Prevalence of Self-Reported Spondyloarthritis Features in a Cohort of Patients with Inflammatory Bowel Disease

BACKGROUND: Musculoskeletal symptoms belonging to the spectrum of ‘seronegative spondyloarthritis’ (SpA) are the most common extraintestinal manifestations in patients with inflammatory bowel disease (IBD) and may lead to important disease burden. Patients with suspected SpA should be referred to a rheumatologist for further evaluation

Effects of Ethanol and Acetaldehyde on Tight Junction Integrity: In Vitro Study in a Three Dimensional Intestinal Epithelial Cell Culture Model

Background: Intestinal barrier dysfunction and translocation of endotoxins are involved in the pathogenesis of alcoholic liver disease. Exposure to ethanol and its metabolite, acetaldehyde at relatively high concentrations have been shown to disrupt intestinal epithelial tight junctions in the conventional two dimensional cell culture models. The present study investigated quantitatively and qualitatively the effects of ethanol at concentrations detected in the blood after moderate ethanol consumption, of its metabolite acetaldehyde and of the combination of both compounds on intestinal barrier function in a three-dimensional cell culture model. Methods and Findings: Caco-2 cells were grown in a basement membrane matrix (Matrigel (TM)) to induce spheroid formation and were then exposed to the compounds at the basolateral side. Morphological differentiation of the spheroids was assessed by immunocytochemistry and transmission electron microscopy. The barrier function was assessed by the flux of FITC-labeled dextran from the basal side into the spheroids' luminal compartment using confocal microscopy. Caco-2 cells grown on Matrigel assembled into fully differentiated and polarized spheroids with a central lumen, closely resembling enterocytes in vivo and provide an excellent model to study epithelial barrier functionality. Exposure to ethanol (10-40 mM) or acetaldehyde (25-200 mu M) for 3 h, dose-dependently and additively increased the paracellular permeability and induced redistribution of ZO-1 and occludin without affecting cell viability or tight junction-encoding gene expression. Furthermore, ethanol and acetaldehyde induced lysine residue and microtubules hyperacetylation. Conclusions: These results indicate that ethanol at concentrations found in the blood after moderate drinking and acetaldehyde, alone and in combination, can increase the intestinal epithelial permeability. The data also point to the involvement of protein hyperacetylation in ethanol- and acetaldehyde-induced loss of tight junctions integrity

Effect of a carotenoid-producing Bacillus strain on intestinal barrier integrity and systemic delivery of carotenoids : a randomised trial in animals and humans

The aim of the present study was to investigate effects of the carotenoid-producing Bacillus indicus strain PD01 on intestinal barrier function and its ability to survive passage through the gastrointestinal tract and to assess systemic bioavailability of these carotenoids in vivo. As model for impaired barrier function, 16 early weaned piglets were randomly assigned to a control diet or control diet with PD01 for 23 days. In addition, 67 overweight/obese, otherwise healthy individuals were randomly assigned to groups receiving PD01 or placebo for 6 weeks. PD01 survived passage through the gastrointestinal tract in piglets and human subjects and resulted in significant accumulation of PD01 derived carotenoids (methyl-glycosyl-apo-8'-lycopenoate and glycosyl-apo-8'- lycopene) in human plasma after 3- and 6-weeks supplementation versus baseline (0.044 and 0.076 vs 0 mu M, respectively; p = 0.104). In summary, PD01 survived transit through the gastrointestinal tract, resulted in systemic carotenoid accumulation and improved compromised barrier function outcomes

The placebo response rate in pharmacological trials in patients with irritable bowel syndrome: a systematic review and meta-analysis

BackgroundClinical trials in irritable bowel syndrome are associated with high placebo response rates. We aimed to identify the magnitude of the placebo response and the contributing factors to this occurrence.MethodsWe did a systematic review and meta-analysis with a search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials between April 1, 1959, and April 30, 2020. We included all randomised controlled trials that compared an active pharmacotherapeutic agent with placebo and had a dichotomous outcome of response to therapy (in terms of global improvement or improvement in abdominal pain) in adults (aged ≥18 years) with irritable bowel syndrome. Exclusion criteria were trials reporting on treatment satisfaction as a dichotomous outcome of response to therapy or clinician-reported outcomes and a treatment duration of less than 4 weeks. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: global improvement, abdominal pain, and US Food and Drug Administration (FDA) endpoints. We extracted information from published reports and pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020170908.FindingsOf the 6863 publications identified, 70 articles describing 73 randomised controlled trials were included in our analysis. The pooled placebo response rate was 27·3% (95% CI 24·3–30·9) using the global improvement endpoint, 34·4% (31·2–37·8) using the abdominal pain endpoint, and 17·9% (15·2–21·0) using the composite FDA endpoint responder definition, all with substantial heterogeneity between the trials. Studies published before 2006, and those done in Europe, with a parallel design, a run-in period of 2 weeks or less, a dose schedule of three times a day or more, or a smaller sample size of the control group were significantly associated with an increased pooled placebo response rate.InterpretationMore than a quarter of patients with irritable bowel syndrome had a placebo response in terms of global improvement, with multiple associated moderators. We recommend future trials apply a run-in period of at least 2 weeks and dose once or twice a day to minimise the placebo response rate

Effect of wheat bran derived prebiotic supplementation on gastrointestinal transit, gut microbiota, and metabolic health: a randomized controlled trial in healthy adults with a slow gut transit

Acute intake of the wheat bran extract Arabinoxylan-Oligosaccharide (AXOS) modulates the gut microbiota, improves stool characteristics and postprandial glycemia in healthy humans. Yet, little is known on how long-term AXOS intake influences gastrointestinal (GI) functioning, gut microbiota, and metabolic health. In this randomized, placebo-controlled, double-blind study, we evaluated the effects of AXOS intake on GI function and metabolic health in adults with slow GI transit without constipation. Forty-eight normoglycemic adults were included with whole-gut transit time (WGTT) of >35 h receiving either 15 g/day AXOS or placebo (maltodextrin) for 12-wks. The primary outcome was WGTT, and secondary outcomes included stool parameters, gut permeability, short-chain fatty acids (SCFA), microbiota composition, energy expenditure, substrate oxidation, glucose, insulin, lipids, gut hormones, and adipose tissue (AT) function. WGTT was unchanged, but stool consistency softened after AXOS. 12-wks of AXOS intake significantly changed the microbiota by increasing Bifidobacterium and decreasing microbial alpha-diversity. With a good classification accuracy, overall microbiota composition classified responders with decreased WGTT after AXOS. The incretin hormone Glucagon-like protein 1 was reduced after AXOS compared to placebo. Energy expenditure, plasma metabolites, AT parameters, SCFA, and gut permeability were unchanged. In conclusion, intake of wheat bran extract increases fecal Bifidobacterium and softens stool consistency without major effects on energy metabolism in healthy humans with a slow GI transit. We show that overall gut microbiota classified responders with decreased WGTT after AXOS highlighting that GI transit and change thereof were associated with gut microbiota independent of Bifidobacterium. NCT02491125.</p

Impact of commonly used drugs on the composition and metabolic function of the gut microbiota

The human gut microbiota has now been associated with drug responses and efficacy, while chemical compounds present in these drugs can also impact the gut bacteria. However, drug–microbe interactions are still understudied in the clinical context, where polypharmacy and comorbidities co-occur. Here, we report relations between commonly used drugs and the gut microbiome. We performed metagenomics sequencing of faecal samples from a population cohort and two gastrointestinal disease cohorts. Differences between users and non-users were analysed per cohort, followed by a meta-analysis. While 19 of 41 drugs are found to be associated with microbial features, when controlling for the use of multiple medications, proton-pump inhibitors, metformin, antibiotics and laxatives show the strongest associations with the microbiome. We here provide evidence for extensive changes in taxonomy, metabolic potential and resistome in relation to commonly used drugs. This paves the way for future studies and has implications for current microbiome studies by demonstrating the need to correct for multiple drug use

Length and site of the small intestine exposed to fat influences hunger and food intake

The site of intestinal fat delivery affects satiety and may affect food intake in humans. Animal data suggest that the length of the small intestine exposed to fat is also relevant. The aim of the present study was to investigate whether increasing the areas of intestinal fat exposure and the way it is exposed would affect satiety parameters and food intake. In the present single-blind, randomised, cross-over study, fifteen volunteers, each intubated with a naso-ileal tube, received four treatments on consecutive days. The oral control (control treatment) was a liquid meal (LM) containing 6 g fat ingested att = 0 min, with saline infusion att = 30–120 min. Experimental treatments were a fat-free LM att = 0 min, with either 6 g oil delivered sequentially (2 g duodenal,t = 30–60 min; 2 g jejunal,t = 60–90 min; 2 g ileal,t = 90–120 min), simultaneously (2 g each to all sites,t = 30–120 min) or ileal only (6 g ileal,t = 30–120 min). Satiety parameters (hunger and fullness) and cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY) secretion were measured untilt = 180 min, whenad libitumfood intake was assessed. Only the ileum treatment reduced food intake significantly over the control treatment. The ileum and simultaneous treatments significantly reduced hunger compared with the control treatment. Compared with control, no differences were observed for PYY, CCK and GLP-1 with regard to 180 min integrated secretion. Ileal fat infusion had the most pronounced effect on food intake and satiety. Increasing the areas of intestinal fat exposure only affected hunger when fat was delivered simultaneously, not sequentially, to the exposed areas. These results demonstrate that ileal brake activation offers an interesting target for the regulation of ingestive behaviour.</jats:p

Artificial intelligence for characterization of diminutive colorectal polyps::A feasibility study comparing two computer-aided diagnosis systems

BACKGROUNDArtificial intelligence (AI) has potential in the optical diagnosis of colorectal polyps.AIMTo evaluate the feasibility of the real-time use of the computer-aided diagnosis system (CADx) AI for ColoRectal Polyps (AI4CRP) for the optical diagnosis of diminutive colorectal polyps and to compare the performance with CAD EYETM (Fujifilm, Tokyo, Japan). CADx influence on the optical diagnosis of an expert endoscopist was also investigated.METHODSAI4CRP was developed in-house and CAD EYE was proprietary software provided by Fujifilm. Both CADx-systems exploit convolutional neural networks. Colorectal polyps were characterized as benign or premalignant and histopathology was used as gold standard. AI4CRP provided an objective assessment of its characterization by presenting a calibrated confidence characterization value (range 0.0-1.0). A predefined cut-off value of 0.6 was set with values &lt; 0.6 indicating benign and values ≥ 0.6 indicating premalignant colorectal polyps. Low confidence characterizations were defined as values 40% around the cut-off value of 0.6 (&lt; 0.36 and &gt; 0.76). Self-critical AI4CRP’s diagnostic performances excluded low confidence characterizations.RESULTSAI4CRP use was feasible and performed on 30 patients with 51 colorectal polyps. Self-critical AI4CRP, excluding 14 low confidence characterizations [27.5% (14/51)], had a diagnostic accuracy of 89.2%, sensitivity of 89.7%, and specificity of 87.5%, which was higher compared to AI4CRP. CAD EYE had a 83.7% diagnostic accuracy, 74.2% sensitivity, and 100.0% specificity. Diagnostic performances of the endoscopist alone (before AI) increased non-significantly after reviewing the CADx characterizations of both AI4CRP and CAD EYE (AI-assisted endoscopist). Diagnostic performances of the AI-assisted endoscopist were higher compared to both CADx-systems, except for specificity for which CAD EYE performed best.CONCLUSIONReal-time use of AI4CRP was feasible. Objective confidence values provided by a CADx is novel and self-critical AI4CRP showed higher diagnostic performances compared to AI4CRP.van der Zander QEW, Schreuder RM, Thijssen A, Kusters CHJ, Dehghani N, Scheeve T, Winkens B, van der Ende - van Loon MCM, de With PHN, van der Sommen F, Masclee AAM, Schoon EJ. Artificial intelligence for characterization of diminutive colorectal polyps: A feasibility study comparing two computer-aided diagnosis systems. Artif Intell Gastrointest Endosc 2024; 5(1): 90574 [DOI: 10.37126/aige.v5.i1.90574

Real-Time In Vivo Imaging of Early Mucosal Changes during Ischemia-Reperfusion in Human Jejunum

BACKGROUND AND STUDY AIMS: Small intestinal ischemia-reperfusion (IR) is a frequent, potentially life threatening phenomenon. There is a lack of non-invasive diagnostic modalities. For many intestinal diseases, visualizing the intestinal mucosa using endoscopy is gold standard. However, limited knowledge exists on small intestinal IR-induced, early mucosal changes. The aims of this study were to investigate endoscopic changes in human jejunum exposed to IR, and to study concordance between endoscopic appearance and histology. PATIENTS AND METHODS: In 23 patients a part of jejunum, to be removed for surgical reasons, was isolated and selectively exposed to ischemia with 0, 30 or 120 minutes of reperfusion. In 3 patients, a videocapsule was inserted in the isolated segment before exposure to IR, to visualize the mucosa. Endoscopic view at several time points was related to histology (Heamatoxylin & Eosin) obtained from 20 patients. RESULTS: Ischemia was characterized by loss of villous structure, mucosal whitening and appearance of punctate lesions. This was related to appearance of subepithelial spaces and breaches in the epithelial lining in the histological view. Early during reperfusion, the lumen filled with IR-damaged, shed cells and VCE showed mucosal erosions, hemorrhage and intraluminal debris. At 60 minutes of reperfusion, the only remaining signs of IR were loss of villous structure and small erosions, indicating rapid mucosal healing. CONCLUSIONS: This study shows a unique, real-time in vivo endoscopic view of early mucosal changes during IR of the human small intestine. Future studies should evaluate its usefulness in diagnosis of patients suspected of IR