Lactose intolerance (LI) is a significant contributor to diarrhea in infants and young children. Recent studies suggest a potential link between rotavirus (RV) infection and alterations in gut microbiota, which may play a role in the mechanism of LI. However, the precise underlying mechanism remains unclear and requires urgent clarification. In this study, we combined insights from immunology and gut microbiome research to propose that the activation of the IL-22/pSTAT3/RegIIIγ signaling pathway, triggered by gut microbiota, may be involved. To investigate this, we established a LI animal model using 7-day-old BALB/c mice, which were infected with RV via oral gavage. The syndromes of mice were carefully recorded and compared during the intervention experiment. Notably, we measured the the expression levels of immunocytokines and phosphorylated signaling proteins, including IL-22, phosphorylated STAT3, and RegIIIγ. Additionally, we assessed the relationships between gut microbiota and these key elements. Our results indicated that RV indeed causes LI, as severe diarrhea was observed in the mice during the first three days of RV infection, subsiding after seven days. ELISA results revealed an increase in IL-22 levels, phosphorylated STAT3, and RegIIIγ, suggesting that the mechanism of LI associated with RV is linked to the classical IL-22/pSTAT3/RegIIIγ signaling pathway. Furthermore, our analysis of the connections between gut microbes and this signaling pathway indicated that "Bacteroidetes" and Firmicutes were significantly positively correlated with IL-22 and lactase, respectively. This finding implies that alterations in gut microbiota may serve as a potential switch for the IL-22/pSTAT3/RegIIIγ signaling pathway, leading to increased lactase levels. In summary, our study demonstrated that the development of LI is associated with the activation of the IL-22/pSTAT3/RegIIIγ signaling pathway alongside changes in gut microbes during RV infection. This provides valuable insights into the mechanisms underlying LI and its clinical treatment through moduLation of the gut microbiome.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder seen by both primary care providers (PCPs) and gastroenterologists, and further diagnostic testing is generally discouraged unless red-flag symptoms are present.

Examine if advanced serologic testing for chronic abdominal pain in IBS patients followed society-specific guidelines and evaluate the diagnostic accuracy of these tests.

The study involved a retrospective cross-sectional analysis of adults aged 18 and older who were seen at our institution between 2013 and 2018. Tests included: C1 esterase inhibitor, MEFV gene, urine porphobilinogen, anti-dsDNA, and heavy metal screening. Patients with preexisting rheumatological conditions or diagnoses such as hereditary angioedema, porphyria, familial Mediterranean fever, or lead poisoning were excluded. An appropriateness scale based on disease-specific guidelines was used to evaluate test suitability.

Among 26,732 IBS patients, 143 underwent advanced laboratory testing, with 85.3% ordered by gastroenterologists. Only 12.5% of tests adhered to society-specific guidelines, and the positive test rate was 2.1%. The total cost of testing was $46,542, with $39,007 spent on tests deemed inappropriate.

The findings emphasize the effectiveness and importance of adhering to Rome IV criteria, as advanced testing often fails to improve diagnostic accuracy and increases unnecessary healthcare costs.

Intestinal barrier function lies at a critical interface of a range of peripheral and central processes that influence disorders of gut-brain interactions (DGBI). Although rigorously tested, the role of barrier dysfunction in driving clinical phenotype of DGBI remains to be fully elucidated. In vitro, in vivo, and ex vivo strategies can test various aspects of the broader permeability and barrier mechanisms in the gut. Luminal mediators of host, bacterial, and dietary origin can influence the barrier function and a disrupted barrier can also influence the luminal milieu. Critical to our understanding is how barrier dysfunction is influenced by stress and other comorbidities that associate with DGBI and the crosstalk between barrier and neural, hormonal, and immune responses. Additionally, the microbiome's significant role in the communication between the brain and gut has led to the integrative model of a microbiome gut-brain axis with reciprocal interactions between brain networks and networks composed of multiple cells in the gut, including immune cells, enterochromaffin cells, gut microbiota and the derived luminal mediators. This review highlights the techniques for assessment of barrier function, appraises evidence for barrier dysfunction in DGBI including mechanistic studies in humans, as well as provides an overview of therapeutic strategies that can be used to directly or indirectly restore barrier function in DGBI patients.

Different diets have emerged as potential therapeutic options for patients with irritable bowel syndrome (IBS).

To identify predictors of improvement after a low-FODMAP, low-starch and low-sucrose diet among patients with IBS.

We performed a descriptive cross-sectional study including patients with IBS according to Rome IV criteria undertaking a social-media based program with a two-week dietary intervention. Patients completed an online survey before and after the intervention including the presence of intestinal and extra-intestinal symptoms, the IBS-SSS (irritable bowel syndrome symptoms severity scale) and the PHQ-9 (patient health questionnaire-9). Clinical improvement was defined as a decrease of at least 50% in IBS-SSS post dietary intervention. Variables associated with symptomatic response were identified with logistic regression analysis. A clinical score to predict response was created and tested with a with a receiver operating characteristic (ROC) curve analysis.

A total of 3583 patients with IBS were included. Mean IBS-SSS before and after dietary intervention was 295.5±52.32 and 240±48.66, respectively (p=0.01); 1178 (32.8%) patients showed clinical improvement. A mean basal IBS-SSS >400 (OR 3.04), chronic headache (OR 1.96), and chronic fatigue (OR 1.81) were significantly associated with symptomatic response. Patients with arthralgia (OR 0.41) and/or fibromyalgia (OR 0.33) were less likely to improve. Each variable received the following individuals scores: IBS-SSS >400: +2, chronic headache: +1.5, chronic fatigue: +1, arthralgia: -1, and fibromyalgia: -1. The ROC curve analysis of the proposed score showed an area under the curve of 0.72 (95% CI 0.69-0.76). A score ≥3 had a sensitivity of 72.64% and specificity of 60.56% for predicting symptomatic improvement.

There are clinical variables that could serve as reliable predictors of response to a low-FODMAP, low-sucrose, low-starch diet among patients with IBS. Further research is needed to understand the link between the presence of extra-intestinal symptoms and clinical improvement after dietary interventions for IBS.

Irritable bowel syndrome (IBS) is a frequent disorder thought to be caused by a disturbance of the gut-brain axis. Nutrition interventions are an essential pillar of its treatment. However, there is no consensus on which outcomes should be applied to assess the effectiveness of nutrition care in IBS. Standardized outcome sets, or "core outcome sets" (COS), have been proposed to harmonize outcomes in clinical research and practice. This project aims to develop a COS for dietitian-provided nutrition care in adults with IBS or food intolerances with intestinal symptoms, to be implemented in routine outpatient practice.

A comprehensive outcomes list was developed based on quantitative and qualitative studies, COS and guidelines on IBS, and important outcomes named by participants. Health service users, dietitians, gastroenterologists, and health care decision makers rated the outcomes in two Delphi survey rounds on their importance and ranked them in a third round. Data was analyzed by panel to account for the different views and sample sizes.

A total of 192 participants registered for the Delphi process. The following 14 outcomes reached consensus in all panels after two rounds: perception of symptom triggering foods/nutrients, intake of trigger foods/nutrients, practicability of diet, adherence, digestive symptoms overall, abdominal pain, abdominal bloating, stool consistency, stool frequency, physical functioning related QoL, nutrition related QoL, social functioning related QoL, empowerment of self-care.

The Delphi process yielded in a 14 outcomes COS, which exceeds what is typically considered feasible in routine nutrition care. Further work is needed to refine the COS and to identify standardized measurement tools for each outcome.

To provide an update of recent studies exploring the role of the gut microbiota and diet in the pathogenesis and treatment of irritable bowel syndrome (IBS).

The human gut microbiome has been recognized as an important, active source of signaling molecules that explain in part the disorder of the gut brain interaction (DGBI) in IBS. Subsequent changes in the metabolome such as the production of short-chain fatty acids (SCFA) and serotonin are associated with IBS symptoms. Dietary components are recognized as important triggers of IBS symptoms and a diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) has been shown effective and safe, even when used long-term. Fecal microbiota transplantation (FMT) in IBS has not shown sustained and effective IBS symptom reduction in controlled clinical trials.

This update elucidates recent developments in IBS as it relates to clinical trial results targeting dietary and gut microbiota interventions. The gut microbiome is metabolically active and affects the bi-directional signaling of the gut-brain axis.

The benefits of regular physical activity (PA) on disease prevention and treatment outcomes have been recognized for centuries. However, only recently has interorgan communication triggered by the release of "myokines" from contracting skeletal muscles emerged as a putative mechanism by which exercise confers protection against numerous disease states. Cross-talk between active skeletal muscles and the gut microbiota reveal how regular PA boosts host immunity, facilitates a more diverse gut microbiome and functional metabolome, and plays a positive role in energy homeostasis and metabolic regulation. In contrast, and despite the large interindividual variation in the human gut microbiome, reduced microbial diversity has been implicated in several diseases of the gastrointestinal (GI) tract, systemic immune diseases, and cancers. Although prolonged, intense, weight-bearing exercise conducted in extreme conditions can increase intestinal permeability, compromising gut-barrier function and resulting in both upper and lower GI symptoms, these are transient and benign. Accordingly, the gut microbiome has become an attractive target for modulating many of the positive effects of regular PA on GI health and disease, although the precise dose of exercise required to induce favourable changes in the microbiome and enhance host immunity is currently unknown. Future efforts should concentrate on gaining a deeper understanding of the factors involved in exercise-gut interactions through the generation of functional 'omics readouts (ie, metatranscriptomics, metaproteomics, and metabolomics) that have the potential to identify functional traits of the microbiome that are linked to host health and disease states, and validating these interactions in experimental and preclinical systems. A greater understanding of how PA interacts with the GI tract and the microbiome may enable targeted therapeutic strategies to be developed for individuals and populations at risk for a variety of GI diseases.

Irritable bowel syndrome (IBS) is prevalent and can be disabling. Many patients remain symptomatic despite behavioral and medical therapies. Psychedelic-assisted therapy (PAT), in which serotonergic agents like psilocybin are administered in a psychotherapeutic context, has shown promise for refractory psychiatric disorders, including major depressive disorder and post-traumatic stress disorder. Emerging evidence suggests PAT may also be beneficial for chronic pain conditions, including fibromyalgia, low back pain, and migraines. IBS is highly comorbid with depression, anxiety, and other chronic pain disorders, suggesting shared cognitive and neurological roots and potentially shared therapeutic targets. In this editorial, we discuss 3 lines of evidence for PAT as a treatment for IBS, under the overarching themes of (1) psychological mechanisms (the findings from historic studies of psychedelics for chronic pain and the elements of psychobiological dysfunction targeted by PAT), (2) central nervous system mechanisms (default mode network modulation and induction of neuroplasticity), and (3) the neurointestinal pathophysiology of IBS that may be modified by PAT. We argue that this evidence suggests PAT is worthy of study as a new therapy for IBS, and potentially for other disorders of gut-brain interaction (DGBI). Successful application of PAT to gastrointestinal disease would represent a major step beyond mind-body dualism, with potential implications for other functional somatic disorders.

Background/Objectives: Growing evidence highlights the pivotal role of gut dysbiosis in the pathophysiology of irritable bowel syndrome (IBS). Despite this, the identification of an "IBS microbiota signature" remains elusive, primarily due to the influence of genetic, dietary, and environmental factors. To address these confounding variables, it is critical to perform comparative analyses using a control group derived from the same community as the IBS patients. This study aimed to evaluate and contrast the gut microbiota composition of IBS patients with healthy controls. Methods: We compared the gut microbiota from stool samples of 25 IBS patients diagnosed according to the Rome IV criteria, and 110 healthy subjects without acute or chronic diseases and not on continuous medication. The high-throughput sequencing of the V3-V4 regions of the 16S rRNA gene was conducted for microbiota analysis. Results: The IBS gut microbiota was richer but exhibited lower alpha diversity compared to the control group, suggesting simplification and imbalance. A beta diversity analysis revealed overall compositional differences between the two groups. A heat tree analysis highlighted key IBS-associated changes, including a decrease in Firmicutes, mainly due to Clostridia, and an increase in Bacteroidota, driven by an expansion of Bacteroidales families. Differential expression analyses identified important genera within these taxa like Bacteroides, Faecalibacterium, and Blautia, which could serve as microbiota-based biomarkers for IBS. Conclusions: Our results reveal both statistically and clinically significant differences in gut microbiota composition and diversity between IBS patients and healthy controls from the same community. These findings provide a deeper understanding of how alterations in the gut microbiota may contribute to IBS symptoms, offering new insights into the diagnosis and potential treatments.

Linaclotide, a guanylate cyclase-C agonist, is indicated for irritable bowel syndrome with constipation (IBS-C). However, real-world data on the safety and patient-reported outcomes (PROs) of linaclotide are scarce in Chinese patients with IBS-C.

To assess the real-world safety and PROs of linaclotide in the Chinese IBS-C population.

Multicenter, prospective observational study.

Adults with IBS-C who had taken or planned to take at least one dose of linaclotide 290 μg were enrolled and followed up for 3 months. Face-to-face visits were conducted at baseline (V1), Week 4 ± 7 days (V2), and Week 12 ± 7 days (V3). Primary endpoints included the incidences of adverse events (AEs), AEs by severity, adverse drug reactions (ADRs), serious AEs (SAEs), and AEs leading to treatment interruption, discontinuation, and death. Secondary endpoints included mean treatment satisfaction at V2 and V3, and mean overall Irritable Bowel Syndrome-Quality of Life (IBS-QoL) at V2.

Out of 3000 enrolled patients, 2963 took at least one dose of linaclotide and were analyzed. Overall, 712 patients (24.0%) reported 1095 AEs, which were mostly mild (89.9%). Diarrhea, reported in 297 out of the 2963 patients analyzed (10.0%), was the most common AE. No severe diarrhea was reported. Totally, 319 patients (10.8%) reported ADRs. Forty-six patients (1.6%) reported 50 SAEs and two cases were considered related to linaclotide treatment. Fifty-one (1.7%) and 70 patients (2.4%) interrupted and discontinued treatment due to AEs, respectively. One patient died of hepatic cancer, which was considered unrelated to linaclotide treatment. During the follow-up, the mean (±SD) treatment satisfaction increased numerically and continuously (V1, 2.8 ± 1.3 (n = 1721); V2, 3.5 ± 1.1 (n = 1705); V3, 3.9 ± 1.0 (n = 833)). The mean (±SD) overall IBS-QoL increased numerically from 73.2 ± 16.6 (n = 1924) at V1 to 80.2 ± 15.5 (n = 1738) at V2.

In the Chinese real-world setting, linaclotide was safe and well tolerated in patients with IBS-C. Numerically, there are trends toward improvement in PROs with linaclotide treatment.

Digital health interventions (DHIs) could be a valuable self-management tool for patients with irritable bowel syndrome (IBS), but little research exists on IBS-focused DHIs and their effectiveness. This review aimed to identify DHIs for IBS and evaluate their characteristics, effectiveness, and feasibility.

Our study team, including patient partners, conducted a systematic review using Medline, PsycINFO, Embase, Web of Science, and CINAHL from database inception to May 2024. Experimental and observational studies evaluating DHIs designed for use by IBS patients were included. Data extraction and assessment included study and DHI characteristics, effectiveness outcomes (symptom severity, quality of life, psychological indices, patient empowerment), and feasibility measures (adherence, usability, user satisfaction). Study quality and bias were assessed using a modified checklist of Downs and Black.

Of the 929 identified, 13 studies of DHIs were included and deemed good quality on average (21,510 total participants) with six primary areas of focus: education, diet, brain-gut behavior skills, physiological support, health monitoring, and community engagement. Most DHIs were self-directed and reported statistically significant improvements in most effectiveness outcomes. Evidence suggests that DHIs focusing on brain-gut behavior skills or health monitoring may be most effective compared to other types of DHIs. However, their feasibility remains unclear, and the generalization of their impacts is limited.

This review underscores the potential of DHIs in supporting IBS patients and improving their outcomes. However, additional research is warranted for continued intervention use in this population, including assessments on feasibility, safety, cost-effectiveness, and patient empowerment and experiences.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder. Growing evidence suggests a significant association between IBS and psychological problems, such as anxiety and depression. This study was conducted to assess the prevalence of anxiety and depression in Vietnamese patients diagnosed with IBS according to Rome IV criteria.

This cross-sectional study recruited 186 consecutive patients who underwent outpatient clinic visits and colonoscopy for gastrointestinal symptoms. IBS diagnosis was established using the validated Rome IV criteria. Anxiety and depression were assessed using a validated Vietnamese version of the Hospital Anxiety and Depression Scale (HADS).

The mean age of IBS patients was 49.5 ± 12.0 years, with females comprising 53.8%. IBS-M was the most prevalent subtype (39.8%), followed by IBS-C (39.2%) and IBS-D (21.0%). Using the HADS cut-off of ≥ 11 points for probable anxiety and depression, the prevalence was 21.0% and 11.8%, respectively. Expanding the criterion to a HADS of ≥ 8, indicating significant symptoms, increased the prevalence to 55.9% for anxiety and 40.8% for depression disorders. Patients with IBS-C, IBS-D, or IBS-M exhibited a significantly higher risk of depressive disorders compared to those without IBS, with odds ratios of 4.261, 7.013, and 6.585, respectively (p < 0.001). Additionally, men were less likely than women to experience depressive disorders.

The findings revealed a high prevalence of depression and anxiety disorders among Vietnamese patients with IBS. Those with the IBS-M or IBS-D subtypes and a greater number of gastrointestinal symptoms were more likely to experience higher levels of depression and anxiety, particularly women.

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine.

Gut-directed hypnotherapy (GDH) treats irritable bowel syndrome (IBS), but its accessibility is limited. This problem may be overcome by digital delivery. The aim of this study was to perform a randomized control trial comparing the efficacy of a digitally delivered program with and without GDH in IBS.

Adults with IBS were randomized to a 42-session daily digital program with the GDH Program (Nerva) or without (Active Control). Questionnaires were completed to assess gastrointestinal symptoms through IBS Symptom Severity Scale (IBS-SSS), quality of life, and psychological symptoms (Depression Anxiety and Stress Scale-21) at regular intervals during the program and 6 months following the conclusion on the intervention. The primary end point was the proportion of participants with ≥50-point decrease in IBS-SSS between the interventions at the end of the program.

Of 240/244 randomized participants, 121 received GDH Program-the median age 38 (range 20-65) years, 90% female, IBS-SSS 321 (interquartile range 273-367)-and 119 Active Control-36 (21-65), 91% female, IBS-SSS 303 (255-360). At program completion, 81% met the primary end point with GDH Program vs 63% Active Control ( P = 0.002). IBS-SSS was median 208 (interquartile range 154-265) with GDH and 244 (190-308) with control ( P = 0.004), 30% reduction in pain was reported by 71% compared with 35% ( P < 0.001), and IBS quality of life improved by 14 (6-25) compared with 7 (1-15), respectively ( P < 0.001). Psychological status improved similarly in both groups.

A digitally delivered GDH Program provided to patients with IBS was superior to the active control, with greater improvement in both gastrointestinal symptoms and quality of life and provides an equitable alternative to face-to-face behavioral strategies.

Multidisciplinary integrated models of care show promise for improving symptoms and quality of life (QoL) in adults with irritable bowel syndrome (IBS).

To describe and evaluate the characteristics of integrated models of care for IBS and identify how digital health is being used in these models of care.

Four databases were searched to March 2024 for studies that included adults with IBS who participated in multidisciplinary integrated models of care that delivered non-pharmacological therapies. The template for intervention description and replication (TIDieR) checklist was used to appraise study quality and extract model of care characteristics, which were mapped against the Project INTEGRATE framework to establish topics.

Sixteen studies (6 randomized controlled trials, 2 quasi-experimental, 8 cohort studies) reported 14 integrated models of care including 2165 patients of which 918 were IBS patients. Integrated models of care led to improved IBS symptoms (n = 11/13 models of care) and QoL (n = 6/9 models of care). Studies showed moderate compliance with the TIDieR checklist. Five topics were established: clinicians involved, therapies provided, location and mode of delivery, coordinating clinical partnerships, and sharing visions and values of integrated care. Most commonly, a gastroenterologist coordinated care with a psychologist, dietitian, and/or nurse in tertiary care. Psychological, dietary, and physical therapies were provided by n = 11, n = 8, and n = 3 integrated models of care, respectively. Six models of care provided joint consultations or group sessions. Four models of care used digital health such as telephone coaching or online modules.

Integrated models of care for IBS exhibited diverse characteristics including the clinicians involved, the therapies provided and the mode of delivery of each therapy. There is a need to evaluate the use of digital health and the delivery of integrated models of care in primary care settings.

Irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease (CeD) present with similar gastrointestinal (GI) symptoms. DNA methylation-based biomarkers have not been investigated as diagnostic biomarkers to classify these disorders. We aimed to study DNA methylation profiles of IBS, IBD, CeD, and healthy controls (HC), develop machine learning-based classifiers, and identify associated gene ontology (GO) terms.

Genome-wide DNA methylation of peripheral blood mononuclear cells from 315 patients with IBS, IBD, CeD, and HC was measured using Illumina's 450K or EPIC arrays. A methylation dataset on 304 IBD and HC samples was used for external validation. Differential methylation was measured using general linear models. Classifiers were developed using penalized generalized linear models using double cross-validation controlling for confounders. Functional enrichment was assessed using GO.

Three hundred and fifteen participants (148 IBS, 47 IBD, 34 CeD, and 86 HC) had DNA methylation data. IBS-IBD and IBD-CeD showed the highest number of differentially methylated CpG sites followed by IBD-HC, CeD-HC, and IBS-HC. IBS-associated genes were enriched in cell adhesion and neuronal pathways, while IBD- and CeD-associated markers were enriched in inflammation and MHC class II pathways, respectively (p < 0.05). Classification performances assessed using area under the receiver operating characteristic curves (AUC) for IBS-IBD, IBS-CeD, and IBD-CeD were 0.80 (95% CI = 0.7-0.87, p = 6.75E-10), 0.78 (95% CI = 0.68-0.86, p = 4.57E-10), and 0.73 (95% CI = 0.62-0.83, p = 0.03), respectively. The performance of IBD-HC was successfully validated using external data (AUC = 0.74 [95% CI = 68-0.80, p < 0.001]).

Blood-based DNA methylation biomarkers can potentially distinguish chronic GI disorders that present with similar symptoms. GO suggested functional significance of the classifiers in disease-specific pathology.

Collaboration between registered dietitians and gastroenterologists has not been evaluated in cystic fibrosis (CF). We surveyed registered dietitians and gastroenterologists regarding the current participation of gastroenterologists in CF centers and identified possible areas to enhance partnership between the two disciplines.

An anonymous online survey was distributed targeting registered dietitians and gastroenterologists involved in CF care through three international listservs (CF Nutrition, CF DIGEST, and PEDGI) over a 6-week period. SurveyMonkey was used, and informed consent was obtained.

A total of 131 respondents participated in this survey, including 80 registered dietitians and 51 gastroenterologists (41 pediatric and 10 adult gastroenterologists). Most respondents (82%) were from the United States, and two-thirds had ≥5 years of experience in CF. A significant number of registered dietitians reported the nonavailability of gastroenterologists for collaboration and there was greater availability of gastroenterologists in pediatric centers. Barriers to interdisciplinary collaboration included lack of CF expertise and dedicated time among the gastroenterologists and difficulties in coordinating the gastroenterology clinics. More gastroenterologists than registered dietitians perceived that they worked collaboratively with the other discipline in various domains (clinical care, quality improvement, research, presentations, and publications). Both disciplines had mutual respect and interest to further the collaboration.

There is an increased need for gastroenterologist participation and collaboration (particularly in adult centers) in CF alongside registered dietitians to enhance comprehensive patient care. Future efforts should focus on training more gastroenterologists in CF and facilitating easier access to gastroenterologists for the CF population.

Here we investigated changes in topological properties of functional brain networks among individuals with Crohn's disease (CD) and to determine whether these changes are related to CD severity, as well as CD-associated anxiety and depression, which are regulated by the brain-gut axis mechanism.

In total, 31 individuals with CD, 21 with irritable bowel syndrome (IBS), and 20 healthy controls underwent functional magnetic resonance imaging. Individuals with CD or IBS were also evaluated using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and Depression (HADS-D) scales, as well as the simple endoscopic score for CD (SES-CD). Graph theory-based methods were applied to calculate the topological properties of brain networks, and comparisons among the three groups were performed using one-way analysis of variance. Partial correlation analysis was used to assess correlations among these properties and HADS-A, HADS-D, and SES-CD scores.

In the CD group, altered global topological properties were identified, and altered local topological properties were observed in 13 brain regions. The functional connectivity (FC) between the default mode network and visual network was increased, and the FC in the limbic system was decreased. In the CD group, local topological properties in the amygdala and precuneus were negatively correlated with HADS-A scores, and local topological properties in the superior occipital gyrus were positively correlated with SES-CD scores.

Both global and regional topologies of brain networks were impaired in individuals with CD, which were correlated with clinical scores, suggesting that these values could serve as neuroimaging metrics reflecting the degree of anxiety caused by CD and CD severity.

Irritable bowel syndrome (IBS) is one of the disorders most frequently diagnosed by gastroenterologists. Probiotics are promising tools for the management of IBS. The objective of the present study was to evaluate the effectiveness and tolerability of a probiotic (Bifidobacterium longum 35624®) in adults (aged 18 or over) with IBS (as defined by the Rome IV criteria). In an open-label, observational, post-market study conducted in Germany, adults with IBS and a prior recommendation for the intake of B. longum 35624® were recruited by family physicians. During the 8-week course of treatment, the study participants filled out a weekly questionnaire that enabled calculation of a total IBS symptom score (TISS, the sum of abdominal pain, bloating, passage of gas, constipation, and diarrhea individual symptom scores) and the well-known IBS severity scoring system (IBS-SSS) score. Thirty-seven patients were included. The course of B. longum 35624® was associated with a significant reduction (43.4%) in the TISS vs. baseline. The mean individual symptom grades for passage of gas and bloating fell significantly from "moderate" at baseline to "very mild to mild" after 8 weeks of treatment, whereas those for abdominal pain and diarrhea fell significantly from "mild to moderate" to "very mild to mild." Over 60% of the participants achieved clinically meaningful reductions in the TISS (> 30%) and the IBS-SSS score (> 50 points). The effectiveness of B. longum 35624® was rated as "good to satisfactory" by study participants and the investigating physicians. One mild adverse event (nausea) was potentially linked to the study treatment. We conclude that an 8-week course of B. longum 35624® was associated with significant, clinically meaningful symptom relief in a typical population of adult patients with IBS.

Background/Objectives: Irritable Bowel Syndrome (IBS) is a disorder of the gut-brain axis for which the gastroenterologist is most often consulted. Gastrointestinal symptoms and decreased quality of life lead to a considerable burden of disease. The exact causes of IBS are not well understood, and no standard therapy has been established. The primary outcome of the study focused on the improvements of the IBS symptoms assessed through the validated questionnaire IBS-Severity Scoring System (IBS-SSS). Similarly, secondary outcomes geared towards the improvement of the quality of life (IBS-Quality of Life (IBS-QoL) and the Gastrointestinal Quality of Life Index (GIQLI)) and specific IBS symptoms (bloating, abdominal distension, feeling of heaviness, abdominal pain, and flatulence), were assessed through self-administered questionnaires. Intestinal habits (consistency and frequency of depositions) through subject stratification into diarrhoea (IBS-D), constipation (IBS-C), mixed type (IBS-M), as well as the treatment tolerability were also evaluated. Methods: A randomised, placebo-controlled, double-blind, clinical trial was conducted on 156 enrolled IBS patients (79 female and 77 male), aged 18-70 years, randomised (1:1 allocation ratio) to receive either two capsules per day of the food supplement (containing 480 mg of a complex of tannin extracts) or a placebo for 56 days. Linear random intercept mixed models (LMM) were used to analyse all experimental variables Results: Supplementation resulted in a significant improvement (p < 0.05) in the primary outcome IBSS score, with respect to the placebo group, changing the IBS condition going from mild (242.3 ± 89.8) to moderate (148.1 ± 60.6). Similarly, all indicators concerning quality of life, and specific intestinal symptoms resulted in a significant improvement (p < 0.05). Furthermore, the tannin-based treatment showed the ability to modulate the response to different symptomatology such as diarrhoea and constipation, without side effects being reported. Conclusions: The use of a supplement based on chestnut and quebracho tannins presents great application potential in the management of IBS-related disorders, with the peculiarity of resolving opposite symptoms, such as diarrhoea and constipation, indiscriminately.

Amitriptyline is prescribed off-label for irritable bowel syndrome (IBS). We conducted a meta-analysis to assess its efficacy.

A systematic literature review was conducted until November 10, 2023, using MEDLINE, Embase, Cochrane Library, and Web of Science to study the efficacy of amitriptyline in patients with IBS. We included all randomized controlled trials that compared amitriptyline to placebo. Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Meta-analyses were performed using a bivariate random-effects model. Statistical analyses were performed using R Software 4.2.3 and heterogeneity was assessed with I2 statistics.

Seven trials were included with 796 patients (61% female). Amitriptyline was associated with better treatment response (OR, 5.30; 95% CI, 2.47 to 11.39; P < 0.001), reduced Irritable Bowel Syndrome Symptom Severity Scores (MD, -50.72; 95% CI, -94.23 to -7.20; P = 0.020) and improved diarrhea (OR, 10.55; 95% CI, 2.90 to 38.41; P < 0.001). No significant difference between the 2 groups regarding the adverse effects was observed. Three trials showed an overall low risk of bias, 2 trials showed an overall high risk of bias due to randomization and missing data, and 2 trials had some concerns regarding missing data.

Amitriptyline was found to be well-tolerated and effective in treating IBS compared to placebo. These findings support the use of amitriptyline for the management of IBS, particularly among patients with the IBS diarrhea subtype. Future research should focus on the dose-dependent effects of amitriptyline in IBS to better guide clinicians in personalized titration regimens.

Brain-gut behaviour therapies (BGBT) have gained widespread acceptance as therapeutic modalities for the management of disorders of gut-brain interaction (DGBI). However, existing treatment evaluation methods in the medical field fail to capture the specific elements of scientific rigour unique to behavioural trial evaluation.

To offer the first consensus on the development and testing of BGBT in DGBI.

An international, interdisciplinary team of experts developed a consensus statement heavily informed by best practice recommendations for behavioural clinical trials for chronic diseases, organised by a selected treatment development model.

We suggest an existing behavioural treatment development model that has an iterative progression aligned with the drug development model with nuances specific to BGBT. We describe the iterative phases through initial discovery and experimental work, assembly of a mechanistic pathway and candidate treatment components, treatment refinement and optimisation, initial proof-of-concept, feasibility of clinical trials and, finally, confirmatory efficacy and effectiveness testing. We delineate recommendations for and provide examples that lend themselves to gastroenterologists planning to develop or test BGBT, reviewing proposals for or results from BGBT studies or writing management guidelines for DGBI.

This working team report facilitates a shared understanding of the elements of scientific rigour necessary for BGBT development and could support future standards on which BGBT are evaluated in gastroenterology.

Fermented foods (FFs) may theoretically benefit irritable bowel syndrome (IBS) symptoms, but the role of FFs for IBS patients in the real world is inconsistent and has not been systematically assessed. We performed a systematic review and meta-analysis to examine this issue.

PubMed, MEDLINE, Embase and Cochrane Library databases were searched up to August 2024. Randomized controlled trials (RCTs) investigating the efficacy of FFs in IBS were eligible for the analysis. Two authors independently screened studies and extracted data. Data were pooled using relative risk (RR) of dichotomous data and standardized mean difference (SMD) for continuous data.

A total of 16 RCTs with 1,264 IBS patients were included. There were 12 RCTs involving 975 patients providing primary outcomes which was defined as symptom relief. The proportion of symptom relief was associated with the administration of FFs (RR 1.22, 95% CI 1.04-1.42, p = 0.01, I 2 = 0%). For secondary outcomes, FFs also exerted a beneficial effect on global symptoms scores (SMD = -0.15; 95% CI -0.29 to -0.02, p = 0.02, I 2 = 46%), but no significant improvement on abdominal pain scores and bloating scores. Subgroup analysis showed that fermented milk had a beneficial effect on symptom relief (RR 1.19, 95% CI 1.01 to 1.39, p = 0.04, I 2 = 0%).

Fermented foods, especially fermented milk with probiotics properties, appear to be efficacious in irritable bowel syndrome. However, given the limitations of current evidence, this conclusion should be interpreted with caution.

This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42024576608.

Chronic gastrointestinal disorders such as inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS) impose significant health burdens globally. IBDs, encompassing Crohn's disease and ulcerative colitis, are multifactorial disorders characterized by chronic inflammation of the gastrointestinal tract. On the other hand, IBS is one of the principal gastrointestinal tract functional disorders and is characterized by abdominal pain and altered bowel habits. Although the precise etiopathogenesis of these disorders remains unclear, mounting evidence suggests that non-coding RNA molecules play crucial roles in regulating gene expression associated with inflammation, apoptosis, oxidative stress, and tissue permeability, thus influencing disease progression. miRNAs have emerged as possible reliable biomarkers, as they can be analyzed in the biological fluids of patients at a low cost. This review explores the roles of miRNAs in IBDs and IBS, focusing on their involvement in the control of disease hallmarks. By an extensive literature review and employing bioinformatics tools, we identified the miRNAs frequently studied concerning these diseases. Ultimately, specific miRNAs could be proposed as diagnostic biomarkers for IBDs and IBS. Their ability to be secreted into biofluids makes them promising candidates for non-invasive diagnostic tools. Therefore, understanding molecular mechanisms through the ways in which they regulate gastrointestinal inflammation and immune responses could provide new insights into the pathogenesis of IBDs and IBS and open avenues for miRNA-based therapeutic interventions.

Irritable bowel syndrome (IBS) is a very common condition worldwide. Treatment options for severe IBS are few. Sacral neuromodulation (SNM) for patients with IBS has been shown to reduce symptoms and improve quality of life in the medium term. This study aimed to evaluate the long-term effectiveness and safety of SNM in diarrhoea-predominant and mixed IBS.

A prospective cohort of patients with IBS treated with SNM were evaluated 1, 3, 5, and 10 years after implantation. The primary end-point was a change in the Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome version questionnaire (GSRS-IBS) from baseline to 10-year follow-up (FU). Secondary end-points were change in the GSRS-IBS score from baseline to 5-year FU and change in the Irritable Bowel Syndrome-Impact Scale questionnaire (IBS-IS) from baseline to 5- and 10-year FU. Adverse events following SNM were observed.

Of 36 patients treated with SNM, 23 were eligible for 5-year FU and 13 for 10-year FU. The GSRS-IBS score was significantly reduced at both 5-year (p < 0.0001) and 10-year (p = 0.0007) FU. The IBS-IS score was also significantly improved at both 5 years (p < 0.0001) and 10 years (p = 0.0002). Fifty-six adverse events were registered. Five patients were explanted because of adverse events.

SNM seems to offer an effective and safe treatment option for highly selected patients with diarrhoea-predominant and mixed IBS.

The present study has not been registered. The latest founding study was registered at ClinicalTrials.gov, NCT01948973.

Neurogastroenterology and motility disorders are complex gastrointestinal conditions that are prevalent worldwide, particularly affecting women and younger individuals. These conditions significantly impact the quality of life of people suffering from them. There is increasing evidence linking these disorders to cirrhosis, with a higher prevalence compared to the general population. However, the link between neurogastroenterology and motility disorders and cirrhosis remains unclear due to undefined mechanisms. In addition, managing these conditions in cirrhosis is often limited by the adverse effects of drugs commonly used for these disorders, presenting a significant clinical challenge in the routine management of patients with cirrhosis. This review delves into this connection, exploring potential pathophysiological links and clinical interventions between neurogastroenterology disorders and cirrhosis.

Confocal laser endomicroscopy (CLE) is a novel technique allowing real time in vivo microscopy during standard endoscopy. Recently, acute mucosal alterations after food administration visualized by CLE have been linked to symptoms in irritable bowel syndrome (IBS). Interestingly, the observed reactions occurred in subjects without demonstrable allergic sensitization to food-this is in line with mechanistic research showing local but not systemic allergic sensitization to foods in an animal model for IBS. Here, European experts conducting CLE with food administration provide a narrative review of the available literature and propose practical guidance on the use of this technique. CLE allows physicians to observe acute mucosal reactions after the application of food to the duodenal mucosa in patients with functional gastrointestinal disorders. Some open-label interventions show a symptomatic benefit when patients exclude the nutrient that triggered an acute mucosal reaction. However, many technical, mechanistic, and clinical questions remain unanswered to date. Technically, the interobserver variability and learning curve requires systematic evaluation and criteria or cutoffs for alterations require validation. Mechanistic studies are needed to enhance our understanding of the mechanisms underlying observed alterations. Finally, rigorous blinded controlled studies are needed to assess a link of these observed alterations with symptom generation. CLE offers a platform allowing scientific insights related to food induced acute mucosal alterations. However, many questions remain unanswered, and more research is warranted to understand the role of acute mucosal alterations visualized upon food administration in IBS pathophysiology and treatment.

This pilot study aimed to develop a liquid formulation of tenapanor and evaluate taste and palatability with different sweetener and flavor combinations.

Tenapanor is a first-in-class, minimally absorbed, small molecule inhibitor of intestinal sodium/hydrogen exchanger 3, indicated (as tablets) to treat adults with constipation-predominant irritable bowel syndrome. It is also approved as add-on therapy to reduce serum phosphorus in adults with chronic kidney disease on dialysis who are intolerant of, or unacceptably responsive to, any dose of phosphate binder therapy. Since many patients have difficulty swallowing pills and pediatric studies are underway, a liquid formulation was developed, and taste profiles were evaluated for overall acceptability.

Formulation of liquid tenapanor targeted a concentration of 5 mg/mL, for a dosing range of 1-50 mg twice daily. Improvements in solubility and stability of tenapanor in water were investigated with the use of buffers, cosolvents, and preservatives. Seven liquid formulations with different sweetener/flavor combinations were assessed for taste and palatability by healthy adult participants using the sip-and-spit method in a randomized design.

An aqueous solution of tenapanor (5 mg/mL), pH 3.4, with 0.05 % (w/v) benzoic acid, was stable at 2-8 °C for 12 months. The formulation with sucralose and raspberry flavor had the greatest improvement in overall acceptability and taste when compared to the reference solution without sweeteners or flavors.

A suitable liquid formulation was identified for progression to patient studies.

Abdominal pain can be an overlooked symptom in patients with ulcerative colitis (UC).

The aim of this study was to investigate the prevalence and factors associated with abdominal pain in active and quiescent UC.

Three study cohorts of adult UC patients were used. Cross-sectional cohorts I and II included 130 (46 active) and 288 (156 active) patients. Longitudinal cohort III included 83 patients with active disease at diagnosis that reached deep remission during follow-up. The Gastrointestinal Symptom Rating Scale was used to assess abdominal pain and other validated questionnaires to assess psychological distress, fatigue and quality of life (QoL).

In the two cross-sectional cohorts, 63% and 58% of the active vs. 54% and 33% of the quiescent UC patients reported abdominal pain (both p ≤ 0.02). In the longitudinal cohort, 71% had abdominal pain at diagnosis vs. 46% when in remission (p < 0.001). In multivariable models, symptoms of anxiety were associated with higher abdominal pain levels in both cross-sectional cohorts (OR 1.75 [IQR 1.11-2.76] and OR 1.99 [1.45-2.73]), whereas in cohort II, active disease (OR 2.68 [1.61-4.45]) and female sex (OR 2.03 [1.21-3.41]) were also associated with pain. QoL was negatively correlated with higher levels of abdominal pain, both in active and quiescent disease.

Abdominal pain in UC is prevalent and associated with lower QoL in both active and quiescent disease. Associated factors are active disease, female sex and psychological symptoms, especially anxiety. We suggest considering a holistic approach when treating UC patients with abdominal pain.

Recent studies show that the increase in breath hydrogen (BH2) and symptoms after ingestion of inulin are reduced by coadministering psyllium (PI).

To determine if slowing delivery of inulin to the colon by administering it in divided doses would mimic the effect of PI. Primary endpoint was the BH2 area under the curve AUC0-24 h. Secondary endpoints included BH2 AUC0-6 h, 6-12 h, and 12-24 h. Exploratory endpoints included the correlation of BH2 AUC0-24 h with dietary fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) intake and in vitro fermentation results.

A total of 17 healthy adults were randomly assigned to a single-blind, 3-arm, crossover trial. All consumed 20 g inulin (I) powder dissolved in 500 mL water and mixed with either 20 g maltodextrin (control) or 20 g PI consumed as a single dose or 20 g inulin given in divided doses (DDI), 62.5 mL every 45 min over 6 h. Twenty-four-hour BH2, dietary FODMAP intake, stool microbiota, and gas production in vitro were measured. Responders were defined as those whose AUC0-24 h BH2 was reduced by PI, whereas nonresponders showed no reduction.

Compared with control, PI did not reduce mean BH2 AUC0-24 h, whereas DDI increased it, P < 0.0002. DDI and PI both significantly reduced BH2 AUC0-6 h compared with the control, P < 0.0001. However, subsequently, DDI significantly increased BH2 from 6 to 12 h (P < 0.0001) and overnight (12-24 h) (P < 0.0001), whereas PI did so only overnight (P = 0.0002). Nonresponders showed greater release of arabinose during in vitro fermentation and higher abundance of 2 species, Clostridium spp. AM22_11AC and Phocaeicola dorei, which also correlated with BH2 production on PI. Dietary FODMAP intake tended to correlate inversely with BH2 AUC0-24 h (r = -0.42, P = 0.09) and correlated with microbiome community composition.

DDI, like PI, reduces early BH2 production. PI acts by delaying transit to the colon but not reducing colonic fermentation over 24 h. Dietary FODMAP intake correlates with BH2 response to inulin and the microbiome. This trial was registered at www.

gov as NCT05619341.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by chronic or recurrent gastrointestinal symptoms without organic changes, and it is also a common disorder of gut-brain interaction (DGBIs).. The symptoms of IBS not only affect the quality of life for individual patients but also place a significant burden on global healthcare systems. The lack of established and universally applicable biomarkers for IBS, along with the substantial variability in symptoms and progression, presents challenges in developing effective clinical treatments. In recent years, preclinical and clinical studies have linked the pathogenesis of IBS to alterations in the composition and function of the intestinal microbiota. Within the complex microbial community of the gut, intricate metabolic and spatial interactions occur among its members and between microbes and their hosts. Amid the multifaceted pathophysiology of IBS, the role of intestinal microenvironment factors in symptom development has become more apparent. This review aims to delve into the changes in the composition and structure of the gut microbiome in individuals with IBS. It explores how diet-mediated alterations in intestinal microbes and their byproducts play a role in regulating the pathogenesis of IBS by influencing the "brain-gut" axis, intestinal barrier function, immune responses, and more. By doing so, this review seeks to lay a theoretical foundation for advancing the development of clinical therapeutics for IBS.

Celiac disease is an autoimmune condition that affects approximately 1% of the worldwide community. Originally thought to be confined mostly to the small intestine, resulting in villous atrophy and nutrient malabsorption, it has more recently been implicated in systemic manifestations as well, particularly when undiagnosed or left untreated. Herein, the physical and psychological symptoms of celiac disease are described and explored. An emphasis is placed on efforts to query prospective and confirmed celiac disease patients via the use of surveys. Suggestions are made regarding the development of efficacious surveys for the purpose of screening for celiac disease in undiagnosed persons, and monitoring efficacy of the gluten-free diet in persons diagnosed with celiac disease. There are broad categories of physical and psychological symptoms associated with celiac disease. There is also an essential interaction between such physical and the psychological symptoms. It is important to capture the association between symptoms, via queries directed toward suspected and confirmed persons with celiac disease. The use of anonymous online surveys can be helpful to determine the qualities and characteristics which may be associated with this condition. It is suggested that personal surveys should be given a greater role in screening and to lessen the time for diagnosis. Querying the subject directly via a survey can provide clues as to the types of symptoms being experienced by those with celiac disease currently, as well as to determine the salient aspects of the symptomatology, which will be useful for rapid screening and monitoring in future work.

Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction that impacts a significant portion of the population and is associated with substantial morbidity, reduced quality of life, and economic impact globally. The pathophysiology of IBS is complex and incompletely understood, and the heterogeneity of IBS is reflected in the variety of pharmaceutical and non-pharmaceutical therapies utilized for the management of IBS. Given limitations with pharmaceutical treatments, many patients with IBS seek non-pharmaceutical options. Several non-pharmaceutical treatments such as the low FODMAP diet and brain-gut behavior interventions such as gut directed hypnosis and cognitive behavioral therapy are now considered standard of care and are part of all major guidelines for the treatment of IBS. However, challenges with access to and optimal implementation of these therapies remain. This review focuses on the current evidence for common non-pharmaceutical treatments for IBS, including the latest advances in dietary and brain-gut behavioral care, in addition other complementary and integrative health practices and emerging therapies.

Irritable bowel syndrome (IBS) is a type of chronic bowel disorder with a poorly understood pathophysiology. Recently, the imbalance of copper has been reported to influence the progression of IBS, suggesting cuproptosis, a new type of copper-induced cell death, may play a role in IBS. This study found 17 cuproptosis-related differentially expressed genes in IBS through bioinformatic analysis. Six hub genes were identified after the protein-protein interaction network analysis, namely myeloid cell leukemia 1 (MCL1), epidermal growth factor receptor 2, cadherin-associated protein beta 1, solute carrier family 25 members 37, solute carrier family 39 members 14, and six transmembrane epithelial antigens of the prostate 3. We selected MCL1 for further verification. Human normal colon epithelial cell line (NCM460) was used to construct models of IBS or cuproptosis in vitro by lipopolysaccharide (LPS) or LPS combined with copper (II) chloride (CuCl2). We observed that overexpression of MCL1 promoted cell viability and proliferation ability, and inhibited the secretion of inflammatory factors and expression of Bax and caspase-3 of NCM460 cells treated with LPS or LPS combined with CuCl2. In addition, up-regulated MCL1 significantly suppressed the protein levels of ferredoxin 1 and lipoyl synthase, two key regulators of cuproptosis. In conclusion, our study demonstrates that cuproptosis is involved in IBS and identifies a cuproptosis-related gene, MCL1, that helps alleviate IBS by promoting cell growth, reducing inflammation, and suppressing cuproptosis, making it a promising therapeutic target in IBS.