Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome.

(1) Background: Predictors of dietary treatment response in irritable bowel syndrome (IBS) remain understudied. We aimed to investigate predictors of symptom improvement during the low FODMAP and the traditional IBS diet for four weeks. (2) Methods: Baseline measures included faecal Dysbiosis Index, food diaries with daily energy and FODMAP intake, non-gastrointestinal (GI) somatic symptoms, GI-specific anxiety, and psychological distress. Outcomes were bloating, constipation, diarrhea, and pain symptom scores treated as continuous variables in linear mixed models. (3) Results: We included 33 and 34 patients on the low FODMAP and traditional IBS diet, respectively. Less severe dysbiosis and higher energy intake predicted better pain response to both diets. Less severe dysbiosis also predicted better constipation response to both diets. More severe psychological distress predicted worse bloating response to both diets. For the different outcomes, several differential predictors were identified, indicating that baseline factors could predict better improvement in one treatment arm, but worse improvement in the other treatment arm. (4) Conclusions: Psychological, nutritional, and microbial factors predict symptom improvement when following the low FODMAP and traditional IBS diet. Findings may help individualize dietary treatment in IBS.

Non-pharmacologic strategies for the management of intestinal inflammation.

Inflammatory bowel diseases, irritable bowel syndrome, and mucositis are characterized by intestinal inflammation, but vary according to their pathological mechanisms, severity, location, and etiology. Significant intestinal inflammation that occurs in these diseases induces weight loss, nutritional depletion, and gastrointestinal tract dysfunction. Nutritional support is important in alleviating symptoms and improving patients' quality of life. In this review, we summarize some nutritional components used to manage intestinal disorders. These include fatty acids, probiotics, parabiotics, postbiotics, prebiotics, synbiotics, and low FODMAP (LFD) diets. These components and LFD diets have been studied and clinical trials have been designed to develop new strategies to alleviate intestinal inflammation and improve the quality of life. Clinical trials on their use in intestinal inflammation do not allow firm conclusions to be drawn mainly because of the heterogeneity of the dose used and the study design or their inconclusive results. However, in the majority of cases, the use of omega-3, probiotics, parabiotics, postbiotics, prebiotics, synbiotics, and LFD improve the health.

Wei Chang An pill regulates gastrointestinal motility in a bidirectional manner.

CONTEXT: Wei Chang An (WCA) is a commercial prescription developed for the coordination of gastrointestinal movement. OBJECTIVE: To investigate the role of WCA in the regulation of diarrhoea and constipation in rats. MATERIAL AND METHODS: The diarrhoea and constipation models were prepared by gavage of Folium senna and diphenoxylate hydrochloride. Rats were randomized equally (n = 6) into the normal group given saline daily, the positive group given Pinaverium Bromide (13.5 mg/kg) or Sennoside A (0.1 mg/kg) and three WCA-treated groups (22, 44, and 88 mg/kg) by gavage daily for 7 consecutive days. The effects of WCA were assessed by a series of faecal symptoms and histopathology. Gastrointestinal parameters were determined by ELISA. The effect of WCA on gastrointestinal tissues was evaluated by strip assay. Expression of ROCK-1 and MLCK was measured by RT-PCR and Western blotting. RESULTS: Data from Bristol stool form scale, diarrhoea index, visceral sensitivity, defaecation time, and intestinal propulsive rate showed that WCA protected rats against diarrhoea and constipation (p < 0.01). The up-regulation of Substance P and 5-hydroxytryptamine in diarrhoea rats and down-regulation of Substance P and vasoactive intestinal polypeptide in constipation rats were inhibited by WCA (p < 0.05). WCA stimulated the gastrointestinal strip contractions but inhibited ACh-induced contractions (p < 0.01). The decreased ROCK-1 and MLCK expression in diarrhoea rats and increased in constipation rats were suppressed by WCA (p < 0.01). CONCLUSIONS: WCA has both antidiarrhea and anti-constipation effects, suggesting its bidirectional role in gastrointestinal modulation, and providing evidence of WCA for irritable bowel syndrome treatment.

[The new guideline on irritable bowel syndrome: what is new?] / Die neue Leitlinie zum Reizdarmsyndrom: Was ändert sich?

IRRITABLE BOWEL SYNDROME: WHAT IS NEW?: The following refers only to irritable bowel syndrome (IBS) in adults. The new guideline includes a separate section on IBS for paediatric patients. Irritable bowel syndrome (IBS) presents as a heterogeneous picture with chronic abdominal complaints related to the bowel. These are usually accompanied by changes in bowel movements and lead to impaired quality of life. The genesis is multifactorial and there are complex underlying pathophysiological mechanisms associated with IBS. Thus, disturbances in various components of the gut-brain axis and the increasing importance of the microbiome can be identified. Various psychological comorbidities also play a role. DIAGNOSTICS: The diagnosis is made by a thorough anamnesis and symptom-oriented exclusion of important differential diagnoses. A subdivision into different subtypes depending on the main symptoms is beneficial for the further management of IBS patients. The diagnosis of IBS should be made as early as possible after reliable exclusion of the important differential diagnoses. If diarrhoea dominates as a symptom, a detailed differential diagnosis and functional diagnosis should be carried out. THERAPY: There is no proven causal and no established standard therapy. Due to the variable genesis and symptom manifestation of IBS, a broad spectrum of therapy options results, whereby there is no individual prediction regarding effectiveness and therefore every therapy is initially probationary. Symptom-independent general therapies that can be used for all subtypes include dietary methods (e. g. the low-FODMAP diet), probiotics, psychotherapy methods and complementary medicine. The choice of symptom-dependent drug treatments is made according to the subtype/main symptom. In the case of diarrhoea, bile acid binders, the non-absorbable antibiotic rifaximin or, in individual cases, 5-HT3-antagonists can be used in addition to loperamide. In constipation, prucalopride and linaclotide have value in addition to the use of soluble fibre and macrogol/other laxatives. For abdominal pain/cramps, studies show good results for spasmolytics, especially peppermint oil, and for tricyclic-type antidepressants. For the main symptom of flatulence, probiotics, rifaximin and especially the low-FODMAP diet can show positive results in studies.

Effect of Low FODMAPs Diet on Irritable Bowel Syndromes: A Systematic Review and Meta-Analysis of Clinical Trials.

We conducted a meta-analysis exploring the effect of a low fermentable oligo-, di-, monosaccharides, and polyols diet (LFD) on the overall symptoms, quality of life, and stool habits of irritable bowel syndrome (IBS) patients. The meta-analysis was performed using a random-effects method. The effect size was presented as weighted standardized mean difference (SMD) and 95% confidence interval (CI). Subgroup analyses were conducted to determine the potential effects of covariates on the outcome. Twenty-two papers were included. The LFD group showed a moderate reduction in symptom severity and a slight improvement in quality of life compared to the control group (SMD, -0.53 and 0.24; 95% CI, -0.68, -0.38 and 0.02, 0.47, respectively). IBS symptom improvement was consistent between subgroups stratified according to proportions of female patients, study durations, IBS subtypes, assessment methods, and control interventions. Three studies regarding stool habits change in IBS-D patients showed a significant decrease in stool frequency (mean differences [MD], -5.56/week; 95% CI, -7.40, -3.72) and a significant improvement in stool consistency (MD, -0.86; 95% CI, -1.52, -0.19) in the LFD group compared to the control group. This is the most updated meta-analysis including studies that adopted diverse control interventions such as dietary interventions, supplementation, habitual diets, and lifestyle changes.

British Society of Gastroenterology guidelines on the management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.

Xiaoyao-san, a traditional Chinese herbal formula, for the treatment of irritable bowel syndrome: A protocol for a systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a disorder which has considerable effect to patient's quality of life and social functioning. Its main symptoms include recurrent abdominal pain and/or bloating associated with abnormal stool form or frequency. The recommendable treatment of IBS is a medication including loperamide, cimetropium, tricyclic antidepressants, and selective serotonin receptor inhibitors, but it has limited effects and several side effects dissatisfy IBS patients. As an alternative therapy, Xiaoyao-san (XYS) is gaining interest for IBS patients. XYS, a traditional Chinese medicine (TCM), has wide scope of indications and it can be prescribed for various gastrointestinal disorders in TCM syndromes but there has been no systematic review on IBS. Therefore, this review aims on systematically validating the curative effect of XYS on IBS. METHODS: Electronic databases, manual search, and contact to author e-mail will be used for searching randomized controlled trials about the use of XYS for IBS. We will select studies by the predefined criteria and collect the data on study participants, interventions, control groups, outcome measurement, adverse events, and risk of bias. Primary outcome will be the efficacy rate, and secondary outcomes will be the IBS-centered indices (abdominal pain score, abdominal distension score, diarrhea or constipation score, bowel symptom severity scale), index about quality of life, and adverse events. Review Manager software and Cochrane Collaboration "risk of bias" tools will be used for meta-analysis and assessment of risk of bias. RESULTS: This review will identify the clinical evidence of XYS's effectiveness and safety for IBS according to formal evaluation aspects. CONCLUSION: This review will further support the evidence-based usage of XYS for IBS treatment. ETHICS AND DISSEMINATION: No ethical approval is required since there is no personal information collection and patient recruitment. TRIAL REGISTRATION NUMBER: Research Registry; reviewregistry986.

Herbal medicine WangShiBaoChiWan improves gastrointestinal health in mice via modulation of intestinal tight junctions and gut microbiota and inhibition of inflammation.

WangShiBoChiWan (WSBCW) is a commonly used Chinese herbal medicine for the treatment of functional gastrointestinal disorders. However, its preclinical efficacy and the mechanisms of action have not been adequately studied. The goals of this study were to evaluate the effects of WSBCW on gastrointestinal health and modulation of related biomarkers. Female C57BL mice were randomly assigned into one of the experimental groups consisting of the control, drug controls, and WSBCW at 40, 120, and 360 mg/kg BW. Whole gut transit, small intestinal motility, and intestinal barrier permeability were determined. The castor oil-induced diarrhea mouse model was used to determine the effect of WSBCW on the diarrhea type of irritable bowel syndrome (IBS-D). WSBCW increased whole gut transit and intestinal motility, improved intestinal permeability in healthy animals and alleviated diarrhea symptoms in IBS-D mice. WSBCW upregulated intestinal junction proteins, increased the abundance of Bifidobacterium genus, Desulfovibrio genus and inhibited Bacteroides fragillis group in the gut microbiota, increased intestinal villi lengths, and decreased blood levels of inflammatory cytokines. Our study provided preclinical evidence to verify the effectiveness of WSBCW in gastrointestinal health and elucidate mechanistic insights. The results warrant further investigations to evaluate the therapeutic efficacy of WSBCW on gastrointestinal disorders, such as IBS and IBD.

The Role of Acupuncture on the Gut-Brain-Microbiota Axis in Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a chronic dysfunction of the gastrointestinal tract, commonly characterized by abdominal pain or abdominal discomfort. These symptoms can substantially reduce the quality of life and work productivity of the patients. The exact pathogenesis of IBS remains unclear, as it has become apparent that multiple pathways are activated in the condition, including inflammation, immunology, neurology and psychology. Recent evidence has shown that symptoms in IBS are related to the dysfunction of the nervous system, particularly the viscerosomatic pathway, through immune-to-brain communication. The potential link between brain-gut relationships is gut microbiota. The management of IBS mostly focuses on symptomatically treating the patients. There are a wide range of standard treatments, including pharmacological to psychological interventions which are effective in some patients. Therefore, a combination of therapies including both standard and complimentary treatments, including Traditional Chinese Medicine (TCM) such as acupuncture, have been used in treating IBS patients. Several in vivo and clinical studies have demonstrated the efficacy of acupuncture in treating IBS. Increasing attention has been paid to research regarding the action mechanisms of acupuncture for IBS. This paper summarizes and discusses the possible mechanisms associated with acupuncture on the pathophysiology of IBS, including gastrointestinal (GI) motility, visceral hypersensitivity, the immune system, neurotransmitters, and the brain-gut axis. The results fromin vivo and clinical studies have been included. In addition, the effects of acupuncture on gut microbiota in IBS are included and any contradictory findings are deliberated.

ACG Clinical Guideline: Management of Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder that significantly reduces patients' quality of life. Advances in diagnostic testing and in therapeutic options for patients with IBS led to the development of this first-ever American College of Gastroenterology clinical guideline for the management of IBS using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Twenty-five clinically important questions were assessed after a comprehensive literature search; 9 questions focused on diagnostic testing; 16 questions focused on therapeutic options. Consensus was obtained using a modified Delphi approach, and based on GRADE methodology, we endorse the following: We suggest that a positive diagnostic strategy as compared to a diagnostic strategy of exclusion be used to improve time to initiating appropriate therapy. We suggest that serologic testing be performed to rule out celiac disease in patients with IBS and diarrhea symptoms. We suggest that fecal calprotectin be checked in patients with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease. We recommend a limited trial of a low fermentable oligosaccharides, disacchardies, monosaccharides, polyols (FODMAP) diet in patients with IBS to improve global symptoms. We recommend the use of chloride channel activators and guanylate cyclase activators to treat global IBS with constipation symptoms. We recommend the use of rifaximin to treat global IBS with diarrhea symptoms. We suggest that gut-directed psychotherapy be used to treat global IBS symptoms. Additional statements and information regarding diagnostic strategies, specific drugs, doses, and duration of therapy can be found in the guideline.

Study on the clinical mechanism of Tong-Xie-An-Chang Decoction in the treatment of diarrheal irritable bowel syndrome based on single-cell sequencing technology.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a kind of functional gastrointestinal disorder with obscure pathogenesis, and exploration about differential gene expression and cell heterogeneity of T lymphocytes in peripheral blood in IBS-D patients still remains unknown. Clinicians tend to use symptomatic treatment, but the efficacy is unstable and symptoms are prone to relapse. Traditional Chinese Medicine (TCM) is used frequently in IBS-D with stable and lower adverse effects. Tong-Xie-An-Chang Decoction (TXACD) has been proven to be effective in the treatment of IBS-D. However, the underlying therapeutic mechanism remains unclear. This trial aims to evaluate the clinical efficacy and safety of TXACD in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXACD based on single-cell sequencing technology. METHODS/DESIGN: This is a randomized controlled, double-blind, double-simulation clinical trial in which 72 eligible participants with IBS-D and TCM syndrome of liver depression and spleen deficiency will be randomly allocated in the ratio of 1:1 to two groups: the experimental group and the control group. The experimental group receives Tong-Xie-An-Chang Decoction (TXACD) and Pinaverium bromide tablets placebo; the control group receives pinaverium bromide tablets and TXACD placebo. Each group will be treated for 4 weeks. The primary outcome: the rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes: TCM syndrome score, adequate relief and IBS-Quality of Life Questionnaire (IBS-QOL). Mechanistic outcome is the single-cell sequencing profiling of the T lymphocytes in peripheral blood from IBS-D participants before and after the treatment and healthy individuals. DISCUSSION: This trial will prove the efficacy and safety of TXACD with high-quality evidence and provide a comprehensive perspective on the molecular mechanism of IBS-D by single-cell sequencing profiling, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXACD.

Altered resting-state functional connectivity and effective connectivity of the habenula in irritable bowel syndrome: A cross-sectional and machine learning study.

Irritable bowel syndrome (IBS) is a disorder involving dysfunctional brain-gut interactions characterized by chronic recurrent abdominal pain, altered bowel habits, and negative emotion. Previous studies have linked the habenula to the pathophysiology of negative emotion and pain. However, no studies to date have investigated habenular function in IBS patients. In this study, we investigated the resting-state functional connectivity (rsFC) and effective connectivity of the habenula in 34 subjects with IBS and 34 healthy controls and assessed the feasibility of differentiating IBS patients from healthy controls using a machine learning method. Our results showed significantly enhanced rsFC of the habenula-left dorsolateral prefrontal cortex (dlPFC) and habenula-periaqueductal grey (PAG, dorsomedial part), as well as decreased rsFC of the habenula-right thalamus (dorsolateral part), in the IBS patients compared with the healthy controls. Habenula-thalamus rsFC was positively correlated with pain intensity (r = .467, p = .005). Dynamic causal modeling (DCM) revealed significantly decreased effective connectivity from the right habenula to the right thalamus in the IBS patients compared to the healthy controls that was negatively correlated with disease duration (r = -.407, p = .017). In addition, IBS was classified with an accuracy of 71.5% based on the rsFC of the habenula-dlPFC, habenula-thalamus, and habenula-PAG in a support vector machine (SVM), which was further validated in an independent cohort of subjects (N = 44, accuracy = 65.2%, p = .026). Taken together, these findings establish altered habenular rsFC and effective connectivity in IBS, which extends our mechanistic understanding of the habenula's role in IBS.

Multi-target Treatment for Irritable Bowel Syndrome with STW 5: Pharmacological Modes of Action.

Irritable bowel syndrome (IBS) is a heterogeneous and complex functional gastrointestinal disorder with a global prevalence of approximately 11% and high geographic variation. IBS encompasses various symptom clusters considered to reflect complex patho-etiological mechanisms, and effective treatment options are limited, with most medications targeting individual mechanisms and symptoms. Therefore, multi-targeted treatment is required. IBS is currently viewed as a disorder of disturbed gut-brain interactions with abnormalities at different sites along the gut-brain axis, including altered gastrointestinal motility, visceral hypersensitivity, increased intestinal permeability, and altered gut microbiota. All of these abnormalities represent individual targets for STW 5, a herbal preparation with nine different extracts indicated for the treatment of functional dyspepsia and IBS. As a multi-targeted medicinal drug, STW 5 possesses multiple pharmacodynamic effects. Several in vitro and in vivo studies have demonstrated STW 5 efficacy on numerous IBS patho-mechanisms targeting gastrointestinal smooth muscles, visceral afferent nerves, inflammation, gut permeability, and the gut microbiome.

Human milk oligosaccharide supplementation in irritable bowel syndrome patients: A parallel, randomized, double-blind, placebo-controlled study.

OBJECTIVES: Human milk oligosaccharides safely and beneficially impact bifidobacteria abundance in healthy adults, while their effects in patients with irritable bowel syndrome (IBS) are unknown. Hence, we aimed to determine the dose of 4:1 mix of 2'-O-fucosyllactose and Lacto-N-neotetraose (2'FL/LNnT) that increases fecal bifidobacteria abundance without aggravating overall gastrointestinal symptoms in IBS patients in a randomized, double-blind, controlled study. Additionally, the impact of 2'FL/LNnT on the fecal bacterial profile was assessed. METHODS: Irritable bowel syndrome patients diagnosed according to the Rome IV criteria received placebo (glucose), or 5 g or 10 g 2'FL/LNnT for 4 weeks followed by a four-week follow-up period. Gastrointestinal Symptom Rating Scale-IBS was used to assess gastrointestinal symptom severity; fecal microbiota composition was evaluated by GA-map™ Dysbiosis Test. RESULTS: Of the included 60 patients, two (one placebo and one 10 g) discontinued prematurely. Fecal bifidobacteria abundance was increased at week 4, but not at week 8, in the 10 g group compared to the other groups. Severity of overall or individual gastrointestinal symptoms did not differ between the groups at week 4 or 8, and no symptom deterioration was seen in any of the groups. The 10 g dose influenced overall fecal microbiota composition, and responders-defined as bifidobacteria increase ≥50%-could be discriminated from non-responders based on fecal microbiota modulation. CONCLUSIONS: The 10 g dose of 2'FL/LNnT induced an increase in the beneficial Bifidobacterium spp. without aggravating gastrointestinal symptoms in patients with IBS. This approach may be worthwhile to modulate gut microbiota of IBS patients toward a healthier profile.

Tadalafil versus linaclotide in gastrointestinal dysfunction and depressive behavior in constipation-predominant irritable bowel syndrome.

BACKGROUND: Intestinal GC-C/cGMP pathway may be involved in visceral hypersensitivity and fluid secretion in irritable bowel syndrome (IBS). The guanylcyclase C agonist linaclotide, approved for IBS- constipation, is contraindicated in children as it may cause severe diarrhea. In contrast, drugs increasing cGMP by inhibiting phosphodiesterase 5 (PDE-5) are well tolerated in children with pulmonary hypertension. Accordingly, we investigated whether beneficial effects of linaclotide in IBS might be shared by PDE-5inhibitor tadalafil without the severe diarrhea reported for linaclotide. Since depression is commonly comorbid with IBS and is implicated in its pathophysiology; and since tadalafil is absorbed systemically and crosses blood brain barrier, whereas linaclotide does not, impact of both drugs on behavioral changes in IBS was also investigated. METHODS: 72 rats were divided into 6groups (control naive, control tadalafil, control linaclotide, untreated IBS, IBS tadalafil, and IBS linaclotide-treated). IBS was induced by 0 to 4 °C intragastric saline for 14 days. RESULTS: Both drugs reduced visceral hypersensitivity and colonic C fos. Tadalafil, and to a greater extent, linaclotide increased colonic cGMP, fecal pellets (8.66 ± 4.6 (IBS),versus14.8 ± 3.3(tadalafil), 20 ± 1.2(linaclotide), fecal water content (29.8 ± 5.5 (IBS), versus 47.83 ± 12.6 (tadalafil), 63.58 ± 11.6 (linaclotide) and reduced intestinal transit time (% distance travelled: 29 ± 6.1(IBS), versus 40.58 + 7.5(tadalafil), 51.83 ± 8.3(linaclotide). Tadalafil, but not linaclotide, increased hippocampal cGMP, and improved behavioral tests scores compared to linaclotide (immobility time: 97.3 ± 12.5 s (IBS) versus 68 ± 12.8(tadalafil), 80 ± 17.06 (linaclotide). CONCLUSION: Systemic PDE-5 inhibitors might be alternatives to locally acting guanyl cyclase agonists in IBS, inducing less severe diarrhea and more beneficial effects on the associated behavioral changes.

Mind-body treatments of irritable bowel syndrome symptoms: An updated meta-analysis.

Irritable bowel syndrome (IBS) is a widespread chronic functional gastrointestinal (GI) disorder having bidirectional comorbidity with psychiatric disorders. This review focuses on psychological treatment of IBS, focusing on symptom severity rather than IBS diagnostic criteria. We chose this dimensional approach in order to assess mind-body effects as an alternative or complement to conventional medical treatment, which focuses on symptom relief. We calculated the effect sizes for various psychosocial-mind-body therapies (MBTs) for IBS symptoms in both children and adults. Therapies included meditation, relaxation, yoga, autogenic training, progressive relaxation, general training in stress coping, hypnotherapy, biofeedback, psycho-education, psychodynamic psychotherapy, and cognitive behavioral therapy. We performed a meta-regression analyses and mixed effects contrasts to find various outcome differences, and we analyzed their relative efficacy in both children and adults. We found 53 studies in 50 reports describing randomized controlled trials. Medium to high effect sizes were found across all methods compared with various controls, with possibly higher effects for children. We found no systematic differences among treatment methods. Meta-regression analyses showed no significant effect for the presence of psychophysiological training, meditation or explicit exposure procedures as treatment components, although most MBTs include exposure as a nonexplicit treatment characteristic, and many relaxation techniques have meditative characteristics. We conclude that there is considerable evidence that an array of mind-body and other psychological therapies can be effective complements to medical treatment for IBS symptom severity, with little evidence for relative superiority of any particular approach. We suggest that the various methods may operate through different mechanisms.

Imaging Brain Mechanisms of Functional Somatic Syndromes: Potential as a Biomarker?

When patients present with persistent bodily complaints that cannot be explained by a symptom-linked organic pathology (medically unexplained symptoms), they are diagnosed with 'functional' somatic syndromes (FSS). Despite their prevalence, the management of FSS is notoriously challenging in clinical practice. This may be because FSS are heterogeneous disorders in terms of etiopathogenesis. They include patients with primarily peripheral dysfunction, primarily centrally driven somatic symptoms, and a mix of both. Brain-imaging studies, particularly data-driven pattern recognition methods using machine learning algorithms, could provide brain-based biomarkers for these clinical conditions. In this review, we provide an overview of our brain imaging data on brain-body interactions in one of the most well-known FSS, irritable bowel syndrome (IBS), and discuss the possible development of a brain-based biomarker for FSS. Anticipation of unpredictable pain, which commonly elicits fear in FSS patients, induced increased activity in brain areas associated with hypervigilance during rectal distention and non-distention conditions in IBS. This was coupled with dysfunctional inhibitory influence of the medial prefrontal cortex (mPFC) and pregenual anterior cingulate cortex (pACC) on stress regulation systems, resulting in the activated autonomic nervous system (ANS) and neuroendocrine system stimulated by corticotropin-releasing hormone (CRH). IBS subjects with higher alexithymia, a risk factor for FSS, showed stronger activity in the insula during rectal distention but reduced subjective sensitivity. Reduced top-down regulation of the ANS and CRH system by mPFC and pACC, discordance between the insula response to stimulation and subjective sensation of pain, and stronger threat responses in hypervigilance-related areas may be a candidate brain-based biomarker.

Desensitization of transient receptor potential vanilloid type-1 (TRPV1) channel as promising therapy of irritable bowel syndrome: characterization of the action of palvanil in the mouse gastrointestinal tract.

TRPV1 are involved in the control of the gastrointestinal (GI) functions and pain sensation. Their activation induces pain but it is followed by desensitization, which in turn causes analgesia. The studies from the last two decades indicate that TRPV1 are involved in visceral hypersensitivity in the GI tract and pathogenesis of irritable bowel syndrome (IBS). Therefore, the aim of this study is to assess the action of fast desensitizing agonist of TRPV1, palvanil (N-palmitoyl-vanillamine), in the murine GI tract and on nociception to evaluate its potential application in the therapy of IBS. The effect of palvanil on smooth muscle contractility was evaluated using organ baths. The impact of palvanil on intestinal secretion was assessed in Ussing chambers. In vivo, the action of palvanil (0.1-1 mg/kg) was assessed in whole GI transit, fecal pellet output, and colonic bead expulsion tests. The antinociceptive potency of palvanil was tested in the mustard oil-induced pain test. Palvanil inhibited colonic contractions (evoked by electrical field stimulation, EFS) and decreased the ion transport in the colon stimulated with forskolin. It did not affect secretion in experiments with veratridine. In vivo, palvanil prolonged whole GI transit at all doses tested. At the lower dose tested, it accelerated colonic motility during first 60 min following injection. By contrast, at the dose of 1 mg/kg, colonic motility was inhibited. Palvanil induced antinociceptive action at all tested doses in mustard oil-induced pain test. TRPV1 fast-desensitizing compounds, i.e., palvanil, may be promising agents in the therapy of IBS since it modulates intestinal motility and reduces visceral pain.

Current US Food and Drug Administration-Approved Pharmacologic Therapies for the Treatment of Irritable Bowel Syndrome with Diarrhea.

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain and alterations in stool form and/or frequency, leading to reduced quality of life. Pharmacologic agents currently approved by the US Food and Drug Administration for treatment of IBS with diarrhea (IBS-D) in adults are the nonsystemic antibiotic rifaximin, the mixed µ- and κ-opioid receptor agonist/δ-opioid antagonist eluxadoline, and the selective serotonin 5-HT3 antagonist alosetron (the last of which is indicated only in women with severe IBS-D refractory to conventional therapy). Both eluxadoline and alosetron are administered as chronic daily therapies; rifaximin is given as a 2-week course of treatment with repeat courses administered as needed for symptom recurrence. Presumed mechanisms of action of rifaximin include modulation of the gut microbiota, anti-inflammatory activity, normalization of visceral hypersensitivity, and reduction in intestinal permeability. Eluxadoline targets opioid receptors in the gastrointestinal (GI) tract, resulting in decreased GI motility, fluid secretion, and visceral pain perception. Alosetron antagonizes serotonergic afferent neural signals and also slows GI motility. The efficacy and safety of these agents have been investigated in several rigorous clinical trials, and it has been demonstrated that they improve global and individual IBS symptoms. This review highlights the pivotal efficacy and safety data of the three pharmacologic agents currently indicated in the USA for the management of IBS-D in adults.Funding: Salix Pharmaceuticals.