Clinical Gastroenterology and Hepatology最新文献

Background & aims: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis, yet its efficacy needs improvement. We conducted a comprehensive evaluation of the current literature on microbial factors affecting outcome, as well as a meta-analysis on some of the largest datasets regarding composition.

Methods: MEDLINE, Embase, and Cochrane were systematically searched through August 2024 for relevant studies. The quality of studies was analyzed with JBI tools and a composite critical appraisal score. Additionally, species-level data from 2 landmark FMT trials (the TURN and FOCUS trials) were reanalyzed from a compositional perspective.

Results: Out of 3755 citations identified, 56 met the inclusion criteria, of which 29 fulfilled quality standards. Higher microbial α-diversity, either in donors or recipients (at baseline or following FMT treatment), was associated with better clinical response rates. Engraftment of the donors' microbiota could not be clearly linked with clinical response, possibly because not every donor has an ideal microbiome. Butyrate-producing species from the Lachnospiraceae and Oscillospiraceae families were often related with response, whereas the reverse was true for Fusobacteria, many Proteobacteria, and Ruminococcus gnavus. Compositional analyses showed that clinical response is associated with a shift from a low-diversity, often Bacteroides-dominant composition to one with higher diversity, either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network, or a moderate/high-diversity composition with abundant but not excessive levels of Prevotella copri.

Conclusions: This systematic review/meta-analysis yielded a coherent picture from a compositional perspective, which may help identify beneficial donor profiles and guide personalized FMT approaches.

Background & aims: Cirrhosis-related inpatient hospitalizations have increased dramatically over the past decade. We used a longitudinal dataset capturing a large metropolitan area in the United States from 2011 to 2021 to evaluate contemporary hospitalization rates and risk factors among frail patients with cirrhosis.

Methods: We conducted a retrospective, longitudinal cohort study using the Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN) database, an electronic health record repository that aggregates de-duplicated data across 7 health care systems in the Chicago metropolitan area, from 2011 to 2021. The primary outcome of our study was the rate of hospitalization encounters. Frailty was defined by the Hospital Frailty Risk Score. Hospitalization rates were reported per 100 patients per year, and a multivariable logistic regression analysis identified predictors of annual hospitalization probability.

Results: During the study period, of 36,971 patients, 16,265 patients (44%) were hospitalized (compensated, 18.4%; decompensated, 81.6%). Hospitalization rates were highest in patients with decompensated cirrhosis, reaching nearly 77.3 hospitalizations/100 patients per year. Hospitalization rates among patients with compensated cirrhosis were also high (14.2 vs 77.3 hospitalization/100 patients per year), with odds of annual hospitalization 3 times (odds ratio, 3.1; 95% confidence interval, 2.9-3.4) as high among compensated patients with intermediate frailty and 5 times (odds ratio, 5.2; 95% confidence interval, 4.5-6.0) as high among those with severe frailty (compared with compensated patients with low frailty).

Conclusion: Compensated and decompensated cirrhosis patients with intermediate to severe frailty face a substantially increased odds of annual hospitalizations compared with those with low frailty. Future work should focus on targeted interventions to incorporate routine frailty screenings into cirrhosis care and to ultimately minimize high hospitalization rates.

The gastrointestinal tract has remarkable capacity to withstand considerable insults from exposure to abrasive food particles, chemicals, allergens, and pathogenic microbes. Maintaining a robust epithelial barrier sequesters these potentially harmful substances in the lumen, preventing absorption into the systemic circulation. Normal functioning of this barrier is central in diverse physiological processes including digestion, immunity, inflammation, and gut-brain signaling. One crucial component of the barrier is the mucus layer covering the epithelium. There is increased appreciation of the importance of mucus in maintenance of the gut barrier, and how dysregulation of the mucus layer contributes to several common gastrointestinal pathologies. This manuscript reviews the physical and chemical properties of mucus, its maintenance and turnover, and its role in maintaining gut barrier integrity. The dynamic interactions of the mucus layer within the gut ecosystem are illustrated by highlighting how a weakened mucus layer or defective mucus production facilitate pathogenic microbial colonization and mucosal biofilm formation. These may potentially contribute to the pathogenesis of gastrointestinal diseases such as inflammatory bowel diseases or result in secretion and mucosal damage and inflammation in bile acid diarrhea. A final goal is to review how certain dietary factors, especially low-fiber diets and emulsifiers common in Western diets, can harm the mucus layer. This report summarizes evidence from preclinical and human studies that document damage to the mucus layer, and reviews approaches, including diets and probiotics, that promote a healthy mucus layer and break down pathogenic biofilms, thereby potentially preventing and/or treating gastrointestinal diseases that impact mucosal integrity.

Background & aims: Limiting the dietary intake of certain carbohydrates has therapeutic effects in some but not all irritable bowel syndrome (IBS) patients. We investigated genetic variation in human Carbohydrate-Active enZYmes (hCAZymes) genes in relationship to the response to a FODMAP-lowering diet in the DOMINO study.

Methods: hCAZy polymorphism was studied in patients with IBS from the dietary (FODMAP-lowering; n = 196) and medication (otilonium bromide; n = 54) arms of the DOMINO trial via targeted sequencing of 6 genes of interest (AMY2B, LCT, MGAM, MGAM2, SI, and TREH). hCAZyme defective (hypomorphic) variants were identified via computational annotation using clinical pathogenicity classifiers. Age- and sex-adjusted logistic regression was used to test hCAZyme polymorphisms in cumulative analyses where IBS patients were stratified into carrier and non-carrier groups (collapsing all hCAZyme hypomorphic variants into a single bin). Quantitative analysis of hCAZyme variation was also performed, in which the number of hCAZyme genes affected by a hypomorphic variant was taken into account.

Results: In the dietary arm, the number of hypomorphic hCAZyme genes positively correlated with treatment response rate (P = .03; odds ratio = 1.51; confidence interval = 0.99-2.32). In the IBS-D group (n = 55), hCAZyme carriers were 6 times more likely to respond to the diet than non-carriers (P = .002; odds ratio = 6.33; confidence interval = 1.83-24.77). These trends were not observed in the medication arm.

Conclusions: hCAZYme genetic variation may be relevant to the efficacy of a carbohydrate-lowering diet. This warrants additional testing and replication of findings, including mechanistic investigations of this phenomenon.

Background & aims: Although participants with inflammatory bowel diseases in clinical trials of biologics and small molecule drugs (henceforth, advanced therapies) frequently receive several medications concomitantly, it is unclear how they modify treatment effect.

Methods: Through an individual patient data pooled analysis of 10 clinical trials of advanced therapies for moderate-to-severe ulcerative colitis, we assessed whether concomitant exposure to corticosteroids, immunomodulators, mesalamine, proton pump inhibitors, histamine receptor antagonists, opiates, antidepressants, and antibiotics modified the effect of the intervention on treatment efficacy and safety outcomes, using modified Poisson regression model.

Results: Of 6044 patients (4280 receiving intervention, 1764 receiving placebo), several received concomitant corticosteroids (47%), immunomodulators (28%), mesalamine (68%), proton pump inhibitors (14%), histamine receptor antagonists (2%), opiates (7%), antidepressants (6%), and/or antibiotics (5%). After adjusting for confounders and examining treatment efficacy of intervention versus placebo, we observed no impact of concomitant exposure to corticosteroids (ratio of relative risk of drug vs placebo with vs without concomitant exposure: ratio of risk ratio [RRR], 0.81 [95% confidence interval, 0.63-1.06]), mesalamine (RRR, 1.04 [0.78-1.39]), proton pump inhibitors (RRR, 0.87 [0.61-1.22]), histamine receptor antagonists (RRR, 1.72 [0.97-14.29]), opiates (RRR, 0.90 [0.54-1.49]), antidepressants (RRR, 1.02 [0.57-1.83]), and antibiotics (RRR, 0.72 [0.44-1.16]) on likelihood of clinical remission. Concomitant exposure to immunomodulators was associated with lower likelihood of achieving clinical remission (RRR, 0.73 [0.55-0.97]), particularly with non-tumor necrosis factor antagonists.

Conclusions: In clinical trials of advanced therapies for ulcerative colitis, baseline concomitant exposure to multiple commonly used class of medications does not impact treatment efficacy or safety. These findings directly inform design of regulatory clinical trials with respect to managing concomitant medications at baseline.