Inflammatory Bowel Diseases最新文献

Background: Down-Regulated in Adenoma (DRA) plays a critical role in intestinal chloride absorption and a decrease in its expression is a key event in diarrheal disorders. Recently, DRA has emerged as an Inflammatory Bowel Disease (IBD) susceptibility gene. Therefore, the strategies to upregulate DRA expression are potentially novel approaches to not only treat IBD-associated diarrhea but also gut inflammation. In this study, the effect of dexamethasone (DEX), an anti-inflammatory corticosteroid on DRA expression was investigated.

Methods: GR (glucocorticoid receptor) overexpressed Caco-2 cells and C57BL/6/J mice and anti-αIL-10R mAb model of IBD were used. Protein expression was assessed by immunoblotting and immunofluorescence. Transcript levels were assessed by quantative-real-time polymerase chain reaction (qRT-PCR) and promoter activity was measured by luciferase assays.

Results: Our results showed that DEX significantly increased DRA mRNA and protein expression in GR overexpressing Caco-2 cells. DEX-induced upregulation of DRA was GR dependent and appeared at least in part to occur via a transcriptional mechanism, as promoter activity of the DRA construct (-1183/+114 bp) was significantly increased in response to DEX. The increase in DRA mRNA was abrogated in the presence of MKP-1 inhibitor, triptolide. Administration of DEX (2 mg/kg body weight) to mice for 24 and 48 hours significantly increased the DRA expression in mouse colon. DEX treatment to mice for 7 days in the αIL-10R mAb model of colitis was able to significantly attenuate the gut inflammation and associated decrease in DRA expression.

Conclusions: We demonstrate that DEX stimulates DRA expression via transcriptional mechanisms and suggest that upregulation of DRA may contribute to both anti-inflammatory and pro-absorptive effects of DEX.

Background: Pouchitis is the most common complication of restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). We previously reported the presence of anti-integrin αvβ6 antibodies in the serum of patients with UC. This study investigated the association between anti-integrin αvβ6 antibodies and the development of pouchitis in patients with UC.

Methods: Serum levels of anti-integrin αvβ6 antibodies were measured by enzyme-linked immunosorbent assay in 16 patients with UC who underwent RPC with IPAA. Integrin αvβ6 expression in the colonic, terminal ileal, and pouch epithelium was examined using immunohistochemistry and western blot analysis.

Results: Anti-integrin αvβ6 antibody levels in patients with UC were significantly decreased at 3, 9, and 12 months after RPC (P < .05). However, in patients who developed pouchitis, antibody levels remained high. The antibody levels at the time of RPC were significantly higher in patients who developed pouchitis compared to those who did not. Kaplan-Meier analysis revealed a significantly higher incidence of pouchitis in patients with antibody levels above the cutoff at the time of RPC. Although integrin αvβ6 was not expressed in the terminal ileal epithelium at the time of RPC, expression became positive in the pouch epithelium of patients with pouchitis.

Conclusions: The anti-integrin αvβ6 antibody levels in patients with UC were decreased after RPC but remained high in patients who developed pouchitis. The antibody levels at the time of RPC may serve as a potential prognostic biomarker for predicting the risk of pouchitis in patients with UC.

Background: Several studies have reported low levels of physical activity (PA) in patients with inflammatory bowel diseases (IBD), possibly related to a lack of information and support, despite the many recognized benefits such as cardiovascular prevention or quality of life (QoL) improvement.

Methods: The purpose of our study was to identify challenges faced by patients and to evaluate IBD impact on PA and QoL by using the International Physical Activity Questionnaire short form and the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32) questionnaire, respectively. We also assessed the expectations and knowledge of patients and healthcare professionals using the MICI-Active questionnaire that we developed.

Results: We included 298 IBD patients in 4 French hospitals, with a mean age of 38 years. We found a decrease in training frequency since IBD diagnosis, regardless of age, gender, symptom intensity, or type of disease. Moreover, there was an increase in low intensity activities like walking and a decrease in competitions and sports club registrations. Intensity of symptoms has a negative impact on QoL, as evidenced by the worsening of IBDQ score. Conversely, a higher PA intensity was correlated with a higher IBDQ score, regardless of symptoms intensity. The main barrier to PA was fatigue (56%), and the main fear was diarrhea (42%). Furthermore, 75% of patients did not feel sufficiently informed, and 61% were interested in coaching. A total of 112 healthcare professionals were interviewed, 62.5% said they had already discussed of PA with their patients, but 98% felt that they lacked knowledge.

Conclusions: Inflammatory bowel disease constraints and symptoms have a strong impact on PA. Work needs to be done to better train practitioners to improve IBD patient management, who have much to gain from better PA.

Background: Despite reassuring clinical safety data, thrombocytosis, anemia, lymphopenia, and liver function derangements have been observed in infants born to women with inflammatory bowel disease (IBD) treated with thiopurines and biologics. We aimed to define the prevalence, course, associations, and clinical impact of hematological and biochemical abnormalities in such infants.

Methods: This multicenter prospective cohort study assessed clinical, hematologic, and biochemical outcomes of infants exposed to thiopurines or biologics in utero for management of maternal IBD. Liver transaminases, full blood examination, and infant thiopurine metabolites (where exposed) were taken at delivery and 6 weeks of age. Abnormal results were repeated until normalization. Infants were followed clinically by a pediatric gastroenterologist up to 2 years of age.

Results: A total of 130 infants were included. Thrombocytosis and elevated alanine transaminase (ALT) were seen in over half of infants up to 6 months of age with no significant clinical impact. Elevated ALT was associated with increasing maternal C-reactive protein in second trimester, while thrombocytosis was associated with increasing maternal C-reactive protein and fecal calprotectin in third trimester. Preceding infection and vaccination were associated with an increased risk of elevated alkaline phosphatase at 3 months. In those exposed to thiopurines, increasing maternal 6-methylmercaptopurine at delivery was associated with increased ALT to 6 months.

Conclusions: Infants born to women with IBD commonly developed thrombocytosis, elevated alkaline phosphatase, and elevated ALT. These findings were associated with exposure to maternal inflammation, elevated 6-methylmercaptopurine at delivery, and infant vaccinations and infections, and had minimal clinical consequence.

Background: Inflammatory bowel disease (IBD) significantly impacts patients and their families. To provide support, understanding the effects on the wider family is crucial. However, limited research exists on the impact of IBD on family members of adults diagnosed with IBD. This study addresses this knowledge gap.

Methods: Underpinned by interpretive phenomenology, this study used in-depth, semi-structured online interviews to explore relatives' experiences. Interviews were audio-recorded and transcribed verbatim. Data were analyzed using reflexive thematic analysis.

Results: Forty-three purposively selected interviewees comprising 17 people with IBD and 26 family members (parents, children, siblings, and partners) revealed 3 main themes: (1) "life is a rollercoaster," (2) "there have been a lot of bridges to cross along the way," and (3) "my life would be better if…" Participants highlighted that IBD has both positive and negative impacts on family members in terms of emotional well-being, relationship, roles and responsibilities, day-to-day burden, and sibling suffering. Some employed adaptive coping strategies such as creating social networks and open communication, while others relied on maladaptive coping strategies, such as avoidance and alcohol abuse. Family members expressed the need for proactive communication, information, and support from healthcare professionals.

Conclusions: IBD affects the emotional and psychosocial well-being of family members, eliciting both adaptive and maladaptive coping strategies. Healthcare professionals need to adopt a holistic approach to managing IBD that considers the psychosocial and emotional challenges faced by individuals and their families.

Background: Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial etiology, still incompletely understood. OCTN1, an organic cation transporter, could have a role in modulating the inflammatory response, and some genetic polymorphisms of this molecule have been associated with increased risk of inflammatory bowel diseases. Until now, limited information exists on its potential in predicting/modulating patient's response to therapies. The aim of this study was to evaluate the role of OCTN1 in modifying gut microbiota and mucosal immunity in response to infliximab therapy in murine colitis.

Methods: A dextran sodium sulphate model of colitis was used to assess the clinical efficacy of infliximab administered intravenously in ocnt1 gene knockout mice and their C57BL/6 controls. Stool, colon, and mesenteric lymph node samples were collected to evaluate differences in gut microbiota composition, histology, and T cell populations, respectively.

Results: Octn1 -/- influences the microbiota profile and is associated with a worse dysbiosis in mice with colitis. Infliximab treatment attenuates colitis-associated dysbiosis, with an increase of bacterial richness and evenness in both strains. In comparison with wild type, octn1-/- mice have milder disease and a higher baseline percentage of Treg, Tmemory, Th2 and Th17 cells.

Conclusions: Our data support the murine model to study OCTN1 genetic contribution to inflammatory bowel diseases. This could be the first step towards the recognition of this membrane transporter as a biomarker in inflammatory conditions and a predictor of response to therapies.

Background: Patients with inflammatory bowel diseases (IBDs) are more likely to have depression and anxiety symptoms compared with healthy individuals and those with other chronic illnesses. Previous studies have shown a link between the microbiome composition and depression symptoms; however, many antidepressant medications have antibacterial activity confounding cross-sectional studies of these populations. Therefore, we aimed to determine whether we could detect longitudinal changes in the microbiome of a subset of patients who participated in a previously published mindfulness-based cognitive therapy (MBCT) study to improve depression symptoms in adolescents and young adults with IBD.

Methods: Stool samples were collected at baseline and 8 weeks (n = 24 participants, 37 total samples, 13 paired samples). During this time, some participants achieved a 50% reduction in their depression symptoms either through MBCT or treatment as usual with their mental health team (responders). The microbiome composition and function of responders were compared with participants who did not improve their depression scores (nonresponders). Depression scores were determined using the depression, anxiety, and stress score (DASS-21), and metagenomic sequencing of stool samples was performed.

Results: No difference in alpha diversity was found between responders and nonresponders. Beta diversity measures were similarly unchanged. Clinical features including fecal calprotectin, C-reactive protein, and serum IL-6 levels were unchanged.

Conclusions: In this small longitudinal study, we were not able to detect longitudinal changes in the microbiome associated with improvement in depression scores. Follow-up studies that are sufficiently powered to detect changes in the microbiome are required to confirm our results.