Deciphering the multi-target mechanism of Magnolia officinalis in irritable bowel syndrome with diarrhea: A combined network pharmacology, machine learning, and in vivo validation study.

β-Hydroxybutyrate modulates intestinal barrier function and visceral sensitivity via a brain AMPK-orexin pathway recruiting histamine H1 receptors, basal forebrain cholinergic neurons, adenosine A2B receptors, and vagal output in rats.

Metabolic disparities of potentially toxic components derived from Psoraleae Fructus and Euodiae Fructus within the Sishen wan influenced by varying compatibilities and physiological conditions in an in vitro gut microbiota model.

High-definition anorectal manometry (HD-ARM), balloon expulsion test (BET), and magnetic resonance defecography (MR defecography) are important tools in studying constipation. Our aim was to evaluate the prevalence of functional defecation disorders and structural anorectal alterations in patients with chronic constipation and compare the findings of HD-ARM and BET with MR defecography. Retrospective cohort study including patients with functional constipation or irritable bowel syndrome with constipation (IBS-C), refractory to medical therapy, submitted to HD-ARM, BET, and MR defecography. Patients were divided into three groups: (a) normal anorectal evacuation in HD-ARM and normal BET; (b) abnormal evacuation pattern and abnormal BET; and (c) normal anorectal evacuation pattern and abnormal BET, or abnormal evacuation pattern and normal BET. A total of 64 patients were included, 49 with functional constipation (76.6%) and 15 with IBS-C (23.4%). In MR defecography, 47 patients had structural alterations (73.4%) and 15 had dyssynergia (23.4%). Overall, 19 patients were diagnosed with dyssynergic defecation (29.7%). Comparing the findings of HD-ARM and BET with MR defecography: in group 1 ( n = 20), 15 patients had structural alterations (75.0%); in group 2 ( n = 11), 8 had structural alterations (72.7%); and in group 3 ( n = 33), 22 patients only had structural alterations (66.7%), 6 only had dyssynergic defecation (18.2%), and 2 had both (6.0%). MR defecography allowed the diagnosis of dyssynergic defecation in 8 patients (24.2%). One third of patients with functional constipation and IBS-C had dyssynergic defecation and three quarters had relevant structural anorectal alterations. Therefore, it is important to combine MR defecography with HD-ARM and BET in the study of constipation.

Acupuncture-like transcutaneous electrical nerve stimulation for patients with irritable bowel syndrome: Pilot mixed-methods study.

Visceral hypersensitivity and impaired intestinal barrier function are key features in the pathophysiology of irritable bowel syndrome (IBS). Activation of central orexin signaling has been shown to ameliorate these gastrointestinal disturbances via vagal pathways mediated by brain orexin and central muscarinic receptors. Given that several studies suggest that L-carnitine, a naturally occurring amino acid, can activate orexin signaling, we hypothesized that L-carnitine attenuates these gastrointestinal abnormalities in a rat model of IBS. Visceral pain thresholds to colonic balloon distension were evaluated by electromyographic recordings of abdominal muscle contractions. Colonic permeability was assessed by measuring Evans blue uptake in lipopolysaccharide (LPS) and corticotropin-releasing factor (CRF) -induced IBS models in male Sprague-Dawley rats. Intragastric administration of L-carnitine (3-200 mg kg-1 day-1 for 3 days) dose-dependently prevented LPS-induced visceral hypersensitivity and colonic hyperpermeability, and attenuated these changes induced by CRF. Intracisternal administration of SB-334867, an orexin 1 receptor antagonist, abolished the effects of L-carnitine in the LPS model. Moreover, atropine, sulpiride, a dopamine D2 receptor antagonist, and NG-nitro-L-arginine methyl ester, a nitric oxide synthesis inhibitor, but not scopolamine butylbromide, a peripheral muscarinic receptor antagonist, blocked the effects of L-carnitine. Additionally, compound C, an AMPK inhibitor, and GW9662, a PPAR-γ antagonist, also abolished L-carnitine's effects. L-Carnitine prevents visceral hypersensitivity and colonic hyperpermeability in IBS models via mechanisms involving brain orexin, as well as central muscarinic, dopamine D2, nitric oxide, AMPK, and PPAR-γ signaling. These findings suggest that L-carnitine may represent a promising therapeutic option for IBS.

Sex-specific effects of chronic electrical acustimulation and sacral nerve stimulation in a rodent model of irritable bowel syndrome.

Delineating key determinants of health-related quality of life (HrQoL) in patients with disorders of the gut-brain-interaction (DGBI) remains challenging due to complex interplay of socioeconomic, psychological, and clinical factors. This exploratory comparative study aimed to identify factors and latent patient-profiles associated with generic and condition-specific HrQoL across different DGBI. Data from 4 clinical patient-cohorts were analyzed, including patients with functional dyspepsia ([FD]; n = 73), fecal incontinence ([FI]; n = 72), and irritable bowel syndrome ([IBS]; n = 419; 2 cohorts). Participants completed questionnaires on gastrointestinal (GI) symptoms, psychological factors, generic HrQoL (EQ-5D-5L), and condition-specific HrQoL. Finite mixture modeling identified latent clusters, and multivariate regression assessed factors associated with HrQoL outcomes. In patients with IBS and FD, higher depression scores and GI symptom severity were significantly associated with lower generic and condition-specific HrQoL (P < .001). In both FI and IBS cohorts, higher anxiety scores were associated with reduced HrQoL. Finite mixture modeling identified distinct latent clusters-2 in FD and FI cohorts, and 3 in IBS cohort-primarily defined by psychological comorbidity. Latent clusters with higher anxiety and depression scores showed markedly lower HrQoL outcomes. In contrast, socioeconomic and lifestyle factors appeared less relevant. There were no significant associations between GI symptom severity and HrQoL in FI. Psychological comorbidity appears the most salient factor associated with HrQoL, which was uniformly seen across different DGBI, whereas GI symptom severity was only associated with HrQoL in patients with FD and patients with IBS, but not in patients with FI. Although causality between psychological factors and HrQoL cannot be ascertained, our findings underscore the importance of holistic DGBI management that extends beyond symptom control to encompass the full spectrum of patient experience.

Enteral formulas are an essential part of nutrition support to prevent or treat malnutrition and minimize hospital length of stay (LOS). Yet not all formulas are tolerated and may leave nutritional needs unmet. Unique pea protein plant-based formulas (PPPBF) are nutritionally complete and have accumulated evidence of good tolerance, but impact on health economic outcomes (HEO) is largely unknown. Aim: To examine differences in patient and clinical characteristics and HEOs of hospitalized adults using PPPBF versus dairy and/or soy protein (DSP) formulas to inform further research. Materials & methods: Retrospective comparative cohort study examined real-world data (Premier Healthcare Database) from adults (≥18year) admitted to US hospitals who were prescribed a formula between 1 January 2020 and 30 September 2023. Patient and clinical characteristics and HEOs were compared between the PPPBF and DSP groups by unadjusted descriptive analysis. Results: Preliminary analyses were conducted on inpatients (n=65,338 DSP; n=243 PPPBF) from 60 US hospitals. PPPBF (versus DSP) group was younger (mean [SD] 63.6 [17.0] vs 66.7 [17.3]years; p=0.006) and had a higher diagnosis rate for malnutrition, weight loss, food allergies, irritable bowel syndrome and/or inflammatory bowel disease on admission. Overall, formula intake was primarily oral but higher in PPPBF versus DSP (100 vs 78.3%, p<0.001). Charlson Comorbidity Index indicated PPPBF (versus DSP) was sicker (median 4.0 vs 3.0; p<0.001). Yet PPPBF group had shorter LOS (by ∼2days; p<0.001) and lower mortality rate by discharge (5.8% vs 11.5%; p=0.005) without significant difference in 90-day readmission/outpatient visit rates after discharge (unadjusted comparisons). Conclusion: Preliminary evidence in hospitalized adults observed a shorter LOS in PPPBF users, despite higher baseline acuity and without significant difference in readmission/outpatient visit rates compared (unadjusted) to DSP users. Adjusted analyses and further research are needed.

Post-infectious irritable bowel syndrome (PI-IBS) is defined by persistent gastrointestinal symptoms that follow recovery from an episode of infectious enteritis, which worsen after experiencing psychological stress. Mucosal neurite outgrowth stimulated by neurotrophins and serotonin/5-hydroxytryptamine receptor subtype 7 (5-HT7) activation is linked to visceral hypersensitivity. Rifaximin (RFX) is a poorly absorbed antibiotic that improves IBS symptoms; however, the exact mechanisms remain unclear. The aims are to evaluate changes in microbiota and neuroplasticity in PI-IBS mice after RFX treatment, and the analgesic effects of combined treatment with a novel 5-HT7 antagonist CYY1005 (CYY). A mouse model with dual triggers of Giardia postinfection and water avoidance stress exhibited intestinal hyperalgesia, as measured by visceromotor responses (VMRs). Higher Shannon diversity and increased relative abundances of Lachnospiraceae, Deholobactericeae, and Ruminococcus gnavus were observed in the microbiota of PI-IBS mice, which were restored to baseline after RFX treatment. Reduced VMRs were associated with attenuated mucosal neurite outgrowth and brain-derived neurotrophic factor (BDNF) expression after RFX treatment. BDNF/TrkB activation induced mTOR-dependent nerve fiber elongation and upregulated tryptophan hydroxylase 2 and 5-HT7 expression via Rac1/ROCK pathway in SH-SY5Y neuron cultures. Combined treatment with RFX and CYY reduced VMRs to levels comparable to those of the control groups. Lastly, bacteria-free colonic mouse supernatants induced neurite elongation in SH-SY5Y cells, which was inhibited by neutralizing anti-BDNF antibodies. In conclusion, microbiota restoration by RFX treatment attenuated BDNF-induced neurite outgrowth and alleviated visceral hypersensitivity in mice. Analgesic combinations of RFX and a 5-HT7 receptor antagonist reduced intestinal nociception to baseline levels.

This review critically examines the therapeutic potential of Glycyrrhiza glabra (licorice) and its bioactive compounds in supporting gastrointestinal health. The botanical profile, historical medicinal applications, and principal bioactive compounds, including glycyrrhizin, flavonoids, and polysaccharides, are described. Mechanistic insights reveal that G. glabra exerts multifaceted actions, including anti-inflammatory, antioxidant, immunomodulatory, barrier-enhancing, and microbiota-regulating effects, which contribute to the maintenance of intestinal homeostasis. An extensive evaluation of experimental and clinical studies demonstrates protective roles for G. glabra in disorders such as inflammatory bowel disease, gastritis, peptic ulcer disease, and irritable bowel syndrome. While clinical investigations and meta-analyses validate its symptom-alleviating properties and favorable safety profile at recommended dosages, potential adverse effects and contraindications warrant consideration. This review concludes by outlining current research gaps and highlighting future directions, emphasizing the need for rigorous clinical trials and mechanistic studies. Collectively, current evidence supports G. glabra as a promising phytopharmacological candidate for further investigation in the integrative management of gut inflammation, although additional clinical validation is required.

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder that requires a symptom-based treatment approach, in which dietary and lifestyle modifications play a central role in reducing symptoms and improving quality of life. Therefore, dietary strategies should be individualized. This study compared the short term effects of low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) and gluten-free diets on symptom severity, health-related quality of life, dietary intake, and anthropometric measurements in individuals with IBS. In this 3-arm, parallel-group randomized controlled trial, 63 adults diagnosed with IBS according to the Rome IV criteria were enrolled. Participants were randomly assigned to a low-FODMAP diet (n = 21), a gluten-free diet (n = 21), or a control group (n = 21). The intervention period lasted 4 weeks. Assessments were conducted at baseline and after the intervention using the IBS Symptom Severity Score (IBS-SSS), IBS Quality of Life questionnaire (IBS-QOL), IBS Visual Analog Scale, 3-day dietary intake records, and anthropometric measurements. Both intervention groups demonstrated reductions in IBS-SSS scores and improvements in IBS-QOL scores (P < .001). After adjustment for baseline values, a significant between-group difference was observed in quality of life (P < .001), whereas no significant difference was found in symptom severity (P > .05). Significant between-group differences were also observed in body weight, body mass index, waist circumference, waist-to-hip ratio, and carbohydrate intake. Low-FODMAP and gluten-free diets may improve quality of life in individuals with IBS in the short term. After adjustment for baseline values, a between-group difference was observed only in quality of life, whereas no difference was found in symptom severity. These findings suggest that both dietary interventions may represent effective nutritional strategies for the management of IBS.

To investigate the heterogeneity of treatment response in patients with concomitant Overactive Bladder (OAB) syndrome and Irritable Bowel Syndrome (IBS), including diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), and mixed-type (IBS-M), by stratifying outcomes by both treatment strategy and IBS subtype. We hypothesized that IBS subtype would predict therapeutic response and define distinct mechanistic phenotypes. In this prospective, observational cohort study (N = 144, screened from 259), patients were allocated to one of four non-randomized cohorts: OAB-Targeted Monotherapy (OAB-TM, n = 45), OAB-Targeted Dual Therapy (OAB-TD, n = 29), IBS-Targeted Monotherapy (IBS-TM, n = 47), or IBS-Targeted Dual Therapy (IBS-TD, n = 23). Outcomes included changes in OABSS, IBS-SSS, PHQ-9, GAD-7, and QOL scores over 8 weeks. Efficacy was compared using ANCOVA, adjusted for baseline scores. Objective data from uroflowmetry parameters and baseline predictors of response were analyzed. Dual therapy demonstrated superior improvement over monotherapy across all symptom, mood, and QOL domains. However, stratified analysis revealed significant heterogeneity. In the IBS-targeted cohort, the superiority of dual therapy for OAB improvement was highly significant in the IBS-D subtype but not in IBS-M or IBS-C subtypes. This corresponded to distinct baseline uroflowmetry parameters: IBS-D patients typically showed high-peak tower-shaped curves, while IBS-C patients showed staccato patterns. Furthermore, baseline anxiety (GAD-7) and depression (PHQ-9) scores significantly predicted OAB cross-organ improvement in the IBS-TM cohort. OAB-IBS comorbidity is not a monolithic entity but comprises distinct clinical phenotypes (pelvic floor-driven, central sensitization-driven, bladder-primary). These findings suggest that a uniform treatment protocol may be suboptimal, supporting a precision-medicine framework where management is tailored based on the patient's specific IBS subtype.

Cinnamon oil exhibits therapeutic potential against constipation-predominant irritable bowel syndrome (IBS-C). This study aimed to evaluate the efficacy and mechanisms of its main components-cinnamaldehyde (CAL), cinnamyl alcohol (COL), and trans-cinnamic acid (TCA)-in IBS-C. This study established an IBS-C mouse model using loperamide hydrochloride and restraint stress, and evaluated indicators such as body weight, the number of fecal pellets, fecal water content, visceral hypersensitivity, and small intestinal propulsion rate. The analysis was performed via HE staining, ELISA, Western blot, qRT-PCR, and 16S rRNA sequencing. All three components ameliorated low-grade immune cell infiltration in colonic tissue and reduced serum levels of IL-6, IL-8, and TNF-α. They also increased motilin (MTL) and acetylcholine (Ach) levels; all except trans-cinnamic acid low-dose (TCA-L) increased gastrin (Gas) levels, and all except TCA-L and trans-cinnamic acid high-dose (TCA-H) increased 5-HT levels. Cinnamaldehyde high-dose (CAL-H), cinnamyl alcohol high-dose (COL-H), and TCA-H upregulated the expression of tryptophan hydroxylase 1 (TPH1), serotonin transporter (SERT), and 5-hydroxytryptamine receptor 4 (5-HT4R) and partially modulated gut microbiota composition. CAL showed favorable effects under the present experimental conditions. The three components alleviated IBS-C symptoms partially through modulating the 5-HT signaling pathway and gut microbiota, with CAL showing the most pronounced effects under the present experimental conditions.

Irritable bowel syndrome (IBS) presents with symptoms of pain, abdominal discomfort, and altered bowel habits. Changes in the intestinal microbiota, including an increase in Enterobacteriaceae like E. coli, have been associated with IBS. The aim of this study was to evaluate the effects of IBS-associated E. coli strains on epithelial inflammatory responses, tight junction-related gene expression, and Toll-like receptor regulation in Caco-2 cells. Results showed that IBS-associated E. coli strains exhibited significantly higher invasion activity and increased production of IL-8 and TNF-α compared to H-E. coli. Furthermore, IBS-associated E. coli strains upregulated TLR-4 and TLR-5 expression and reduced the expression of tight junction proteins.

Milk extracellular vesicles attenuate pre-inflammatory bowel disease via Lactobacillus murinus-mediated TLR2 signaling modulation.

The intestinal microbiome is essential for maintaining a balanced and healthy gut environment. Certain Escherichia coli strains can disrupt it through various pathogenic factors and have been linked to gastrointestinal diseases. In this study, E. coli strains were isolated from individuals with irritable bowel syndrome (IBS) and healthy controls. Identification was performed using microbiological and molecular methods. The presence of key virulence factors, including adhesins (iha, lpfA, afaC, sfaDE, papC, focG, aafII), iron acquisition systems (chuA, iroN, fepC, irp2, iutA, ireA), hemolysin (hlyA), microcins and colicins (cva, colY), and multifunctional factors (malX, yajQ), was assessed by polymerase chain reaction. The genes lpfA, papC, iroN, ireA, cva, and malX were found to be significantly more prevalent in IBS-associated isolates following Bonferroni correction (p < 0.0031). A higher prevalence of sfaDE, focG, chuA, and hlyA was also observed, though these differences were not statistically significant. Conversely, the genes iha and irp2 were significantly more common in E. coli isolates from healthy individuals. Notably, none of the isolates harbored the afaC and aafII genes. This study demonstrates significant differences in the distribution of specific virulence genes between E. coli isolates from IBS patients and healthy individuals. The higher prevalence of specific genes in IBS isolates may contribute to their pathogenic potential, whereas the frequent occurrence of iha and irp2 in healthy individuals may suggest a role in maintaining a balanced gut microbiome. These findings highlight distinct virulence gene profiles, suggesting a potential association between these E. coli factors and IBS disease status.

Even in the absence of active inflammation, patients with inflammatory bowel diseases (IBD) frequently report symptoms consistent with irritable bowel syndrome (IBS), which may lead to restrictive dietary patterns and ultimately increase the risk of avoidant/restrictive food intake disorder (ARFID). The aim was to evaluate the prevalence of patients at risk of ARFID among individuals with quiescent IBD and IBS-type symptoms, and to evaluate its association with the FODMAP intake. A cross-sectional study was conducted on adult IBD patients followed in a tertiary Belgian center whose recent work-up showed endoscopic and biological remission as per STRIDE II criteria. Self-administered questionnaires (NIAS-Fr, SCOFF-F, FFQ-FODMAP-BE, GAD-7, PHQ-9, IBS SSS, PRO-2, HBI) were completed remotely via REDCap. Univariate and multivariate logistic regressions were performed, with the significant threshold fixed at 5%. Sixty-two patients were enrolled (65% female, 66% Crohn's disease, mean age 39 ± 14years). Overall, 16 patients (26%) were screened positive for ARFID risk. Among these 16 patients, the distribution across subscales (picky eater, small appetite, fear of eating) was as follows: 63% (10/16) fulfilled one subscale, 31% (5/16) fulfilled two subscales, 6% (1/16) fulfilled all three. Higher IBS symptom severity was associated with a higher risk of positive screening for ARFID. In a multivariate logistic regression model, positive screening for risk of ARFID was associated with mild FODMAP consumption (FFQ-FODMAP-BE < 1.80) and anxiety. One in four patients with quiescent IBD has a positive screening for ARFID. Anxiety and low FODMAP intakes are associated with positive screening.

The clinician-patient relationship is a vital component of therapeutic success in disorders of gut-brain interaction (DGBI), recently codified as the foundational "Level 1" psychosocial care within the Rome V biopsychosocial framework. This systematic review aimed to identify evidence-based methods for building and maintaining effective clinician-patient relationships in adult DGBI care. Following the PRISMA 2020 and Synthesis Without Meta-analysis (SWiM) guidelines, we searched PubMed, Cochrane CENTRAL, and Ichushi Web for studies published through January 2026. Quality assessment was performed using AMSTAR 2 and RoB 2/ROBINS-I tools, facilitated by a human-AI collaborative verification process. Twelve studies (four systematic reviews and eight primary studies) were identified. Narrative synthesis revealed that "augmented encounters," characterized by empathy, warmth, and active listening improved clinical outcomes, including symptom severity and quality of life, particularly in irritable bowel syndrome. Strategic communication providing a confident positive diagnosis and psychoeducation regarding the gut-brain axis (rather than a diagnosis of exclusion) was found to be superior for enhancing treatment adherence in functional dyspepsia. Furthermore, multidisciplinary care models (spanning from provider-delivered self-management education to fully integrated Level 3 gastropsychology) and the use of non-deceptive placebos optimized the therapeutic context. The review also identified potential cultural moderators, hypothesizing that disease-centered reassurance might play a distinct role in certain East Asian clinical settings compared to Western contexts, though this warrants further investigation. This review structurally organized multiple relational tools, highlighting their fundamental role in DGBI management. Although current evidence is heterogeneous and partly relies on indirect findings, these promising supportive strategies conceptually align with Rome V psychosocial care. Further high-quality, direct clinical studies are needed to clarify which relational strategies are most effective for specific DGBI populations and clinical contexts. CRD420251126617.

ABSTRACT Psychological treatments are effective in alleviating symptoms of irritable bowel syndrome (IBS). However, many individuals living with IBS may find psychotherapy difficult to access due to barriers such as treatment costs, limited access to trained therapists, and scalability constraints. The aim of this systematic review was to investigate whether psychotherapeutic interventions that are self-administered or involve minimal contact with a therapist are effective in reducing the severity of symptoms in patients with IBS. A search using Scopus, PubMed, Web of Science, CINAHL, SciELO and PsycINFO was conducted in January 2025. Only randomized controlled trials (RCTs) were included. The primary outcome was overall IBS symptom severity, as assessed by any validated instrument. The only measures of this construct identified across the included studies were the IBS Symptom Severity Scale (IBS-SSS) and the Gastrointestinal Symptom Rating Scale – IBS version (GSRS-IBS). Of the 2428 studies identified, nine were included. Apart from one study of expressive writing, all other types of interventions were found to have positive effects in IBS severity. Cognitive-behavioural therapy-based interventions appear particularly promising for the treatment of IBS, as they have been more extensively studied and demonstrate long-term benefits. The findings indicate that self-administered and minimal-contact psychotherapeutic interventions can effectively reduce IBS symptom severity.