Inflammatory Bowel Diseases最新文献

Background: Recent studies hint at mitochondrial genes influencing UC patient response to anti-TNF treatment. We evaluated this hypothesis by following a targeted strategy to identify gene expression that captures the relationship between mitochondrial dysregulation and response to treatment. Our objective was to initially examine this relationship in colon samples and subsequently assess whether the resulting signal persists in the bloodstream.

Methods: We analyzed the transcriptome of colon samples from an anti-TNF-treated murine model characterized by impaired mitochondrial activity and treatment resistance. We then transferred the findings that linked mitochondrial dysfunction and compromised treatment response to an anti-TNF-treated UC human cohort. We next matched differential expression in the blood using monocytes from the peripheral blood of controls and IBD patients, and we evaluated a classification process at baseline with whole blood samples from UC patients.

Results: In human colon samples, the derived gene set from the murine model showed differential expression, primarily enriched metabolic pathways, and exhibited similar classification capacity as genes enriching inflammatory pathways. Moreover, the evaluation of the classification signal using blood samples from UC patients at baseline highlighted the involvement of mitochondrial homeostasis in treatment response.

Conclusions: Our results highlight the involvement of metabolic pathways and mitochondrial homeostasis in determining treatment response and their ability to provide promising classification signals with detection levels in both the colon and the bloodstream.

Background: CD4+ T cells contribute to chronic inflammation and fibrosis in inflammatory bowel disease (IBD), but the cellular mechanisms remain elusive. We have found that the mitogen-activated protein kinase 2 (MK2) pathway plays a major role in inflammation and overall pathology in IBD. Thus, here, we examined the role of MK2 in regulating CD4+ T cell responses in IBD models.

Methods: Interleukin-10 (IL-10) knockout (KO) mice treated with MK2 inhibitors (MK2i) and CD4-specific MK2 knockdown mice treated with chronic dextran sodium sulfate (DSS) treatments were used to examine inflammation and fibrosis by multiplex array, gene expression, flow cytometry, and histology. Human tissues were treated with MK2i to examine Th1 and Th17 markers.

Results: IL-10 KO mice treated with MK2i therapeutically showed significantly reduced interferon gamma (IFNγ) and interleukin-17A (IL-17A) and a significantly reduced number of IFNγ+ and IL-17A+ producing CD4+ T cells by flow cytometry. To investigate the direct role of MK2 in CD4+ T cells during IBD, we utilized CD4-specific MK2 knockdown mice in chronic DSS colitis. A decrease in colonic inflammation, IFNγ and IL-17, pro-fibrotic genes, and extracellular matrix deposition was observed in mice with MK2 knockdown in CD4+ T cells compared to control mice. Additionally, IL-17A and IFNγ directly regulated the expression of fibrosis genes in colon tissues.

Conclusions: The MK2 pathway regulates inflammatory CD4+ T cells and fibrosis in IBD models and is a potential therapeutic target.

Background: Fecal microbiota transplantation (FMT) is emerging as a potential treatment modality for individuals living with inflammatory bowel disease (IBD). Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical investigation. Notwithstanding differences in methodologies, current studies demonstrate its potential for inducing remission in UC patients. Therefore, standardized and robust randomized clinical trials (RCTs) are needed to further support its efficacy for managing UC. The aim of the second Rome Consensus Conference was to address gaps and uncertainties identified in previous research regarding FMT and to offer a robust framework for future studies applied to the treatment of UC.

Methods: Global experts in the field of clinical IBD, mucosal immunology, and microbiology (N = 48) gathered to address the need for standardized clinical trials in FMT investigation. The group focused on key issues, such as stool donation, donor selection, characterization of fecal biomass, potential administration routes, as well as the process of induction, maintenance, and endpoint readouts.

Results and conclusions: The consensus achieved during this conference established standardization of methods and protocols to enhance the current quality of research, with the aim of eventual implementation of FMT in managing UC and the ultimate goal of improving patient outcomes.

Cluster-randomized trials randomize entire groups of participants, instead of individual participants, to different treatment arms. For certain interventions (eg, institutional policies, processes of care, treatment algorithms), these designs protect against contamination between study arms. However, cluster trials are logistically complex to implement and have unique vulnerabilities that must be evaluated for accurate interpretation. Here, we provide a general overview of the design and statistical issues in cluster trials to facilitate their interpretation by clinicians.

Background: Pediatric-onset ulcerative colitis (pUC) represents a more aggressive disease phenotype compared with adult-onset UC. We hypothesized that this difference can, in part, be explained by the composition of the microbiota.

Methods: In a prospective, longitudinal study, we included pediatric (N = 30) and adult (N = 30) patients with newly or previously (>1 year) diagnosed UC. We analyzed the microbiota composition in the mucosa-adherent microbiota at baseline, using 16S rRNA gene sequencing, and the fecal microbiota at baseline and at 3-month intervals, using shotgun metagenomics.

Results: For fecal samples, the bacterial composition differed between pUC and aUC in newly diagnosed patients (β-diversity, Bray Curtis: R2 = 0.08, P = .02). In colon biopsies, microbial diversity was higher in aUC compared with pUC (α-diversity, Shannon: estimated difference 0.54, P = .006). In the mucosa-adherent microbiota, Alistipes finegoldii was negatively associated with disease activity in pUC while being positively associated in aUC (estimate: -0.255 and 0.098, P = .003 and P = .02 in pUC and aUC, respectively). Finally, we showed reduced stability of the fecal microbiota in pediatric patients, evidenced by a different composition of the fecal microbiota in newly and previously diagnosed pUC, a pattern not found in adults.

Conclusions: Our results indicate that pediatric UC patients have a more unstable fecal microbiota and a lower α diversity than adult patients and that the microbiota composition differs between aUC and pUC patients. These findings offer some explanation for the observed differences between pUC and aUC and indicate that individualized approaches are needed if microbiota modifications are to be used in the future treatment of UC.

Background and aims: Biases in healthcare pose challenges for inflammatory bowel disease (IBD) patients from underrepresented races and ethnicities. Our study aimed to assess the quality of and access to care among underrepresented racial and ethnic populations using a diverse database.

Methods: We used the OneFlorida Data Trust, representing over half of Florida's population. We performed a retrospective study from 2012 to 2020. Advanced IBD therapies included a prescription of at least 1 biologic agent or tofacitinib. Disease activity markers included C-reactive protein (CRP), hemoglobin (Hgb), albumin, and white blood cell (WBC). Regression analyses compared the rates of medication use, healthcare utilization, and disease severity by race and ethnicity. Geographic distribution of advanced IBD therapy was analyzed at the county level.

Results: Our study included 10 578 patients. Hispanic patients utilized more biologics than non-Hispanic White (NHW) patients (odds ratio [OR]: 1.3, P < .0001). Non-Hispanic Black patients utilized more steroids than NHW (OR: 1.2, P = .0004). Hispanics had fewer visits to emergency departments (EDs) and fewer admissions compared with NHW (OR: 0.7 and 0.6, respectively; P < .0001). Non-Hispanic Black patients visited ED more frequently than NHW patients (OR: 1.3, P < .0001). Hispanics had lower disease activity markers than NHW based on CRP (OR: 0.5, P = .005), Hgb (OR: 0.4, P < .0001), albumin (OR: 0.7, P < .0001), and WBC (OR: 0.5, P < .0001). Geographic distribution of advanced IBD therapy showed clustered areas in southern and northern Florida.

Conclusions: Our data show an improved access to care pattern in Hispanic patients. However, disparities still exist, and this is evident in the healthcare utilization trends observed among non-Hispanic Black patients.

Introduction: Little is known about patterns of opioid prescribing in inflammatory bowel disease (IBD), but pain is common in persons with IBD. We estimated the incidence and prevalence of opioid use in adults with IBD and an unaffected reference cohort and assessed factors that modified opioid use.

Methods: Using population-based health administrative data from Manitoba, Canada, we identified 5233 persons with incident IBD and 26 150 persons without IBD matched 5:1 on sex, birth year, and region from 1997 to 2016. New and prevalent opioid prescription dispensations were quantified, and patterns related to duration of use were identified. Generalized linear models were used to test the association between IBD, psychiatric comorbidity, and opioid use adjusting for sociodemographic characteristics, physical comorbidities, and healthcare use.

Results: Opioids were dispensed to 27% of persons with IBD and to 12.9% of the unaffected reference cohort. The unadjusted crude incidence per 1000 person-years of opioid use was nearly twice as high for the IBD cohort (88.63; 95% CI, 82.73-91.99) vs the reference cohort (45.02; 95% CI, 43.49-45.82; relative risk 1.97; 95% CI, 1.86-2.08). The incidence rate per 1000 person-years was highest in those 18-44 years at diagnosis (98.01; 95% CI, 91.45-104.57). The relative increase in opioid use by persons with IBD compared to reference cohort was lower among persons with psychiatric comorbidity relative to the increased opioid use among persons with IBD and reference cohort without psychiatric comorbidity.

Discussion: The use of opioids is more common in people with IBD than in people without IBD. This does not appear to be driven by psychiatric comorbidity.

Background and aims: Individuals with inflammatory bowel disease (IBD) experience a high symptom burden, including abdominal pain, fatigue, anxiety, depression, and sleep disturbances; yet, little is known regarding the relationship between sex and gender on symptoms. We sought to report symptom severity for cisgender men, cisgender women, and transgender and gender-diverse (TGD) individuals. In addition, we used network analysis to identify core symptoms and explore if symptoms and their relationships differ between cisgender men and cisgender women.

Methods: This was a cross-sectional study. We recruited adults with IBD online through ResearchMatch. Individuals responded to Patient-Reported Outcomes Measurement Information symptom questionnaires, as well as demographic and clinical questionnaires. Network analysis was used to identify the core symptoms driving the symptom structure.

Results: One-hundred and fifty-seven (63.3%) participants identified as cisgender women, 84 (33.9%) as cisgender men, and 7 (2.8%) as TGD. Cisgender men (M = 61.8) and TGD (M = 61.3) groups reported higher abdominal pain levels compared with cisgender women (M = 57.8; P = .02). Transgender and gender-diverse individuals reported higher depression levels (M = 64.8) compared with cisgender men (M = 56.7) and cisgender women (M = 54.4; P = .01). Using a network analysis approach, anxiety and fatigue emerged as core symptoms for the entire sample (clinically active and inactive disease), and among only those with active clinical disease. Fatigue was a top core symptom for cisgender women; anxiety emerged as a top core symptom for cisgender men.

Conclusions: This study highlights that fatigue and anxiety are core symptoms among individuals with IBD and demonstrates a potential sex and/or gender difference in core symptoms. Replication of this study is needed with further consideration of inclusion of TGD patients.