Jencks, Kara

This pilot, randomized, double-blind trial in a relatively small sample of patients with IBS-related pain shows rimegepant significantly reduced sensations of gas, urgency, and pain during rectal distention and decreased rectal compliance. Decrease in compliance implies that changes in physical properties or distensibility of rectum did not contribute to alterations in rectal sensation. Same dose of rimegepant did not significantly impact daily abdominal pain, BM frequency, or colonic transit. There were no serious adverse events.

ABSTRACT Levator ani syndrome (LAS) explains up to 7.4% of anorectal pain cases. Classic symptoms include rectal pain or pressure with sitting. We present 2 patients, ages 32 and 25 years, presenting initially with “diarrhea” and perianal hyperhidrosis. History revealed rectal discomfort, tenesmus, urgency, and sensation of incomplete evacuation. Puborectalis tenderness was present on digital rectal examination. Therapies were tailored to each patient, including pelvic floor physical therapy with biofeedback, bowel regulation, rectal diazepam, and ileostomy. These presentations offer insights into potential pathophysiological mechanisms in LAS and highlight the importance of considering LAS in non-pain presentations.

INTRODUCTION: Altered intestinal permeability (IP) is implicated in multiple gastrointestinal and systemic disease conditions; an experimental model of perturbed IP in healthy subjects is needed. Traditional approaches to perturbing IP include use of nonsteroidal anti-inflammatory drugs. METHODS: We conducted a single-center, randomized, placebo-controlled pilot study of dose-related effects of castor oil (CO) (and its ingredient ricinoleic acid) at 750, 1,500, or 3,000 mg daily doses on IP. Permeability was assessed using validated 13 C-mannitol and lactulose urine excretion at 0–2, 8–24, and 0–24 hours after oral administration. RESULTS: Permeability analysis across all groups demonstrated significant difference among the groups for 0–2 hours 13 C-mannitol, 0–24 hours 13 C-mannitol, and borderline significant difference for 2–8 hours 13 C-mannitol ( P = 0.060) and 0–24 hours lactulose ( P = 0.056). Direct comparison of 3,000 mg CO vs placebo ( t test) demonstrated higher excretion of 13 C-mannitol and lactulose at 0–2, and 0–24 hours, and lactulose at 2–8 hours. DISCUSSION: CO may perturb small intestinal and colonic permeability in healthy adults.

Background/Objectives: Our objective was to review published studies of the intestinal barrier and permeability, the deleterious effects of dietary components (particularly fat), the impact of altered intestinal permeability in disease models and human diseases, the role of the microbiome and epigenomics in control of barrier function, and the opportunities to restore normal barrier function with dietary interventions and products of the microbiota. Methods: We conducted a literature review including the following keywords alone or in combination: intestinal barrier, permeability, microbiome, epigenomics, diet, irritable bowel syndrome, inflammatory bowel disease, probiotics. Results: Intestinal permeability is modified by a diet including fat, which increases permeability, and nutrients such as fiber, glutamine, zinc, vitamin D, polyphenols, emulsifiers, and anthocyanins, which decrease permeability. There is significant interaction of the microbiome and barrier function, including the inflammatory of luminal/bacterial antigens, and anti-inflammatory effects of commensals or probiotics and their products, including short-chain fatty acids. Epigenomic modification of barrier functions are best illustrated by effects on junction proteins or inflammation. Detailed documentation of the protective effects of diet, probiotics, prebiotics, and microbiota is provided. Conclusion: intestinal permeability is a critical factor in protection against gastrointestinal diseases and is impacted by nutrients that preserve or heal and repair the barrier and nurture anti-inflammatory effects.

AbstractBackgroundColonic transit (CT) measured by validated scintigraphy using 111In‐labeled activated charcoal particles is summarized using geometric center (GC) of isotopic distribution in four colonic regions and stool at 24 and 48 h. Diagnosis of rapid CT is currently based on GC24 ≥4.4 in females and >4.7 in males, which lack sensitivity. Our aim was to evaluate, in patients with chronic diarrhea with normal CT by GC24 and GC48, the diagnostic utility of CT change (∆GC) relative to sex‐matched normal values.MethodsWe evaluated two adult patient cohorts: 701 clinical patients (1994–2023) with chronic diarrhea and 76 research participants with irritable bowel syndrome with diarrhea (N = 63) or bile acid diarrhea (BAD, N = 13). Results of ∆GC were compared to 220 healthy controls' 95th percentiles (%ile) (≥2.0 females and ≥2.2 males). In the research cohort, we also analyzed (Spearman correlation) colonic ∆GC with ascending colon emptying T1/2 (AC T1/2), average stool frequency and consistency based on a daily diary, total fecal bile acid (BA) concentration, and % primary BA in a single stool sample.Key ResultsAmong 701 clinical patients with normal GC24, 160 (22.3%) had rapid CT based on ∆GC 95th %ile in health. Among 76 research participants, an additional 20.6% IBS‐D and 23% BAD had rapid CT ∆GC. Younger age and absence of diabetes mellitus were predictive of rapid ∆GC. ∆GC significantly correlated with AC T1/2 and with fecal BA.Conclusions & Inferences∆GC identified an additional 21%–23% patients with rapid colonic transit among patients with diarrhea and normal GC24.

AbstractBackgroundMany patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)‐like symptoms. Although these symptoms cause significant reductions in quality of life, evidence‐based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS‐like symptoms in IBD patients with quiescent disease.MethodsWe performed a single‐center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 μg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS‐like symptoms in IBD patients.Key ResultsA total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0–82.0) 63.3 per 1000 person‐years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g.Conclusions & InferencesMood disorder and Crohn's disease were positively associated with IBS‐like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS‐like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS‐like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course.