Citations

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.

INTRODUCTION: Indomethacin is often used experimentally to induce intestinal hyperpermeability, enabling evaluation of interventions targeting barrier function. METHODS: We conducted a randomized, double-blind, placebo-controlled study (NCT05538247) in healthy volunteers to assess whether a supplement could mitigate indomethacin-induced hyperpermeability. Participants received 150 mg/d of indomethacin for 6 days, either before or during placebo/supplement administration. Permeability was measured using 13 C-mannitol and lactulose urinary excretion. RESULTS: Contrary to expectations, indomethacin failed to increase 13 C-mannitol excretion in either group. No meaningful elevations in serum (zonulin, claudins) or fecal (calprotectin) biomarkers were observed. DISCUSSION: Our findings suggest that the expected increase in intestinal permeability after indomethacin administration may not be consistently observed in healthy volunteers. These results highlight the need to carefully consider the reproducibility and sensitivity of this model in future clinical studies aiming to investigate gut barrier function.

ABSTRACT Background Bile acid diarrhoea, a common cause of diarrhoea‐predominant irritable bowel syndrome, has a similar prevalence to coeliac disease and inflammatory bowel diseases. The mainstay of treatment is bile acid sequestrants (BAS). The effectiveness of using bile acid‐targeted therapies remains unclear. Aim To compare BAS with placebo for bile acid diarrhoea. Methods We conducted a systematic review and meta‐analysis of randomised controlled trials comparing BAS to placebo using a comprehensive search of databases from inception to 8/1/2023. Inclusion required unequivocal diagnosis using serum or faecal biochemical parameters, or 75 SeHCAT. Co‐primary endpoints were ≥ 30% improvement in bowel movement consistency and frequency averaged over 7 days. Adverse effects were also summarised. Results Database search resulted in 1152 citations; 1 additional study was added. Ultimately, 6 trials (5 parallel arm, 1 crossover) involving 182 participants evaluated the effectiveness of BAS over 1–8 weeks. Participants were between the third and seventh decades of life and mostly female. The risk of bias was low except in one parallel and one crossover trial. Meta‐analysis of parallel‐design trials of sequestrants only showed a clinically significant reduction in stool consistency and frequency with pooled relative risks of 1.50 (95% CI: 1.14–1.96) and 2.80 (95% CI: 1.68–4.67), respectively. There was no observable heterogeneity ( I 2 = 0%), and the certainty of evidence was moderate. There was no statistically significant difference in adverse effects. Conclusions This study quantifies the significant and rapid improvement in both stool consistency and frequency with BAS in patients with objective diagnosis of bile acid diarrhoea. Sequestrants also appear well tolerated.

ABSTRACTIntroductionUpper and lower gastrointestinal (GI) dysfunctions frequently coexist, potentially mediated by gastrocolonic or cologastric neural reflexes. This study aims to assess the prevalence of impaired gastric accommodation (GA) and delayed gastric emptying (GE) among patients with slow colonic transit (CT), dyssynergic defecation (DD), and to evaluate relationships between CT or DD with impaired GA and delayed GE.MethodsWe reviewed records of 178 adult patients at Mayo Clinic (2005–2025) with documented slow CT or DD (respectively based on scintigraphy and high‐resolution anorectal manometry [ARM] and balloon expulsion [BE]) who underwent 99mTc‐SPECT measurement of GA and scintigraphic GE of 320‐kcal, 30% fat egg meal. Slow CT was defined by geometric center (GC) at 48 h < 2.1 for males and < 1.9 for females. Abnormal GA ratio was assessed as reduced < 2.62 or increased > 3.85, and delayed GE % < 75% at 4 h. Correlations were assessed using Spearman rank test.ResultsReduced GA was found in 23.7% with DD and 26.7% with slow CT, while increased GA was observed in 30.1% and 24.4%, respectively. Delayed GE was present in 20.5% DD patients and 35.6% slow CT patients. GC 48 h and 24 h were positively correlated with GE% 4 h (Rs = 0.279, and Rs = 0.294 respectively, both p < 0.001) suggesting slow CT retards GE. GC 48 h was moderately correlated with resting anal pressure (Rs = 0.259, p < 0.001) and negatively with the rectoanal pressure gradient (Rs = −0.166, p = 0.027). No significant correlations were observed between CT and GA.ConclusionSlow CT is associated with slower GE, suggesting cologastric reflex inhibition, but not with GA. There is a high prevalence of impaired GA and delayed GE in slow CT and DD.

A 32-year-old woman with Alport syndrome and prior history of diffuse leiomyomatosis of the oesophagus and bronchial tree presented with severe constipation. MRI revealed extensive leiomyomatosis of the anorectum with obstructed defecation. Colonic manometry showed megacolon, and the patient underwent total colectomy. Surgical pathology confirmed leiomyomatosis and neuronal loss in the anorectum and reduced enteric ganglion cells in the colon. Prior literature suggests obstruction-induced enteric neuropathy as a potential mechanism for megacolon. This report shows that Alport syndrome with diffuse leiomyomatosis may have other gastrointestinal involvement including megacolon in affected patients presenting with constipation.

Coeliac disease is characterised by immune-mediated damage to the small intestine in response to dietary gluten in genetically predisposed individuals. Increased intestinal permeability is a central component to its pathophysiology. This review explores the evidence for increased permeability in coeliac disease and the underlying mechanisms, including the roles of zonulin, inflammatory cytokines, microbial alterations and immune responses to gliadin peptides. We also review comprehensively the therapies targeting barrier integrity and normalising intestinal permeability, including particular diets and supplements, and experimental and improved medications including larazotide acetate and IMU-856. Finally, we highlight the need for reliable biomarkers for evaluating increased permeability in coeliac disease and advocate for further research on therapies which normalise barrier function, particularly as a strategy to maintain remission.

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 .

ABSTRACTBackgroundThe intestinal barrier protects humans from potentially deleterious ingested material. It consists of several components: commensal organisms, mucus, and transepithelial pathways, and immune functions.AimsTo review, with major focus on human studies, the methods to measure intestinal barrier function in vivo and the impaired intestinal barrier function in non‐inflammatory conditions, and the deleterious or beneficial effects of dietary components on the intestinal barrier.MethodsPUBMED literature search was intentionally focused, when possible, on human studies conducted in vivo.ResultsAlthough many gastrointestinal, rheumatological, and degenerative neurological diseases are attributed to impaired intestinal barrier function, often termed “leaky gut,” methods of accurate measurement of intestinal barrier function in vivo in humans are still being developed. In vivo measurements provide an overall assessment of barrier function at a whole organ level, whereas ex vivo or in vitro measurements using mucosal biopsies address mechanistic information at the cellular level. Several dietary components are detrimental to the barrier, including ethanol, fat, sugars, gliadin, food additives, emulsifiers, and microbial transglutaminase. Conversely, dietary components improving barrier function include fibre and metabolites such as short‐chain fatty acids, anthocyanins, polyphenols, vitamins (such as A and D), zinc, specific amino acids (such as glutamine) and probiotics.ConclusionsCurrently, data are not exclusively from human studies, and research is needed to corroborate observations in animals or further validate in humans. There are several practical dietary approaches that can be instituted for restoration of the intestinal barrier in humans.