Diarrhea-predominant Irritable Bowel Syndrome Research Articles

Da-Jian-Zhong decoction alleviates diarrhea-predominant irritable bowel syndrome via modulation of gut microbiota and Th17/Treg balance

Ethnopharmacological relevanceDa-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with DJZD has received increasing attention, but the underlying mechanism of action remains elusive. Aim of the studyWe aimed to evaluate the therapeutic effect of DJZD on IBS-D rats and to elucidate the underlying mechanisms. Materials and methodsAn IBS-D rats model was constructed using a two-factor superposition method of neonatal maternal separation and Senna folium aqueous extract lavage. Moreover, the effect of DJZD was evaluated based on the body weight, rectal temperature, abdominal withdrawal reflex (AWR), and Bristol stool scale score (BSS). The factors that regulate the DJZD effects on IBS-D were estimated using whole microbial genome, transcriptome sequencing (RNA-Seq), flow cytometry, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses. ResultsWe found that DJZD alleviated the symptoms of IBS-D rats, with the low-dose (2.4 g/kg) as the better ones, as shown by the higher body mass and lower AWR score and BSS. At the phylum level, the relative abundance of Bacteroidetes was obviously increased, and at the genus level, Bacteroides was increased, while that of Firmicutes_bacterium_424 and Ruminococcus gnavus was decreased in DJZD group. The significantly enriched GO terms after treatment with DJZD mainly included the immune response, positive regulation of activated T cell proliferation, and positive regulation of interleukin-17 (IL-17) production. Importantly, flow cytometry analysis further revealed that the T helper cell type 17/regulatory T cell (Th17/Treg) balance contributed to the DJZD-induced alleviation of IBS-D symptoms, as DJZD downregulated Th17/Treg ratio and Th17 cell-related cytokines IL-17 and IL-6 levels in the colon. ConclusionsThese results demonstrate that DJZD has a good therapeutic effect on IBS-D rats, probably by maintaining the homeostasis of gut microbiota and regulating Th17/Treg balance and its related inflammatory factors.

Different acupuncture and moxibustion therapies in the treatment of IBS-D with anxiety and depression: A network meta-analysis.

Currently, a variety of Western medical interventions are available for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with comorbid anxiety and depression. However, the attendant negative effects also emerge, putting pressure on healthcare resources and socio-economic structures. In recent years, the benefits of acupuncture (ACU) and moxibustion in the treatment of IBS-D with anxiety and depression have gradually emerged. However, there are many types of ACU-moxibustion-related treatments, and the aim of this study is to examine the effectiveness of different ACU-moxibustion therapies in the treatment of anxiety and depression in IBS-D patients. Searched and identified randomized controlled trials (RCTS) of ACU for the treatment of anxiety and depression in patients with irritable bowel syndrome (IBS). The search spanned from the establishment of the database until September 1, 2023. Revman 5.4 and Stata 15.0 software were used for network meta-analysis (NMA), and the included interventions were ranked by the area under the cumulative ranking curve. A total of 26 articles involving 8 interventions were included. In terms of improving HAMA score, MOX was superior to EA, combined therapies, CH, WM and placebo; In terms of improving HAMD score, MOX was superior to ACU, EA, combined therapies, WM and placebo; In terms of improving the SAS score, The combined therapies were superior to EA, CH and WM; In terms of improving SDS scores, The combined therapies were superior to EA, CH and WM; In terms of improving IBS-SSS score, The combined therapies were superior to WM; In terms of reducing recurrence rates, CH was superior to combined therapies; In terms of improving total effective rates, MOX was superior to EA, CH, WM and placebo; MOX, combined therapies, ACU and EA ranked higher in SUCRA of different outcome indicators. MOX, combined therapies, ACU and EA have certain curative effect on anxiety and depression in patients with IBS-D, and their safety is high. ACU and MOX combined with other therapies also have significant advantages in the treatment effect.

[Bile Acid Diarrhea].

Diarrhea is a very common gastrointestinal symptom, and the presence of higher concentrations of bile acid in the colon leads to bile acid diarrhea (BAD). In BAD patients, a portion of bile from the small intestine that is normally controlled by enterohepatic circulation is present at a high concentration in the lumen of the large intestine, resulting in increased motility and secretion of the large intestine. The prevalence of BAD is estimated to be 1-2% of the general population, and it comprises one-third of the instances of diarrhea-predominant irritable bowel syndrome. The clinical symptoms of BAD include chronic diarrhea, increased frequency of defecation, urgency to defecate, fecal incontinence, and cramping abdominal pain. The pathophysiology of BAD has not yet been fully elucidated. However, recent studies have reported increased intestinal permeability, shortened intestinal transit time, and changes in the intestinal microbial community to be the possible causes of BAD. Although fecal and serum bile acid tests are widely used for diagnosis, new test methods that are non-invasive, inexpensive, and have high sensitivity and specificity are needed at various institutions to facilitate the diagnosis. The selenium homo-tauro-cholic acid (SeHCAT) test is the gold standard for BAD diagnosis and severity assessment. The validation of several other serum markers, such as 7-hydroxy-4-cholesten-3-one (serum 7αC4) and the fibroblast growth factor 19 (FGF19) for use in clinical practice is ongoing. Although bile acid sequestrants are the mainstay of treatment, the development of drugs that are more effective and have better compliance is required. Farnesoid X receptor (FXR) agonists are showing promising results.

Chang-Kang-Fang alleviates diarrhea predominant irritable bowel syndrome (IBS-D) through inhibiting TLR4/NF-κB/NLRP3 pathway

Ethnopharmacological relevanceChang-Kang-Fang (CKF), originated from traditional Chinese medicine (TCM) formulas, has been utilized to treat diarrhea predominant irritable bowel syndrome (IBS-D) based on clinical experience. However, the underlying mechanism of CKF for treating IBS-D remains unclear and need further clarification. Aim of the studyThe objective of this present investigation was to validate the efficacy of CKF on IBS-D model rats and to uncover its potential mechanism for the treatment of IBS-D. Materials and methodsWe first established the IBS-D rat model through neonatal maternal separation (NMS) in combination with restraint stress (RS) and the administration of senna decoction via gavage. To confirm the therapeutic effect of CKF on treating IBS-D, abdominal withdrawal reflex (AWR) scores, the quantity of fecal pellets, and the fecal water content (FWC) were measured to evaluate the influence of CKF on visceral hypersensitivity and the severity of diarrhea symptom after the intragastric administration of CKF for 14 days. Subsequently, enzyme linked immunosorbent assay (ELISA) was applied to assess the effect of CKF on neuropeptides substance P (SP) and 5-hydroxytryptamine (5-HT), as well as inflammatory cytokines in serum and in intestinal tissues. Further, colonic pathological changes, the amount of colonic mast cells, and the expression level of occludin in rat colon tissues, were investigated by hematoxylin-eosin (HE) staining, toluidine blue staining, and immunohistochemistry, respectively. To explore the underlying mechanisms, alterations in colonic RNA transcriptomics for the normal, model, and CKF treatment groups were assessed using RNA sequencing (RNA-Seq). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB), and immunofluorescence (IF) assays were applied to validate the effect of CKF on predicted pathways in vivo and in vitro. In addition, to elucidate the potential active compounds in CKF, 11 representative components found in CKF were selected, and their anti-inflammation potentials were evaluated using LPS-treated RAW264.7 cell models. ResultsCKF treatment significantly reduced the number of fecal pellets, attenuated visceral hypersensitivity, and decreased 5-HT and SP concentrations in serum and colon tissues, along with a reduction in colonic mast cell counts, correlating with improved symptoms in IBS-D rats. Meanwhile, CKF treatment reduced the colonic inflammatory cell infiltration, lowered the levels of IL-6, TNF-α, and IL-1β in serum and colon tissues, and increased the occludin protein expression in colon tissues to improve inflammatory response and colonic barrier function. RNA-Seq, in conjugation with our previous network pharmacology analysis, indicated that CKF might mitigate the symptoms of IBS-D rats by inhibiting the Toll like receptor 4/Nuclear factor kappa-B/NLR family pyrin domain-containing protein 3 (TLR4/NF-κB/NLRP3) pathway, which was confirmed by WB, IF, and qRT-PCR experiments in vivo and in vitro. Furthermore, coptisine, berberine, hyperoside, epicatechin, and gallic acid present in CKF emerged as potential active components for treating IBS-D, as they demonstrated in vitro anti-inflammatory effects. ConclusionOur findings demonstrate that CKF effectively improves the symptoms of IBS-D rats, potentially through the inhibition of the TLR4/NF-κB/NLRP3 pathway. Moreover, this study unveils the potential bioactive components in CKF that could be applied in the treatment of IBS-D.

Modified Gwakjeongtang for Diarrhea-Predominant Irritable Bowel Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Pilot Clinical Trial.

Irritable bowel syndrome (IBS) is a chronic condition characterized by recurrent abdominal pain associated with bowel movements. Modified Gwakjeongtang (MGT), an herbal prescription rooted in traditional East Asian medicine, consists of thirteen botanical drugs known for their potential to enhance intestinal barrier function, regulate gastrointestinal motility, and exhibit anti-inflammatory and antioxidant properties. Despite a few previous clinical trials highlighting MGT's potential for IBS symptom management, limited evidence exists with placebo control. In this pilot randomized clinical trial protocol, we aim to exploratively evaluate the efficacy and safety of MGT in patients with diarrhea-predominant IBS (IBS-D) by comparing it with a placebo. A total of 60 IBS-D patients will be enrolled, and eligible participants will be randomly allocated to either the MGT or placebo groups. Over a 4-week period, they will receive MGT or placebo granules three times a day. The primary endpoint will be the overall response rate post-treatment, determined through daily assessments of abdominal pain intensity and stool consistency. This clinical trial protocol has received approval from the Korean Ministry of Food and Drug Safety for an investigational new drug application and Institutional Review Board of the Kyung Hee University Korean Medicine Hospital. The research findings will be submitted and published in international peer-reviewed journal. Clinical research information service (registration number: KCT0008523).

Prolonged Intake of Luvos Healing Earth does not alter the Composition of the Gut Microbiota in Patients with Diarrhea-predominant Irritable Bowel Syndrome and Healthy Controls.

The mineral compound Luvos Healing Earth (LHE) is a commercially available remedy empirically used for a variety of gastrointestinal disorders. The aim of this study was to investigate the possible effect of prolonged LHE therapy on gut microbiota in healthy individuals and in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). In this prospective exploratory study, a total of 20 participants, including 12 healthy controls and 8 patients with IBS-D, received treatment with LHE (Magenfein Granulat, 1 sachet bid) for 6 weeks. Fecal samples were collected for microbiota analysis in the morning fasting state at regular intervals at 6 different timepoints: 2 weeks before starting therapy (Screen), and every 2 weeks during LHE therapy (V0-V3). Additionally, a follow-up visit was scheduled 4 weeks after the end of treatment (V4). Microbiota analysis was performed using the GA-map® Dysbiosis Test Lx v2. Dysbiosis Index, bacterial diversity, as well as the balance or imbalance of functionally important bacteria were assessed. The microbiota analysis revealed an overlap in gut microbiota profiles between healthy controls and patients with IBS-D. Bacterial communities were consistently stable during the entire treatment period, and no significant variations in composition were observed 4 weeks after the end of the therapeutic intervention. There was a remarkable stability of microbiota profiles over time within each individual and a high inter-individual variation. The majority of fecal samples exhibited profiles, reflecting an eubiotic state, with no significant changes in dysbiosis index, functional bacteria profiles, or bacterial diversity. Our findings indicate intraindividual resilience of microbiota consortia during the entire study period. Prolonged intake of LHE does not cause significant alterations in fecal microbiota profiles in healthy controls and patients with IBS-D. Luvos Healing Earth does not affect the stability of gut microbial diversity and bacterial functions.

Development and Validation of a High-Performance Liquid Chromatography Method to Quantify Marker Compounds in Lysimachia vulgaris var. davurica and Its Effects in Diarrhea-Predominant Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS), a common gastrointestinal disorder worldwide, is characterized by chronic abdominal pain, bloating, and disordered defecation. IBS is associated with several factors, including visceral hypersensitivity, gut motility, and gut-brain interaction disorders. Because currently available pharmacological treatments cannot adequately improve symptoms and may cause adverse effects, the use of herbal therapies for managing IBS is increasing. Lysimachia vulgaris var. davurica (LV) is a medicinal plant used in traditional medicine to treat diarrhea. However, information on whether LV can effectively improve diarrhea-predominant IBS (IBS-D) remains limited. In this study, using an experimental mouse model of IBS-D, we elucidated the effects of the LV extract. The methanol extract of LV decreased fecal pellet output in the restraint stress- or 5-hydroxytryptamine (5-HT)-induced IBS mouse model and inhibited 5-HT-mediated [Ca2+]i increase in a dose-dependent manner. Furthermore, we developed and validated a high-performance liquid chromatography method using two marker compounds, namely, chlorogenic acid and rutin, for quality control analysis. Our study results suggest the feasibility of the methanol extract of LV for developing therapeutic agents to treat IBS-D by acting as a 5-HT3 receptor antagonist.

A multi-omics study reveals the therapeutic effect of Linderae Radix water extract on irritable bowel syndrome (IBS-D)

Linderae Radix (Lindera aggregata (Sims) Kosterm) is a traditional Chinese medicine known for its capability to regulate qi and relieve pain, particularly in the context of gastrointestinal disorders. While our previous research has demonstrated the efficacy of the Linderae Radix water extract (LRWE) in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), the precise mechanisms remain elusive. This study aims to provide a comprehensive understanding of the therapeutic effects of LRWE on IBS-D through multi-omics techniques. 16 S rRNA gene sequencing combined with LC-MS metabolomics was employed to investigate the effect of LRWE on the gut microbiota and metabolites of IBS-D rats. Spearman correlation analysis was performed on the gut microbiota and metabolites. LRWE administration significantly ameliorated IBS-D rats' symptoms, including diarrhea, visceral hypersensitivity, and low-grade intestinal inflammation. Gut microbiota analysis revealed that LRWE influenced the diversity of the gut microbiota in IBS-D rats by significantly reducing the relative abundance of Patescibacteria and Candidatus Saccharimonas, while increasing the relative abundance of Jeotgalicoccus. Serum metabolomic analysis identified 16 differential metabolites, associated with LRWE's positive effects on IBS-D symptoms, focusing on glyoxylate and dicarboxylic acid metabolism, and cysteine and methionine metabolism. Spearman analysis demonstrated a strong correlation between cecal microbiota composition and serum metabolite levels. This study elucidates that LRWE plays a crucial role in the comprehensive therapeutic approach to IBS-D by restoring the relative abundance of gut microbiota and addressing the disturbed metabolism of endogenous biomarkers. The identified bacteria and metabolites present potential therapeutic targets for IBS-D.

Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

BACKGROUND Serotonin receptor 2B (5-HT2B receptor) plays a critical role in many chronic pain conditions. The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea (IBS-D) was investigated in the present study. AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D. METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls. The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores. The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint. Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1 (TRPV1) expression were examined following 5-HT2B receptor antagonist administration. Changes in visceral sensitivity after administration of the TRPV1 antagonist were recorded. RESULTS Here, we observed greater expression of the 5-HT2B receptor in the colonic mucosa of patients with IBS-D than in that of controls, which was correlated with abdominal pain scores. Intracolonic instillation of acetic acid and wrap restraint induced obvious chronic visceral hypersensitivity and increased fecal weight and fecal water content. Exogenous 5-HT2B receptor agonist administration increased visceral hypersensitivity, which was alleviated by successive administration of a TRPV1 antagonist. IBS-D rats receiving the 5-HT2B receptor antagonist exhibited inhibited visceral hyperalgesia. Moreover, the percentage of 5-HT2B receptor-immunoreactive (IR) cells surrounded by TRPV1-positive cells (5-HT2B receptor I+) and total 5-HT2B receptor IR cells (5-HT2B receptor IT) in IBS-D rats was significantly reduced by the administration of a 5-HT2B receptor antagonist. CONCLUSION Our finding that increased expression of the 5-HT2B receptor contributes to visceral hyperalgesia by inducing TRPV1 expression in IBS-D patients provides important insights into the potential mechanisms underlying IBS-D-associated visceral hyperalgesia.

Effect of moxibustion on colonic low-grade inflammatory response in rats with diarrhea-predominant irritable bowel syndrome based on mast cell degranulation.

To observe the effects of moxibustion on colonic mast cell degranulation and inflammatory factor expression in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), and explore the potential mechanism of moxibustion in treating IBS-D. Forty-five rat pups born from 5 healthy SPF-grade pregnant SD rats, with 8 rats were randomly selected as the normal group. The remaining 37 rats were intervened with maternal separation, acetic acid enema, and chronic restraint stress to establish the IBS-D model. The successfully modeled 32 rats were then randomly assigned to a model group, a ketotifen group, a moxibustion group, and a moxibustion-medication group, with 8 rats in each group. The rats in the ketotifen group were intervened with intragastric administration of ketotifen solution (10 mL/kg); the rats in the moxibustion group were intervened with suspended moxibustion on bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37); the rats in the moxibustion-medication group were intervened with suspended moxibustion combined with intragastric administration of ketotifen solution. All interventions were administered once daily for 7 consecutive days. The diarrhea rate and minimum volume threshold of abdominal withdrawal reflex (AWR) were calculated before and after modeling, as well as after intervention. After intervention, colonic tissue morphology was observed using HE staining; colonic mucosal ultrastructure was examined by scanning electron microscopy; colonic mast cell ultrastructure was observed using transmission electron microscopy; mast cell degranulation was assessed by toluidine blue staining; serum and colonic levels of histamine, interleukin (IL)-1β, IL-6, IL-1α, trypsin-like enzyme, and protease-activated receptor 2 (PAR-2) were measured by ELISA; the Western blot and real-time quantitative PCR were employed to evaluate the protein and mRNA expression of colonic IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2; the immunofluorescence was used to detect the positive expression of histamine, IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 in the colonic tissue. Compared to the normal group, the rats in the model group exhibited extensive infiltration of inflammatory cells in colonic tissue, severe damage to the colonic mucosa, disordered arrangement of villi, reduced electron density, and a significant decrease in granule quantity within mast cells. The diarrhea rate and mast cell degranulation rate were increased (P<0.01), AWR minimum volume threshold was decreased (P<0.01); the serum and colonic levels of histamine, IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 were elevated (P<0.01); the positive expression of histamine, as well as protein, mRNA and positive expression of IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 in the colon were all elevated (P<0.01). Compared to the model group, the rats in the ketotifen group, the moxibustion group, and the moxibustion-medication group exhibited significantly reduced infiltration of inflammatory cells in colonic tissue, relatively intact colonic mucosa, orderly arranged villi, increased electron density, and an augmented number of mast cell granules; the diarrhea rate and mast cell degranulation rate were decreased (P<0.01), and AWR minimum volume threshold was increased (P<0.01); the serum and colonic levels of histamine, IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 were reduced (P<0.01); the positive expression of histamine, as well as protein, mRNA and positive expression of IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 in the colon were all decreased (P<0.01). Compared to the ketotifen group, the moxibustion group showed decreased serum levels of histamine, IL-6, and trypsin-like enzyme (P<0.01, P<0.05), as well as reduced colonic levels of IL-1β and IL-6 (P<0.01, P<0.05); the protein expression of colonic IL-1β, IL-1α, and PAR-2 was reduced (P<0.05), and the positive expression of colonic IL-1β and trypsin-like enzyme was reduced (P<0.01, P<0.05). Compared to both the ketotifen group and the moxibustion group, the moxibustion-medication group exhibited decreased diarrhea rate and mast cell degranulation rate (P<0.01), an increased AWR minimum volume threshold (P<0.01), reduced serum and colonic levels of histamine, IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 (P<0.01), decreased protein expression of colonic IL-1β, trypsin-like enzyme, and PAR-2 (P<0.01, P<0.05), reduced mRNA and positive expression of colonic IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 (P<0.01, P<0.05), and decreased positive expression of colonic histamine (P<0.01). Moxibustion on "Tianshu" (ST 25) and "Shangjuxu" (ST 37) might inhibit low-grade inflammatory reactions in the colon of IBS-D model rats. The mechanism may be related to the inhibition of histamine and trypsin-like enzyme secreted by mast cell, thereby reducing the expression of related inflammatory factors.

Probiotics plus vitamin D in irritable bowel syndrome: a prospective multicentric non-interventional study.

Patients with irritable bowel syndrome (IBS) experience recurrent symptoms and anxiety disorders that significantly impact their quality of life (QoL). The aim of the study was to assess in daily practice the benefit of the combination of three probiotic strains (Lactobacillus plantarum CETC 7484 and CETC 7485; Pediococcus acidilactici CECT 7483) plus vitamin D in patients with diarrhea-predominant IBS (IBS-D) or IBS with mixed bowel movements (IBS-M). This was a prospective, multicenter, non-interventional study in adult patients with IBS-D or IBS-M (Rome IV criteria) followed by private-practice gastroenterologists. Patients received daily one sachet of a combination of probiotics (3×109 CFU) and vitamin D (10 μg) for 42 days. The primary endpoint was the responder rate at D42 (≥50% and/or ≥100-point decrease of IBS-Severity Scoring System; IBS-SSS). Gut-related anxiety was measured with the Visceral Sensitivity Index (VSI). The full analysis set population included 246 patients (mean age, 51.2±15.4 years; women, 73.2%; IBS-D, 56.1%; IBS-M, 43.9%). At D42, among the 89 patients with evaluable data, the responder rate was 62.9% with a mean decrease of IBS-SSS of 146.6±125.9 (P<0.0001). Changes of IBS-SSS were significantly correlated with changes of IBS-QoL (r=-0.78; P<0.0001), HAD-anxiety (r=0.46; P<0.0001), HAD-depression (r=0.61; P<0.001) and VSI (r=0.74; P<0.0001). These real-life results are in line with a previous randomized clinical trial demonstrating the benefits of this combination in IBS-D and IBS-M. Symptom relief was associated with improvement of IBS-QoL, anxiety, depression and specifically gut-related anxiety.

Healthcare Utilization Patterns: Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Gastroesophageal Reflux Disease.

Limited information is available about patterns of healthcare utilization for prevalent gastrointestinal conditions and their link to symptom burden. To identify patterns of healthcare utilization among outpatients with highly prevalent gastrointestinal conditions and define the link between healthcare utilization, symptom burden, and disease group. We randomly selected patients from the gastroenterology outpatient clinic at Princess Alexandra Hospital who had chronic gastrointestinal conditions such as constipation-predominant irritable bowel syndrome (IBS-C, n = 101), diarrhea-predominant IBS (IBS-D, n = 101), mixed IBS (n = 103), inflammatory bowel disease with acute flare (n = 113), IBD in remission (n = 103), and gastroesophageal reflux disease (n = 102). All had presented at least 12months before and had a 12-month follow-up after the index consultation. Healthcare utilization data were obtained from state-wide electronic medical records over a 24-month period. Intensity of gastrointestinal symptoms was measured using the validated Structured Assessment of Gastrointestinal Symptoms (SAGIS) Scale. Latent class analyses (LCA) based on healthcare utilization were used to identify distinct patterns of healthcare utilization among these patients. LCA revealed four distinct healthcare utilization patterns across all diagnostic groups: Group A: Emergency department utilizers, Group B: Outpatient focused care utilizers, Group C: Inpatient care utilizers and Group D: Inpatient care and emergency department utilizers. LCA groups with high emergency utilization were characterized by high gastrointestinal symptom burden at index consultation regardless of condition (Mean (standard deviation)) SAGIS score Group A: 24.63 (± 14.11), Group B: 19.18 (± 15.77), Group C: 22.48 (± 17.42), and Group D: 17.59 (± 13.74, p < 0.05). Distinct healthcare utilization patterns across highly prevalent gastrointestinal conditions exist. Symptom severity rather than diagnosis, likely reflecting unmet clinical need, defines healthcare utilization.

The function of the gut microbiota-bile acid-TGR5 axis in diarrhea-predominant irritable bowel syndrome.

Visceral hypersensitivity and intestinal mucosal barrier damage are important factors that cause abnormal brain-gut interaction in diarrhea-predominant irritable bowel syndrome (IBS-D). Recently, it was found that the imbalance of the gut microbiota-bile acid axis is closely related to them. Therefore, understanding the structure and function of the gut microbiota and bile acids and the underlying mechanisms by which they shape visceral hypersensitivity and mucosal barrier damage in IBS-D is critical. An examination of intestinal feces from IBS-D patients revealed that alterations in gut microbiota and bile acid metabolism underlie IBS-D and symptom onset. We also expanded beyond existing knowledge of well-studied gut microbiota and bile acid and found that Bacteroides ovatus and chenodeoxycholic acid may be potential bacteria and bile acid involved in the pathogenesis of IBS-D. Moreover, our data integration reveals the influence of the microbiota-bile acid-TGR5 axis on barrier function and visceral hypersensitivity.

Efficacy of Glycicumarin and Isoliquiritigenin in Suppressing Colonic Peristalsis in Both an Animal Model and a Clinical Trial.

Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) show excessive peristalsis, and antispasmodic agents may be useful therapeutic agents. There are few reports on the use of Kampo medicines for the treatment of IBS-D. Shakuyakukanzoto (SKT) is a Kampo medicine that is effective against abdominal pain. We examined the relationship between SKT and intestinal peristalsis in an animal model and a prospective study. In the animal model, SKT and its components were administered from the serosal side of the colon and colonic peristalsis was evaluated using intraluminal pressure and spatiotemporal mapping before and after the administration of SKT and its components. In this clinical trial, we used abdominal ultrasonography (US) to obtain long-axis images of the sigmoid colon of 11 patients. The frequency of intestinal peristalsis was measured using US in five patients with SKT and six patients without medication after the ingestion of a test meal. The primary outcome was the frequency of peristalsis. The Clinical Trial Registry Website (Trial No. UMIN-CTR; UMIN000051547). In the animal model, peony did not suppress peristalsis frequency, but SKT (p = 0.005) and glycyrrhiza (p = 0.001) significantly suppressed peristalsis frequency compared with saline and peony. Among the glycyrrhiza components, glycycoumarin and isoliquiritigenin suppressed the peristalsis frequency compared to dimethyl sulfoxide (control) (p = 0.001, 0.01, respectively). In a clinical trial, peristalsis was significantly suppressed after oral administration in patients taking SKT (p = 0.03). Administration of SKT was found to inhibit colonic peristalsis, with glycicumarin and isoliquiritigenin being particularly relevant among its components.

The role of Weizmannia (Bacillus) coagulans LMG S-31876 in treating IBS-diarrhea.

Irritable bowel syndrome (IBS) is a common gastrointestinal condition. Some studies have shown the efficacy of probiotics in the treatment of irritable bowel syndrome (IBS). Weizmannia (Bacillus) coagulans LMG S-31876 has been marketed as a dietary ingredient, but to date, its efficacy in diarrhea-predominant irritable bowel syndrome (IBS) condition has not been clinically elucidated. Thus, a double-blind placebo-controlled multi-centered trial was planned to evaluate the safety and efficacy of Weizmannia (Bacillus) coagulans LMG S-31876 in diarrhea-predominant IBS patients. Study participants (n = 50) diagnosed with IBS prominent symptoms that include abdominal pain and other GI-related symptoms were treated with ProBC Plus (2 billion CFU) along with a placebo capsule once daily for approximately 8 weeks. Study participants were evaluated for the treatment success determined by the differences in stool consistency and frequency per day between the intervention and placebo groups over the study period. The vital signs and the biochemistry parameters were under the normal range; the other parameters showed a significant result as compared to the placebo during the study period. This study depicts a significant decline in the clinical symptoms such as abdominal pain, bloating, diarrhea, and frequency of the stool as compared to the placebo. All the parameters such as hematology, lipid profile, and vital signs were in the normal range during the supplementation of ProBC Plus for a period of 8 weeks. Furthermore, the study verified that Weizmannia (Bacillus) coagulans LMG S-31876 and its probiotic product ProBC Plus at a dose of 2 billion/CFU/day has a prominent action in the relief from the clinical symptoms of IBS-D. Therefore, the product is intended safe to utilize for IBS-related symptoms.Clinical trial registration: The clinical study has been registered with CTRI/2023/01/048644 with https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=77708&EncHid=24313.96864&userName=CTRI/2023/01/048644 [CTRI/2023/01/048644].

The alteration of mucosal bile acid profile is associated with nerve growth factor expression in mast cells and bowel symptoms in diarrhea-predominant irritable bowel syndrome.

Mucosal bile acid (BA) profile is still unestablished in diarrhea-predominant irritable bowel syndrome (IBS-D). The aim of this study was to explore colonic mucosal BAs and their associations with mucosal mast cell (MMC)-derived nerve growth factor (NGF) and bowel symptoms in IBS-D. Colonic mucosal biopsies from 36 IBS-D patients and 35 healthy controls (HCs) were obtained for targeted BA profiling. MMC count and the expression of NGF and tight junction proteins (TJPs) were examined. We found that colonic mucosal BA profile was altered in the IBS-D cohort. The proportion of primary BAs was significantly higher and that of secondary BAs was lower in IBS-D patients. According to the 90th percentile of total mucosal BA content of HCs, IBS-D patients were divided into BA-H (n = 7, 19.4%) and BA-L (n = 29, 80.6%) subgroups. BA-H patients showed significantly higher total mucosal BA content compared to BA-L subgroup and HCs. The mucosal content of 11 BA metabolites significantly increased in BA-H subgroup, e.g., cholic acid (CA) and taurocholic acid (TCA). Moreover, BA-H patients displayed significantly elevated MMC count and NGF expression, with decreased expression of TJPs (claudin-1, junctional adhesion molecule-A and zonula occludens-1). Correlation analyses revealed that mucosal TCA content positively correlated with MMC count, MMC-derived NGF levels, and abdominal pain while negatively correlated with TJP expression. In conclusion, IBS-D patients showed an altered BA profile in the colonic mucosa. Approximately 20% of them exhibit elevated mucosal BA content, which may be associated with MMC-derived NGF signaling and bowel symptoms.

Clinical Effect of Modified Shengyang Yiwei Decoction in the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome due to Spleen and Stomach Weakness

Objective: To explore the therapeutic effect of Shengyang Yiwei Decoction in patients with diarrhea-predominant irritable bowel syndrome (IBS) due to spleen and stomach weakness. Methods: 40 patients with diarrhea-predominant IBS who were treated from April 2018 to April 2020 were taken as samples. TCM (traditional Chinese medicine) syndrome differentiation found that they were all due to spleen and stomach weakness. They were randomly divided into two groups. Group A was treated with modified prescriptions of Shengyang Yiwei Decoction, while Group B was treated with Western medicine. The therapeutic effects in the two groups were compared. Results: The treatment efficacy in Group A was higher than that in Group B (P &lt; 0.05); the symptom scores of Group A such as loose stools, chills, physical weakness, poor appetite, and abdominal distension after meals were all lower than those in Group B (P&lt; 0.05); the SF-36 (36-Item Short Form Health Survey) scores of patients with diarrhea-predominant IBS in Group A were higher than those in Group B (P &lt; 0.05); the treatment satisfaction of Group A was higher than that of Group B (P&lt; 0.05). Conclusion: Treatment of diarrhea-predominant IBS patients with spleen and stomach weakness by Shengyang Yiwei Decoction can promote the disappearance of gastrointestinal discomfort symptoms, improve the quality of life, and enhance treatment efficacy. Hence, it is an efficient and feasible treatment for diarrhea-predominant IBS due to spleen and stomach weakness.

Natural products derived from herbs as promising source for diarrhea predominant-irritable bowel syndrome via gut microbiota-serotonin pathway.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, with diarrhea predominant IBS (IBS-D) as the most common subtype. Increasing evidence reported that the gut microbiota-mediated serotonin pathway plays a crucial role in the pathogenesis of IBS-D. In this study, potential herbal medicine, plant extracts and its monomers that can be employed as the candidate molecules for IBS-D through gut microbiota-mediated serotonin pathway were reviewed. The bacteria indigenous to gut microbiota regulates serotonin pathway, mainly increasing tryptophan hydroxylase (TPH) and decreasing serotonin reuptake transporter (SERT), by activating cyclooxygenase/prostaglandin E2 (COX/PGE2) signaling. It further accelerated gastrointestinal motility and visceral hyperalgesia. Herbal medicine prescription including Tongxie yaofang and Shugan decoction, as well as some monomers of flavonoid and polyphenol compounds can be regarded as the potential agents for IBS-D. The predominate mechanisms were related to regulating serotonin pathway by driving on the specific bacterial abundance (such as Firmicutes and Bacteroidetes). However, there are few reports on which specific bacteria species play a regulatory role in serotonin pathway, and most of these effective agents were only evidenced by preclinical studies. We hope this review will provide some useful directions for the treatment strategy of IBS-D.

Protective effect of Pediococcus pentosaceus Li05 on diarrhea-predominant irritable bowel syndrome in rats.

Pediococcus pentosaceus Li05 (Li05) has demonstrated potential benefits in various intestinal and liver diseases, but its potential and mechanisms in relieving diarrhea have not been understood. The objective of this research was to examine the effects and mechanisms of Li05 in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) induced by wrap restrain stress (WRS) and 4% acetic acid. The results demonstrated that Li05 effectively alleviated weight loss, visceral sensitivity and diarrhea in rats with IBS-D. It also improved intestinal and systemic inflammation by reducing the levels of chemokines and proinflammatory cytokines (GRO/KC, RANTES, IL-1β, IL-7, and IL-18). The 5-hydroxytryptamine (5-HT) signaling pathway is involved in regulating excessive intestinal motility and secretion in IBS-D. Li05 effectively reduced the expression levels of the 5-HT3B receptor (5-HT3BR) (p < 0.01) in the intestine. Additionally, Li05 intervention had a regulatory effect on the gut composition, with a decrease in the abundance of [Ruminococcus] gauvreauii group, Dubosiella, Erysipelatoclostridium and Blautia, and an increase in the abundance of Alloprevotella, Anaerotruncus and Mucispirillum. Furthermore, Li05 induced significant changes in fatty acid and amino acid metabolism in the gut of rats with IBS-D. These findings indicate that Li05 exhibits an effective improvement in IBS-D symptoms by reducing inflammation and modulating gut microbiota and metabolism. Based on the above results, Li05 holds promise as a potential probiotic for managing IBS-D.

Electroacupuncture protects the intestinal mucosal barrier in diarrhea-predominant Irritable Bowel Syndrome rats by regulating the MCs/Tryptase/PAR-2/MLCK pathway.

The pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D) is related to damage to the intestinal mucosal barrier function. Based on the Mast cell (MC)/Tryptase/Protease-activated receptor-2 (PAR-2)/Myosin light chain kinase (MLCK) pathway, this study explored the effect of electroacupuncture (EA) on IBS-D rats and its possible mechanism of protecting the intestinal mucosal barrier. The IBS-D rat model was established by mother-offspring separation, acetic acid enema, and chronic restraint stress. The efficacy of EA on IBS-D rats was evaluated by observing the rate of loose stool (LSP) and the minimum volume threshold of abdominal withdrawal reflex (AWR) in rats. Mast cells and the ultrastructure of intestinal mucosa were observed by H&E staining, toluidine blue staining, and transmission electron microscopy. The expression levels of Tryptase, PAR-2, MLCK, zonula occludens-1 (ZO-1), and Occludin in rats were detected by ELISA, qRT-PCR, and western blot. After 7 days of intervention, compared to the IBS-D group, the loose stool rates of rats in IBS-D + EA group and IBS-D + ketotifen group were decreased (P < 0.01), the minimum volume thresholds of AWR were improved (P < 0.01), the inflammation of colon tissue decreased, the number of MCs were decreased (P < 0.01), the expression of Tryptase, PAR-2, and MLCK were lowered (P < 0.01, P < 0.05), and the expression of ZO-1 and Occludin were enhanced (P < 0.01, P < 0.05). Compared to the EA group, there was no significant difference in each index between the ketotifen groups (P > 0.05). EA has a good therapeutic effect on IBS-D rats. Regulating the MCs/Tryptase/PAR-2/MLCK pathway may be a mechanism to protect the intestinal mucosal barrier.