Inflammatory Bowel Diseases最新文献

Background: Crohn's disease (CD) is a refractory inflammatory bowel disease with an unclear etiology. CircularRNA (circRNA) has been highlighted as a novel class of functional noncoding RNAs associated with the pathogenesis of various diseases. However, the functions of circRNA in CD remain unclear.

Methods: Biopsies were obtained from noninflammatory sites in the terminal ileum of the CD group (n = 4) and non-CD group (n = 4) and analyzed for circRNA expression using RNA sequencing. The significantly altered circRNAs were validated in the CD group (n = 45) and non-CD group (n = 15) using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Transcriptome analysis was conducted using circRNA-downregulated macrophage-like THP-1 cells. Reactive oxygen species (ROS) levels, cytokine mRNA expression, phagocytosis, and migration were evaluated in circRNA-downregulated THP-1 cells.

Results: CircularRNA sequencing analysis revealed significant differences in 31 circRNAs between the CD group and non-CD group. Quantitative reverse transcriptase-polymerase chain reaction analysis for each circRNA demonstrated significant upregulation of hsa_circ_0015388 in the CD group. Hsa_circ_0015388 was expressed in THP-1 cells, but not in HCEC-1CT and Caco-2/bbe. Transcriptome analysis in THP-1 cells transfected with scramble or hsa_circ_0015388 siRNA (small interfering RNA) showed a significant alteration in innate immune response related pathway. Reactive oxygen species production was significantly increased in the hsa_circ_0015388 downregulated THP-1 cells. Reactive oxygen species induction in the hsa_circ_0015388 knocked down THP-1 was diminished by the inhibition of TNFSF10.

Conclusion: A comprehensive analysis of circRNA expression revealed that 31 circRNAs were dysregulated in the CD group. Hsa_circ_0015388 is expressed in macrophages and negatively regulates ROS function inhibiting the TNFSF10 pathway. This study first revealed that hsa_circ_0015388 plays a role in the pathogenesis of CD by suppressing ROS production in macrophages.

Background: The efficacy of 5-aminosalicylic acid (5-ASA) in combination with advanced therapies (ADTs), particularly ustekinumab (UST), for the treatment of inflammatory bowel disease (IBD) remains unclear.

Methods: This retrospective cohort analysis used data from the Medical Data Vision database, including patients with ulcerative colitis (UC) and Crohn's disease (CD) who had initiated UST therapy. Cumulative UST continuation rates and factors associated with UST failure were analyzed, and post hoc subgroup analyses based on prior ADT use were conducted.

Results: A total of 1971 patients with CD and 1284 patients with UC were included. Overall, the concomitant use of 5-ASA did not significantly affect UST failure in either CD or UC. Post hoc subgroup analysis suggested a protective effect of 5-ASA in ADT-naïve patients with CD or UC who had been previously exposed to ADT.

Conclusions: 5-ASA did not provide a significant overall benefit when used in combination with UST for CD or UC. However, post hoc subgroup analyses indicated a potential role for 5-ASA in specific subgroups. Further studies are necessary to confirm these findings and explore personalized treatment strategies.

Background: Women with inflammatory bowel disease (IBD) face complexities of disease management during pregnancy and childbirth. Apprehension regarding vaginal delivery in pregnant individuals with IBD persists due to concern for perianal disease and perineal trauma. The incidence of poor wound healing after obstetric anal sphincter injury is approximately 4% in the general population. In an IBD population, risk of developing and difficulty healing perineal tears and episiotomy is not well described.

Methods: In a multicenter prospective cohort of pregnant individuals with IBD, we collected demographic information, IBD disease and treatment history, pregnancy and labor history, and reports of delayed wound healing >1 month from episiotomy, vaginal tear, or Cesarean (C-) section. Prospective data were collected using questionnaires that were administered each trimester of pregnancy, at delivery, and in the year postpartum.

Results: There were 743 patients in the PIANO registry who answered questions pertaining to postpartum wound healing, with 330 (44%) reporting a C-section and 413 (56%) reporting a vaginal delivery. Of 119 C-section deliveries assessed for delayed wound healing, only 1 (0.8%) patient reported this complication. Episiotomies were reported in 59 (14%) patients, with 9 (15%) reporting delayed wound healing. Vaginal tears were reported in 252 (64%) patients. Delayed wound healing from vaginal tear was reported in 9% of patients. Use of immunomodulators was associated with delayed wound healing from episiotomy (33% vs 0% for those on no medications, P = .024). No difference was seen in wound healing time for episiotomy with other medications, including corticosteroids, anti-tumor necrosis factor, or anti-integrin use. Delayed wound healing from vaginal tear was not associated with any class of IBD medication.

Conclusions: Episiotomy was a common occurrence in patients with IBD. Immunomodulator, but not biologic, use was found to be associated with delayed wound healing. This association could reflect a direct medication effect on episiotomy wound healing or inadequate treatment of underlying active disease prior to delivery. Vaginal tears were also common but delayed wound healing was not associated with IBD therapy. C-section occurred at high rates, particularly in Crohn's disease patients, with no reported delays in postpartum wound healing.

Background: Patients with ulcerative colitis (UC) exhibit abnormal amino acid (AA) metabolism. Taste receptors play a crucial role in the detection of intestinal AAs. Nevertheless, it remains unclear whether UC patients exhibit abnormal expression of these receptors in the colon.

Methods: An observational, multicenter study was conducted involving adult patients with active UC and healthy controls (HCs), recruited from July 2023 to March 2024. Fresh feces and rectosigmoid mucosal tissues were obtained from each participant. The concentrations of fecal AAs and the expression of taste receptors, including calcium-sensing receptor (CaSR), G protein-coupled receptor family C group 6 member A (GPRC6A), taste receptor type 1 member 1 (T1R1), and metabotropic glutamate receptor 4 (mGLuR4), in the colon were measured. Additionally, the correlation between colonic mucosal taste receptors and clinical characteristics was evaluated.

Results: Except for GPRC6A, the expression levels of CaSR, mGLuR4, and T1R1 in the colonic mucosa of UC patients were significantly elevated compared to HC. The expression of CaSR was negatively correlated with C-reactive protein and erythrocyte sedimentation rate (ESR). T1R1 expression positively correlated with defecation frequency and an Improved Mayo Endoscopic Score. The total and subtype concentrations of fecal AAs were elevated in UC patients and demonstrated a negative correlation with ESR and fecal calprotectin.

Conclusions: The increased levels of taste receptors and fecal AAs in the colon of UC patients suggest an abnormal nutrient-sensing mechanism, potentially playing a crucial role in the development of the disease.

Background: Limited data are available on the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). We describe the natural history of pre-existing IBD and de novo IBD after SOT.

Methods: This was a retrospective, multicenter study that included patients with pre-existing IBD at the time of SOT and patients with de novo IBD after SOT. The primary outcome was IBD progression, defined by escalation of medical treatment, surgical therapy, or hospitalization due to refractory IBD. Risk factors were identified using multivariate Cox proportional hazard analysis.

Results: A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) were included. Most patients with pre-existing IBD (92.5%) were in remission before SOT. During follow-up, 32% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 (interquartile range, 1.3-4.6) years. In the de novo cohort, 55% of patients had disease progression with a median time to flare of 1.9 (interquartile range, 0.8-3.9) years after diagnosis. In the pre-existing IBD cohort, active IBD at the time of SOT (hazard ratio, 1.80; 95% confidence interval, 1.14-2.84; P = .012) and the presence of extraintestinal manifestations (hazard ratio, 3.10; 95% confidence interval, 1.47-6.54; P = .003) were predictive factors for IBD progression.

Conclusions: One-third of patients with pre-existing IBD and about half of patients with de novo IBD have disease progression after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for IBD progression.

Background: Patients with inflammatory bowel disease (IBD) presenting to primary care may experience diagnostic delays. We aimed to evaluate this and assess whether time to diagnosis is associated with clinical outcomes.

Methods: A retrospective cohort study using English primary care data from January 1, 2010, to December 31, 2019, linked to hospital admission data was undertaken. Patients were followed from the first IBD-related presentation in primary care to IBD diagnosis. Associations of time to diagnosis exceeding a year were assessed using a Robust Poisson regression model. Associations between time to diagnosis and IBD-related emergency hospital admissions and surgery were assessed using Poisson and Cox proportional hazards models, respectively.

Results: Of 28 092 IBD patients, 60% had ulcerative colitis (UC) and 40% had Crohn's disease (CD). The median age was 43 (interquartile range, 30-58) years and 51.9% were female. Median time to diagnosis was 15.6 (interquartile range, 4.3-28.1) months. Factors associated with more than a year to diagnosis included female sex (adjusted risk ratio [aRR], 1.23; 95% CI, 1.21-1.26), older age (aRR, 1.05; 95% CI, 1.01-1.10; comparing >70 years of age with 18-30 years of age), obesity (aRR, 1.03; 95% CI, 1.00-1.06), smoking (aRR, 1.05; 95% CI, 1.02-1.08), CD compared with UC (aRR, 1.13; 95% CI, 1.11-1.16), and a fecal calprotectin over 500 μg/g (aRR, 0.89; 95% CI, 0.82-0.95). The highest quartile of time to diagnosis compared with the lowest was associated with IBD-related emergency admissions (incidence rate ratio, 1.06; 95% CI, 1.01-1.11).

Conclusion: Longer times to IBD diagnoses were associated with being female, advanced age, obesity, smoking, and Crohn's disease. More IBD-related emergency admissions were observed in patients with a prolonged time to diagnosis.

Background: Immune cell populations in the intestinal muscularis propria during colitis are poorly resolved. Maintaining homeostasis in this niche is critical, highlighted by the poorer prognosis of inflammatory bowel disease associated with muscularis propria inflammation.

Methods: This study utilizes single-cell RNA sequencing to survey the immune cell populations within the muscularis propria of normal colon and dextran sodium sulfate-induced colitis. Findings are validated by immunohistochemistry, flow cytometry and cell-lineage tracing in vivo, and in vitro assays with muscularis macrophages (MMφ).

Results: In naïve conditions, transcriptional duality is observed in MMφs with 2 major subpopulations: conventional resident Cx3cr1+ MMφs and Lyve1+ MMφs. The Lyve1+ population is phagocytic and expresses several known MMφ markers in mouse and human, confirming their identity as a bona fide MMφ subset. Single-cell transcriptomics indicate that resident MMφs are retained during colitis and exhibit plasticity toward an inflammatory profile. Lyve1+ MMφs, which express anti-inflammatory marker CD163, are absent during colitis, as confirmed by flow cytometry. In contrast, lineage tracing finds that resident Cx3cr1+ MMφs remain during colitis and are not completely replaced by the inflammatory infiltrating monocytes. In vitro studies provide biological evidence of the plasticity of resident Cx3cr1+ MMφs in response to lipopolysaccharide (LPS), mirroring transcriptional observations in vivo of their inflammatory plasticity. Potential markers for colitic MMφs, validated in animal models and in individuals with ulcerative colitis, are identified.

Conclusions: Our findings contribute to the understanding of the immune system in the muscularis propria niche during colitis by resolving the heterogeneity and origins of colitic MMφs.