Inflammatory Bowel Diseases最新文献

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: 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.

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: Intestinal fibrosis, a complex complication of colitis, is characterized by excessive extracellular matrix (ECM) deposition. Estrogen receptor (ER) β may play a role in regulating this process.

Methods: Intestinal tissue samples from stenotic and nonstenotic regions were collected from Crohn's disease (CD) patients. RNA sequencing was conducted on a mouse model to identify differentially expressed mRNAs. Histological, immunohistochemical, and semiquantitative Western blotting analyses were employed to assess ECM deposition and fibrosis. The roles of relevant pathways in fibroblast transdifferentiation, activity, and migration were examined.

Results: Estrogen receptor β expression was found to be downregulated in the stenotic intestinal tissue of CD patients. Histological fibrosis score, collagen deposition, and profibrotic molecules in the colon of an intestinal fibrosis mouse model were significantly decreased after activation of ERβ. In vitro, ERβ activation alleviated transforming growth factor (TGF)-β-induced fibroblast activation and migration, as evidenced by the inhibition of col1α1, fibronectin, α-smooth muscle actin (α-SMA), collagen I, and N-cadherin expression. RNA sequencing showed that ERβ activation affected the expression of genes involved in ECM homeostasis and tissue remodeling. Enrichment analysis of differentially expressed genes highlighted that the downregulated genes were enriched in ECM-receptor interaction, TGF-β signaling, and Toll-like receptor (TLR) signaling. Western blotting confirmed the involvement of TGF-β/Smad and TLR4/MyD88/NF-κB signaling pathways in modulating fibrosis both in vivo and in vitro. The promoter activity of TGF-β1 and TLR4 could be suppressed by ERβ transcription factor.

Conclusion: Estrogen receptor β may regulate intestinal fibrosis through modulation of the TGF-β/Smad and TLR4/MyD88/NF-κB signaling pathways. Targeting ERβ activation could be a promising therapeutic strategy for treating intestinal fibrosis.