Patients with inflammatory bowel disease (IBD) are often prescribed antispasmodics for chronic abdominal pain. Large-scale data regarding efficacy and impact on clinical outcomes are lacking.

To examine the association between antispasmodic use and outcomes of abdominal pain and opioid use before and after propensity matching key demographic and clinical characteristics.

We used TriNetX Diamond Network, a medical and claims database. Patients were stratified by baseline abdominal pain and opioid use. Secondary outcomes were corticosteroid use, IBD-related complications and surgeries, emergency room (ER) visits, hospitalisation and mortality.

We included 85,859 patients (median age 50; 53.8% female) with IBD; 5661 used antispasmodics. On follow-up, those with antispasmodic use had higher rates of abdominal pain and opioid use (p < 0.001) regardless of baseline abdominal pain or opioid use. After matching, 5629 patients remained per group. Patients who used antispasmodics had higher rates of abdominal pain at 1 month, regardless of baseline abdominal pain. Opioid-naïve patients who used antispasmodics had higher rates of opioid use at follow-up (1.1% vs. 0.2%; p < 0.001). The likelihood of corticosteroid use, clinic visits, ER visits and hospitalisation were higher in those with antispasmodic use. No differences in IBD-related complications, surgery or mortality were observed.

Antispasmodic use in patients with IBD was associated with increased abdominal pain and opioid use in opioid-naïve patients. Antispasmodic use was associated with increased likelihood of corticosteroid use, clinic and ER visits and hospitalisation.

Irritable bowel syndrome (IBS) is prevalent and can be disabling. Many patients remain symptomatic despite behavioral and medical therapies. Psychedelic-assisted therapy (PAT), in which serotonergic agents like psilocybin are administered in a psychotherapeutic context, has shown promise for refractory psychiatric disorders, including major depressive disorder and post-traumatic stress disorder. Emerging evidence suggests PAT may also be beneficial for chronic pain conditions, including fibromyalgia, low back pain, and migraines. IBS is highly comorbid with depression, anxiety, and other chronic pain disorders, suggesting shared cognitive and neurological roots and potentially shared therapeutic targets. In this editorial, we discuss 3 lines of evidence for PAT as a treatment for IBS, under the overarching themes of (1) psychological mechanisms (the findings from historic studies of psychedelics for chronic pain and the elements of psychobiological dysfunction targeted by PAT), (2) central nervous system mechanisms (default mode network modulation and induction of neuroplasticity), and (3) the neurointestinal pathophysiology of IBS that may be modified by PAT. We argue that this evidence suggests PAT is worthy of study as a new therapy for IBS, and potentially for other disorders of gut-brain interaction (DGBI). Successful application of PAT to gastrointestinal disease would represent a major step beyond mind-body dualism, with potential implications for other functional somatic disorders.

Irritable Bowel Syndrome (IBS) is a chronic functional gastrointestinal disorder. Despite its common occurrence, the pathophysiology of IBS remains not fully understood. Emerging evidence suggests that IBS is a multifactorial condition characterized by low-grade inflammation, immune system activation, impaired gut permeability, intestinal hypersensitivity, and alterations in intestinal microbiota. Recent data have highlighted the potential role of vitamin D in modulating these underlying mechanisms. Vitamin D is known to influence various cellular processes, including the regulation of the gut microbiome, immune response modulation, and anti-inflammatory effects, which may alleviate the altered gut function observed in IBS. Research indicates that individuals with IBS often have lower levels of vitamin D compared to healthy controls, suggesting a possible link between vitamin D deficiency and IBS. Vitamin D supplementation has been associated with improvements in IBS symptoms, such as bloating, flatulence, abdominal pain, constipation, and overall quality of life. The mechanisms by which vitamin D exerts these effects may involve direct or indirect modulation of immune responses, the production of antimicrobial peptides, and the regulation of gene expression related to serotonergic metabolism. Despite these promising findings, the exact pathways through which vitamin D affects IBS pathophysiology remain unclear. The aim of this review is to outline the current knowledge and evidence regarding these mechanisms, as well as the therapeutic potential of vitamin D supplementation in IBS patients. Exploring the connection between vitamin D and IBS may pave the way for innovative interventions, enhancing both management strategies and the quality of life for those affected by the disorder.

Irritable bowel syndrome (IBS) is a common clinical functional gastrointestinal disease. It has a complex pathophysiological mechanism, in which the imbalance of gut microbiota might play an important role. Lacidophilin tablets (LH) can regulate gut microbiota, but their effect on IBS is unknown. In this study, the IBS model was established by acetic acid enema combined with the constrained stress method, and rats were fed LH for 2 weeks. LH significantly reduced visceral sensitivity and intestinal propulsion rate and improved IBS-induced anxiety and depressive behavior in IBS rats. LH elevated the expression levels of mucin 2, claudin1, and occludin, and ameliorated IBS-induced structural damage to colonic tissues. The gut microbiota analysis revealed that LH altered the structure and composition of the gut microbiota in IBS rats. In addition, LH reduced the expression levels of inflammatory factor-related genes. These results suggest that LH could significantly improve the visceral sensitivity and intestinal motility disorders of IBS rats, relieve anxiety and depression levels, and alleviate the symptoms of IBS rats by regulating gut microbiota and reducing intestinal inflammation.

Different diets have emerged as potential therapeutic options for patients with irritable bowel syndrome (IBS).

To identify predictors of improvement after a low-FODMAP, low-starch and low-sucrose diet among patients with IBS.

We performed a descriptive cross-sectional study including patients with IBS according to Rome IV criteria undertaking a social-media based program with a two-week dietary intervention. Patients completed an online survey before and after the intervention including the presence of intestinal and extra-intestinal symptoms, the IBS-SSS (irritable bowel syndrome symptoms severity scale) and the PHQ-9 (patient health questionnaire-9). Clinical improvement was defined as a decrease of at least 50% in IBS-SSS post dietary intervention. Variables associated with symptomatic response were identified with logistic regression analysis. A clinical score to predict response was created and tested with a with a receiver operating characteristic (ROC) curve analysis.

A total of 3583 patients with IBS were included. Mean IBS-SSS before and after dietary intervention was 295.5±52.32 and 240±48.66, respectively (p=0.01); 1178 (32.8%) patients showed clinical improvement. A mean basal IBS-SSS >400 (OR 3.04), chronic headache (OR 1.96), and chronic fatigue (OR 1.81) were significantly associated with symptomatic response. Patients with arthralgia (OR 0.41) and/or fibromyalgia (OR 0.33) were less likely to improve. Each variable received the following individuals scores: IBS-SSS >400: +2, chronic headache: +1.5, chronic fatigue: +1, arthralgia: -1, and fibromyalgia: -1. The ROC curve analysis of the proposed score showed an area under the curve of 0.72 (95% CI 0.69-0.76). A score ≥3 had a sensitivity of 72.64% and specificity of 60.56% for predicting symptomatic improvement.

There are clinical variables that could serve as reliable predictors of response to a low-FODMAP, low-sucrose, low-starch diet among patients with IBS. Further research is needed to understand the link between the presence of extra-intestinal symptoms and clinical improvement after dietary interventions for IBS.

We aimed to determine the prevalence of intestinal and extra-intestinal symptoms according to depression severity in a large cohort of patients with irritable bowel syndrome (IBS).

A consecutive series of patients with diagnosis of IBS according to Rome IV criteria undertaking a social-media based program (B15 program) were analyzed. The B15 program provides evidence-based dietary and non-pharmacological recommendations (i.e., mindfulness techniques and exercise) to improve gastrointestinal health. All patients completed the symptom-severity questionnaire (IBS-SSS) to determine severity of disease and the patient health questionnaire (PHQ9) to assess depressive symptoms. Patients' depression severity was stratified according to the PHQ9 score: none (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), and severe (20-27). Demographics, IBS phenotype and prevalence of intestinal and extra-intestinal symptoms were compared among groups.

A total of 15,675 patients with IBS were included; 895 (12.1%) with none, 5709 (36.4%) with mild, 4279 (27.3%) with moderate, 2457 (15.7%) with moderately severe, and 1335 (8.5%) with severe depression. Mean IBS-SSS score was significantly higher in patients with depressive symptoms (none 256.5 vs. severe 324.1, p<0.0001). IBS-M (mixed bowel habits alternating constipation and diarrhea) was more frequent in those with depression (p<0.0001). The presence of bloating, heartburn, dyspepsia, and belching were significantly more common in patients with higher levels of depression (p<0.0001). The prevalence and number of extra-intestinal symptoms were also associated with the severity of depression (p<0.0001).

The presence and severity of depression are strongly associated with the prevalence of intestinal and extra-intestinal symptoms in patients with IBS. Stratifying patients based on both their symptomatic and psychological profile could help targeting therapy.

The study was aimed to investigate the clinical effect and mechanism of Shugan-Jieyu-Jianpi (SGJYJP) formula for the treatment of irritable bowel syndrome (IBS) combined with non-alcoholic fatty liver disease (NAFLD). The clinical efficacy of SGJYJP was evaluated in 54 patients with IBS-NAFLD. The potential molecular mechanism of SGJYJP formula was investigated by network pharmacology. Animal models were constructed to explore the related mechanism. From clinical studies, the total effective rate of patients in SGJYJP group was significantly higher than that in pinaverium group. The protein expression of TGFB1 was declined in IBS-NAFLD rats, together with the increased expression of PTGS2 and TNF, which was abolished by SGJYJP treatment. SGJYJP significantly reduced the expression of TNF signalling related molecules of TRAF2, caspase-8, and elevated the expression of Bcl-xl in IBS-NAFLD animal models. SGJYJP may exert therapeutic effect on IBS-NAFLD by targeting PTGS2, TGFB1, and TNF genes and TNF signalling.

Digestive and psychiatric disorders tend to co-occur, yet mechanisms remain unclear. Leveraging genetic and transcriptomic data integration, we conduct multi-trait analysis of GWAS (MTAG) and weighted gene co-expression network analysis (WGCNA) to explore shared mechanism between psychiatric and gastrointestinal disorders. Significant genetic correlations were found between these disorders, especially in irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), depression (DEP), and neuroticism (NE). MTAG identify 60 novel pleiotropic loci for IBS and 14 for GERD, predominantly located near genes associated with neurological pathways. Further WGCNA identifies multiple co-expression modules enriched with genes involved in neurological pathways in digestive tissues, with some modules strongly preserved across brain and digestive tissues. Moreover, our network analysis suggests BSN, CELF4, and NRXN1 as central players in the regulation of the gut-brain axis (GBA). This study enhances our understanding of the GBA and underscores BSN, CELF4, and NRXN1 as crucial targets for future research.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by chronic or recurrent gastrointestinal symptoms without organic changes, and it is also a common disorder of gut-brain interaction (DGBIs).. The symptoms of IBS not only affect the quality of life for individual patients but also place a significant burden on global healthcare systems. The lack of established and universally applicable biomarkers for IBS, along with the substantial variability in symptoms and progression, presents challenges in developing effective clinical treatments. In recent years, preclinical and clinical studies have linked the pathogenesis of IBS to alterations in the composition and function of the intestinal microbiota. Within the complex microbial community of the gut, intricate metabolic and spatial interactions occur among its members and between microbes and their hosts. Amid the multifaceted pathophysiology of IBS, the role of intestinal microenvironment factors in symptom development has become more apparent. This review aims to delve into the changes in the composition and structure of the gut microbiome in individuals with IBS. It explores how diet-mediated alterations in intestinal microbes and their byproducts play a role in regulating the pathogenesis of IBS by influencing the "brain-gut" axis, intestinal barrier function, immune responses, and more. By doing so, this review seeks to lay a theoretical foundation for advancing the development of clinical therapeutics for IBS.

Irritable bowel syndrome (IBS) is the functional gastrointestinal disorder, characterized by abdominal pain and altered bowel habits. The interest in intestinal immune activation as a potential disease mechanism for IBS has increased exponentially in recent years. This study was designed to summarize the Chinese herbal medicine (CHM) that potentially exert protective effects against IBS through inhibition of intestinal immune activation. We detailed the current evidence that immune activation contributes to the pathology of IBS and discussed the potential mechanisms involved. Then, therapeutic effects and possible mechanisms related to immune response of herbal medicine prescriptions, extracts, and monomers were analyzed. The reasons leading to the aberrant and persistent immune activation noted in IBS are mainly associated with the increased number of mast cells, CD3[Formula: see text] T cells, and CD4[Formula: see text] T cells. The mechanisms mainly focused on the gut microbiota disorder induced alteration of the PGE2/COX2/SERT/5-HT, TLR4/MyD88/NF-κB, and BDNF/TrkB pathways. Most of the CHM alleviated IBS through interventions of intestinal immune activation via gut microbiota related to the TLR4/MyD88/NF-κB and SCF/c-kit pathways. We hope this review will provide some clues for the further development of novel candidate agents for IBS and other intestinal immune disorders.

The transient receptor potential vanilloid 4 channel (TRPV4) is an important member of the TRP superfamily of cation channels. The channel can be activated by different physical and chemical stimuli, such as heat, osmotic, and mechanical stress. It regulates the release of nociceptive peptides (substance P and calcitonin gene-related peptide), and mediates neurogenic inflammation, which indicates the involvement of TRPV4 as a nociceptor. Previous studies show that TRPV4 regulates the contraction of intestinal smooth muscle, mucosal barrier permeability, intestinal ion transport, activation of submucosal enteric neurons, and generation of immune cells. TRPV4 is involved in various pathophysiological activities, and altered TRPV4 expression has been detected in some intestinal diseases (IBD, IBS, intestinal tumors, etc). Evidence indicates that TRPV4 plays a noxious role in intestinal barrier function when the intestine is damaged. This review focuses on the role of the TRPV4 channel in the physiological and pathological functions of the intestine, and evaluates the potential clinical significance to target TRPV4 channel in the treatment of intestinal diseases.

Functional dyspepsia (FD) is a common digestive disease. Jianwei Xiaoshi (JWXS) tablet is composed of Radix Pseudostellariae (TZS), Pericarpium Citri Reticulatae (CP), Rhizoma Dioscoreae (SY), fired Hordei Fructus Germinatus (CMY) and Crataegi Fructus (SZ). It is a commonly used drug in the treatment of FD in China and has good therapeutic effects. However, there is very little research about the substance basis and action mechanism of JWXS tablet. In this research, ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) and network pharmacology were used to explore the substance basis and action mechanism of the JWXS tablet. Finally, 19, 79, 22, 22 and 39 constituents were identified in the extracts of TZS, CP, SY, CMY and SZ, respectively. Based on these findings, a total of 104 ingredients were identified in JWXS tablet and 29 potentially absorbed ingredients were detected in rat plasma. The results of network pharmacology indicated that the inhibition of gastric acid secretion, the regulation of gastrointestinal motility, inflammation and immune response were the key approaches for treating FD with JWXS tablet. The material basis and potential action mechanism of JWXS tablet in treating FD were comprehensively clarified for the first time. This study will improve our understanding of JWXS tablet.

Treatments targeting the gut-brain axis (GBA) are effective at reducing symptom burden in irritable bowel syndrome (IBS). The prevalence of common mental disorders and IBS-type symptom reporting is significantly higher in inflammatory bowel disease (IBD) than would be expected, suggesting potential GBA effects in this setting. Manipulation of the GBA may offer novel treatment strategies in selected patients with IBD. We present a narrative review of the bi-directional effects of the GBA in IBD and explore the potential for GBA-targeted therapies in this setting.

We searched MEDLINE, EMBASE, EMBASE Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for relevant articles published by March 2024.

The bi-directional relationship between psychological well-being and adverse longitudinal disease activity outcomes, and the high prevalence of IBS-type symptom reporting highlight the presence of GBA-mediated effects in IBD. Treatments targeting gut-brain interactions including brain-gut behavioural treatments, neuromodulators, and dietary interventions appear to be useful adjunctive treatments in a subset of patients.

Psychological morbidity is prevalent in patients with IBD. The relationship between longitudinal disease activity outcomes, IBS-type symptom reporting, and poor psychological health is mediated via the GBA. Proactive management of psychological health should be integrated into routine care. Further clinical trials of GBA-targeted therapies, conducted in selected groups of patients with co-existent common mental disorders, or those who report IBS-type symptoms, are required to inform effective integrated models of care in the future.

Introduction Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder frequently associated with psychological conditions such as stress, anxiety, and depression. Given the high-stress work environments of nurses and the lack of studies on this topic in the Al-Qassim region, this cross-sectional study aimed to investigate the prevalence of IBS and its association with anxiety and depression among nurses in this area of Saudi Arabia. The research hypothesis was that nurses with IBS would report higher levels of anxiety and depression compared to those without IBS. Methods This cross-sectional study was conducted among 96 nurses working at King Fahd Specialty Hospital (KFSH) in the Al-Qassim region. Nurses were selected using systematic sampling, with a total sample size initially calculated to be 189, but only 96 participated. Data were collected using a validated self-administered questionnaire, which included sociodemographic information and psychological assessments based on the Rome III criteria for IBS diagnosis and the Depression, Anxiety, and Stress Scales-21 (DASS-21) to measure psychological distress. Descriptive and inferential statistics were applied, with significance set at p < 0.05. Results In a sample of 96 nurses, the prevalence of IBS was found to be 19.8%, indicating a notable presence within this population. The majority of participants were female. No significant associations were observed between IBS and demographic or lifestyle factors. However, a higher prevalence of IBS was noted among nurses with more than 10 years of experience (27.3%, n=21) compared to those with less experience (10.5%, n=two), although this difference did not reach statistical significance (p=0.126). This study also revealed a high prevalence of stress, anxiety, and depression in the nurse population. Moreover, nurses diagnosed with IBS reported significantly higher levels of stress, depression, and anxiety compared to their counterparts without IBS (all p-values < 0.05). Conclusion There was a high prevalence of IBS among nurses, particularly those with higher levels of psychological distress. This study highlights the importance of developing targeted mental health interventions for nurses. However, the small sample size and cross-sectional design limit the generalizability and causality of the findings. Future studies should include larger, more diverse samples, and longitudinal designs to further explore these associations.

Diarrhea is commonly associated with irritable bowel syndrome, inflammatory bowel disease, microscopic colitis, and other gastrointestinal dysfunctions. Spontaneously occurring idiopathic chronic diarrhea is frequent in rhesus macaques, but has not been used as a model for the investigation of diarrhea or its treatment. We characterized this condition and present preliminary data demonstrating that left vagal nerve stimulation provides relief.

Stool consistency scores were followed for up to 12 years. Inflammation was assessed by plasma C-reactive protein, [18F]fluorodeoxyglucose (FDG) uptake, measured by positron emission tomography (PET), multiplex T cell localization, endoscopy and histology. The vagus was stimulated for 9 weeks in conscious macaques, using fully implanted electrodes, under wireless control.

Macaques exhibited recurrent periods of diarrhea for up to 12 years, and signs of inflammation: elevated plasma C-reactive protein, increased bowel FDG uptake and increased mucosal T helper1 T-cells. The colon and distal ileum were endoscopically normal, and histology revealed mild colonic inflammation. Application of vagal nerve stimulation to conscious macaques (10 Hz, 30 s every 3 h; 24 h a day for 9 weeks) significantly reduced severity of diarrhea and also reduced inflammation, as measured by FDG uptake and C-reactive protein.

These macaques exhibit spontaneously occurring diarrhea with intestinal inflammation that can be reduced by VNS. The data demonstrate the utility of this naturally occurring primate model to study the physiology and treatments for chronic diarrhea and the neural control circuits influencing diarrhea and inflammation that are not accessible in human subjects.

The gut-brain axis plays important roles in both gastrointestinal diseases (GI diseases) and schizophrenia (SCZ). Moreover, both GI diseases and SCZ exhibit notable abnormalities in brain subcortical volumes. However, the genetic mechanisms underlying the comorbidity of these diseases and the shared alterations in brain subcortical volumes remain unclear.

Using the genome-wide association studies data of SCZ, 14 brain subcortical volumes, and 8 GI diseases, the global polygenic overlap and local genetic correlations were identified, as well as the shared genetic variants among those phenotypes. Furthermore, we conducted multi-trait colocalization analyses to bolster our findings. Functional annotations, cell-type enrichment, and protein-protein interaction (PPI) analyses were carried out to reveal the critical etiology and pathology mechanisms.

The global polygenic overlap and local genetic correlations informed the close relationships between SCZ and both GI diseases and brain subcortical volumes. Moreover, 84 unique lead-shared variants were identified. The associated genes were linked to vital biological processes within the immune system. Additionally, significant correlations were observed with key immune cells and the PPI analysis identified several histone-associated hub genes. These findings highlighted the pivotal roles played by the immune system for both SCZ and GI diseases, along with the shared alterations in brain subcortical volumes.

These findings revealed the shared genetic architecture contributing to SCZ and GI diseases, as well as their shared alterations in brain subcortical volumes. These insights have substantial implications for the concurrent development of intervention and therapy targets for these diseases.

Irritable bowel syndrome (IBS) is a functional disorder commonly associated with extra-intestinal symptoms. However, the prevalence of these symptoms according to IBS subtype is not well established.

To compare the prevalence of extra-intestinal symptoms among patients with different subtypes of IBS.

A descriptive cross-sectional study including patients with IBS according to Rome IV criteria was performed between July 2022 and April 2023. Patients were classified according their subtype of IBS: IBS-D (diarrhea-predominant), IBS-C (constipation-predominant), and IBS-M (mixed bowel habits). Patients completed the IBS severity scoring system questionnaire (IBS-SSS) to determine severity of IBS symptoms and patient health questionnaire- 9 (PHQ-9) to define presence and severity of depressive symptoms. The prevalence of reported extra-intestinal symptoms was also assessed and compared between groups.

A total of 4862 patients with IBS were included; 608 IBS-D (12.5%), 1978 IBS-C (40.7%), and 2276 IBS-M (46.8%). Patients with IBS-C had significantly lower IBS-symptoms severity (mean IBS-SSS 290 vs. 310 and 320 for IBS-D and IBS-M, respectively, p = 0.03). The prevalence of obesity was also significantly lower in these patients (17.1% vs. 30.9% IBS-D and 27.9% IBS-M, p = 0.0001). Patients with IBS-D showed a significantly higher prevalence of food intolerance perception (9.5%, p = 0.03), history of cholecystectomy (17.8%, p = 0.03), and fecal incontinence (36.2%, p = 0.0001) as compared to the other groups. Patients with IBS-M had significantly higher mean PHQ-9 score (12.7 vs. 11.1 IBS-D and 10.5 IBS-C, p = 0.001) and prevalence of depressive symptoms (80.0%, p = 0.01). Patients with IBS-M also had higher prevalence of extra-intestinal symptoms such as arthralgia (62.4%, p = 0.0001), extremity numbness (64.5%, p = 0.0001), atopic dermatitis (28.2%, p = 0.02), and chronic cervicalgia (81.0%, p = 0.01).

The prevalence of most extra-intestinal symptoms is higher among patients with IBS-M. Further research is needed to better characterize IBS subtypes, which could potentially help refining tailored therapeutic strategies.

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, encompassing diarrhea-predominant irritable bowel syndrome (IBS-D). Here, we utilized 16S rDNA gene sequencing to identify potential microbial drivers of IBS-D.

A total of 30 healthy relatives and 27 patients with IBS-D were recruited. Clinical data and fecal samples were collected from patients and controls. 16S rDNA gene sequencing was performed to obtain fecal bacterial data. Differences in community composition were evaluated utilizing analysis of similarity (ANOSIM) using Bray-Curtis dissimilarity. The Wilcoxon rank sum test was used to compare differences in taxa and functional pathways. Finally, the key gut microbiota was identified using the random forest algorithm. Gut microbiota diversity, estimated through the Observe, Chao1, and abundance-based coverage estimator (ACE) indices, was significantly lower in the IBS-D patients than in the healthy relatives. ANOSIM analysis further confirmed significant differences in the composition of the gut microbiota between IBS-D patients and healthy relatives, with an R value of 0.106 and a P-value of 0.005. Notably, the IBS-D patients exhibited a significant enrichment of specific bacterial genera, including Fusicatenibacter, Streptococcus, and Klebsiella, which may possess potential pathogenic properties. In particular, the bacterial genus Klebsiella demonstrated a positive correlation with irritable bowel syndrome severity scoring system scores. Conversely, healthy subjects showed enrichment of bacterial genera such as Alistipes, Akkermansia, and Dialister, which may be beneficial bacteria in IBS-D. Utilizing the random forest model, we developed a discriminative model for IBS-D based on differential bacterial genera. This model exhibited impressive performance, with an area under the curve value of 0.90. Additionally, our analysis did not reveal any gender-specific differences in the microbiota community composition among IBS-D patients.

Our findings offer preliminary insights into the potential relationship between intestinal microbiota and IBS-D. The identification model for IBS-D, grounded in gut microbiota, holds promising prospects for improving early diagnosis of IBS-D.

Patients with short bowel syndrome (SBS) have multiple risk factors for eosinophilic gastrointestinal diseases (EGIDs) including increased risk for intestinal dysbiosis and food allergy compared to their counterparts with normal anatomy. However, there is limited data on the prevalence of EGIDs in children with SBS. We aimed to define the prevalence of EGIDs in an SBS cohort and its association with different risk factors via a retrospective chart review of patients with SBS at Children's National Hospital. The prevalence of eosinophilic esophagitis in our SBS cohort was 10%, eosinophilic gastritis was 4.9%, and eosinophilic enteritis was 4.9%. SBS patients with history of allergy or atopy were more likely to have esophageal and intestinal eosinophilia on biopsy than patients without allergy. The prevalence of EGIDs in our SBS cohort is significantly higher than in the general population and may be associated with allergic polarization.

The inflammatory response in ulcerative colitis (UC) could be relieved by the conventional immunomodulatory agents; 5-aminosalicylic acid, corticosteroids, or azathioprine. However, the low remission rates and the intolerance to these agents necessitate investigation of gene expression signature in UC that could influence the therapeutic efficacy of drugs, as well as the interference with persistence genes by novel therapeutic option. Three microarray datasets (GSE66407, GSE38713 and GSE14580) from the NCBI-GEO database were utilized. Differentially expressed genes between samples of patients with UC and healthy ones were analyzed using R software. In addition, in vivo study using oxazolone-induced UC in BALB/c mice was carried out to investigate the proposed therapeutic efficacy of dichloroacetate (DCA). The bioinformatics analysis revealed the persistence of NLRP3, NFATC1, and IL1B in UC despite treatment with common therapeutic agents. DCA administration to oxazolone-treated mice showed remarkable interference with those persistence genes. Western blotting analysis for NLRP3, NFATC1, nuclear/total NF-κB, and cleaved caspase-1 revealed the ability of DCA to reduce the expression levels of these proteins in oxazolone-treated mice. Additionally, the inflammatory cytokines IL-1β and IL-13 were reduced in colonic tissue by DCA treatment. The therapeutic efficacy of DCA was further confirmed by the apparent reduction in histopathological scoring, disease activity index, and the normalization of colon length. Therefore, DCA could be suggested as a novel and promising therapeutic option in UC based on its ability to interfere with the persistence of NFATC1/NLRP3/IL1B signaling. That merits further safety/toxicological pre-clinical assessment and update of bioavailability/metabolism data prior to clinical investigation.

Stress has been linked to the development of irritable bowel syndrome (IBS), and various methods have been explored to model IBS in combination with other stimuli. However, it remains unclear whether stress alone can induce IBS in animals. This study aimed to investigate the impact of chronic unpredictable mild stress (CUMS) on gastrointestinal sensation and function in mice and assess the potential of CUMS as a modeling approach for IBS. To evaluate the mice's behavior, we conducted open field test, sucrose preference test and weighed the mice, revealing that CUMS indeed induced anxiety and depression in the mice and caused weight loss. Further analyses, including fecal analysis, a total gastrointestinal transport test, and a colon propulsion test, demonstrated that CUMS led to abnormal defecation and disruptions in gastrointestinal motility in the mice. Additionally, the abdominal withdrawal reflex test indicated an increase in visceral sensitivity in CUMS-exposed mice. Histological examination using hematoxylin and eosin staining revealed no significant histological alterations in the colons of CUMS-exposed mice, but it did show a minor degree of inflammatory cell infiltration. In summary, the findings suggest that CUMS can replicate IBS-like symptoms in mice, offering a novel top-down approach to modeling IBS.

Cryptosporidium is an apicomplexan parasite that causes gastrointestinal disease in a wide variety of hosts and is associated with waterborne outbreaks. Nonetheless, the parasite is underdiagnosed. Cryptosporidium has been proposed as an etiological cause of irritable bowel syndrome (IBS) in several studies. However, the exact mechanism of pathogenesis is unknown, and no direct link has been discovered. This review will discuss several parasite-induced modifications, such as immunological, microbiome, and metabolite modifications, as well as their interactions. To summarize, Cryptosporidium causes low inflammation, dysbiosis, and unbalanced metabolism, which leads to a lack of homeostasis in the intestine in a comparable pattern to postinfectious IBS.

Shuganjianpi Therapy (SGJP), Jianpi Therapy (JP), Shugan Therapy (SG), Jianpiwenshen Therapy (JPWS), and Shuganjianpiwenshen Therapy (SGJPWS), consisting of formulas from Chinese herbal medicine (CHM), have been tremendously applied to irritable bowel syndrome (IBS). However, it remains uncertain when exploring the preferable option among different CHM therapies for diarrhea-predominant irritable bowel syndrome (IBS-D).

To compare and rank the efficacy and safety of different CHM therapies for IBS-D.

We searched randomized, double-blinded, placebo-controlled trials through mainstream databases from their inception to October 31, 2022. Eligible randomized controlled trials (RCTs) applied one of the CHM therapies as the experimental group and placebo as the control group. Two authors independently extracted data into a form and evaluated the quality of the retrieved articles by the Cochrane Risk of Bias Tool. At least one of the following outcomes was assessed: Serotonin, Neuropeptide Y (NPY), Incidence of Adverse Events (AE), and Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS) with its subscales of Severity of Abdominal Pain (SAP), Frequency of Abdominal Pain (FAP), Severity of Abdominal Distension (SAD), Dissatisfaction with Bowel Habits (DBH), and Interference with Quality of Life (IQOL). A Bayesian network meta-analysis on a random-effect model was conducted using R 4.2.2 software.

1367 records were retrieved from databases in an initial search. Fourteen studies involving six interventions with 2248 participants were identified. Provided pairwise comparisons, the surface under the cumulative ranking curve (SUCRA) ranking, and cluster analysis, JPWS was the best option for ameliorating clinical symptoms simultaneously, which included IBS-SSS, SAP, FAP, SAD, DBH, and IQOL. As for AE, JPWS contributed to fewer adverse events than others as well. In respect of serum indicators, we noticed the dominance of SGJP in regulating both serotonin and NPY.

JPWS and SGJP were the most prominent CHM therapies for IBS-D in terms of clinical symptoms, including abdominal pain, distension, bowel habits, and improvement of quality of life. The effect of JP and SG for IBS-D required further investigation. As a potential candidate, SGJP may well treat IBS-D by mediating dysmotility, visceral hypersensitivity, and the gut-brain axis with an increase of NPY and a reduction of serotonin. For safety, JPWS was ideal for the fewest adverse events in the treatment of IBS-D. On account of a small sample size and possible geographical publication bias, more double-blinded and placebo-controlled trials with larger samples worldwide would be necessary for strengthening current evidence.

Irritable bowel syndrome is a common functional gastrointestinal disorder, and it has been shown that the etiology of irritable bowel syndrome is a multifactorial complex of neurological, inflammatory, and immunological changes. There is growing evidence of low-grade chronic inflammation in irritable bowel patients. The peripheral action response of their intestinal immune factors is integrated into the central nervous system, while the microbiota interacts with the brain-gut axis contributing to the development of low-grade chronic inflammation. The objective of this review is to present a discussion about the impact of immune-brain-gut axis-inflammation interactions on irritable bowel syndrome, its clinical relevance in the course of irritable bowel syndrome disease, and possible therapeutic modalities.

The extent of gut inflammation depends largely on the gut barrier's integrity and enteric neuroimmune interactions. However, the factors and molecular mechanisms that regulate inflammation-related changes in the enteric nervous system (ENS) remain largely unexplored. Eph/ephrin signaling is critical for inflammatory response, neuronal activation, and synaptic plasticity in the brain, but its presence and function in the ENS have been largely unknown to date. This review discusses the critical role of Eph/ephrin in regulating gut homeostasis, inflammation, neuroimmune interactions, and pain pathways. Targeting the Eph/ephrin system offers innovative treatments for gut inflammation disorders, offering hope for enhanced patient prognosis, pain management, and overall quality of life.

Functional gastrointestinal disorders (FGID) are disorders of gut-brain interactions characterized by chronic recurrent gastrointestinal symptoms and are reported to be more common in obese individuals. The aim of the study was to evaluate FGID in obese children. A total of 405 children (6-18 years) were enrolled in this cross sectional study. The children were divided into two groups according to body mass index (BMI) as < 85th percentile and > 95th percentile. Diagnosis of FGID was based on ROME VI criteria. Demographic and clinical characteristics of the patients were evaluated. FGID and subgroups were determined. The mean age of the children was 12.73 ± 3.17 years; 52% (n = 211) of them was female and 47.9% (n = 194) was male. A total of 50.6% patients had BMI > 95th percentile, and 55.1% of those patients had FGID. The subgroups of FGID, functional abdominal pain disorders and functional defecation disorders were significantly more common in obese children than non-obese group (P < 0.01). Additionally, constipation-predominant irritable bowel syndrome (IBS), diarrhea-predominant IBS, functional diarrhea, and abdominal distention were significantly more common in obese children than non-obese children (P < 0.01).

 FGID in obese children was found to be increased significantly. Assessment of functional gastrointestinal symptoms in obese children will prevent unnecessary examinations.

• Functional gastrointestinal disorders are reported to be more common in obese individuals.

• Functional abdominal pain disorders and functional defecation disorders were significantly more common in obese children than non-obese group. • Constipation-predominant irritable bowel syndrome (IBS), diarrhea-predominant IBS, functional diarrhea, and abdominal distention were significantly more common in obese children than non-obese children.

More than half of patients with irritable bowel syndrome (IBS) report aggravating their symptoms with certain foods. Currently, Low fermentable oligo-, di-, and monosaccharides and polyols diet (LFD) is the most accepted dietary intervention for IBS. Recent randomized controlled trials (RCTs) have been suggested that gluten restriction may reduce the symptoms of patients with IBS. However, the results from these studies are conflicting. This study filled this knowledge gap by evaluating the impact of the gluten-free diet (GFD) on IBS symptoms.

A systematic search was carried out in Pubmed/Medline, Cochrane CENTRAL, Scopus, and Web of Science up to April 2023. A random-effect model was applied to estimate the standardized mean difference (SMD) and 95% confidence interval (95% CI) for each outcome.

A total of nine controlled trials were included in the meta-analysis. In contrast to gluten-containing diet, GFD was unable to reduce overall symptoms (SMD - 0.31; 95% CI -0.92, 0.31), bloating (SMD -0.37; 95% CI -1.03, 0.30), and quality of life (SMD -0.12, 95% CI -0.64, 0.39); but had a slight trend to reduce abdominal pain (SMD -0.68; 95% CI -1.36, -0.00). Also, LFD significantly reduced the IBS-Severity score system (SMD 0.66, 95% CI 0.31, 1.01) and improved quality of life (SMD -0.36, 95% CI -0.70, -0.01), compared to GFD.

A GFD is not robust enough to be routinely recommended for IBS patients, and its efficacy is significantly lower than that of an LFD. Only a certain subgroup of IBS patients may benefit from GFD; further studies are needed to target this subgroup.

Visceral hypersensitivity is considered a key symptom in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), both of which seriously affect health-related quality of life (HrQoL). Previous findings are mostly based on invasive procedures that may interfere with the assessment of visceral perception. The current study, therefore, investigates whether IBD and IBS are characterized by altered perception of 'natural' gastric distensions ('interoception').

Twenty IBD patients in remission (13 Crohn's disease, 7 ulcerative colitis), 12 IBS patients, and 20/12 matched healthy control (HC) individuals, respectively, underwent the water load test, in which they could drink ad libitum until the subjective thresholds of satiation (stage 1) and fullness (stage 2) were reached. Gastric motility was assessed using electrogastrography.

IBD patients drank significantly more water until satiation than IBS patients, whereas no differences between patients and HC groups were observed. Electrogastrographic patterns were comparable between groups, suggesting no pathologies in gastric motility in IBD or IBS. The amount of water consumed until satiation negatively correlated with HrQoL related to bowel symptoms in IBD patients, but was positively associated with emotional well-being in IBS patients.

Our findings implicate relative gastric hypersensitivity in IBS, and relative hyposensitivity in IBD patients, which are both related to specific HrQoL aspects.

Pain is common in inflammatory bowel disease (IBD), yet many patients feel their pain is not addressed by healthcare professionals. Listening to a patient's concerns about pain, assessing symptoms and acknowledging the impact these have on daily life remain crucial steps in addressing pain in IBD. While acute pain may be effectively controlled by pain medication, chronic pain is more complex and often pharmacological therapies, particularly opioids, are ineffective. Low-dose tricyclic antidepressants and psychological approaches, including cognitive-behavioural therapy, have shown some promise in offering effective pain management while lifestyle changes such as a trial of low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet in those with overlapping irritable bowel syndrome may also reduce pain. Patients benefit from a long-term, trusting relationship with their healthcare professional to allow a holistic approach combining pharmacological, psychological, lifestyle and dietary approaches to chronic pain. We present a practical review to facilitate management of chronic abdominal pain in IBD.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder marked by chronic abdominal pain, bloating, and irregular bowel habits. Effective treatments are still actively sought. Kappa-casein glycomacropeptide (GMP), a milk-derived peptide, holds promise because it can modulate the gut microbiome, immune responses, gut motility, and barrier functions, as well as binding toxins. These properties align with the recognized pathophysiological aspects of IBS, including gut microbiota imbalances, immune system dysregulation, and altered gut barrier functions. This review delves into GMP's role in regulating the gut microbiome, accentuating its influence on bacterial populations and its potential to promote beneficial bacteria while inhibiting pathogenic varieties. It further investigates the gut microbial shifts observed in IBS patients and contemplates GMP's potential for restoring microbial equilibrium and overall gut health. The anti-inflammatory attributes of GMP, especially its impact on vital inflammatory markers and capacity to temper the low-grade inflammation present in IBS are also discussed. In addition, this review delves into current research on GMP's effects on gut motility and barrier integrity and examines the changes in gut motility and barrier function observed in IBS sufferers. The overarching goal is to assess the potential clinical utility of GMP in IBS management.

To explore the perspectives, experience, and concerns of patients with irritable bowel syndrome (IBS) in China.

We used data mining to investigate posts shared in Baidu Tieba concerned with IBS; we collected the data through the crawler code, and mined the cleaned data's themes based on Latent Dirichlet allocation (LDA) and the Grounded theory.

We found 5746 network posts related to IBS. LDA analysis generated 20 topics, and grounded theory analysis established eight topics. Combining the two methods, we finally arranged the topics according to five concepts: difficulty in obtaining disease information; serious psychosocial problems; dissatisfied with the treatment; lack of social support; and low quality of life.

Social media research improved patient-centric understanding of patients' experiences and perceptions. Our study may facilitate doctor-patient communication and assist in the formulation of medical policies.

During the last decade, scientific interest in and consumer attention to sourdough fermentation in bread making has increased. On the one hand, this technology may favorably impact product quality, including flavor and shelf-life of bakery products; on the other hand, some cereal components, especially in wheat and rye, which are known to cause adverse reactions in a small subset of the population, can be partially modified or degraded. The latter potentially reduces their harmful effects, but depends strongly on the composition of sourdough microbiota, processing conditions and the resulting acidification. Tolerability, nutritional composition, potential health effects and consumer acceptance of sourdough bread are often suggested to be superior compared to yeast-leavened bread. However, the advantages of sourdough fermentation claimed in many publications rely mostly on data from chemical and in vitro analyzes, which raises questions about the actual impact on human nutrition. This review focuses on grain components, which may cause adverse effects in humans and the effect of sourdough microbiota on their structure, quantity and biological properties. Furthermore, presumed benefits of secondary metabolites and reduction of contaminants are discussed. The benefits claimed deriving from in vitro and in vivo experiments will be evaluated across a broader spectrum in terms of clinically relevant effects on human health. Accordingly, this critical review aims to contribute to a better understanding of the extent to which sourdough bread may result in measurable health benefits in humans.

Irritable bowel syndrome (IBS) is a complex multifactorial condition including alterations of the gut-brain axis, intestinal permeability, mucosal neuro-immune interactions, and microbiota imbalance. Recent advances proposed epigenetic factors as possible regulators of several mechanisms involved in IBS pathophysiology. These epigenetic factors include biomolecular mechanisms inducing chromosome-related and heritable changes in gene expression regardless of DNA coding sequence. Accordingly, altered gut microbiota may increase the production of metabolites such as sodium butyrate, a prominent inhibitor of histone deacetylases. Patients with IBS showed an increased amount of butyrate-producing microbial phila as well as an altered profile of methylated genes and micro-RNAs (miRNAs). Importantly, gene acetylation as well as specific miRNA profiles are involved in different IBS mechanisms and may be applied for future diagnostic purposes, especially to detect increased gut permeability and visceromotor dysfunctions. In this review, we summarize current knowledge of the role of epigenetics in IBS pathophysiology.

The Rome IV criteria have been established as an international standard for diagnosing disorders of gut-brain interaction. In this study, we aimed to examine the upper gastrointestinal (GI) endoscopic findings and symptoms of subjects with functional constipation (FC) and irritable bowel syndrome (IBS) of individuals undergoing a medical check-up.

A total of 13,729 subjects underwent a medical check-up at Osaka City University-affiliated clinic, MedCity21, between April 2018 and March 2019. Among the 5,840 subjects who underwent screening upper GI endoscopy and completed a questionnaire based on the Rome IV criteria, 5,402 subjects were consecutively enrolled after excluding subjects with a large amount of gastric residue (n = 6), those who had previously undergone partial or total gastrectomy (n = 40), or those with daily use of low-dose aspirin (n = 82), nonsteroidal anti-inflammatory drugs (n = 63), or acid secretion inhibitors (n = 308).

Robust Poisson regression analyses adjusted for age, sex, Helicobacter pylori infection status, alcohol intake, and smoking habits showed a significant association between FC and corpus erosion (adjusted prevalence ratio [aPR], 2.93; 95% confidence interval [CI], 1.51-5.67; p < 0.01) and red streaks (aPR, 3.83; 95% CI, 2.53-5.79; p < 0.01), whereas IBS was significantly associated with erosive gastritis (aPR, 8.46; 95% CI, 4.89-14.67; p < 0.01) and duodenitis (aPR, 7.28; 95% CI, 3.64-14.59; p < 0.01). Red streaks tended to be associated with IBS (aPR, 1.96; 95% CI, 1.00-3.83; p = 0.05). Subjects with IBS were the most to complain of both upper and lower GI symptoms and psychological symptoms, followed by those with FC and controls. IBS subjects with erosive gastritis or duodenitis had significantly more complaints of stomachache and feeling stressed than those without erosive gastritis or duodenitis (54.5% vs. 18.8%; p = 0.03 and 66.7% vs. 25.0%; p = 0.01).

Subjects with FC and IBS had a variety of upper GI and psychological symptoms. In the upper GI endoscopic findings, corpus erosion and red streaks were associated with FC, and erosive gastritis, duodenitis, and possibly red streaks were associated with IBS.

Percutaneous electrical nerve field stimulation (PENFS) has documented efficacy for irritable bowel syndrome (IBS) via plausible vagal neuromodulation effects. The vagus nerve may affect gut microbiome composition via brain-gut-microbiome signaling. We aimed to investigate gut microbiome alterations by PENFS therapy in adolescent IBS patients.

A prospective study of females with IBS aged 11-18 years receiving PENFS therapy for 4 weeks with pre- and post-intervention stool sampling was conducted. Outcome surveys completed pre-therapy, weekly, and post-therapy included IBS-Severity Scoring System (IBS-SSS), Visceral Sensitivity Index (VSI), Functional Disability Inventory (FDI), and the global symptom response scale (SRS). Bacterial DNA was extracted from stool samples followed by 16S rRNA amplification and sequencing. QIIME 2 (version 2022.2) was used for analyses of α and β diversity and differential abundance by group.

Twenty females aged 15.6 ± 1.62 years were included. IBS-SSS, VSI, and FDI scores decreased significantly after PENFS therapy (P < 0.0001, P = 0.0003, P = 0.0004, respectively). No intra- or interindividual microbiome changes were noted pre- versus post-therapy or between responders and non-responders. When response was defined by 50-point IBS-SSS score reduction, α diversity was higher in responders compared with non-responders at week 4 (P = 0.033). There was higher abundance of Blautia in excellent responders versus non-responders.

There were no substantial microbial diversity alterations with PENFS. Subjects with excellent therapeutic response showed an enrichment of relative abundance of Blautia, which may indicate that patients with specific microbial signature have a more favorable response to PENFS.

Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder which affects a great number of patients globally. Clinical trials and meta-analyses have evaluated different therapies for IBS. Some of them have shown that probiotics play a significant role in the management of IBS-patients. Nevertheless, results are controversial, and the efficacy of the administration of probiotics remains to be confirmed, especially in regard to which type of probiotic-strains are beneficial.

The aim of the present meta-analysis is to assess the efficacy and safety of the administration of probiotics to IBS-patients with a diagnosis based on Rome IV criteria, which is performed for the first time.

Electronic databases (Pubmed, Scopus and Cochrane) were searched until 26.01.2023 for randomized controlled trials (RCTs) studying the administration of probiotics in adult IBS-patients, who were categorized according to the Rome IV criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (ROB) 2.0. Weighted and standardized mean difference with the 95% confidence intervals were used for the synthesis of the results. Primary outcomes were the decrease of IBS-Symptom Severity Score (IBS-SSS) and decrease of abdominal pain. The secondary outcomes were the improvement in quality of life (QoL) and the decrease of bloating. Lastly, the adverse effects of probiotics were evaluated. The protocol of the study has been registered at protocols.io (DOI dx.doi.org/10.17504/protocols.io.14egn218yg5d/v1).

Six double-blind (N = 970) placebo-control RCTs fulfilled the inclusion criteria and overall, nine different strains of probiotics were examined. No significant reduction in IBS-SSS (WMD -43.2, 95% CI -87.5 to 1.0, I2 = 82.9%) was demonstrated, whereas a significant decrease regarding abdominal pain (SMD -0.94, 95% CI -1.53 to -0.35, I2 = 92,2) was shown. Furthermore, no correlation between improvement of QoL and the use of probiotics (SMD -0.64, 95% CI -1.27 to 0.00, I2 = 93,9%) was shown. However, probiotics were associated with a significant reduction in bloating (SMD -0.28, 95% CI -0.47 to -0.09, I2 = 36,0%). A qualitative synthesis was conducted about adverse events and showed that the use of probiotics' is safe without severe adverse events.

The administration of probiotics to IBS-patients demonstrated a positive effect on pain and bloating, but due to significant heterogeneity and confounding factors, that were not examined in the included studies, a definitive statement cannot be made. Moreover, probiotics did not lead to an improvement in other parameters. There is a need for larger RCTs in IBS-patients diagnosed according to Rome IV (not III) criteria and especially it is essential to be conducted RCTs which examine the administration of specific strains and have similar methodological characteristics.

The system physiology approaches that emerge in western countries in recent years echo the holistic view of ancient Traditional Chinese Medicine (TCM) practices that deal with the root, rather than only the symptoms of diseases. Particularly, TCM practices, including acupuncture, emphasize the mobilization of self-healing mechanisms to bring back body homeostasis. Acupuncture has been practiced for over two thousand years to modulate body physiology via stimulation at specific body regions (acupoints). With the development of various research on acupuncture therapy, its regulatory effect on the immune system has been gradually recognized, especially on immunological diseases, including infectious and allergic diseases. In this study, we reviewed the immunomodulatory mechanism of acupuncture and systematically integrates existing research to respectively elucidate the modulatory mechanisms of acupuncture on the innate immune system, adaptive immune system, and well-known neuroanatomical mechanisms, including intact somatosensory-autonomic reflex pathway. With the advances made in recent systems physiology studies, we now have a great opportunity to gain insight into how acupuncture modulates immunity, and subsequently improves its efficacy.

Irritable bowel syndrome (IBS) is the most prevalent disorder of brain-gut interactions that affects between 5 and 10% of the general population worldwide. The current symptom criteria restrict the diagnosis to recurrent abdominal pain associated with altered bowel habits, but the majority of patients also report non-painful abdominal discomfort, associated psychiatric conditions (anxiety and depression), as well as other visceral and somatic pain-related symptoms. For decades, IBS was considered an intestinal motility disorder, and more recently a gut disorder. However, based on an extensive body of reported information about central, peripheral mechanisms and genetic factors involved in the pathophysiology of IBS symptoms, a comprehensive disease model of brain-gut-microbiome interactions has emerged, which can explain altered bowel habits, chronic abdominal pain, and psychiatric comorbidities. In this review, we will first describe novel insights into several key components of brain-gut microbiome interactions, starting with reported alterations in the gut connectome and enteric nervous system, and a list of distinct functional and structural brain signatures, and comparing them to the proposed brain alterations in anxiety disorders. We will then point out the emerging correlations between the brain networks with the genomic, gastrointestinal, immune, and gut microbiome-related parameters. We will incorporate this new information into a systems-based disease model of IBS. Finally, we will discuss the implications of such a model for the improved understanding of the disorder and the development of more effective treatment approaches in the future.