A randomized, double-blinded, placebo-controlled clinical trial on Lactobacillus-containing cultured milk drink as adjuvant therapy for depression in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is frequently linked with coexisting mental illnesses. Our previous study discovered that 32.1% of IBS patients had subthreshold depression (SD), placing them at higher risk of developing major depression. Gut microbiota modulation through psychobiotics was found to influence depression via the gut-brain axis. However, the efficacy of lessening depression among IBS patients remains ambiguous. The study's aim was to investigate the roles of cultured milk drinks containing 109 cfu Lactobacillus acidophilus LA-5 and Lactobacillus paracasei L. CASEI-01 on depression and related variables among IBS participants with SD. A total of 110 IBS participants with normal mood (NM) and SD, were randomly assigned to one of four intervention groups: IBS-NM with placebo, IBS-NM with probiotic, IBS-SD with placebo, and IBS-SD with probiotic. Each participant was required to consume two bottles of cultured milk every day for a duration of 12 weeks. The following outcomes were assessed: depression risk, quality of life, the severity of IBS, and hormonal changes. The depression scores were significantly reduced in IBS-SD with probiotic and placebo from baseline (p < 0.001). Only IBS-SD with probiotic showed a significant rise in serotonin serum levels (p < 0.05). A significantly higher life quality measures were seen in IBS-SD with probiotic, IBS-SD with placebo, and IBS-NM with placebo (p < 0.05). All groups, both placebo and probiotic, reported significant improvement in IBS severity post-intervention with a higher prevalence of remission and mild IBS (p < 0.05). Dual strains lactobacillus-containing cultured milk drink via its regulation of relevant biomarkers, is a potential anti-depressive prophylactic agent for IBS patients at risk.

Overexpression of EphB2 in the basolateral amygdala is crucial for inducing visceral pain sensitization in rats subjected to water avoidance stress.

AIMS: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process. METHODS: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety- and depression-like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot. RESULTS: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety-like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety-like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N-methyl-D-aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety-like behaviors. CONCLUSIONS: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS-like symptoms. These findings may give insight into the treatment of IBS and related psychological distress.

Hypnotherapy as a medical treatment: Evidence-based or pseudoscience?

BACKGROUND: Hypnotherapy continues to be a controversial practice in medicine. It is surrounded by myth and misuses that instill doubts about its legitimacy and usefulness. PURPOSE: In this paper, we will distinguish pseudoscientific claims from evidence-based uses of hypnotherapy. RESULTS: The use and acceptability of hypnotherapy has varied over history. Pseudoscientific uses, based on outdated theories that it can access the unconscious mind, have delegitimized hypnotherapy. Modern theories that hypnosis uses common social, emotional, and cognitive processes combined with evidence-based methods have re-established the use of hypnotherapy in many physical and mental health disorders and symptoms. Currently it is a widely accepted and recommended treatment for irritable bowel syndrome, with evidence building for many other applications. CONCLUSION: Hypnotherapy, as a pseudoscience, can become unethical and cause distress for the patient and their families. Hypnotherapy, as an evidence-based treatment, can be used as a powerful tool to treat physical and psychological symptoms related to medical ailments.

Comparing the effectiveness of transdiagnostic treatment with acceptance and commitment therapy on emotional disorders, rumination, and life satisfaction in patients with irritable bowel syndrome: a randomized clinical trial.

OBJECTIVE: The present study was conducted to compare the effectiveness of transdiagnostic treatment (UP) with the acceptance and commitment therapy (ACT) on the emotional disorders, rumination, and life satisfaction in the patients with irritable bowel syndrome (IBS). METHOD: The present study was a randomized clinical trial with a pre-test and post-test design. Between the winter of 2021 and the end of spring 2022, Taleghani Hospital in Tehran received referrals from the statistical population of IBS patients. Of them, 30 individuals (15 in each group) were chosen by convenience sampling and then randomly allocated to groups. UP (It is emotion-based and intervenes in comorbid symptoms), and ACT treatments were provided to the participants online. The participants in the UP and ACT groups received the desired treatments in eight weekly sessions of 45-60 min. RESULTS: There was no significant difference between UP pre-test and ACT regarding depression, anxiety, rumination, and life satisfaction (P > 0.05). There was no significant difference between UP and ACT post-test in terms of depression, rumination, and life satisfaction (P > 0.05), but due to anxiety, their difference was significant (P < 0.05). Besides, there was a significant difference between pre-test and post-test phases of UP and ACT regarding depression, anxiety, and rumination (P < 0.05). Still, they had no significant difference regarding life satisfaction (P > 0.05). CONCLUSION: Therefore, it is suggested that specialists use UP and ACT as effective psychological treatments for the emotional symptoms of IBS patients to improve psychological symptoms.

Experiences of Irritable Bowel Syndrome Patients in a Virtual Yoga Program: Qualitative Findings from a Clinical Trial.

BACKGROUND AND AIMS: In-person yoga interventions have shown feasibility and effectiveness in improving the outcomes of patients with irritable bowel syndrome (IBS), but experiences in virtual yoga interventions have not been examined. This study aimed to explore patients' experiences of a virtually delivered yoga intervention for IBS. METHODS: An embedded qualitative substudy was included in a randomized controlled trial examining the feasibility and effectiveness of a virtual yoga program among adult patients with IBS. Semi-structured interviews captured participants' past and current experiences, program satisfaction, perceived impact on IBS symptoms and overall physical and mental health, facilitators and barriers to participation, perceptions of social support and supervised learning, and input on improving future programming. Data were coded and analyzed in duplicate using NVivo 12. An analytic template based on the interview guide was developed and thematic analysis identified themes, as well as the relationship between themes and subthemes. RESULTS: Among the 14 participants (all female, mean age 47.7 years), three major themes were identified: (1) positive experience in the yoga program, (2) incorporating yoga into IBS management post-study, and (3) recommendations for program improvement. CONCLUSION: Patients with IBS experience in a virtual yoga program was positive with improvements in physical and mental health outcomes. Considering the barriers and facilitators to participating in an online yoga program along with participant recommendations may improve future intervention design and delivery to increase self-efficacy and confidence among patients with IBS.

Clinical trial: predictive factors for response to gut-directed hypnotherapy for refractory irritable bowel syndrome, a post hoc analysis.

BACKGROUND: Gut-directed hypnotherapy is effective for patients with irritable bowel syndrome (IBS). Despite its considerable evidence base, gut-directed hypnotherapy is not widely available and remains a limited resource. This emphasises the need to select patients who are most likely to benefit. AIM: To determine whether baseline patient characteristics were predictive of response to gut-directed hypnotherapy in patients with IBS METHODS: We conducted a secondary analysis of outcomes of 448 patients with refractory Rome III IBS who participated in a randomised study confirming non-inferiority of 6 compared to 12 sessions of gut-directed hypnotherapy. We compared baseline patient characteristics, including age, sex, IBS subtype, quality of life and IBS-Symptom Severity Scale (IBS-SSS), non-colonic symptom score and Hospital Anxiety and Depression (HAD) score between responders and non-responders. We defined response as ≥50-point decrease in IBS-SSS or ≥30% reduction in pain severity scores. RESULTS: Overall, 76.3% achieved ≥50-point decrease in IBS-SSS. Responders had a higher baseline non-colonic symptom score (p = 0.005). Those who achieved ≥30% improvement in abdominal pain scores (59.8%) had higher baseline IBS-SSS (p = 0.03), and lower baseline HAD-depression score (p = 0.012). Fifty-four patients (12%) dropped out of gut-directed hypnotherapy. Compared to completers, dropouts had higher baseline HAD-anxiety score (p = 0.034). CONCLUSIONS: These data suggest that patients with a higher burden of gastrointestinal and extraintestinal symptoms are most likely to benefit from gut-specific behavioural intervention for refractory IBS. Clinical assessment of gastrointestinal, somatic and psychological symptom profiles may play a role in selecting patients for gut-directed hypnotherapy.

Novel Symptom Subgroups in Individuals With Irritable Bowel Syndrome Predict Disease Impact and Burden.

BACKGROUND & AIMS: Current classification systems based on bowel habit fail to capture the multidimensional nature of irritable bowel syndrome (IBS). We previously derived and validated a classification system, using latent class analysis, incorporating factors beyond bowel habit. We applied this in another cohort of people with IBS to assess its ability to capture the impact of IBS on the individual, the health care system, and society. METHODS: We collected demographic, symptom, and psychological health data from adults in the community self-identifying as having IBS, and meeting Rome IV criteria. We applied our latent class analysis model to identify the 7 subgroups (clusters) described previously, based on overall gastrointestinal symptom severity and psychological burden. We assessed quality of life, health care costs (£1 = $1.20), employment status, annual income, work productivity, and ability to perform work duties in each cluster. RESULTS: Of 1278 responders, 752 (58.8%) met Rome IV criteria. The 7-cluster model fit the data well. The patients in the 4 clusters with the highest psychological burden, and particularly those in cluster 6 with high overall gastrointestinal symptom severity and high psychological burden, showed lower educational levels, higher gastrointestinal symptom-specific anxiety, were more likely to have consulted a gastroenterologist, and used more drugs for IBS. IBS-related and generic quality of life were impaired significantly in these 4 clusters and significantly fewer individuals reported earning ≥£30,000 per year. Productivity and the ability to work, manage at home, engage in social and private leisure activities, and maintain close relationships all were impacted significantly, and IBS-related health care costs over the previous 12 months were highest in these 4 clusters. In those in cluster 6, costs were more than £1000 per person per year. CONCLUSIONS: Our clusters identify groups of individuals with significant impairments in quality of life, earning potential, and ability to work and function socially, who are high utilizers of health care.

Development and Current State of Digital Therapeutics for Irritable Bowel Syndrome.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a common, debilitating disorder characterized by abdominal pain and disordered bowel habits. Current pharmacologic treatments often provide incomplete symptom relief and may be poorly tolerated. Furthermore, alleviation of gastrointestinal symptoms does not always translate into improved quality of life for IBS patients. Current treatment guidelines recommend brain-gut behavior therapy (BGBT) in conjunction with other IBS therapies, and, in randomized controlled trials, BGBT has been shown to improve symptoms, patient satisfaction, functioning, and quality of life. Access to BGBT is limited by lack of adequately trained gastrointestinal psychologists, patient time constraints, and cost. Furthermore, clinician knowledge that BGBT is specific, and different from psychotherapy approaches for common mental health disorders, may limit referrals even where available. This review provides an overview of the pathophysiology of IBS, disease burden, unmet therapeutic needs, evidence base of novel digital therapeutics for IBS, and guidance on the introduction and appropriateness of these interventions for patients. METHODS: We searched the literature for available published data relating to the use of novel digital therapeutics to provide cognitive behavioral therapy and gut-directed hypnotherapy in the treatment of irritable bowel syndrome. RESULTS: Clinical trial data support the development and utility of digital therapeutics designed to deliver self-guided cognitive behavioral therapy and hypnotherapy for the treatment of IBS. CONCLUSIONS: BGBTs are effective, guideline-recommended treatments for IBS. Digital therapeutic devices offer accessible, cost-effective treatment options for delivery of adjunctive BGBT for the treatment of IBS. The decision to recommend digital BGBTs should be guided by careful patient assessment that includes mental health screening and risk assessment.

Inflammatory Bowel Disease and Irritable Bowel Syndrome: What Differences in Mentalization Abilities? A Scoping Review.

Mentalization is a psychological process that enables individuals to understand the self and others in terms of intentional mental states. The aim of this scoping review was to provide an overview of the findings on mentalization in patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). A literature search, in line with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols extension for Scoping Review guidelines, was conducted in the following bibliographic databases: PubMed, PsycINFO, and Scopus. Databases were queried using the following strings (with Boolean operators): ("mentaliz*" OR "metacogniti*" OR "theory of mind" OR "ToM" OR "reflective function*") AND ("irritable bowel syndrome" OR "IBS" OR "inflammatory bowel disease" OR "IBD"). In line with the eligibility criteria, seven articles were included. Results showed that no significant differences in metacognitive ability were found between patients in the IBD and IBS groups. This review revealed the mentalizing difficulties for patients with IBD and IBS. These results should be interpreted with caution since they are based on a few studies that used different instruments to assess mentalizing processes. Future studies are needed to clarify the role of mentalization in patients with these gastrointestinal conditions.

Exploring new subgroups for irritable bowel syndrome using a machine learning algorithm.

Irritable bowel syndrome (IBS) is a complicated gut-brain axis disorder that has typically been classified into subgroups based on the major abnormal stool consistency and frequency. The presence of components other than lower gastrointestinal (GI) symptoms, such as psychological burden, has also been observed in IBS manifestations. The purpose of this research is to redefine IBS subgroups based on upper GI symptoms and psychological factors in addition to lower GI symptoms using an unsupervised machine learning algorithm. The clustering of 988 individuals who met the Rome III criteria for diagnosis of IBS was performed using a mixed-type data clustering algorithm. Nine sub-groups emerged from the proposed clustering: (I) High diarrhea, pain, and psychological burden, (II) High upper GI, moderate lower GI, and psychological burden, (III) High psychological burden and moderate overall GI, (IV) High constipation, moderate upper GI, and high psychological burden, (V) moderate constipation and low psychological burden, (VI) High diarrhea and moderate psychological burden, (VII) moderate diarrhea and low psychological burden, (VIII) Low overall GI, and psychological burden, (IX) Moderate lower GI, and low psychological burden. The proposed procedure led to the discovery of new homogeneous clusters in addition to certain well-known Rome sub-types for IBS.

Feasibility and Acceptability of an Online Yoga Study Among Individuals with Irritable Bowel Syndrome (IBS).

Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain that is often comorbid with psychiatric disorders and other pain-related conditions. The practice of yoga improves symptoms among patients with IBS, although the virtual delivery of yoga in this patient population remains understudied. The purpose of this article is to report feasibility and acceptability of a 6-week pilot yoga intervention among IBS and healthy control participants, which was transitioned to an online format in response to the COVID-19 pandemic. Participants attended 3 virtual study visits and received 60-minute private yoga sessions twice weekly for 6 weeks via Zoom. Sixteen females (n = 8 in IBS group, n = 8 in control group) with a mean age of 34.7 identified as White (87.5%) and Asian (12.5%). All participants attended all 3 study visits; 14 participants attended 12 yoga sessions, 1 attended 11, and 1 attended 9. At the end of the study, 81.3% of participants strongly agreed that participating in the online study was beneficial and convenient, and 87.5% strongly agreed that participating in the online yoga program was beneficial. Our online study and yoga intervention was feasible and acceptable; future studies with larger and more diverse populations will be conducted to investigate health effects among individuals with IBS.

Washed microbiota transplantation targeting both gastrointestinal and extraintestinal symptoms in patients with irritable bowel syndrome.

OBJECTIVE: Fecal microbiota transplantation (FMT) has been reported with the treatment potential for irritable bowel syndrome (IBS). However, the knowledge of its effect on extraintestinal symptoms of IBS is limited. This study aimed to evaluate the efficacy of the improved methodology of FMT, washed microbiota transplantation (WMT), on sleep disturbances, and psychological and gastrointestinal symptoms among patients with IBS. METHODS: This was a prospective observational study involving patients with IBS who underwent WMT. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The Gastrointestinal Symptom Rating Scale (GSRS) and IBS Severity Scoring System (IBS-SSS) were used to evaluate gastrointestinal symptoms and IBS severity, respectively. The Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) were used to evaluate depression and anxiety, respectively. All the symptoms were evaluated at baseline and one month after WMT. A multiple logistic regression model was used to determine the predictive factors of sleep improvement one month after WMT. RESULTS: Seventy-three patients with IBS were included in the study. Sleep quality (Z = -4.211, P < 0.001), anxiety (Z = -4.775, P < 0.001), depression (Z = -4.610, P < 0.001), gastrointestinal symptoms (Z = -5.364, P < 0.001), and IBS severity (Z = -6.468, P < 0.001) significantly improved one month after WMT in all patients. The scores of the five components of PSQI including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, and sleep disturbances decreased in 52 patients with poor sleep quality (all P < 0.05). Baseline sleep duration scores were identified as an independent predictive factor of sleep improvement one month after WMT in patients with poor sleep quality (OR 2.180 [95% CI = 1.017-4.673]; P = 0.045). Patients that experienced sleep improvement demonstrated greater alleviation in depression (Z = -1.990, P = 0.047) and IBS severity (Z = -2.486, P = 0.013) compared with patients without sleep improvement. CONCLUSION: This study suggested that WMT might be a promising therapy for patients with IBS, especially those with comorbid sleep and psychological disorders.

Pain Catastrophizing and Clinical Outcomes Among Patients Receiving a Novel Cognitive-Behavioral Therapy for Irritable Bowel Syndrome: An Experimental Therapeutics Approach.

Irritable bowel syndrome (IBS) is the most common gastrointestinal (GI) condition treated by GI and primary care physicians. Although IBS symptoms (abdominal pain, bowel problems) are generally refractory to medical therapies, consistent research has shown that they improve following cognitive-behavioral therapy (CBT). Notwithstanding empirical support for CBT, there is less research explicating the reasons for why or how it works. Like other pain disorders, the focus on change mechanisms for behavioral pain treatments has focused on pain-specific cognitive-affective processes that modulate pain experience, few of which are more important than pain catastrophizing (PC). The fact that PC changes are seen across treatments of differing theoretical and technical orientation, including CBT, yoga, and physical therapy, suggests that it may be a nonspecific (vs. theory-based) change mechanism akin to therapeutic alliance and treatment expectancy. Therefore, the current study examined change in PC as a concurrent mediator of IBS symptoms severity, global GI symptom improvement, and quality of life among 436 Rome III-diagnosed IBS patients enrolled in a clinical trial undergoing two dosages of CBT versus a nonspecific comparator emphasizing education and support. Results from structural equation modeling parallel process mediation analyses suggest that reduction in PC during treatment are significantly associated with improvement in IBS clinical outcomes through 3-month follow-up. Results from the current study provide evidence that PC may be an important, albeit nonspecific change mechanism, during CBT for IBS. Overall, reducing the emotional unpleasantness of pain through cognitive processes is associated with improved outcomes for IBS.

Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them. METHODS: We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date. RESULTS: IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety. CONCLUSIONS: These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.

Patients' perspectives on irritable bowel syndrome: a qualitative analysis based on social media in China.

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

The Usefulness of the Low-FODMAP Diet with Limited Tryptophan Intake in the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome.

(1) Background: A low-FODMAP diet is often recommended in the treatment of irritable bowel syndrome, but it does not improve abdominal symptoms in all patients, and an alternative diet is desirable. The purpose of this study was to evaluate the efficacy of a low-FODMAP diet with a concomitant reduction in tryptophan (TRP) intake in irritable bowel syndrome with diarrhea predominance (IBS-D) in relation to its metabolism via the serotonin and kynurenine pathways. (2) Methods: 40 healthy people (Group I, Controls) and 80 patients with IBS-D were included in the study. IBS-D patients were randomly divided into two groups of 40 each (Groups IIA and IIB). In Group IIA, the low-FODMAP diet was recommended, while in Group IIB, the same diet was recommended but with limited TRP intake for 8 weeks. The TRP intake was analyzed with the use of the nutritional calculator. Abdominal complaints were assessed using the Gastrointestinal Symptom Rating Scale (GSRS-IBS), and psychological status was simultaneously determined using two scales: the Hamilton Anxiety Scale (HAM-A) and the Hamilton Depression Scale (HAM-D). TRP and its metabolites: 5-hydoxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) were measured in urine using liquid chromatography tandem mass spectrometry (LC-MS/MS). (3) Results: The consumption of TRP per mg/kg/b.w./24 h has decreased in Group IIA from 20.9 ± 2.39 to 17.45 ± 2.41 (16.5%) and in Group IIB from 21.3 ± 2.33 to 14.32 (34.4%). Significantly greater improvement was found after nutritional treatment in patients in Group IIB as compared to Group IIA (GSRS score: 38.1% vs. 49.8%; HAM-A: 38.7% vs. 49.9%; HAM-D: 13.8% vs. 35.0%; p < 0.01). Reducing TRP intake showed a negative correlation with the degree of improvement in the GSRS score. (4) Conclusions: Lowering the TRP content in a low-FODMAP diet may be useful in treating IBS-D.

Gut enterochromaffin cells drive visceral pain and anxiety.

Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain1. For the growing population afflicted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved2. Irritable bowel syndrome also exhibits a strong sex bias, afflicting women three times more than men1. Here, we focus on enterochromaffin (EC) cells, which are rare excitable, serotonergic neuroendocrine cells in the gut epithelium3-5. EC cells detect and transduce noxious stimuli to nearby mucosal nerve endings3,6 but involvement of this signalling pathway in visceral pain and attendant sex differences has not been assessed. By enhancing or suppressing EC cell function in vivo, we show that these cells are sufficient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterial short-chain fatty acid associated with GI inflammation7,8. Remarkably, prolonged EC cell activation produced persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Furthermore, perturbing EC cell activity promoted anxiety-like behaviours which normalized after blockade of serotonergic signalling. Sex differences were noted across a range of paradigms, indicating that the EC cell-mucosal afferent circuit is tonically engaged in females. Our findings validate a critical role for EC cell-mucosal afferent signalling in acute and persistent GI pain, in addition to highlighting genetic models for studying visceral hypersensitivity and the sex bias of gut pain.

Elderberry diet improves gut-brain axis dysfunction, neuroinflammation, and cognitive impairment in the rat model of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is related to a problem in the gut-brain axis. This experimental research aimed to shed light on the potential therapeutic application of elderberry (EB), which can work on the axis and get better the IBS symptoms. There were three groups (36 Sprague-Dawley rats) in this experiment, including control, IBS, and IBS with EB diet (IBS + EB). Making use of intracolonic instillation of 1 ml of 4% acetic acid for 30 s, IBS was induced. 7 days later, the EB extract (2%) was added to the diets of all animals for 8 weeks. Some histological, behavioral, and stereological techniques were used to detect the effects of EB on the gut and brain tissues. The findings showed that the EB diet improved locomotion and decreased anxiety-like behavior in the rat models of IBS. Moreover, the diet dropped the expression of TNF-α and increased mucosal layer thickness and the number of goblet and mast cells in colon tissue samples. In the hippocampal samples, administration of EB prevented astrogliosis and astrocyte reactivity. Although hippocampal and cortical neurons decreased markedly in the IBS group, EB prevented the drop in the number of neurons. Although lots of research is needed to elucidate the effectiveness of EB in IBS and its exact molecular mechanism, the result of this study showed that EB as an antioxidant and immune-modulatory agent could be a promising research target to prevent the impairment in the gut-brain axis, and could ameliorative classic IBS symptoms.

Factors Associated With Placebo Treatment Response in Functional Dyspepsia Clinical Trials.

INTRODUCTION: Controlling for potential placebo effects is an important aspect of gaining an accurate estimate of how much the therapy alone changes patient symptoms or other end points. When the placebo effect is large, this can lead to only a small fraction of changes seen in the active therapy group being attributed to the therapy itself. This problem has been well studied in some disorders of brain-gut interaction but not in functional dyspepsia where placebo response rates of 40% and higher have been reported. Understanding risk factors for placebo response might lead to changes in trial design that could reduce the magnitude of the problem. This study sought to identify risk factors for the placebo effect in a functional dyspepsia clinical trial with a longer-term aim of suggesting trial design changes that might minimize the problem. METHODS: A secondary analysis of the clinical trial data was undertaken using 2 arms deemed to involve placebo therapy. Potential predictors were drawn from a wide range of patient characteristics including psychological, clinical, and physiological features. RESULTS: Predictors of a stronger placebo effect on the gastrointestinal symptom rating scale included higher functional dyspepsia symptom burden at baseline ( b = -0.101), coexisting irritable bowel syndrome ( b = -0.436), and higher scores on the Nepean Dyspepsia Index eat/drink domain (-0.005). Baseline symptom burden and coexisting irritable bowel syndrome were found to be independent placebo predictors, explaining 13% of the variance in change in gastrointestinal symptom rating scale. Anxiety, childhood sexual abuse, sleep amount, and frequent abdominal pain were also found to be predictors of change in individual symptom scores. DISCUSSION: The findings of this study yield actionable insights into trial methodology that may help to reduce the magnitude of the placebo effect in future functional dyspepsia treatment trials.