Search Results (9)

Background: The mixed type of irritable bowel syndrome (IBS-M) is characterized by recurrent constipation and diarrhea. The cause of the variability of these symptoms is not sufficiently understood. The aim of this study was to perform metagenomic and metabolic assessment of the gut microbiome in constipation and diarrheal period of IBS-M. Methods: This study included 30 women, aged 28–47 years old, with the symptoms which aligned with those of IBS-M, according to the Rome IV Criteria. Results: In both periods of the disease, the dysbiosis index (DI), the Shannon diversity index (SDI), the hydrogen–methane and ammonia breath tests, as well as the selected bacterial metabolites (-p-hydroxyphenyl acetic acid (HPA), 3-indoxyl sulfate (Indican, 3-IS)), and hippuric acid (A) in urine, were determined. The dysbiosis index (DI) in the period of constipation was 3.73 ± 0.90 points, and in the diarrheal period it did not change significantly 3.93 ± 0.75 points (p > 0.05). During the diarrheal period, the diversity of bacteria increases from 2.16 ± 0.59 to 2.74 ± 0.50 points on the Shannon dietary index (p < 0.001). The gut microbiome profile also changed, especially during the diarrheal period where an abundance of Bifidobacterium spp. and Lactobacillus spp. decreased significantly. In addition, during this period, the levels of hydrogen and ammonia in breath air increased, while the methane level decreased. The differences also concern the results of urinary metabolites, especially related to hippuric acid and indican. During the diarrheal period, the levels of hydrogen and ammonia ions increased, while the methane level decreased. The differences also concern the results of urinary metabolites, especially related to hippuric acid and indican. Conclusions: In patients with IBS-M, periodic changes in the profile and metabolism of the gut microbiome occur, which coexist with recurrent symptoms such as constipation and diarrhea. Full article

Diarrheal irritable bowel syndrome (IBS-D) is a chronic bowel condition that leads to intestinal dysfunction and is typically accompanied by diarrhea, stomach pain, and abdominal distension. Ribes nigrum L. polyphenols (RNPs), which are natural plant polyphenols, are the subject of this study, which aims to assess their potential in improving IBS-D and to explore the underlying mechanisms through a network pharmacology analysis and 16S rRNA sequencing. Next, mice models of diarrhea-predominant irritable bowel were established, and the mice with IBS-D were treated with RNPs. The effect of RNPs was then evaluated in terms of body weight, abdominal withdrawal reflex (AWR), Bristol score, fecal water percentage, diluted fecal volume, total intestinal transit time, immune index, histopathological observation, and changes in inflammatory factors. Finally, 16S rRNA sequencing and reverse q-RTPCR were utilized to evaluate the components that mediate the impact of RNPs on IBS-D. It was found that when RNP treatment was administered to mice with IBS-D, they decreased the water content in their stools, raised their immunological scores, and decreased the amount of inflammatory substances in their bodies. Moreover, through 16S rRNA sequencing, it was shown that the RNP treatment increased the relative abundances of Bacteroides, Alloprevotella, and Alistipes, which led to the remodeling of gut microbiota. In summary, RNPs significantly improved the conditions of mice with IBS-D by inhibiting the FoxO pathway and enhancing gut microbiota. This study concludes that RNPs could significantly improve the symptoms of mice with IBS-D through these means. Full article

Background: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder that causes diarrheal and intestinal barrier disruptions. Although pomegranate peel extract (PPE) has been reported for the treatment of diarrheal and intestinal inflammation, its effectiveness and mechanisms specifically for the treatment of IBS-D remain unknown. Objectives: This study aimed to explore the therapeutic effect of PPE on IBS-D and elucidate its underlying mechanisms. Methods: A high-fat diet, restraint stress, and senna gavage were combined to establish a rat model mimicking IBS-D, to evaluate the therapeutic effects of PPE. Network pharmacology analysis, serum medicinal chemistry, and transcriptomics were employed to investigate potential downstream signaling pathways. Findings were further validated through molecular docking and Western blot analysis. Results: The findings revealed that PPE significantly improved the symptoms of IBS-D, ameliorated intestinal inflammation, and promoted intestinal barrier function. The target genes in the MAPK and NF-κB signaling pathways were significantly enriched and down-regulated. Molecular docking and Western blot assays were performed to verify that PPE had a high affinity for the protein candidates in these pathways, and significantly down-regulated the expression of p-IκB, p-p65, p-JNK, p-p38, and p-ERK1/2. Conclusions: The present study is the first to demonstrate that PPE alleviates diarrheal and intestinal damage in IBS-D, potentially by inhibiting MAPK and NF-κB signaling pathways. These findings suggest that PPE may provide a novel therapeutic option for IBS-D. Full article

Background and objectives: Although a reasonable diet is essential for promoting human health, precise nutritional regulation presents a challenge for different physiological conditions. Irritable Bowel Syndrome (IBS) is characterized by recurrent abdominal pain and abnormal bowel habits, and diarrheal IBS (IBS-D) is the most common, seriously affecting patients’ quality of life. Therefore, the implementation of precise nutritional interventions for IBS-D has become an urgent challenge in the fields of nutrition and food science. IBS-D intestinal homeostatic imbalance involves intestinal flora disorganization and impaired intestinal epithelial barrier function. A familiar interaction is evident between intestinal flora and intestinal epithelial cells (IECs), which together maintain intestinal homeostasis and health. Dietary patterns, such as the Mediterranean diet, have been shown to regulate gut flora, which in turn improves the body’s health by influencing the immune system, the hormonal system, and other metabolic pathways. Methods: This review summarized the relationship between intestinal flora, IECs, and IBS-D. It analyzed the mechanism behind IBS-D intestinal homeostatic imbalance by examining the interactions between intestinal flora and IECs, and proposed a precise dietary nutrient intervention strategy. Results and conclusion: This increases the understanding of the IBS-D-targeted regulation pathways and provides guidance for designing related nutritional intervention strategies. Full article

Patients with a mixed type of irritable bowel syndrome (IBS-M) experience constipation and diarrhea, which alternate between weeks or months. The pathogenesis of this syndrome is still little understood. The aim of the study was mainly to evaluate the urinary excretion of selected tryptophan (TRP) metabolites during the constipation and diarrhea periods of this syndrome. In 36 patients with IBS-M and 36 healthy people, serum serotonin level was measured by ELISA and urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN) and indican (3-IS) were determined using the LC-MS/MS method. The levels of all above metabolites were higher in the patient group, and increased significantly during the diarrheal period of IBS-M. In particular, the changes concerned 5-HIAA (3.67 ± 0.86 vs. 4.59 ± 0.95 mg/gCr, p < 0.001) and 3-IS (80.2 ± 17.4 vs. 93.7 ± 25.1 mg/g/Cr, p < 0.001). These changes coexisted with gut microbiome changes, assessed using hydrogen-methane and ammonia breath tests. In conclusion, the variability of TRP metabolism and the gut microbiome may cause the alternation of IBS-M symptoms. Full article

Background: In patients with diarrhea-predominant irritable bowel syndrome (IBS-D), the diarrheal mechanisms are largely unknown, and they were examined in this study on colon biopsies. Methods: Electrophysiological measurements were used for monitoring functional changes in the diarrheic colon specimens. In parallel, tight junction protein expression was analyzed by Western blot and confocal laser-scanning microscopy, and signaling pathway analysis was performed using RNA sequencing and bioinformatics. Results: Epithelial resistance was decreased, indicating an epithelial leak flux diarrheal mechanism with a molecular correlate of decreased claudin-1 expression, while induction of active anion secretion and impairment of active sodium absorption via the epithelial sodium channel, ENaC, were not detected. The pathway analysis revealed activation of barrier-affecting cytokines TNF-α, IFN-γ, IL-1β and IL-4. Conclusions: Barrier dysfunction as a result of epithelial tight junction changes plays a role in IBS-D as a pathomechanism inducing a leak flux type of diarrhea. Full article

Treatment of functional digestive disorders is not always effective. Therefore, a search for new application points for potential drugs is perspective. Our aim is to evaluate the effect of rebamipide on symptom severity, intestinal barrier status, and intestinal microbiota composition and function in patients with diarrheal variant of irritable bowel syndrome overlapping with functional dyspepsia (D-IBSoFD). Sixty patients were randomized to receive trimebutine (TRI group), trimebutine + rebamipide (T + R group), or rebamipide (REB group) for 2 months. At the beginning and end of the study, patients were assessed for general health (SF-36), severity of digestive symptoms (Gastrointestinal Symptom Rating and 7 × 7 scales), state of the intestinal barrier, and composition (16S rRNA gene sequencing) and function (short-chain fatty acid fecal content) of the gut microbiota. The severity of most digestive symptoms was reduced in the REB and T + R groups to levels similar to that observed in the TRI group. The duodenal and sigmoidal lymphocytic and sigmoidal eosinophilic infiltration was decreased only in the REB and T + R groups, not in the TRI group. Serum zonulin levels were significantly decreased only in the REB group. A decrease in intraepithelial lymphocytic infiltration in the duodenum correlated with a decrease in the severity of rumbling and flatulence, while a decrease in infiltration within the sigmoid colon correlated with improved stool consistency and decreased severity of the sensation of incomplete bowel emptying. In conclusion, rebamipide improves the intestinal barrier condition and symptoms in D-IBSoFD. The rebamipide effects are not inferior to those of trimebutine. Full article

Eluxadoline (ELD), a recently approved drug, exhibits potential therapeutic effects in the management and treatment of IBS-D. However, its applications have been limited due to poor aqueous solubility, leading to a low dissolution rate and oral bioavailability. The current study’s goals are to prepare ELD-loaded eudragit (EG) nanoparticles (ENPs) and to investigate the anti-diarrheal activity on rats. The prepared ELD-loaded EG-NPs (ENP1-ENP14) were optimized with the help of Box–Behnken Design Expert software. The developed formulation (ENP2) was optimized based on the particle size (286 ± 3.67 nm), PDI (0.263 ± 0.01), and zeta potential (31.8 ± 3.18 mV). The optimized formulation (ENP2) exhibited a sustained release behavior with maximum drug release and followed the Higuchi model. The chronic restraint stress (CRS) was successfully used to develop the IBS-D rat model, which led to increased defecation frequency. The in vivo studies revealed a significant reduction in defecation frequency and disease activity index by ENP2 compared with pure ELD. Thus, the results demonstrated that the developed eudragit-based polymeric nanoparticles can act as a potential approach for the effective delivery of eluxadoline through oral administration for irritable bowel syndrome diarrhea treatment. Full article

Recent clinical evidence supports the efficacy of a traditional medicinal product (TMP) containing a combination of myrrh (Commiphora myrrha (Nees) Engl.), coffee charcoal (Coffea arabica L.), and chamomile flower dry extract (Matricaria chamomilla L.) in the therapy of diarrhea and inflammatory bowel disease. Mast cells seem to play a key role in the symptom generation of irritable bowel syndrome (IBS). To evaluate the use of the TMP in IBS treatment, the effects of the herbal extracts on the release of mast-cell mediators from stimulated RBL-2H3 cells were investigated. Therefore, degranulation was induced by phorbol-12-myristate-13-acetate (PMA) and calcium ionophore A13187 (CI) or IgE stimulation, and the amounts of released β-hexosaminidase and histamine were quantified. The extracts showed no effect on the mediator release of PMA- and CI-stimulated RBL-2H3 cells. Myrrh and chamomile were able to reduce the β-hexosaminidase release of IgE-stimulated cells, while myrrh showed stronger inhibition of the mediator release than chamomile, which reduced only IgE-stimulated histamine release. Thus, these results indicate a mechanistic basis for the use of the herbal combination of myrrh, coffee charcoal, and chamomile flower extract in the symptom-oriented treatment of IBS patients with diarrheal symptoms. Full article