Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments.

Chronic visceral pain is one of the most common reasons for patients with gastrointestinal disorders, such as inflammatory bowel disease or disorders of brain-gut interaction, to seek medical attention. It represents a substantial burden to patients and is associated with anxiety, depression, reductions in quality of life, and impaired social functioning, as well as increased direct and indirect health care costs to society. Unfortunately, the diagnosis and treatment of chronic visceral pain is difficult, in part because our understanding of the underlying pathophysiologic basis is incomplete. In this review, we highlight recent advances in peripheral pain signaling and specific physiologic and pathophysiologic preclinical mechanisms that result in the sensitization of peripheral pain pathways. We focus on preclinical mechanisms that have been translated into treatment approaches and summarize the current evidence base for directing treatment toward these mechanisms of chronic visceral pain derived from clinical trials. The effective management of chronic visceral pain remains of critical importance for the quality of life of suffers. A deeper understanding of peripheral pain mechanisms is necessary and may provide the basis for novel therapeutic interventions.

Neuroimmunophysiology of the gastrointestinal tract.

Gut physiology is the epicenter of a web of internal communication systems (i.e., neural, immune, hormonal) mediated by cell-cell contacts, soluble factors, and external influences, such as the microbiome, diet, and the physical environment. Together these provide the signals that shape enteric homeostasis and, when they go awry, lead to disease. Faced with the seemingly paradoxical tasks of nutrient uptake (digestion) and retarding pathogen invasion (host defense), the gut integrates interactions between a variety of cells and signaling molecules to keep the host nourished and protected from pathogens. When the system fails, the outcome can be acute or chronic disease, often labeled as "idiopathic" in nature (e.g., irritable bowel syndrome, inflammatory bowel disease). Here we underscore the importance of a holistic approach to gut physiology, placing an emphasis on intercellular connectedness, using enteric neuroimmunophysiology as the paradigm. The goal of this opinion piece is to acknowledge the pace of change brought to our field via single-cell and -omic methodologies and other techniques such as cell lineage tracing, transgenic animal models, methods for culturing patient tissue, and advanced imaging. We identify gaps in the field and hope to inspire and challenge colleagues to take up the mantle and advance awareness of the subtleties, intricacies, and nuances of intestinal physiology in health and disease by defining communication pathways between gut resident cells, those recruited from the circulation, and "external" influences such as the central nervous system and the gut microbiota.

Constipated patients with functional defecatory disorder have secondary rectal hyposensitivity due to altered rectal biomechanics.

BACKGROUND AND AIM: Rectal hyposensitivity (RH) is common in constipation and often coexists with functional defecatory disorder (FDD). Rectal sensory thresholds are routinely evaluated with the anorectal manometry probe; however, the gold standard for the assessment of rectal sensitivity is with a barostat, use of which is limited by time constraints and availability. A novel rapid barostat bag (RBB) may facilitate measurements of rectal sensitivity. The aim is to evaluate the relationship between RH (measured by the RBB) and FDD (defined as any minor disorder of rectoanal coordination by the London classification) in constipated patients. METHODS: Consecutive constipated patients referred for anorectal function testing underwent anorectal manometry with the 3D-HDAM probe as well as rectal sensation testing with the RBB pump. RH was defined by volume to first sensation >30%, urge to defecate >80%, or discomfort >100% (normalized to rectal capacity). RESULTS: Fifty-three percent of constipated patients had RH. Patients with FDD had a significantly increased volume to first sensation (134.5 mL vs 102.0, P = 0.02), urge to defecate (187.0 mL vs 149.0, P = 0.04), and rectal capacity (253.5 mL vs 209.0, P = 0.04) compared to constipated patients without FDD. There was no difference in normalized sensory thresholds (percent of rectal capacity) nor the prevalence of hyposensitivity to each sensory threshold nor overall hyposensitivity. CONCLUSION: Patients with FDD, when measured with the RBB, have increased sensory thresholds on volumetric distension, but RH was not observed when sensory threshold volume were normalized to rectal capacity. This may reflect "secondary" RH due to altered rectal biomechanics.

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.

Epidemiologic Burden and Projections for Eosinophilic Esophagitis-Associated Emergency Department Visits in the United States: 2009-2030.

BACKGROUND & AIMS: Patients with poorly controlled eosinophilic esophagitis (EoE) may require unplanned emergency department (ED) visits for the management of dysphagia or food impactions. We evaluated the epidemiologic burden of EoE on ED utilization in the United States. METHODS: Data from the US Nationwide Emergency Department Sample were used to estimate weighted annual EoE-associated ED visits from 2009 to 2019. Temporal trends in population-adjusted rates of EoE visits were assessed using joinpoint regression. Autoregressive integrated moving average models were used to project EoE-associated ED visits to 2030. We also evaluated endoscopic utilization, requirement for hospitalization, and ED-related charges in patients with EoE presenting to the ED. RESULTS: A total of 11,125 unweighted (49,507 weighted) ED visits for EoE were included (69.0% male; mean age, 32.4 y). The annual volume of EoE-associated ED visits increased from 2934 (95% CI, 2437-3431) in 2009 to 8765 (95% CI, 7514-10,015) in 2019, and is projected to reach 15,445 (95% prediction interval, 14,672-16,218) by 2030. From 2009 to 2019, the number of EoE-associated ED visits increased by an average of 11.5% per year (95% CI, 10.3%-12.7%). The proportion of patients admitted to the hospital from the ED decreased from 25.6% in 2009 to 2011 to 14.0% in 2017 to 2019. Half of EoE patients presenting to the ED required an endoscopy, and nearly 40% required an esophageal foreign body removal. Total mean inflation-adjusted charges for an EoE-associated ED visit were $9025 US dollars in 2019. CONCLUSIONS: The volume of EoE-associated ED visits tripled between 2009 and 2019 and is projected to further double by 2030. This represents a substantial burden of unanticipated health care resource utilization and highlights a potential opportunity to optimize outpatient EoE care.

Meditation and Yoga for Irritable Bowel Syndrome: A Randomized Clinical Trial.

INTRODUCTION: Delivered in person, yoga is effective in managing irritable bowel syndrome (IBS) symptoms. The evidence for efficacy, feasibility, and safety of virtually delivered yoga for patients with IBS is unknown. METHODS: Adults diagnosed with IBS were randomized to either Hatha yoga intervention of 8 weekly online classes delivered virtually or an advice-only control group and assessed at baseline and postintervention. We used an unadjusted ANOVA to determine differences between and within groups on the primary outcome (decrease of ≥50 points in IBS Symptom Severity Scale [IBS-SSS]) and secondary outcomes (quality of life, anxiety and depression, fatigue, somatic symptoms, perceived stress, COVID-19 stress, and self-compassion). We assessed feasibility through recruitment and attrition rates, adherence, participant satisfaction, and safety (i.e., adverse events). RESULTS: Seventy-nine people participated (mean age 45.4 years [SD = 14.0], 92% women, 20% attrition rate). IBS-SSS decreased significantly in the treatment group (Δ change = 54.7, P = 0.028), but not in the control group (Δ change = 22.6, P = 0.277). Fourteen patients (37%) in the yoga group reached a clinically relevant decrease of ≥50 points on the IBS-SSS postintervention compared with 8 patients (20%) in the control group ( P = 0.242). No significant difference was found between groups in IBS-SSS score postintervention ( P = 0.149), but significant differences in favor of the treatment group for quality of life ( P = 0.030), fatigue ( P = 0.035), and perceived stress ( P = 0.040) were identified. The yoga program demonstrated feasibility. Intention to practice yoga decreased significantly in both groups from baseline to postintervention ( P < 0.001). However, the decline in intention did not correlate with practice minutes. DISCUSSION: Virtually delivered yoga is safe and feasible, and effective in reducing IBS symptoms. Based on the primary end point, the intervention was not superior to an advice-only control group.

Postendoscopy Care for Patients Presenting With Esophageal Food Bolus Impaction: A Population-Based Multicenter Cohort Study.

INTRODUCTION: Esophageal food bolus impactions (FBI) are a common gastrointestinal emergency. Appropriate management includes not only index endoscopy for disimpaction but also medical follow-up and treatment for the underlying esophageal pathology. We evaluated the appropriateness of postendoscopy care for patients with FBI and assessed patient-related, physician-related, and system-related factors that may contribute to loss to follow-up. METHODS: We conducted a retrospective, population-based, multicenter cohort study of all adult patients undergoing endoscopy for FBI in the Calgary Health Zone, Canada, from 2016 to 2018. Appropriate postendoscopy care was defined by a composite of a clinical or endoscopic follow-up visit, appropriate investigations (e.g., manometry), or therapy (e.g., proton-pump inhibitors or endoscopic dilation). Predictors of inappropriate care were assessed using multivariable logistic regression. RESULTS: A total of 519 patients underwent endoscopy for FBI: 25.2% (131/519) did not receive appropriate postendoscopy care. Half of the patients (55.3%, 287/519) underwent follow-up endoscopy or attended clinic, and among this group, 22.3% (64/287) had a change in their initial diagnosis after follow-up, including 3 new cases of esophageal cancer. Patients in whom a suspected underlying esophageal pathology was not identified at the index endoscopy were 7-fold (adjusted odds ratio 7.28, 95% confidence interval 4.49-11.78, P < 0.001) more likely to receive inappropriate postendoscopy follow-up and treatment, even after adjusting for age, sex, rural residence, timing of endoscopy, weekend presentation, and endoscopic interventions. DISCUSSION: One-quarter of patients presenting with an FBI do not receive appropriate postendoscopy care. This is strongly associated with failure to identify a potential underlying pathology at index presentation.

Prevalence and Risk Factors for Fatigue in Adults With Inflammatory Bowel Disease: A Systematic Review With Meta-Analysis.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a chronic relapsing and remitting disease with high morbidity, substantial health care costs, and increasing incidence. Fatigue is one of the most common symptoms that impacts quality of life and is a leading concern for patients with IBD. The aim of this study was to determine the global prevalence, risk factors, and impact of fatigue in adults with IBD. METHODS: A systematic review and meta-analysis was conducted. Data were retrieved from Medline, Embase, CINAHL, and PsycINFO from database inception to October 2019. A pooled prevalence of fatigue was calculated using a random-effects model. Stratified meta-analyses explored sources of between-study heterogeneity. Study quality was assessed using an adapted checklist from Downs and Black. RESULTS: The search yielded 4524 studies, of which 20 studies were included in the systematic review and meta-analysis. Overall, the studies were of good quality. The pooled prevalence of fatigue was 47% (95% confidence interval, 41%-54%), though between-study heterogeneity was high (I2 = 98%). Fatigue prevalence varied significantly by the definition of fatigue (chronic: 28%; high: 48%; P < .01) and disease status (active disease: 72%; remission: 47%; P < .01). Sleep disturbance, anxiety, depression, and anemia were the most commonly reported fatigue-related risk factors. CONCLUSIONS: The prevalence of fatigue in adults with IBD is high, emphasizing the importance of additional efforts to manage fatigue to improve the care and quality of life for patients with IBD.

Epidemiologic Burden and Treatment of Chronic Symptomatic Functional Bowel Disorders in the United States: A Nationwide Analysis.

BACKGROUND & AIMS: Functional bowel disorders (FBDs) are the most common gastrointestinal problems managed by physicians. We aimed to assess the burden of chronic symptomatic FBDs on ambulatory care delivery in the United States and evaluate patterns of treatment. METHODS: Data from the National Ambulatory Medical Care Survey were used to estimate annual rates and associated costs of ambulatory visits for symptomatic irritable bowel syndrome, chronic functional abdominal pain, constipation, or diarrhea. The weighted proportion of visits associated with pharmacologic and nonpharmacologic (stress/mental health, exercise, diet counseling) interventions were calculated, and predictors of treatment strategy were evaluated in multivariable multinomial logistic regression. RESULTS: From 2007-2015, approximately 36.9 million (95% CI, 31.4-42.4) weighted visits in patients of non-federally employed physicians for chronic symptomatic FBDs were sampled. There was an annual weighted average of 2.7 million (95% CI, 2.3-3.2) visits for symptomatic irritable bowel syndrome/chronic abdominal pain, 1.0 million (95% CI, 0.8-1.2) visits for chronic constipation, and 0.7 million (95% CI, 0.5-0.8) visits for chronic diarrhea. Pharmacologic therapies were prescribed in 49.7% (95% CI, 44.7-54.8) of visits compared to nonpharmacologic interventions in 19.8% (95% CI, 16.0-24.2) of visits (P < .001). Combination treatment strategies were more likely to be implemented by primary care physicians and in patients with depression or obesity. The direct annual cost of ambulatory clinic visits alone for chronic symptomatic FBDs is approximately US$358 million (95% CI, 233-482 million). CONCLUSIONS: The management of chronic symptomatic FBDs is associated with considerable health care resource use and cost. There may be an opportunity to improve comprehensive FBD management because fewer than 1 in 5 ambulatory visits include nonpharmacologic treatment strategies.

Yoga as a Therapy for Irritable Bowel Syndrome.

The aim of this state-of-the-art narrative review is to evaluate the current evidence about the effectiveness of yoga as therapy for IBS and explore its potential mechanisms of action. The current literature suggests yoga is effective and safe and may target multiple mechanisms involved in treatment of IBS. Evidence from randomized controlled trials identified yoga as more effective compared to pharmacological treatment and equally effective as dietary interventions or moderate-intensity walking. Improvements were seen in both physical health (IBS symptom severity, gastric motility, autonomic and somatic symptom scores, and physical functioning) and mental health outcomes (depression, anxiety, gastrointestinal-specific anxiety, and quality of life). Given favorable changes in IBS-related physical and mental health outcomes, preliminary data supports yoga as beneficial in this population. However, the relatively low-quality evidence resulting from heterogeneity of study designs, interventions, and outcome measures limit our ability to make specific recommendations about the use of yoga as therapy for patients with IBS.

Stress activates pronociceptive endogenous opioid signalling in DRG neurons during chronic colitis.

AIMS AND BACKGROUND: Psychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways. METHODS: Mouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca2+ imaging techniques. RESULTS: Supernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca2+ responses. Stress hormones decreased signalling induced by human and mouse supernatants. This effect resulted from stress hormones signalling directly to DRG neurons and indirectly through signalling to the immune system, leading to decreased opioid levels and increased acute inflammation. The net effect of stress was a change endogenous opioid signalling in DRG neurons from an inhibitory to an excitatory effect. This switch was associated with a change in G protein-coupled receptor excitatory signalling to a pathway sensitive to inhibitors of protein kinase A-protein, phospholipase C-protein and G protein ßϒ subunits. CONCLUSIONS: Stress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD.

Histamine Receptor H1-Mediated Sensitization of TRPV1 Mediates Visceral Hypersensitivity and Symptoms in Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Histamine sensitizes the nociceptor transient reporter potential channel V1 (TRPV1) and has been shown to contribute to visceral hypersensitivity in animals. We investigated the role of TRPV1 in irritable bowel syndrome (IBS) and evaluated if an antagonist of histamine receptor H1 (HRH1) could reduce symptoms of patients in a randomized placebo-controlled trial. METHODS: By using live calcium imaging, we compared activation of submucosal neurons by the TRPV1 agonist capsaicin in rectal biopsy specimens collected from 9 patients with IBS (ROME 3 criteria) and 15 healthy subjects. The sensitization of TRPV1 by histamine, its metabolite imidazole acetaldehyde, and supernatants from biopsy specimens was assessed by calcium imaging of mouse dorsal root ganglion neurons. We then performed a double-blind trial of patients with IBS (mean age, 31 y; range, 18-65 y; 34 female). After a 2-week run-in period, subjects were assigned randomly to groups given either the HRH1 antagonist ebastine (20 mg/day; n = 28) or placebo (n = 27) for 12 weeks. Rectal biopsy specimens were collected, barostat studies were performed, and symptoms were assessed (using the validated gastrointestinal symptom rating scale) before and after the 12-week period. Patients were followed up for an additional 2 weeks. Abdominal pain, symptom relief, and health-related quality of life were assessed on a weekly basis. The primary end point of the study was the effect of ebastine on the symptom score evoked by rectal distension. RESULTS: TRPV1 responses of submucosal neurons from patients with IBS were potentiated compared with those of healthy volunteers. Moreover, TRPV1 responses of submucosal neurons from healthy volunteers could be potentiated by their pre-incubation with histamine; this effect was blocked by the HRH1 antagonist pyrilamine. Supernatants from rectal biopsy specimens from patients with IBS, but not from the healthy volunteers, sensitized TRPV1 in mouse nociceptive dorsal root ganglion neurons via HRH1; this effect could be reproduced by histamine and imidazole acetaldehyde. Compared with subjects given placebo, those given ebastine had reduced visceral hypersensitivity, increased symptom relief (ebastine 46% vs placebo 13%; P = .024), and reduced abdominal pain scores (ebastine 39 ± 23 vs placebo 62 ± 22; P = .0004). CONCLUSIONS: In studies of rectal biopsy specimens from patients, we found that HRH1-mediated sensitization of TRPV1 is involved in IBS. Ebastine, an antagonist of HRH1, reduced visceral hypersensitivity, symptoms, and abdominal pain in patients with IBS. Inhibitors of this pathway might be developed as a new treatment approach for IBS. ClinicalTrials.gov no: NCT01144832.

The Relationship between Upper Esophageal Sphincter Manometry Function and Esophageal Motility Disorders.

OBJECTIVE: High-resolution manometry (HRM) provides measures of esophageal function which are used to classify esophageal motility disorders based on the Chicago Classification system. Upper esophageal sphincter (UES) measures are obtained from HRM, but are not included in the classification system, rendering the relationship between UES measures and esophageal motility disorders unclear. Furthermore, changes in the acceptable amount of esophageal dysfunction between versions of this classification system has created controversy. The objective of this study was to determine the relationship between UES measures and esophageal function. STUDY DESIGN: Cross-sectional study. SETTING: Referral centre. METHODS: HRM studies from the Calgary Gut Motility Center were reviewed for UES mean basal pressure, mean residual pressure, relaxation time-to-nadir, relaxation duration, and recovery time. Patients were grouped by number of failed swallows according to different iterations of the Chicago Classification: 0 to 4 (Group 1), 5 to 7 (Group 2), and 8 to 10 (Group 3). RESULTS: 2114 patients (65.1% female, median age 56 y) were included. There were significant increases in UES mean basal pressure (P < .001), mean residual pressure (P < .001), relaxation duration (P < .001), and recovery time (P < .001) between groups. Positive correlations existed between number of failed swallows and UES mean basal pressure (r = 0.143; P < .001), mean residual pressure (r = 0.201; P < .001), relaxation duration (r = 0.145; P < .001), and recovery time (r = 0.168; P < .001). CONCLUSIONS: Differences in UES measures exist among patients with failed swallows, with a positive correlation between UES dysfunction and increasing dysmotility. Our findings illustrate that UES measures are closely related to esophageal function, and that even minor esophageal dysfunction is related to UES dysfunction.

Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.

Background: Fecal microbiota transplantation (FMT) is a promising treatment for active ulcerative colitis (UC). Understanding patient preferences can identify treatment features that may impact treatment decisions, improve shared decision-making, and contribute to patient-centered care, which is especially important in the context of novel treatments like FMT. Objectives: We aimed to quantify preferences for active UC treatments, specifically FMT and biologics, and identify patient characteristics associated with different preference patterns. Design: This is a cross-sectional survey study. Methods: We administered a discrete choice experiment (DCE) survey to elicit preferences in a sample of Canadian adults with UC. DCE data were analyzed using a main-effects mixed logit model and used to predict uptake of hypothetical scenarios reflecting alternative combinations of treatment features. Latent class modeling identified heterogeneity in patient preference patterns. Results: Participants' (n = 201) mean age was 47.1 years (SD: 14.5 years), 58% were female, and most (84%) had at least some post-secondary education. Almost half were willing to undergo FMT. When considering treatments for active UC, the most important attributes were chance of remission and severity of rare unknown side effects. All else equal, participants were most likely to uptake treatment that involves oral capsules/pills. Participants in the class with the highest utility for chance of remission were younger, had more severe disease, and 58% indicated that they would be willing to undergo FMT. Conclusion: We identified characteristics of UC patients who are more likely to be interested in FMT using preference elicitation methods. Patient-centered care can be enhanced by knowing which patients are more likely to be interested in FMT, potentially improving satisfaction with and adherence to treatments for active UC to maximize the effectiveness of treatment while considering heterogeneity in patient preferences.

Background and aims: Fecal microbiota transplantation (FMT) is a promising new treatment for active ulcerative colitis. Questions remain around the benefits and risks of FMT treatment for patients with ulcerative colitis. Understanding how patients weigh the treatment features and how treatment features influence their decisions may improve shared decision-making and contribute to patient-centered care, which is especially important for novel treatments like FMT.Using an experimentally designed survey, we aimed to:1. Elicit patient preferences for features of active ulcerative colitis treatments, specifically FMT and biologics; and,2. Identify patient characteristics associated with different preference patterns. Results: We found that younger patients with more severe disease are more likely to try FMT for the treatment of active ulcerative colitis. Oral capsules/pills are the preferred mode of treatment administration. Conclusions: These findings can enhance patient-centered care by characterizing patients who are more likely to be interested in FMT. Aligning treatment with the features that are important to patients can potentially improve satisfaction with and adherence to treatments for active ulcerative colitis to maximize their effectiveness for individual patients.

Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.

Sex-specific post-inflammatory dysbiosis mediates chronic visceral pain in colitis.

BACKGROUND: Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner. METHODS: Males, cycling females, ovariectomized, and sham-operated females were given dextran sodium sulfate to induce colitis and allowed to recover. Germ-free recipients received sex-appropriate and cross-sex fecal microbial transplants (FMT) from post-inflammatory donor mice. Visceral sensitivity was assessed by recording visceromotor responses to colorectal distention. The composition of the microbiota was evaluated via 16S rRNA gene V4 amplicon sequencing, while the metabolome was assessed using targeted (short chain fatty acids - SCFA) and semi-targeted mass spectrometry. RESULTS: Post-inflammatory cycling females developed visceral hyperalgesia when compared to males. This effect was reversed by ovariectomy. Both post-inflammatory males and females exhibited increased SCFA-producing species, but only males had elevated fecal SCFA content. FMT from post-inflammatory females transferred visceral hyperalgesia to both males and females, while FMT from post-inflammatory males could only transfer visceral hyperalgesia to males. CONCLUSIONS: Female sex, hormonal status as well as the gut microbiota play a role in pain modulation. Our data highlight the importance of considering biological sex in the evaluation of visceral pain.

Gastroenterologist and Patient Attitudes Toward Yoga as a Therapy for Irritable Bowel Syndrome: An Application of the Theory of Planned Behaviour.

Objectives: To identify irritable bowel syndrome (IBS) patients' attitudes, subjective norms, perceived control and intention to practice yoga and gastroenterologists' attitudes and current yoga recommendations for their patients with IBS. Methods: Gastroenterologists and IBS patients completed online surveys including Theory of Planned Behaviour (TPB) constructs. Among IBS patients, multiple linear regression determined the multivariate associations between TPB variables and intention to practice yoga while controlling for significant socio-demographic variables. Gastroenterologists were asked about their attitudes and current yoga recommendations for patients with IBS. Chi-square analyses examined associations between gastroenterologists' demographics and recommending yoga. Binomial logistic regression described associations between attitude variables and current yoga recommendations. Results: For patients (n = 109), controllability (ß = 0.5, P < 0.001), affective attitude (ß = 0.4, P < 0.05) and self-efficacy (ß = 0.3, P < 0.05) were significantly associated with intention to do yoga in the regression model. TPB variables explained 34% of the variance in patients' intentions to practice yoga. The binomial regression analysis revealed that gastroenterologists (n = 79) who have confidence in recommending yoga (39%) were seven times more likely to recommend it (odds ratio = 7.3, P = 0.002) and those who agreed yoga improves IBS symptom severity (54%) were 10 times more likely to recommend yoga (odds ratio = 10.1, P < 0.001). Most (86%) wanted more evidence to support efficacy of yoga for IBS and 44% asked for more knowledge on how to refer a patient. Conclusion: Controllability, affective attitude and self-efficacy predicted IBS patients' intentions to practice yoga. Although gastroenterologists believed yoga is safe and beneficial for IBS patients, most do not recommend yoga due to lack of confidence and scientific evidence.

Esophageal motility in systemic sclerosis before and after autologous hematopoietic cell transplantation.

INTRODUCTION: Systemic sclerosis (SSc) is associated with esophageal dysmotility. Autologous hematopoietic cell transplantation (HCT) results in improvement of skin tightness and lung function. Whether esophageal motility improves after HCT is unknown. METHODS: Esophageal motility was studied using high-resolution esophageal manometry in 21 SSc patients before and at multiple time points after autologous HCT. Median posttransplant follow-up was 2 years (range, 6 months to 5 years). RESULTS: Prior to HCT, all 21 patients had abnormal motility-10 (48%) had unmeasurable and 11 (52%) had measurable peristalsis. Manometric diagnosis in the former 10 patients was "absent contractility" and in the latter 11 patients "ineffective esophageal motility (IEM)." After HCT, among the 10 patients with absent contractility, 9 continued to have absent contractility and one demonstrated weak measurable peristalsis. Of the 11 patients with IEM, 5 experienced SSc relapse, and 2 out of these 5 patients developed absent contractility. Among the 6 non-relapsed patients, 4 continued to have IEM, and 2 developed normal motility. CONCLUSIONS: HCT appears to have no beneficial effect on motility in patients with unmeasurable peristalsis. In patients with measurable peristalsis, HCT appears to stabilize and in some normalize motility, unless relapse occurs. Key Points • In patients with systemic sclerosis, esophageal dysmotility is a significant contributor to morbidity and so far, there has been no data describing the effects of hematopoietic cell transplantation on esophageal motility. • Our work demonstrated that in patients with systemic sclerosis and unmeasurable esophageal peristalsis prehematopoietic cell transplantation, there was no measurable beneficial effect of transplantation on esophageal motility. • In patients with systemic sclerosis and measurable peristalsis prehematopoietic cell transplantation, esophageal motility stabilized, except in relapsed patients.