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Irritable bowel syndrome with diarrhoea (IBS‐D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS‐D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work‐up and management. A Delphi consensus was performed with experts from 10 European countries who conducted a literature summary and voting process on 31 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus (defined as >80% agreement) was reached for all the statements. The panel agreed with the potential overlapping of IBS‐D and FDr. In terms of diagnosis, the consensus supports a symptom‐based approach also with the exclusion of alarm symptoms, recommending the evaluation of full blood count, C‐reactive protein, serology for coeliac disease, and faecal calprotectin, and consideration of diagnosing bile acid diarrhoea. Colonoscopy with random biopsies in both the right and left colon is recommended in patients older than 50 years and in presence of alarm features. Regarding treatment, a strong consensus was achieved for the use of a diet low fermentable oligo‐, di‐, monosaccharides and polyols, gut‐directed psychological therapies, rifaximin, loperamide, and eluxadoline. A weak or conditional recommendation was achieved for antispasmodics, probiotics, tryciclic antidepressants, bile acid sequestrants, 5‐hydroxytryptamine‐3 antagonists (i.e. alosetron, ondansetron, or ramosetron). A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of IBS‐D and FDr.

Irritable Bowel Syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain associated with defecation or a change in bowel habits. Gut microbiota, which acts as a real organ with well-defined functions, is in a mutualistic relationship with the host, harvesting additional energy and nutrients from the diet and protecting the host from pathogens; specific alterations in its composition seem to play a crucial role in IBS pathophysiology. It is well known that diet can significantly modulate the intestinal microbiota profile but it is less known how different nutritional approach effective in IBS patients, such as the low-FODMAP diet, could be responsible of intestinal microbiota changes, thus influencing the presence of gastrointestinal (GI) symptoms. The aim of this review was to explore the effects of different nutritional protocols (e.g., traditional nutritional advice, low-FODMAP diet, gluten-free diet, etc.) on IBS-D symptoms and on intestinal microbiota variations in both IBS-D patients and healthy subjects. To date, an ideal nutritional protocol does not exist for IBS-D patients but it seems crucial to consider the effect of the different nutritional approaches on the intestinal microbiota composition to better define an efficient strategy to manage this functional disorder.

Background Irritable bowel syndrome (IBS) affects 10–15% of adults in the US, and is associated with significant impairment in health-related quality of life (HRQoL); however, information specific to the diarrhea subtype (IBS-D) is lacking. We assessed the impact of IBS-D on HRQoL, work productivity, and daily activities, and the associated indirect costs, among a sample of the US population. Methods Respondents (≥18 years) from the 2012 US National Health and Wellness Survey who reported an IBS-D diagnosis by a physician or symptoms consistent with Rome II criteria for IBS-D were identified as having IBS-D. Controls included respondents without IBS-D or inflammatory bowel disease. HRQoL was assessed via the Short Form 36 Health Survey version 2 questionnaire and summarized into Mental and Physical Component Summary (MCS; PCS) scores and a Short Form-6 dimension (SF-6D) utility score. Work and activity impairment were assessed via the Work Productivity and Activity Impairment Questionnaire: General Health version (WPAI:GH), which measures absenteeism, presenteeism, overall work productivity loss, and daily activity impairment. Indirect costs were calculated using unit cost data from the Bureau of Labor Statistics and variables from the WPAI:GH. Generalized linear models were used to examine differences in health outcomes between respondents with IBS-D and controls, controlling for demographic and health characteristics. Results In total, 66,491 respondents (1102 IBS-D; 65,389 controls) were analyzed. Mean age was 48.7 years; 50% were female. Compared with controls, the IBS-D cohort reported significantly lower HRQoL (mean MCS: 45.16 vs. 49.48; p  < 0.001; mean PCS: 47.29 vs. 50.67; p  < 0.001; mean SF-6D: 0.677 vs. 0.741; p  < 0.001) and greater absenteeism (5.1% vs. 2.9%; p  = 0.004), presenteeism (17.9% vs. 11.3%; p  < 0.001), overall work productivity loss (20.7% vs. 13.2%; p  < 0.001), and activity impairment (29.6% vs. 18.9%; p  < 0.001). Respondents with IBS-D also incurred an estimated $2486 more in indirect costs ($7008 vs. $4522; p  < 0.001). Conclusions Compared with controls, IBS-D is associated with significantly lower HRQoL, greater impairments in work and daily activities, and higher indirect costs, imposing a substantial burden on patients and employers. These findings suggest a significant unmet need exists for effective IBS-D treatments.

Objective Recently, the authors demonstrated altered gene expression in the jejunal mucosa of diarrhoea-predominant irritable bowel syndrome patients (IBS-D); specifically, the authors showed that genes related to mast cells and the intercellular apical junction complex (AJC) were expressed differently than in healthy subjects. The aim of the authors here was to determine whether these alterations are associated with structural abnormalities in AJC and their relationship with mast cell activation and IBS-D clinical manifestations. Design A clinical assessment and a jejunal biopsy were obtained in IBS-D patients (n=45) and healthy subjects (n=30). Mucosal mast cell number and activation were determined by quantifying CD117+ cells/hpf and tryptase expression, respectively. Expression and distribution of AJC specific proteins were evaluated by western blot and confocal microscopy. AJC ultrastructure was assessed by transmission electron microscopy. Results Compared with healthy subjects, IBS-D patients exhibited: (a) increased mast cell counts and activation; (b) increased protein expression of claudin-2, reduced occludin phosphorylation and enhanced redistribution from the membrane to the cytoplasm; and (c) increased myosin kinase expression, reduced myosin phosphatase and, consequently, enhanced phosphorylation of myosin. These molecular alterations were associated with ultrastructural abnormalities at the AJC, specifically, perijunctional cytoskeleton condensation and enlarged apical intercellular distance. Moreover, AJC structural alterations positively correlated both with mast cell activation and clinical symptoms. Conclusion The jejunal mucosa of IBS-D patients displays disrupted apical junctional complex integrity associated with mast cell activation and clinical manifestations. These results provide evidence for the organic nature of IBS-D, a heretofore model disease of functional gastrointestinal disorders.

Diet plays an important role in human health and disease. Of all human diseases, diarrheal illnesses bring diet into sharp focus as it has a direct causal and therapeutic relationship. With the advent and widespread use of next generation sequencing, significant advances have been made in unraveling the etiologies of congenital diarrheas and enteropathies, some of which are eminently treatable with dietary modification. Early institution of appropriate dietary therapy is lifesaving in congenital osmotic diarrheas. Chronic diarrhea in older children and adolescents often have an underlying dietary basis, depending on the etiology. Identification and exclusion of the offending food in the diet results in dramatic improvement in symptoms. It is equally important to be prudent and cautious in the use of exclusion diets in management of chronic diarrhea as it is associated with micronutrient deficiencies, needless escalation of cost and enable maladaptive food intake behaviors. In this review, authors discuss etiology specific dietary management of diarrhea in children with emphasis on congenital diarrheas and enteropathies.

[This corrects the article DOI: 10.3389/fphar.2022.955421.].

Irritable bowel syndrome with diarrhea (IBS-D) is the most prevalent subtype of IBS, characterized by chronic gastrointestinal symptoms in the absence of identifiable pathological findings. This study aims to investigate the molecular mechanisms underlying IBS-D using transcriptomic data. By employing causal network inference methods, we identify key transcriptomic modules associated with IBS-D. Utilizing data from public databases and applying advanced computational techniques, we uncover potential biomarkers and therapeutic targets. Our analysis reveals significant molecular alterations that affect cellular functions, offering new insights into the complex pathophysiology of IBS-D. These findings enhance our understanding of the disease and may foster the development of more effective treatments.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community. Emerging research spotlights the intricate involvement of microbiota dysbiosis in IBS pathogenesis. Studies have demonstrated reduced microbial diversity and stability and specific microbial alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and even diet, offer exciting prospects for managing IBS. However, definitive conclusions are hindered by the heterogeneity of these studies. Further research should focus on elucidating the mechanisms, developing microbiome-based diagnostics, and enabling personalized therapies tailored to an individual’s microbiome profile. This review takes a deep dive into the microscopic world inhabiting our guts, and its implications for IBS. Our aim is to elucidate the complex interplay between gut microbiota and each IBS subtype, exploring novel microbiota-targeted treatments and providing a comprehensive overview of the current state of knowledge.

Impaired gut barrier function plays a pivotal role in the pathophysiology of irritable bowel syndrome (IBS), particularly in IBS with diarrhea. Mucoprotectants, such as xyloglucan, gelatin tannate and pea protein tannins, offer a novel therapeutic approach by restoring intestinal permeability and reducing inflammation. This review assesses preclinical and clinical evidence supporting mucoprotectants in IBS with diarrhea management. Preclinical studies indicate their efficacy in reducing intestinal permeability and inflammation, while clinical trials demonstrate improvements in stool consistency, abdominal pain and bloating. Despite these promising results, comparative studies are needed to establish the superiority of specific mucoprotectants and their optimal use in clinical practice.

Background of the study: Diarrhea‐predominant irritable bowel syndrome (IBS‐D) is a common disease of the brain–gut axis with clinical manifestations such as abdominal pain and abdominal leakage. It is usually accompanied by anxiety and depression, which severely affects the activities of daily living of patients. After Cimicifuga Rhizoma (CR) is processed through the honey bran, the effect of replenishing qi to increase yang is enhanced, and it is often used to treat abdominal pain, diarrhea, and other gastrointestinal discomforts. Honey Bran CR (HBCR) is clinically available for the treatment of IBS‐D, but there is a lack of research on its material basis and mechanism of action, among other aspects. Aim of the study: This study aimed to investigate the material basis of HBCR for replenishing qi to increase yang and predict its mechanism of action in treating IBS‐D. Materials and Methods: First, the chemical constituents of different fractionated extracts of HBCR were identified by UPLC‐Q‐TOF‐MS/MS, and the ingredient library was established. Second, the therapeutic effects of different parts on IBS‐D model rats were compared. Third, the spectrum–effect relationship between the chemical components and pharmacodynamic indexes of HBCR was established by gray correlation analysis. Network pharmacology and molecular docking techniques were utilized to validate the effectiveness of the effector components. Finally, the action mechanism of HBCR for IBS‐D was further analyzed by serum metabolomics. Results: A total of 61 chemical constituents were identified by UPLC‐Q‐TOF‐MS/MS. They included 40 for the petroleum ether group, 48 for the dichloromethane group, 26 for the ethyl acetate group, 37 for the N‐butanol group, and 19 for the water group. The results of AWR experiments showed that the IBS‐D rat model was successfully constructed. The NGF and TRPV1 immunohistochemical sections; TNF‐α, VIP, and 5‐HT expressions in the colon; and SP, BDNF, and 5‐HT expressions in the hypothalamus showed that different extracted parts of HBCR had curative effects on IBS‐D model rats, and the treatment effect of the ethyl acetate group was the best. So the different extracted parts of HBCR could inhibit the release of TRPV1 and SP mediators by downregulating the expressions of BDNF and NGF. It could also affect the production of 5‐HT to alleviate the development of visceral hypersensitivity and inhibit the production of inflammatory factors such as TNF‐α and the downregulation of gastrointestinal motility by VIP to treat IBS‐D. Six potential effective components were screened using the spectrum–effect relationship: fukiic acid (Peak 1), cimicifugic acid C (Peak 26), piscidic acid (Peak 3), cimicifugic acid B (Peak 30), cimicifugic acid A (Peak 29), and cimicifugic acid D (Peak 25). The results of network pharmacology and molecular docking showed that the effective components played a role in replenishing qi to increase yang through multiple targets and pathways. Metabolomics studies have revealed that different fractionated extracts of HBCR can regulate unsaturated fatty acid biosynthesis metabolism, arachidonic acid metabolism, pyruvic acid metabolism, and other pathways to play a therapeutic role in the treatment of IBS‐D. Conclusion: In this study, we developed a library of chemical constituents of different extracted parts of HBCR for the first time, and the effective components for replenishing qi to increase yang were screened using the spectrum–effect relationship. This study preliminarily elucidated the action mechanism of different extracted parts of HBCR for the treatment of IBS‐D. This laid a foundation for the study of the pharmacokinetics and quality standards of HBCR and provided a scientific basis for its clinical application.