Matar, Ayah

ABSTRACT Background Bile acid (BA) malabsorption (BAM) is a common cause of chronic diarrhoea and may occur in some patients due to abnormalities of the gut microbiota. Effects of probiotics on faecal secretory BAs, particularly the primary BA, chenodeoxycholic acid, are unclear. Aim/Methods We conducted a randomized, double‐blind, placebo‐controlled trial of the De Simone formulation 8‐strain probiotic in 24 patients previously diagnosed with BAM. Patients were randomized to 3 weeks of the probiotic (900 billion bacteria) or placebo (maltose), both administered three times daily. Symptoms, serum 7 α C4, faecal primary BAs, intestinal permeability by 13 C‐mannitol‐lactulose test (0.1 and 1 g of the sugars respectively) over 24 h, faecal short chain fatty acids (SCFA), microbiome, and metabolome were assessed at baseline and post‐intervention. Results Data from 22 patients were included. Probiotic supplementation was associated with a significant decrease in % faecal primary BAs (chenodeoxycholic acid and cholic acid) with median change from baseline −5.7 [IQR −10.3, 0.9]% compared to 9.8 [IQR 0.2, 20.6]% on placebo ( p = 0.012). The faecal microbiome was significantly different in the probiotic group after intervention, driven by probiotic‐specific species. There were no significant differences in symptoms, intestinal permeability, or SCFA. However, there was a numerical difference in the changes from baseline in 0‐2 h 13 C‐mannitol excretion −1.9 [−13.9, 4.2] mg for the probiotic and 1.0 (−0.5, 12.7) mg for placebo ( p = 0.084). Conclusions The De Simone formulation probiotic induced significant microbiome and metabolome changes in patients with BAM, ultimately leading to a decrease in % faecal primary BAs and possible reduction in intestinal permeability. Clinical Trials.gov registration NCT #06609148, January 2, 2025.

ABSTRACT Background Chronic megacolon is an uncommon neurogastrointestinal disorder typically characterized by a persistent increase in colonic diameter. Methods Our aim was to identify adults with medical treatment‐refractory constipation without radiographic criteria for megacolon but with increased colonic compliance (refractory constipation with colonic hypercompliance (RCCH)), and to compare the colonic compliance in 7 identified patients with “RCCH” to colonic compliance in 10 patients with chronic megacolon by radiographic criteria (i.e., megacolon) and 40 healthy volunteers. After endoscopic placement, compliance of left or transverse colon was measured using a 10‐cm‐long infinitely compliant balloon connected to an electronically controlled rigid piston barostat. The barostat inflated the balloon from 0 to 44 mmHg in 4‐mmHg steps at 30‐s intervals to measure colonic compliance (pressure‐volume relationship). Eligibility criteria for inclusion were increased colonic compliance based on a functional assessment without meeting radiographic criteria for megacolon (i.e., RCCH). In the three groups, we compared colonic volumes at intra‐balloon pressure of 8, 16, 20, 32, and 44 mmHg, the pressure at half maximum volume, and the slope of the colonic compliance curve using ANOVA on ranks and Dunn's pairwise comparison test. Other features of colonic motility were documented. Results Colonic volumes at all pressures (8‐44 mmHg) and the pressure at half maximum volume were significantly greater in patients with megacolon and RCCH than in healthy controls ( p < 0.001 for both), but compliance was not significantly different between RCCH and megacolon. Conclusion A subset of patients with medically‐refractory chronic constipation has colonic compliance similar to that of patients with megacolon.

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.

INTRODUCTION: To perform a proof-of-concept study to evaluate the performance of individual and combined anorectal manometry and balloon expulsion testing (BET) parameters for diagnosing dyssynergic defecation (DD) using machine learning (ML). METHODS: A single gastrointestinal motility specialist assessed (2008–2018) 307 patients. A ML model was constructed on anorectal manometry/BET data. BET was weight-based in 235 patients and time-based in 72 patients. Missing data were imputed. Data were split 75% train/25% test with preprocessing performed. Five common ML models were trained, and performance was compared using receiver operating characteristic (ROC) area under the curve and accuracy based on 100 bootstrapped samples. The most accurate models were fine-tuned and evaluated on the test set. RESULTS: The median age was 40 years, body mass index 22.2 kg/m 2 , and 81% were women. Two-hundred and 22 (72.3%) patients had a clinical diagnosis of DD. Compared with patients without clinical diagnosis of DD, patients with DD had significantly lower rectoanal pressure gradient (RAG) (median −34.7 [IQR −57.1, −13.0] vs −24.6 [IQR −44.5, −2.4] mm Hg, P = 0.009) and more abnormal BET (59.5% vs 11.8%, P < 0.001). Four features were retained in the optimized model as predictors of DD: abnormal BET, greater resting anal pressure (RAP), and more negative RAG. The optimal parameter was abnormal BET ( P = 0.003), but combinations of 2 manometry results (RAP and RAG) yielded positive predictive values (PPVs) >80%. The optimized logistic regression model had an area under the curve of 0.878, with a sensitivity of 75.0% and specificity of 81.8% at a probability threshold of 0.704. DISCUSSION: Abnormal BET, or a combination of 2 manometric parameters (RAP and RAG), provides >80% positive predictive value for diagnosing DD in patients with chronic constipation.

ABSTRACT Background Microbial overgrowth (MO) in the small intestine can cause gastrointestinal symptoms and may arise from stasis, such as dysmotility. Microtypes of MO include small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO). Dyssynergic defecation (DD) is associated with constipation and slow colonic transit (STC). Our aim was to assess the relationship between DD and MO. Methods We retrospectively identified patients who underwent both anorectal manometry (ARM) and balloon expulsion testing (BET) for DD, and MO testing using either small intestinal aspirate culture or breath testing. SIBO was analyzed using two culture thresholds: ≥ 10 5 CFU/mL and ≥ 10 3 CFU/mL. Chi‐square tests compared positive vs. negative results. Key Results 436 patients underwent culture of SB aspirates. At the ≥ 10 5 CFU/mL threshold, 41.7% were diagnosed with SIBO, and 87.4% at ≥ 10 3 CFU/mL. At ≥ 10 5 CFU/mL, percent anal relaxation was significantly lower in SIBO‐positive patients. SIBO patients were more likely to have reduced anal relaxation ( p = 0.032), but no other ARM parameters or BET > 60 s. At ≥ 10 3 CFU/mL, a more negative recto‐anal pressure differential (RAPD) was observed, along with a combination of RAPD < −45 mmHg and resting anal pressure > 90 mmHg. 637 patients underwent breath testing for MO, with 174 positive results, predominantly showing IMO (73%). In this group, BET was significantly longer, and anal relaxation was significantly lower. SIBO at ≥ 10 3 CFU/mL was more prevalent in DD than STC (85.5% vs. 64.7%, p = 0.002). IMO was more common in DD than STC ( p = 0.021). Conclusion/Inferences DD may be a risk factor for MO, often with evidence of methanogenesis.

ABSTRACT Background In healthy controls, higher gastric accommodation (GA) was associated with slower gastric emptying (GE) of solids. Aims In patients with gastroparesis: (1) To investigate the association between GA and GE of solids. (2) To assess the prevalence of abnormally high GA. Methods An electronic medical records (EMR) review (2010–2024) was conducted on 745 adult patients with measured GA following 300 kcal Ensure using SPECT, and scintigraphy‐based GE of solids (320 kcal, 30% fat, egg meal). Among these patients, 284 had gastroparesis (GE < 25% emptied at 2 h or < 75% emptied at 4 h). Spearman correlation analysis examined associations between GA volume or ratio and GE at 1, 2, and 4 h, and GE T 1/2 . Results Weak positive correlations were observed between GA volume and GE of solids % at 1 and 2 h (respectively R s = 0.148, p = 0.0234, and R s = 0.121, p = 0.042). In addition, there was a correlation between GA ratio and GE of solids % at 2 h ( R s = 0.143, p = 0.0160). However, there were no significant correlations of GA with GE % at 4 h or GE T 1/2 . Among the 284 patients with gastroparesis, we had documented increased GA, assessed by postprandial minus preprandial gastric volume (> 640 mL), in 7.75%, and increased GA by GA ratio > 3.85 in 22.9%. Conclusions Among patients with gastroparesis, higher GA is associated with accelerated GE of solids in the first 2 h, though the effect size is small. There is no significant effect on delayed GE at 4 h or GE T 1/2 .

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.