting 87% (p=0.04), fibre modification 59% versus 6% (p<0.0001), low FODMAP 25% versus 10% (p=0.0001), low lactose 12% versus 62% (p<0.0001) and GFD 6% to 23% (p<0.0001). CONCLUSIONS: TDA remains the choice of diet for dietitians. After our educational event, the use of low-lactose and gluten-free diet significantly increased. Factors influencing the decision-making process were based on patient acceptability, counselling time, supporting evidence base and dietary triggers.

The low-FODMAP diet.

In this article we present a protocol for the use of the low-FODMAP diet in paediatric patients and review of the current evidence on its efficacy. These short-chain carbohydrates, which can be fermented by the intestinal microbiota, are found in a wide variety of foods, mainly of plant origin. The low-FODMAP diet is a therapeutic tool used for the management of gastrointestinal disorders such as irritable bowel syndrome. The sources we used were PubMed, Web of Science, Google Scholar and institutional websites. Following consumption of FODMAP-rich foods, a series of end products are generated that are not absorbed, giving rise to symptoms. Before starting a low-FODMAP diet, it is important to carry out a diagnostic evaluation including any applicable tests. Treatment is structured in 3 phases: elimination, reintroduction and personalization phase. In the first phase, FODMAP-rich foods are eliminated for 2-3 weeks. In the second phase, lasting 8 weeks, FODMAP-rich foods are gradually reintroduced. The last phase consists in customizing the diet according to individual tolerance. This article details which foods contain FODMAPs and possible substitutes. In addition, specific food diary/intake tracking and educational materials are provided in a series of appendices to facilitate adherence to the diet. Although most studies have been conducted in adults, there is also some evidence on the beneficial effects in the paediatric age group, with a reduction of symptoms, especially in patients with functional gastrointestinal disorders. Nevertheless, more research is required on the subject.

Global research trend and hotspot in the low FODMAP diet: a bibliometric analysis.

BACKGROUND: According to national guidelines, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is a second-line therapy option for irritable bowel syndrome (IBS) and improves functional intestinal symptoms. Numerous noteworthy results have been published in this field over the past fifteen years. This study aims to analyze the global research trend and hotspot of the low FODMAP diet research, and provide a comprehensive perspective and direction for researchers. METHODS: The Science Citation Index-Expanded of the Web of Science Core Collection (WoSCC) was used to identify low FODMAP diet-related articles and reviews. Three bibliometric programs (CiteSpace, VOSviewer, Scimago Graphic) were utilized to analyze and visualize the annual publications, authors, countries, institutions, journals, citations, and keywords. RESULTS: In total, 843 documents related to the low FODMAP diet research were published in 227 journals by 3,343 authors in 1,233 institutions from 59 countries. The United States, which was the most engaged nation in international collaboration, had the largest annual production and the fastest growth. The most productive organization was Monash University, and the most fruitful researcher was Gibson PR. Nutrients ranked first in terms of the number of published documents. The article "A diet low in FODMAPs reduces symptoms of irritable bowel syndrome" (Halmos EP, 2014) received the most co-citations. Keywords that appear frequently in the literature mainly involve two main aspects: the clinical efficacy evaluation and mechanism exploration of the low FODMAP diet. The term "gut microbiota" stands out as the most prominent keyword among the burst keywords that have remained prevalent till date. CONCLUSION: The restriction stage of the low FODMAP diet is superior to other dietary therapies for IBS in terms of symptom response, but it has a negative impact on the abundance of gut Bifidobacteria and diet quality. Identification of biomarkers to predict response to the low FODMAP diet is of great interest and has become the current research hotspot.

[Gastrointestinal symptoms and dietary intake of patients with irritable bowel syndrome following a low FODMAP diet].

INTRODUCTION: High FODMAP (fermentable oligo-, di, monosaccharides and polyols) foods have been linked with worsening symptoms of IBS patients. The aim was to compare gastrointestinal symptoms and dietary intake of patients with irritable bowel syndrome following a low FODMAP diet, with or without individual nutrition therapy. MATERIALS AND METHODS: A total of 54 patients that met Rome IV criteria for IBS were randomized into two groups, guided group (individual nutrition therapy, n=28) and self-management group (learned about low FODMAP diet online, n=26). Both groups followed low FODMAP diet for 4 weeks. Four-day food records were used to assess dietary intake. Symptoms were assessed by the IBS-severity scoring system (ISB-SSS). RESULTS: The number of subjects who did not complete the study was 13, thereof five in the nutrition therapy and eight in the self-management group, leaving 23 and 18 subjects available for analysis, respectively. Symptoms declined from baseline to endpoint in both groups, by 183±101 points on average in the group receiving nutrition therapy (p< 0.001) and 132±110 points in the self-management group (p< 0.001), with no difference between groups. At baseline, about 80% of meals in both groups contained food high in FODMAP's. The corresponding proportion was 9% and 36% in week 3 in the nutrition therapy and self-management group, respectively (p< 0.001). CONCLUSION: Both groups experienced relieve of symptoms, but compliance to the low FODMAP diet was better in the group receiving individual nutrition therapy compared with the group who only received instructions on how to learn about low FODMAP diet online.

The efficacy and real-world effectiveness of a diet low in fermentable oligo-, di-, monosaccharides and polyols in irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND & AIMS: A diet low in fermentable oligo-, di-, monosaccharides, and polyols (LFD) has been shown to effectively reduce irritable bowel syndrome (IBS) symptoms. Effects resulting from real-world studies may differ from those seen in efficacy studies because of the diversity of patients in real-world settings. This systematic review and meta-analysis aimed to compare the effect of the LFD on reducing IBS symptoms and improving the quality of life (QoL) in efficacy trials and real-world studies. METHODS: Major databases, trial registries, dissertations, and journals were systematically searched for studies on the LFD in adults with IBS. Meta-analysis was conducted using a random effects model with standardized mean differences (SMD) and 95% confidence intervals (CI). Outcomes of interest were all patient-reported: stool consistency, stool frequency, abdominal pain, overall symptoms, adequate symptom relief, IBS-specific QoL and adherence to the LFD. RESULTS: Eleven efficacy and 19 real-world studies were reviewed. The meta-analysis results for abdominal pain (SMD 0.35, 95% CI 0.16 to 0.54) and QoL (SMD 0.23, 95% CI -0.05 to 0.50) showed the LFD was beneficial in efficacy studies with no statistically significant results for stool frequency (SMD 0.71, 95% CI 0.34 to 1.07). Real-world studies found improvements in abdominal pain and QoL. Due to heterogeneity, no meta-analysis was done for stool consistency and overall symptoms. In these outcomes, results were mostly supportive of the LFD, but they were not always statistically significant. CONCLUSIONS: The results of this systematic review and meta-analysis suggest the LFD improves outcomes compared to a control diet (efficacy studies) or baseline data (real-world studies). Because of diverse study designs and heterogeneity of results, a clear superiority of the LFD over control diets could not be concluded. There are no indications of an efficacy-effectiveness gap for the LFD in adults with IBS.

Nutritional safety and status following a 12-week strict low FODMAP diet in patients with irritable bowel syndrome.

BACKGROUND: A low FODMAP diet (LFD) is an established dietary treatment for patients with irritable bowel syndrome (IBS). However, knowledge on the extended effects of the restriction phase regarding nutrient intake, symptom severity, and quality of life (QoL) is sparse. Therefore, our objectives were to evaluate the safety of a dietitian-led 12-week strict LFD on measures of blood biochemistry, nutritional status, symptom severity, and QoL. METHODS: In this open-label dietitian-led 12-week strict LFD intervention for IBS patients with predominantly diarrhea or mixed stool pattern (IBS-D/-M), we collected data on diet intake (3-day dietary record), overnight fasting routine blood samples, body weight, IBS symptoms (IBS Severity Scoring System (IBS-SSS)), and IBS-related QoL (IBS-QoL) at baseline and after 12 weeks. KEY RESULTS: Thirty-six participants completed the 12-week follow-up (mean age: 37 years, 67% women, IBS-SSS: 242 (101)). All blood parameters measured were within established reference values at both time points. We found no change in intake of macro- or micronutrients, but several micronutrients were below the recommendations both before and after 12 weeks. BMI slightly decreased, primarily driven by participants with BMI >25 (p < 0.005). QoL improved among most subdomains (p ≤ 0.002), except food avoidance and social reaction. CONCLUSION: An extended dietitian-guided LFD (12 weeks) is not inferior to the participants' baseline diet, since no clinically meaningful changes in nutritionally related blood samples and no changes in macro- or micronutrient intake were observed. However, the intake of several nutrients was below the recommendations at both time points indicating low diet quality.

Effects of a low FODMAP diet on the symptom management of patients with irritable bowel syndrome: a systematic umbrella review with the meta-analysis of clinical trials.

A low FODMAP diet (LFD) is a common restrictive diet to manage the symptoms of irritable bowel syndrome (IBS). However, there is no consensus on the alleviating effects of this diet. Herein, a systematic umbrella review with meta-analysis was conducted to investigate the effect of an LFD on IBS symptoms and its secondary outcomes in patients, which were not reported in previous meta-analyses. We performed a systematic literature search in PubMed, Scopus, and ISI Web of Science up to December 2023. The methodological quality of systematic reviews and their included trials was evaluated using AMSTAR 2 and the Cochrane risk of bias, respectively. The certainty of the evidence tool was evaluated using the GRADE approach. The data related to IBS symptoms, quality of life (QoL), microbiome diversity, and stool short-chain fatty acids were extracted. A random-effect (if RCTs ≥ 6) or fixed-effect model (if RCTs < 5) was used to recalculate effect sizes and 95% CIs and report them in both qualitative and quantitative terms (pooled risk ratio, Hedges' g, and weighted mean difference). A total of 658 articles were initially identified, with 11 meta-analyses and 24 RCTs reporting 28 outcomes with 1646 participants included. An LFD significantly affected the clinical improvement of total symptoms according to the IBS-SSS questionnaire (RR: 1.42; 95% CI: 1.02, 1.97; P = 0.04) in all the subtypes of IBS and also had favorable effects on stool consistency (WMD: -0.48; 95% CI: -0.902, -0.07) and frequency (WMD: -0.36; 95% CI: -0.61, -0.10) and some other GI symptoms in both less and more than 4 weeks of diet intervention except for stool consistency, which needed more than 4 weeks of LFD implementation. A significant QoL improvement was observed but not in the anxiety and depression state. Furthermore, some studies showed that an LFD may increase fecal pH and dysbiosis and reduce SCFA and the abundance of Bifidobacterium. In conclusion, an LFD can alleviate symptoms and QoL in IBS patients, although dysbiosis may occur. Considering the low certainty of evidence, strong RCTs with more appropriate designs are needed.

Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target.

Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.