Including Irritable Bowel Syndrome Research Articles

Presence and characteristics of disordered eating and orthorexia in irritable bowel syndrome.

Orthorexia, a harmful obsession with eating healthily, may develop from illnesses characterized by dietary restriction, including irritable bowel syndrome (IBS) and eating disorders (ED). Evidence of disordered eating in IBS exists, but orthorexia has not been assessed. This cross-sectional study in adults (≥18 years) assessed presence and characteristics of disordered eating and orthorexia in IBS, compared to control subjects (CS) and ED. IBS participants met Rome IV, and ED participants met DSM-5 criteria. Disordered eating was assessed using "sick, control, one-stone, fat, food" (SCOFF, ≥2 indicating disordered eating), and orthorexia by the eating habits questionnaire (EHQ). Secondary measures included stress (PSS); anxiety (HADS-A); food-related quality of life (Fr-QoL), and dietary intake (CNAQ). In 202 IBS (192 female), 34 ED (34 female), and 109 CS (90 female), more IBS (33%) and ED (47%) scored SCOFF≥2 compared to CS (16%, p < 0.001, chi-square). IBS and ED had higher orthorexia symptom severity compared to CS (EHQ IBS 82.9 ± 18.1, ED 90.1 ± 19.6, and CS 73.5 ± 16.9, p < 0.001, one-way ANOVA). IBS and ED did not differ for SCOFF or EHQ (p > 0.05). Those with IBS and disordered eating had higher orthorexia symptom severity (EHQ 78.2 ± 16.6 vs. 92.4 ± 17.5, p < 0.001, independent t-test), worse symptoms (IBS-SSS 211.0 ± 78.4 vs. 244.4 ± 62.5, p = 0.008, Mann-Whitney U test), higher stress (p < 0.001, independent t-test), higher anxiety (p = 0.002, independent t-test), and worse FR-QoL (p < 0.001, independent t-test). Disordered eating and orthorexia symptoms occur frequently in IBS, particularly in those with worse gastrointestinal symptoms, higher stress, and anxiety. Clinicians could consider these characteristics when prescribing dietary therapies.

Brain histamine improves colonic hyperpermeability through the basal forebrain cholinergic neurons, adenosine A2B receptors and vagus nerve in rats

Intestinal barrier dysfunction, leaky gut, is implicated in various diseases, including irritable bowel syndrome (IBS) and neurodegenerative conditions like Alzheimer's disease. Our recent investigation revealed that basal forebrain cholinergic neurons (BFCNs), critical for cognitive function, receive signals from butyrate and orexin, playing a role in regulating intestinal barrier function through adenosine A2B signaling and the vagus. This study explores the involvement and function of brain histamine, linked to BFCNs, in the regulation of intestinal barrier function. Colonic permeability, assessed by quantifying absorbed Evans blue in rat colonic tissue, showed that histamine did not affect increased colonic permeability induced by LPS when administered subcutaneously. However, intracisternal histamine administration improved colonic hyperpermeability. Elevating endogenous histamine levels in the brain with SKF91488, a histamine N-methyltransferase inhibitor, also improved colonic hyperpermeability. This effect was abolished by intracisternal chlorpheniramine, an histamine H1 receptor antagonist, not ranitidine, an H2 receptor antagonist. The SKF91488-induced improvement in colonic hyperpermeability was blocked by vagotomy, intracisternal pirenzepine (suppressing BFCNs activity), or alloxazine (an adenosine A2B receptor antagonist). Additionally, intracisternal chlorpheniramine injection eliminated butyrate-induced improvement in colonic hyperpermeability. These findings suggest that brain histamine, acting via the histamine H1 receptor, regulates intestinal barrier function involving BFCNs, adenosine A2B signaling, and the vagus. Brain histamine appears to centrally regulate intestinal barrier function influenced by butyrate, differentiating its actions from peripheral histamine in conditions like IBS, where mast cell-derived histamine induces leaky gut. Brain histamine emerges as a potential pharmacological target for diseases associated with leaky gut, such as dementia and IBS.

A63 RESTRAINED STRESS IN MICE INDUCES TRANSLOCATION OF GUT COMMENSAL BACTERIAL INTO DISTAL ORGANS

Abstract Background Bacterial translocation is defined as the migration of bacteria from the intestinal lumen into extraintestinal tissues; this process has been implicated in the pathophysiology of gastrointestinal disorders including irritable bowel syndrome (IBS) and central nervous system disorders. In our recent study, we found that gut bacteria from patients with IBS can disrupt the mucus layer and penetrate into the lamina propria in our microbiota-humanized mouse model. It is well known that psychological stress triggers or exacerbates IBS symptoms. Furthermore, experimental stress models have been able to reproduce some features of IBS and demonstrate that gut bacteria can translocate into the mesenteric lymph node (MLN), liver, and spleen. These studies suggested that bacterial translocation might induce changes in behavior and brain function. However, the direct causal relationship between bacterial translocation and behavioral changes, and the mechanism of bacterial translocation remains unclear. Aims To investigate translocation of commensal bacteria within the gut wall and their migration into distant organs using a mouse stress model. Methods SPF C57BL/6 mice were split into 2 groups: restraint stress group (3 hrs x 7 days, n=9) and non-stress control group (n=8). After the last session of stress, we conducted light/dark preference and tail suspension tests. We collected jejunum, ileum, and colon samples for histology. We also sampled blood, MLN, liver, spleen, and brain for histology and bacterial cultures. The tissues were collected under aseptic conditions. The blood or organ homogenates were plated and incubated in aerobic and anaerobic conditions. Intestinal tissues were submitted to fluorescence in situ hybridization staining with a bacterial universal probe in combination with immunofluorescence to co-stain with e-cadherin and CD103. The images were taken by confocal microscopy. Results The chronic restrain stress-induced anxiety-like, but not depressive behavior, as assessed by the light/dark test. Compared to the controls, bacterial culture was more frequently positive in the stress group: blood (0% vs 25%), MLN (0% vs 50%), spleen (0% vs 25%), liver (0% vs 25%), and brain (25% vs 74%). The histology showed that intestinal bacteria were present within the gut wall and brain in the stress group. Interestingly, these bacteria co-localized with the goblet cells in the jejunum, ileum and colon, and CD103+ dendritic cells in the colon (Fig. 1). Conclusions We found that mice subjected to the restraint stress exhibit abnormal behavior, accompanied by bacterial infiltration into the gut wall, as well as bacterial translocation into distal organs, including brain. Our histology data suggest a potential contribution of goblet cells-dendritic cells pathway in commensal gut bacteria translocation in the restrained stress model. Intestinal bacteria were present within the gut wall in the stress group. Funding Agencies CIHR Farncombe Innovation Fund

Washed microbiota transplantation improves symptoms and intestinal barrier function in patients with functional bowel disorders: a propensity-score matching analysis

BackgroundAlterations in the intestinal microbiota may play a role in the pathogenesis of functional bowel disorders (FBDs). Probiotics are widely used to improve intestinal dysbacteriosis in FBDs. In the context of FBDs, washed microbiota transplantation (WMT) appear to be a promising therapeutic option. We aimed to compare probiotics with WMT by using a propensity-score matching analysis (PSMA).MethodsWe conducted a retrospective investigation of 103 patients with FBDs, including irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FDr), functional abdominal bloating (FAB). Patients were divided into the WMT group or probiotics group (taking probiotics capsules). Data on the following parameters were matched for PSMA: age; sex; disease course; body mass index; anxiety; insomnia; tobacco smoking; alcohol consumption; and levels of D-lactate, diamine oxidase, and lipopolysaccharide. Intestinal barrier function (IBF) and symptoms were evaluated both before and after treatment initiation. Prognostic factors were assessed by Cox proportional hazards regression analysis.ResultsPSMA identified in 34 matched pairs (11 IBS, 12 FC, 7 FDr, and 4 FAB in the probiotics group and 14 IBS, 13 FC, 5 FDr, and 2 FAB in the WMT group. Improvement of FBD symptoms was greater with WMT than probiotics (P = 0.002). The WMT group had significantly fewer patients with intestinal barrier damage than the probiotics group (38.2% vs. 67.6%, P = 0.041). This improvement of FBD with WMT was further reflected as a reduction in D-lactate levels (P = 0.031). Increased D-lactate levels which were identified as a prognostic factor for FBDs (HR = 0.248, 95%CI 0.093–0.666, P = 0.006) in multivariate Cox regression analysis.ConclusionWMT could improve symptoms and IBF in patients with FBDs. Increased D-lactate levels in patients with FBDs may predict a favorable response to WMT treatment.

A Mendelian randomization study on the effects of plasma lipids on irritable bowel syndrome and functional dyspepsia

Although functional gastrointestinal disorder (FGID) is a common clinical condition, its risk factors remain unclear. We performed a Mendelian randomization study to explore the association between plasma lipids and the risk of FGID. Instrumental variables closely related to six plasma lipids were obtained from the corresponding genome-wide association studies, and summary-level data on FGID, including irritable bowel syndrome (IBS) and functional dyspepsia (FD), were extracted from the FinnGen study. The primary inverse variance weighted method and other supplementary analyses were used to evaluate the causal relationship between diverse plasma lipids and FGID. For each increase in the standard deviation of triglyceride levels, there was a 12.0% increase in the risk of IBS rather than that of FD. Low- and high-density lipoprotein cholesterol, total cholesterol, apolipoprotein A, and apolipoprotein B levels were not associated with the risk of IBS or FD. Through this study, we identified the causal role of triglycerides in the pathogenesis of IBS, which could benefit further basic and clinical research.

Lactobacillus plantarum AR495 improves colonic transport hyperactivity in irritable bowel syndrome through tryptophan metabolism

Lactobacillus plantarum AR495 is a widely used probiotic in treating various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of L. plantarum AR495 relieving IBS remain unclear....

Treatment of functional bowel disorders in an integrative medicine clinic resulting in improved digestive tract symptoms.

Functional bowel disorders (FBDs), including irritable bowel syndrome (IBS) and others, are conditions without a physically identifiable etiology that, as a result, are difficult to treat. Alternatives to traditional medical interventions are needed because IBS patients require more of physician time and higher healthcare spending. The goal of this study was to determine the efficacy of alternative lifestyle interventions for patients with FBDs seen in an integrative medicine (IM) clinic at an academic medical center. We performed a retrospective chart review to determine whether patients with FBDs had improvement in symptoms following predominantly nutrition-based IM interventions that included recommendations for dietary supplements and elimination diets. We measured symptoms before and after intervention (average time between measurements 8.75 months) using a medical symptoms questionnaire (MSQ) commonly used to quantify symptom change in IM clinics. Digestive tract symptoms, as measured by the MSQ, improved significantly in patients (n = 57) with FBDs following IM intervention. The MSQ Digestive Tract subtotal for FBD patients decreased from 10.2 (SD, 5.4) to 7.2 (SD, 5.2) (P < 0.001) after IM intervention. Patients in an IM clinic had improved digestive tract symptoms scores following IM intervention. Because nutrition-based interventions were the primary intervention recommended by IM providers, primary care physicians and gastroenterologists may wish to consider referring FBD patients to registered dietitian-nutritionists (RDNs) skilled in implementing elimination diets.

Exploration of the causal effects of leukocyte telomere length and four gastrointestinal diseases: a two-sample bidirectional Mendelian randomization study

BackgroundTo explore the underlying causality between leukocyte telomere length (LTL) and four gastrointestinal diseases, we designed a two-sample bidirectional Mendelian randomization study.MethodsTwo-sample Mendelian randomization (MR) was used to explore genetic causality between LTL and four gastrointestinal diseases, including irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), gastrointestinal ulcers disease (GUD), and nonalcoholic fatty liver disease (NAFLD). We utilized inverse-variance weighted (IVW) as the primary method for MR analysis. Supplementary analyses were conducted using methods such as MR-Egger regression, weighted-median, Maximum Likelihood (MaxLik), Robust adjusted profile score (MR-RAPS), Contamination mixture (ConMix), and MR-mix. Cochran’s Q was calculated to check for heterogeneity. The MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) were detected for pleiotropy.ResultsThe IVW analysis suggests that there may be a potential causal relationship between LTL and two diseases (odds ratio (OR): 1.062; 95% confidence interval (CI): 1.003, 1.124; p = 0.038 for IBS and OR: 0.889; 95% CI: 0.798, 0.990; p = 0.032 for GERD). However, other methods do not entirely align with the results of the IVW analysis. In the reverse MR analysis, we did not find statistically significant associations between LTL and these four diseases.ConclusionThe current evidence does not definitively rule out a causal relationship between LTL and these four gastrointestinal diseases but suggests a potential association between LTL and IBS, or LTL and GERD. Exploring the relationship between gastrointestinal diseases and LTL may offer new insights into the onset, progression, and treatment of these diseases.

Causal associations of 25-hydroxyvitamin D with functional gastrointestinal disorders: a two-sample Mendelian randomization study

BackgroundPrevious observational studies have shown associations between vitamin Ds and FGIDS[Including irritable bowel syndrome(IBS) and functional dyspepsia(FD)]. However, the association is controversial and the causality remains unknown. In this study, two-sample MR was cited to explore the causal effect on FGIDS caused by vitamin D level and serum 25-hydroxyvitamin D.MethodThe GWASs of vitaminD and 25-hydroxyvitamin D, with 57–99 strongly related SNPs were all obtained from UK biobank. The GWASs of IBS and FD were obtained from FinnGen biobank with respectively 187,028 and 194,071 participants involved. Fixed-effect inverse variance weighted regression was used to evaluate causal estimates. Other statistical methods such as MR Egger, weighted median estimation, maximum likelihood estimation and penalty-weighted median estimation are also used to verify the accuracy of the main results.ResultsMeasuring by the IVW method, our research indicated that no causal relationship was detected between vitamin D intake and Functional gastrointestinal disorders [IVW, OR(vitamin D-IBS) = 0.909, 95% CI 0.789–1.053, p = 0.2017); OR(vitamin D-FD) = 1.0662, 95% CI 0.9182–1.2380, p = 0.4000]. As for serum 25-hydroxyvitamin D, no causal relationship was detected on FD(IVW, OR(25-hydroxyvitamin D-FD) = 0.9635, 95% CI 0.8039–1.1546, p = 0.6869). Nevertheless, a negative causal relationship was revealed between 25-hydroxyvitamin D and IBS(IVW, OR(25-hydroxyvitamin D-IBS) = 0.832, 95% CI 0.696–0.995, p = 0.0436). Sensitive analysis supported the main findings but did not suggest bias due to pleiotropy.ConclusionsOur Mendelian randomization analyses suggest a negative causal relationship between 25-hydroxyvitamin D and IBS. For each additional SD increase of genetically determined 25-hydroxyvitamin D levels, the risk of IBS decreased by 16.8%.

Glucocorticoid receptor-mediated Nr1d1 chromatin circadian misalignment in stress-induced irritable bowel syndrome

Stress-elevated glucocorticoids cause circadian disturbances and gut-brain axis (GBA) disorders, including irritable bowel syndrome (IBS). We hypothesized that the glucocorticoid receptor (GR/NR3C1) might cause chromatin circadian misalignment in the colon epithelium. We observed significantly decreased core circadian gene Nr1d1 in water avoidance stressed (WAS) BALB/c colon epithelium, like in IBS patients. WAS decreased GR binding at the Nr1d1 promoter E-box (enhancer box), and GR could suppress Nr1d1 via this site. Stress also altered GR binding at the E-box sites along the Ikzf3-Nr1d1 chromatin and remodeled circadian chromatin 3D structures, including Ikzf3-Nr1d1 super-enhancer, Dbp, and Npas2. Intestinal deletion of Nr3c1 specifically abolished these stress-induced transcriptional alternations relevant to IBS phenotypes in BALB/c mice. GR mediated Ikzf3-Nr1d1 chromatin disease related circadian misalignment in stress-induced IBS animal model. This animal model dataset suggests that regulatory SNPs of human IKZF3-NR1D1 transcription through conserved chromatin looping have translational potential based on the GR-mediated circadian-stress crosstalk.

Role of stimulator of interferon genes (STING) in the enteric nervous system in health and disease.

Stimulator of Interferon Genes (STING) is a crucial protein that controls the immune system's reaction to bacterial and viral infections. As a pattern-recognition receptor, STING is found in immune cells as well as in neurons and glia in the enteric nervous system (ENS). Recent studies have linked STING to the pathogenesis of several neurological disorders like multiple sclerosis (MS), Alzheimer's disease (AD), and gastrointestinal disorders, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), which are characterized by chronic inflammation and dysregulation of the enteric nervous system (ENS) in the digestive tract. STING plays a crucial role in the pathway that induces the production of interferon in response to viral infection in the central nervous system (CNS). A new study by Dharshika et al. in the current issue of Neurogastroenterology and Motility has demonstrated distinct roles for STING in enteric neurons and glia, namely activation of STING leads to IFN-β production in enteric neurons but not in glia and reducing STING activation in enteric glia does not modulate the severity of Dextran sulfate sodium (DSS) colitis or subsequent loss of enteric neurons. Rather, the role of STING in enteric glia is related to enhancing autophagy. STING can influence gastrointestinal motility and barrier function and therefore be involved in the pathophysiology of IBS and IBD. This mini review highlights the current knowledge of STING in the pathophysiology of CNS and gastrointestinal diseases as well as these newly uncovered roles STING in enteric neurons and glia.

Fermented Vegetables as a Potential Treatment for Irritable Bowel Syndrome

Foods and supplements containing microorganisms with expected beneficial effects are increasingly investigated and utilized in the treatment of human illness, including irritable bowel syndrome (IBS). Research points to a prominent role of gut dysbiosis in the multiple aberrations in gastrointestinal function, immune balance, and mental health seen in IBS. The proposition of the current Perspective is that fermented vegetable foods, in combination with a healthy and stable diet, may be particularly useful for addressing these disturbances. This is based on the recognition that plants and their associated microorganisms have contributed to shaping human microbiota and adaptation over evolutionary time. In particular, lactic acid bacteria with immunomodulatory, antipathogenic, and digestive properties are prevalent in products such as sauerkraut and kimchi. Additionally, by adjusting the salt content and fermentation time, products with a microbial and therapeutic potential beyond that of regular ferments could potentially be produced. Although more clinical data are required to make firm assertions, the low-risk profile, combined with biological considerations and reasoning and considerable circumstantial and anecdotal evidence, indicate that fermented vegetables are worthy of consideration by health professionals and patients dealing with IBS-related issues. To maximize microbial diversity and limit the risk of adverse effects, small doses of multiple products, containing different combinations of traditionally fermented vegetables and/or fruits, is suggested for experimental research and care.

Anxiety and depression in Indian patients with irritable bowel syndrome: Ameta-analysis.

Functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome (IBS), are associated with psychological abnormalities, such as anxiety and depression. Though the data on this are plenty in global literature, Indian data are sparse. We performed a systematic review and meta-analysis of Indian data on anxiety and depression among patients with IBS to estimate their pooled prevalence and to identify the shortcomings so that future areas of research can be identified. A comprehensive literature search was performed for studies applying tests for psychological issues in patients with IBS. After applying prospectively decided exclusion criteria, the eligible papers were examined using a meta-analysis approach for the prevalence of anxiety and depression in IBS patients using different tests. The odds ratios (OR) of anxiety and depression among subjects with IBS were calculated compared to controls. Of seven studies (590 IBS patients and 1520 controls) included in the meta-analysis, the pooled OR of anxiety was 8.060 (95% confidence interval [CI] 4.007-16.213) as compared to controls (random-effect model). The pooled OR of depression was 7.049 (95% CI 3.281-15.147) compared to controls (random-effect model). There was significant heterogeneity in the included studies. The current meta-analysis shows that the patients with IBS from India have eightfold greater risks of anxiety and sevenfold greater risks of depression than the controls. However, most of these data were from tertiary urban centers, and hence, there might be recruitment bias over-estimating the frequency.

Improvement of the intestinal epithelial barrier during laxative effects of phlorotannin in loperamide-induced constipation of SD rats

BackgroundDisruptions of the intestinal epithelial barrier (IEB) are frequently observed in various digestive diseases, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). This study assessed the improvement in the IEB during the laxative activity of phlorotannin (Pt) harvested from Ecklonia cava in constipation by examining the changes in the expression of the regulatory proteins for the tight junction (TJ) and adherens junction (AJ), and inflammatory cytokines in Sprague Dawley (SD) rats with loperamide (Lm)-induced constipation after a Pt treatment.ResultsThe Pt treatment induced laxative activity, including the improvement of feces-related parameters, gastrointestinal transit rate, and histological structure of the mid colon in Lm-treated SD rats. In addition, significant recovery effects were detected in the histology of IEB, including the mucus layer, epithelial cells, and lamina propria in the mid colon of Lm + Pt treated SD rats. The expression levels of E-cadherin and p120-catenin for AJ and the ZO-1, occludin, and Claudin-1 genes for TJ in epithelial cells were improved remarkably after the Pt treatment, but the rate of increase was different. Furthermore, the Pt treatment increased the expression level of several inflammatory cytokines, such as TNF-α, IL-6, IL-1β, IL-13, and IL-4 in Lm + Pt treated SD rats.ConclusionsThese results provide the first evidence that the laxative activity of Pt in SD rats with Lm-induced constipation phenotypes involve improvements in the IEB.

[Clinical efficacy of a modern probiotic for the correction of intestinal microflora in patients with irritable bowel syndrome with diarrhea and antibiotic-associated diarrhea].

Despite the fact that dietary supplements (DS) are not medicines, an increasing number of publications testify to the effectiveness of probiotics consumed with food in the complex treatment and prevention of a number of diseases of the gastrointestinal tract, including irritable bowel syndrome (IBS) and antibiotic-associated diarrhea (AAD). The purpose of the study was to evaluate the effectiveness of the complex probiotic in the relief of diarrheal syndrome associated with intestinal microbiota dysbiosis in patients with IBS with diarrhea and AAD. Material and methods. The study included 54 patients (31 with IBS with diarrhea and 23 with idiopathic AAD) aged 18 to 50 years. All patients included in the study were prescribed 1 capsule (350 mg) of the DS Neobiotic Lactobalance® per day for 21 days. One capsule contains: bifidobacteria (Bifidobacterium longum CBT BG7, Bifidobacterium lactis CBT BL3 Bifidobacterium bifidum CBT BF3), lactobacilli (Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5), lactic acid bacteria (Streptococcus thermophilus CBT ST3), fructooligosaccharides, vitamin C. The daily intake of bifidobacteria was 8.7×108 CFU, lactobacilli - 6.1×109 CFU, lactic acid bacteria 3.1×108 CFU and vitamin C - 12 mg. The severity of symptoms was assessed in points (from 0 to 7 points) using the GSRS questionnaire (Gastrointestinal Symptom Rating Scale). All patients underwent a microbiological analysis of feces with an assessment of the degree of dysbiosis before and after the administration of DS. Results. In patients with IBS with diarrhea, the assessment of the manifestations of diarrheal syndrome according to the GSRS questionnaire decreased statistically significantly from 17 to 6 points (2.9 times), abdominal pain - from 12 to 4 points (3.0 times) and dyspeptic syndrome - from 8 to 3 points (in 2.7 times). In patients with AAD, also according to the GSRS questionnaire, the manifestations of diarrheal syndrome decreased statistically significantly from 13 to 3 points (4.3 times), abdominal pain - from 4 to 1 points (4.0 times) and dyspepsia syndrome - from 5 to 2 points (in 2.5 times). Against the background of DS intake, according to the data of bacteriological examination of feces, intestinal microbiota normalized by day 21 due to an increase in the number of lacto- and bifidobacteria (p=<0.05). Conclusion. The study showed that the DS Neobiotic Lactobalance® contributes to the normalization of the intestinal microbiota and reduces the severity of clinical manifestations (diarrheal disorders or manifestations of diarrhea) in IBS and idiopathic AAD.

Management of patients with chronic abdominal pain due to disorders of gut-brain interaction. Review

Disorders of gut‑brain interaction (DGBI), including irritable bowel syndrome (IBS), functional dyspepsia (FD), and centrally‑mediated abdominal pain (CMAP), are present in more than 40 % of the worldwide population. At the first stages, most of the DGBI patients receive treatment with therapeutic agents aimed at visceral stimuli, such as eating and bowel movements. Unfortunately, a large subset of DGBI patients continue to experience chronic abdominal pain, which adversely affects health‑related quality of life and often leads to excessive unwarranted diagnosis and treatment, including surgery. Management of patients with abdominal pain who do not respond to first‑line therapy for visceral stimuli is complex and involves exposure to a number of cognitive, affective, and behavioral factors, including education, pain expectations, and other psychosocial modifiers such as mood disorders and anxiety disorders. Effective treatment of pain requires establishing a trusting relationship between the patient and the physician and avoiding medications that patients may abuse, such as opioids. Management options include both non‑pharmacological methods and pharmacological therapy. The paper presents an updated clinical review prepared by experts from the American Gastroenterological Association, focusing on the management of patients with DGBI in whom pain does not decrease under the influence of first‑line therapy aimed at visceral stimuli. This review is presented in the form of best clinical advice, although it does not discuss the use of additional non‑traditional or alternative therapies, such as marijuana, and does not cover the treatment of abdominal wall or pelvic pain syndromes.&#x0D;  

Fermented Foods of Korea and Their Functionalities

Fermented foods are loved and enjoyed worldwide and are part of a tradition in several regions of the world. Koreans have traditionally had a healthy diet since people in this region have followed a fermented-foods diet for at least 5000 years. Fermented-product footprints are evolving beyond boundaries and taking the lead in the world of food. Fermented foods, such as jang (fermented soybean products), kimchi (fermented vegetables), jeotgal (fermented fish), and vinegar (liquor with grain and fruit fermentation), are prominent fermented foods in the Korean culture. These four major fermented foods have been passed down through the generations and define Korean cuisine. However, scientific advancements in the fermentation process have increased productivity rates and facilitated global exports. Recently, Korean kimchi and jang have garnered significant attention due to their nutritional and health-beneficial properties. The health benefits of various Korean fermented foods have been consistently supported by both preclinical and clinical research. Korean fermented foods effectively reduce the risk of cardiovascular and chronic metabolic diseases, such as immune regulation, memory improvement, obesity, diabetes, and high blood pressure. Additionally, kimchi is known to prevent and improve multiple metabolic diseases, including irritable bowel syndrome (IBS), and improve beneficial intestinal bacteria. These functional health benefits may reflect the synergistic effect between raw materials and various physiologically active substances produced during fermentation. Thus, fermented foods all over the world not only enrich our dining table with taste, aroma, and nutrition, but also the microorganisms involved in fermentation and metabolites of various fermentations have a profound effect on human health. This article describes the production and physiological functions of Korean fermented foods, which are anticipated to play a significant role in the wellness of the world’s population in the coming decades.

Self-Medication for the Treatment of Abdominal Cramps and Pain-A Real-Life Comparison of Three Frequently Used Preparations.

Functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome (IBS), are frequently handled by self-management with over-the-counter (OTC) products such as hyoscine butylbromide (HBB), alone or in combination with paracetamol, and natural products such as peppermint oil. To obtain real-world information, we have performed an anonymous pharmacy-based patient survey among 1686 users of HBB, HBB + paracetamol, and peppermint oil. Based on the distinct but overlapping indications for the three OTC products, multiple logistic regression was applied to compare them in users reporting gastrointestinal cramps and pain, bloating, flatulence, or IBS as cardinal symptoms. All three treatments reduced symptoms and associated impairments of work/daily chores, leisure activities, and sleep by approximately 50%. Based on the four cardinal symptoms and the four dependent continuous variables of interest (change in intensity of symptoms and of the three impairment domains) a total of 16 logistic regression models were applied. HBB, HBB + paracetamol, and peppermint oil had similar reported overall effectiveness in those models. Gender, age, baseline symptom severity, and impairment in one of three domains had small and inconsistent effects on perceived treatment success. We provide evidence that HBB, HBB + paracetamol, and peppermint oil have comparable effectiveness in their approved indications under real-world conditions in an OTC setting.

The role of mechanosensitive ion channels in the gastrointestinal tract.

Mechanosensation is essential for normal gastrointestinal (GI) function, and abnormalities in mechanosensation are associated with GI disorders. There are several mechanosensitive ion channels in the GI tract, namely transient receptor potential (TRP) channels, Piezo channels, two-pore domain potassium (K2p) channels, voltage-gated ion channels, large-conductance Ca2+-activated K+ (BKCa) channels, and the cystic fibrosis transmembrane conductance regulator (CFTR). These channels are located in many mechanosensitive intestinal cell types, namely enterochromaffin (EC) cells, interstitial cells of Cajal (ICCs), smooth muscle cells (SMCs), and intrinsic and extrinsic enteric neurons. In these cells, mechanosensitive ion channels can alter transmembrane ion currents in response to mechanical forces, through a process known as mechanoelectrical coupling. Furthermore, mechanosensitive ion channels are often associated with a variety of GI tract disorders, including irritable bowel syndrome (IBS) and GI tumors. Mechanosensitive ion channels could therefore provide a new perspective for the treatment of GI diseases. This review aims to highlight recent research advances regarding the function of mechanosensitive ion channels in the GI tract. Moreover, it outlines the potential role of mechanosensitive ion channels in related diseases, while describing the current understanding of interactions between the GI tract and mechanosensitive ion channels.

Histamine production by the gut microbiota induces visceral hyperalgesia through histamine 4 receptor signaling in mice.

The gut microbiota has been implicated in chronic pain disorders, including irritable bowel syndrome (IBS), yet specific pathophysiological mechanisms remain unclear. We showed that decreasing intake of fermentable carbohydrates improved abdominal pain in patients with IBS, and this was accompanied by changes in the gut microbiota and decreased urinary histamine concentrations. Here, we used germ-free mice colonized with fecal microbiota from patients with IBS to investigate the role of gut bacteria and the neuroactive mediator histamine in visceral hypersensitivity. Germ-free mice colonized with the fecal microbiota of patients with IBS who had high but not low urinary histamine developed visceral hyperalgesia and mast cell activation. When these mice were fed a diet with reduced fermentable carbohydrates, the animals showed a decrease in visceral hypersensitivity and mast cell accumulation in the colon. We observed that the fecal microbiota from patients with IBS with high but not low urinary histamine produced large amounts of histamine in vitro. We identified Klebsiella aerogenes, carrying a histidine decarboxylase gene variant, as a major producer of this histamine. This bacterial strain was highly abundant in the fecal microbiota of three independent cohorts of patients with IBS compared with healthy individuals. Pharmacological blockade of the histamine 4 receptor in vivo inhibited visceral hypersensitivity and decreased mast cell accumulation in the colon of germ-free mice colonized with the high histamine-producing IBS fecal microbiota. These results suggest that therapeutic strategies directed against bacterial histamine could help treat visceral hyperalgesia in a subset of patients with IBS with chronic abdominal pain.