Intestinal Research最新文献

Background/aims: The gut microbiota plays a crucial role in the pathogenesis and treatment of inflammatory bowel diseases (IBD). This study aimed to investigate the effects of active, heat-inactivated, and cell-free supernatant (CFS) forms of Bacteroides thetaiotaomicron, alone or in combination with infliximab, in dextran sodium sulfate (DSS)-induced colitis in mice. Colitis was induced by oral administration of DSS for seven days. B. thetaiotaomicron in its various forms was orally administered at a dose of 1 × 108 CFU prior to and during colitis induction. Infliximab was intraperitoneally injected from days 3 to 5 of DSS exposure. Colitis severity, gene expression, tumor necrosis factor alpha levels, and gut microbiota were assessed by disease activity index, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and qPCR, respectively.

Results: Active B. thetaiotaomicron and its CFS form significantly alleviated colitis symptoms compared to the heat-inactivated form. Furthermore, co-administration of active B. thetaiotaomicron and infliximab significantly modulated the colonic mRNA expression of Ocln, Tff3, Muc2 (upregulated), and Ace2 (downregulated). This combination also exhibited synergistic improvement in colitis severity in treated mice.

Conclusions: These findings underscore the therapeutic potential of B. thetaiotaomicron in IBD, either alone or in combination with infliximab, and support further development of microbiota-based strategies for IBD prevention and treatment.

Background/aims: Endoscopy serves as the gold standard for assessing disease activity in inflammatory bowel disease (IBD). Noninvasive biomarkers have been under exploration as potential alternatives. This study aims to examine the diagnostic effectiveness of fecal immunochemical tests, along with levels of fecal calprotectin (FC) and fecal lactoferrin (FL), in stool samples from patients with early-onset IBD.

Methods: Children with childhood-onset IBD who visited the Department of Pediatrics and Adolescent Medicine at Juntendo University Hospital between August 2019 and July 2023 were included. FC levels, FL levels, and fecal immunochemical test results were measured using a colloidal gold agglutination assay. Fecal biomarker results and endoscopic findings were reviewed retrospectively.

Results: Sixty-five patients had ulcerative colitis (UC), 20 had Crohn's disease (CD), and 3 had unclassified IBD. The participants, aged 3-27 years (median, 18.0 years), included 56 males and 32 females. Stool samples (n = 1,105) were analyzed, from 803 with UC, 251 with CD, and 51 with IBD. Endoscopic evaluations were conducted in 45 UC patients and 18 CD patients. A significant correlation was found between the FC and FL. These biomarkers were significantly correlated with the endoscopic activity index in both UC and CD patients.

Conclusions: FC is valuable for diagnosing endoscopic inflammation and predicting recurrence. A significant correlation was observed between FC and FL. In patients with UC and CD, both markers strongly correlated with endoscopic activity. Thus, FC and FL can serve as a reliable alternative to endoscopic evaluation in pediatric patients with childhood-onset IBD.

Background/aims: The introduction of anti-tumor necrosis factor-α antibodies transformed the landscape of inflammatory bowel disease (IBD) treatment. Because biologics are associated with increased medical costs, the use of biosimilars (BS) is recommended. However, high-quality evidence on the efficacy of BS in Japan remains limited. Therefore, this study aimed to evaluate the efficacy and safety of BS in patients with IBD.

Methods: Patients with IBD who underwent a non-medical switch (NMS) from infliximab originator (IFX-O) to IFX-BS at Fukuoka University Chikushi Hospital were prospectively evaluated. The observation period was up to 56 weeks after the NMS, and the rate of continuation, clinical remission at 56 weeks, safety, and changes in trough concentration were analyzed. Moreover, a questionnaire survey regarding BS and NMS was conducted.

Results: A total of 167 patients were included in this study. The continuation rate for IFX-BS therapy after NMS was high (95.6%). The remission maintenance rate at 56 weeks was 85.7% for patients with Crohn's disease and 77.8% for patients with ulcerative colitis. Adverse events were observed in 22.8% of patients. However, only 2 severe adverse events were recorded. The ratios of trough concentrations at 8, 24, and 56 weeks to that at week 0 were 115.6%, 101.2%, and 123.5%, respectively, indicating statistical non-inferiority. In a questionnaire survey, only 6.2% of the patients were aware of BS, however, more than half of them agreed with the NMS recommendation.

Conclusions: The efficacy and safety of IFX-BS after NMS are high. In addition, its trough concentration is serologically non-inferior to baseline values.

The incidence of rectal neuroendocrine tumors has been gradually increasing, primarily due to the widespread use of screening colonoscopy and growing awareness of the disease. Most rectal neuroendocrine tumors are small ( < 10 mm), well-differentiated, and low-grade lesions at the time of diagnosis, and they are usually asymptomatic. Given these characteristics, endoscopic resection is considered a feasible treatment option for early-stage lesions. However, due to their inherent malignant potential, a comprehensive initial diagnostic evaluation is essential. Lymph node or distal metastasis can be present at diagnosis or may develop long after apparently successful primary treatment. Therefore, achieving complete resection using the most optimal resection method is crucial. Modified endoscopic mucosal resection and endoscopic submucosal dissection are recommended over conventional forceps or snare polypectomy, which are associated with high incomplete resection rates. In case of incomplete resection, additional endoscopic resection can be a feasible option in selected cases. Furthermore, regular post-resection surveillance is needed, especially in patients with high-risk of recurrence such as poor pathologic result or incomplete resection.

Background/aims: Surgery remains a crucial treatment option for Crohn's disease (CD), even with the introduction of biological agents. This nationwide cohort study in Taiwan investigates surgery trends and the impacts of biologics in a region with a low prevalence of CD.

Methods: This retrospective population-based cohort study used Taiwan's National Health Insurance Database from 2003 to 2018. The cohort included 725 CD patients. Patient characteristics, surgery outcomes, and impact of the biologic era on surgical risk were analyzed.

Results: During the study period, 292 CD patients (40.3%) underwent surgery, with 125 in the pre-biologic era and 167 in the post-biologic era. The incidences of intestinal surgery (IS) and perianal surgery (PS) have significantly decreased. The cumulative probabilities of IS were 20%, 35%, and 44% after 1, 5, and 10 years, respectively; the PS incidences were 3%, 5%, and 7%, respectively. The cumulative incidence of IS was significantly lower in the post-biologic era compared to the pre-biologic era (P= 0.049). CD patients had high second IS incidences of 31% at 5 years after the first IS.

Conclusions: Our study demonstrates the surgical incidences have decreased in the biologic era but remained relatively high in a region with low disease prevalence. This suggests the need for further improvements in CD management.

Background/aims: A previous health insurance claims study of Japanese patients with newly diagnosed Crohn's disease (CD) reported an increase in "step-up" approach from 2010 to 2020, with biologic use in the first year remaining stable. This study examined systemic corticosteroid (SCS) use for newly diagnosed CD in Japan and compared patients who were escalated ("step-up") and were not escalated to biologics.

Methods: This retrospective longitudinal cohort study used health insurance claims data (JMDC database). Patients diagnosed with CD from 2010 to 2020 who had no CD-related claims for ≥ 1 year before index, were traceable for ≥ 1 year after index, and treated with ≥ 1 pre-defined treatment were included. Patients classified by SCS and/or biologic use within 1 year after diagnosis were compared.

Results: Of 823 patients, 379 (46.1%) received SCS in the first year; of these, 43.5% escalated to biologics (step-up group) and 56.5% did not (SCS group). The proportion of patients receiving SCS increased from 25.8% in 2010-2011 to 55.5% in 2020; proportion escalated to biologics increased from 33.8% in 2016-2017 to 51.0% in 2020. The step-up group was significantly younger, more likely to have perianal lesions, and received more intensive treatments than the SCS group. In terms of SCS use, the step-up group was more likely to have shorter time-to-SCS initiation, and a higher initial SCS dose, than the SCS group.

Conclusions: Escalation from SCS to biologics in Japanese patients with newly diagnosed CD increased between 2016 and 2020, particularly in patients with younger onset CD or perianal complications.

Inflammatory bowel disease (IBD) is characterized by the presence of gastrointestinal inflammation, that in some individuals leads on to complications, including strictures. IBD can be associated with significant morbidity with disruption of daily activities. Although the precise cause of IBD is unknown, epidemiologic studies indicate that diet is one contributory factor. Furthermore, various specific nutritional interventions have roles in the management of IBD. While the contribution of the Mediterranean diet (MedDiet) to the development or management of IBD has not yet been clearly delineated, available data are generally supportive. The MedDiet includes the consumption of a pattern of particular foods, such as plentiful vegetables, fruit, seafood, and olive oil, along with lifestyle features. Adherence to a MedDiet is associated with enrichment of beneficial components of the intestinal microbiome and enhanced barrier function: outcomes that are likely beneficial to individuals with IBD. The focus of this review was to highlight the evidence for the MedDiet in the setting of IBD, whilst giving an overview of the underlying health impacts of the MedDiet and the putative mechanisms of this dietary approach.

Background/aims: Timely detection with highly accurate biomarkers would be helpful in effectively managing colorectal cancer (CRC). We aim to investigate the accuracy of 3 emerging biomarkers-miR-21, miR-24, and miR-145-in detecting synchronous metastases in CRC.

Methods: We recruited newly diagnosed CRC patients with extensive investigations to determine cancer staging and metastatic status. The expression levels of miR-21, miR-24, and miR-145 in tumor biopsy were measured using reverse transcription quantitative polymerase chain reaction. Multivariate and receiver operating characteristic analyses were conducted to evaluate the association and performance of these miRNAs in identifying various metastases.

Results: Out of the 63 Indonesian patients involved, 37 (58.7%) were diagnosed with localized CRC, whereas the remaining 26 (41.3%) were identified as having metastases: 31.7% liver, 14.3% lung, 3.2% bone, and 4.8% other metastases. There was a significant downregulation of miR-24 expression in metastatic CRC patients compared to those without metastases (0.024 [4.680] vs. 12.900 [42.376], P< 0.01). Overexpression of miR-21 was identified as an independent risk factor of synchronous metastasis (odds ratio [OR], 1.016; 95% confidence interval [CI], 1.003-1.030; P< 0.05), particularly lung (OR, 1.011; 95% CI, 1.002-1.020; P< 0.05) and bone (OR, 1.022; 95% CI, 1.001-1.043; P< 0.05) metastases. No association was found between miR-145 expression and metastatic status. The miR-21/24 ratio accurately identified synchronous metastases irrespective of organ site, with an area under the curve (95% CI) of 0.833 (0.722-0.944) and positive predictive value of 94.4%.

Conclusions: Alteration of miR-21 and miR-24 expression levels was associated with a high incidence of synchronous metastases in Indonesian CRC. The mir-21/24 ratio demonstrated significant potential as a biomarker for detecting synchronous metastases in CRC.

The rising incidence of ulcerative colitis (UC) globally highlights the necessity for treatment strategies that extend beyond symptom control to include inducing and maintaining remission, achieving biochemical and endoscopic remission, and restoring quality of life. Janus kinase inhibitors, such as filgotinib (FIL), show promise in treating UC. This review consolidates evidence on FIL in treating UC from the SELECTION and SELECTIONLTE trials, and real-world studies. Overall, FIL demonstrated rapid symptom relief (e.g., improved rectal bleeding and stool frequency) within 7 days and durable efficacy (e.g., clinical remission, Mayo Clinic Score response) up to 4 years. Improvements in health-related quality of life (HRQoL) and reduced corticosteroid dependency were also observed. The 200 mg dose generally elicited greater efficacy responses than the 100 mg dose, and hence may potentially be a more suitable choice for optimizing treatment outcomes. Although FIL may be an effective long-term treatment option regardless of prior biologic experience, biologic-naive patients may experience greater sustained clinical improvements. Safety outcomes indicated that FIL was well tolerated with no unexpected safety signals in SELECTION and SELECTIONLTE. These findings support FIL's potential as a robust therapeutic option for UC, due to its acceptable safety profile and benefits across clinical and HRQoL outcomes.

Background/aims: The gender-specific impact of inflammatory bowel disease (IBD) on women in low- and middle-income countries remains underexplored. We aimed to assess the effects of IBD on different domains of women's health.

Methods: A cross-sectional study was conducted in women with IBD at a tertiary care center in North India. Women with IBD were interviewed using a structured questionnaire assessing menstrual, reproductive, sexual, mental, social, and financial health, and healthcare access.

Results: Two hundred and two women (median age, 41 years; ulcerative colitis [n = 155, 76.7%]) were enrolled. Anemia was present in 161 women (79.7%), with a median hemoglobin of 10.5 g/dL. Among menstruating women (n = 138), 69 (50%) had irregular cycles, and 39 (28.3%) experienced IBD exacerbations during menstruation. Sexual dysfunction was reported in 82.5% (n = 137/166). Pregnancy-related concerns were common (n= 120, 59.4%), mainly due to risk of heritability and safety of IBD medication. Ten women (4.9%) attributed pregnancy loss to disease activity. Cervical cancer screening (3.0%) and human papillomavirus vaccination (4.0%) rates were low. The median SICC-IBD (social impact of chronic conditions in IBD) score was 0.6. Forty-three women (21.3%) reported difficulties in finding a partner due to IBD. Limited access to IBD specialists (n = 150, 74.3%) and medications (n = 164, 81.2%) were reported in hometown. Fifty-five women (27.2%) relied on loans to manage treatment expenses.

Conclusions: IBD affects women across physical, reproductive, social, and financial domains. Culturally sensitive, multidisciplinary care models are essential to address these unmet needs.