Inflammatory Bowel Diseases最新文献

Background and aims: Our previous studies of adult Crohn's disease (CD) suggested ileal microvillus length (MVL) as a prognostic biomarker for therapy response. We investigated if ileal MVL also differed in pediatric CD versus controls and tested for associations with stricturing or penetrating disease behavior outcomes.

Methods: We determined the average ileal MVL of 412 CD and 88 control H&E-stained ileal histology samples from a subset of the RISK cohort and 2 validation cohorts. The RISK sub-cohort had an average follow-up of >60 months and was used to test for associations between ileal MVL and clinical data, RNA-seq molecular profiles, and histopathological scores.

Results: Ileal MVL was shorter in CD relative to control (median of 1.396 µm vs. 1.598 µm, respectively). Ileal MVL generally did not associate with demographics or clinical disease activity indices. However, there was a significant association between shorter ileal MVL and increased risk of development of complicated disease behavior. Furthermore, CD samples with shorter ileal MVL showed a significantly shorter time to development of complicated disease behavior. Ileal MVL positively associated with a gene signature enriched for brush border membrane and negatively associated with a gene signature enriched for extracellular matrix, inflamed macrophages, and fibroblasts. Accordingly, ileal MVL was negatively correlated with histopathological scores.

Conclusions: Short ileal MVL is associated with the development of complicated disease behaviors in pediatric CD, supporting the potential use of this histological phenotype as a biomarker for CD prognosis.

Systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD) are both categorized as autoimmune disorders and have similar non-specific gastrointestinal symptoms. SLE and IBD have shown shared genetic architecture in European ancestry; however, given the ancestry-specificity of genetic architecture, the shared genetic structure in East Asian ancestry remains unclear. This study reveals significant global and local genetic overlap between SLE and IBD subtypes in East Asian ancestry by using genetic correlation analyses. Cross-trait and colocalization analyses identify 64 shared loci and 19 causal variant credible sets between SLE and IBD subtypes. Notably, pleiotropic genes (HIC2, UBE2L3, ARAP1, ATG16L2, ANKS1A, and TULP1) were validated through Gene Expression Omnibus databases and previous studies. The major histocompatibility complex region emerges as a critical hub for shared genetic correlations and pleiotropic effects in SLE-IBD pathogenesis. Gene-level enrichment analyses implicate chemokine and lipid binding as underlying shared biological mechanisms.

Background and aims: Microbiome studies reveal distinct microbial differences in inflammatory bowel disease (IBD), indicating its potential role in pathophysiology and as a noninvasive diagnostic biomarker. This study aims to profile the gut microbiome in children with IBD, compared to both healthy controls (HC) and controls with gastrointestinal symptoms (CGI), and to assess the potential of microbiome profiles as noninvasive diagnostic markers for de novo treatment-naïve pediatric IBD, and as early predictive markers for therapy response.

Methods: We analyzed baseline fecal samples and clinical data from 103 therapy-naïve children with IBD, 75 CGI, and 356 age and sex matched HC. Metagenomic sequencing was performed, and prediction models assessed diagnostic potential and prediction of induction therapy response at 3 months.

Results: Alpha diversity progressively decreased from HC to CGI (P < .001) and decreased even further in IBD patients (P = .0056). Beta diversity analysis showed significant clustering differences (P < .001, R2 = 0.045). Differential abundance analysis revealed 116 species differing between HC and IBD, and 30 species between CGI and IBD. Prediction models based on microbiome features accurately distinguished IBD from HC (area under the curve [AUC] = 0.96) and from CGI (AUC = 0.71). However, these models were outperformed by clinical features, such as fecal calprotectin. Microbiome-based prediction of response to induction therapy in general showed limited accuracy (AUC = 0.63), as well as for response to nutritional induction therapy (AUC = 0.67).

Conclusions: We observed profound gut microbiome differences between de novo, therapy-naïve pediatric IBD patients and controls. While microbiome profiles hold promise for improving diagnostic precision, their predictive value for therapy response seems limited.

This commentary examines the progressive decline in biologic efficacy in inflammatory bowel disease, highlighting pharmacologic, immunologic, and cellular mechanisms of resistance. It advocates for early, biomarker-guided, and mechanistically informed sequencing to preserve long-term therapeutic response and overcome the emerging "therapeutic ceiling."

Background: There is paucity of data on the risk of infection-related hospitalization among inflammatory bowel disease (IBD) patients exposed to newer biologics. Our aim was to assess the overall and comparative risk of infection-related hospitalization, among IBD patients exposed to different IBD medication classes.

Methods: This was a retrospective cohort study of adult IBD patients in the Veterans Health Administration. New initiators of different IBD medication classes were identified, and the primary outcome was infection requiring hospitalization. Survival analysis methods were used to evaluate the association between time-updated IBD medications and these outcomes, adjusted for key confounders.

Results: The cohort included 14 554 IBD patients. There were 3131 infection hospitalizations over a median follow-up of 49.5 months (interquartile range, 21.2-60.0 months). No other class of medication was associated with a statistically significant difference in the risk of acquiring an infection-related hospitalization compared with patients exposed to a combination therapy of anti-tumor necrosis factor (TNF) inhibitors and thiopurines (TPs). There was a significantly increased risk of gastrointestinal infections with vedolizumab (hazard ration, 1.42; 95% confidence interval, 1.13-1.80; P = .003) relative to anti-TNF inhibitors + TPs. Anti-TNF inhibitor monotherapy had a lower risk when compared with vedolizumab.

Conclusions: In this nationwide IBD cohort, there was not an increased risk of infection-related hospitalization among patients exposed to vedolizumab, ustekinumab, and tofacitinib as compared with patients on anti-TNF inhibitor and TP combination therapy and rates of infection-related hospitalization were low overall. These findings should guide clinical decision making and patient-physician discussions when selecting a therapeutic agent with the primary emphasis on efficacy.