Inflammatory Bowel Diseases最新文献

Background: The consumption of ultra-processed foods has increased significantly worldwide and is associated with the rise in inflammatory bowel diseases. However, any causative factors and their underlying mechanisms are yet to be identified. This study aimed to further elucidate whether different types of the dietary emulsifier carrageenan (CGN) can alter the permeability and inflammatory state of the intestinal epithelium.

Methods: Caco-2/HT29-MTX cocultures (n = 4) were exposed to either κ-, ι-, or λ-CGN (100 µg mL-1) for 24 hours. Organoid-derived monolayers from patients with Crohn's Disease (CD) were exposed to κ-CGN (100 µg mL-1) for 48 hours (n = 10). In both models, an inflamed condition was established by adding a mix of inflammatory stimuli. Changes in permeability were measured by transepithelial electrical resistance (TEER). In the organoid-derived monolayers, cytokines were quantified in the apical and basolateral supernatant and gene expression was analyzed with RT-qPCR.

Results: None of the CGN subtypes altered permeability of non-inflamed or inflamed Caco-2/HT29-MTX cocultures. In organoid-derived monolayers, κ-CGN did not affect TEER, but induced alterations in the gene expression of tight junctions and mucus proteins. Expression of TNF, IL8, and IL1B increased upon κ-CGN stimulation, both in inflamed and non-inflamed monolayers. Cytokine release in the supernatant was increased by κ-CGN for IL-6, IL-13, IL-4, IL-2, and IL-10.

Conclusions: Dietary CGN caused upregulation of inflammatory markers and affected cytokine release of intestinal epithelial cells from CD patients, while permeability remained unaltered. When inflammation was already present, this pro-inflammatory effect was more pronounced, suggesting a role for dietary CGN during active CD.

Background: Defects in SLC26A3, the major colonic Cl-/HCO3- exchanger, result in chloride-rich diarrhea, a reduction in short-chain fatty acid (SCFA)-producing bacteria, and a high incidence of inflammatory bowel disease in humans and in mice. Slc26a3-/- mice are, therefore, an interesting animal model for spontaneous but mild colonic inflammation and for testing strategies to reverse or prevent the inflammation. This study investigates the effect of Escherichia coli Nissle (EcN) application on the microbiome, SCFA production, barrier integrity, and mucosal inflammation in slc26a3-/- mice.

Methods: In vivo fluid absorption and bicarbonate secretion were assessed in the gut of slc26a3+/+ and slc26a3-/- mice before and during luminal perfusion with 100 mM sodium acetate. Age-matched slc26a3+/+ and slc26a3-/- mice were intragastrically gavaged twice daily with 2 × 108 CFU/100 µL of EcN for 21 days. Body weight and stool water content were assessed daily, and stool and tissues were collected for further analysis.

Results: Addition of sodium acetate to the lumen of the proximal colon significantly increased fluid absorption and luminal alkalinization in the slc26a3-/- mice. Gavage with EcN resulted in a significant increase in SCFA levels and the expression of SCFA transporters in the slc26a3-/- cecum, the predominant habitat of EcN in mice. This was accompanied by an increase in mucus-producing goblet cells and a decrease in the expression of inflammatory markers as well as host defense antimicrobial peptides. EcN did not improve the overall diversity of the luminal microbiome but resulted in a significant increase in SCFA producers Lachnospiraceae and Ruminococcaceae in the slc26a3-/- feces.

Conclusions: These findings suggest that EcN is able to proliferate in the inflamed cecum, resulting in increased microbial SCFA production, decreased inflammation, and improved gut barrier properties. In sufficient dosage, probiotics may thus be an effective anti-inflammatory strategy in the diseased gut.

Background: Small bowel video capsule endoscopy (SB-VCE) assesses mucosal inflammation in Crohn's disease (CD), while intestinal ultrasound (IUS) examines transmural involvement. We aimed to correlate SB-VCE with IUS in evaluating active CD and monitoring treatment response over time.

Methods: Patients with active SB-CD who initiated biologics were prospectively followed with fecal calprotectin (FC), SB-VCE, and IUS at baseline and after 14 and 52 weeks. The Lewis score (LS), Limberg index (LI), and terminal ileum bowel wall thickness (TI-BWT) were documented, and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) was retrospectively calculated. Biochemical, endoscopic, and ultrasonographic remission were defined as FC < 150 μg/g, LS < 135, and LI < 2 + TI-BWT ≤ 3 mm, respectively. A therapeutic response for each index was defined as a 25% reduction compared to baseline.

Results: Seventy-one patients were included (median age: 30 years [23-43], 49.3% male). The median interval between SB-VCE and IUS was 3 days (0-25). Initially, the LS strongly correlated with TI-BWT (r = 0.647, P < .001), LI (r = 0.597, P < .001), and IBUS-SAS (r = 0.647, P < .001), but these correlations weakened over time (TI-BWT: r = 0.344, P = .002; LI: r = 0.471, P = .001; IBUS-SAS: r = 0.236, P = .122). Moderate agreement was found between ultrasonographic and endoscopic treatment responses (LS and TI-BWT: K = 0.51, P = .015; LS and LI: K = 0.44, P = .063), with fair agreement for remission (K = 0.27, P = .006). TI-BWT best cutoffs for mild (LS ≥ 135) and moderate-to-severe (LS ≥ 790) inflammation were 2.25 mm and 3.6 mm, respectively.

Conclusions: IUS measures are strongly correlated with VCE-inflammatory LS in active CD and may provide an assessment of endoscopic response and remission over time.

Background and aims: The emergence of biologic therapy has coincided with a decline in surgery rates for Crohn's disease (CD). This study aims to describe the disease course, including intra-abdominal surgery rates, biologic therapy use, and variables associated with biologic therapy initiation in a cohort of newly diagnosed CD patients.

Methods: The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study. From 2017 to 2019, newly diagnosed inflammatory bowel disease patients were included for prospective follow-up. The present study included CD patients ≥ 18 years. Clinical, endoscopic, and demographic data were collected at diagnosis and 1-year follow-up. Data were analyzed by using the Kaplan-Meier method and regression analyses.

Results: In total, 424 CD patients (median age 37.0 years (range 18-80), female 55.0%) were included. At diagnosis, 50.5% presented with ileal disease and 80.7% with inflammatory behavior. Within a 1-year follow-up, 39.6% of patients received their first biologic therapy and 5.2% required intra-abdominal surgery. Systemic steroid treatment, CRP ≥ 5.0 mg dL-1, Harvey-Bradshaw Index score > 4, ileocolonic disease and penetrating disease behavior at diagnosis were independently associated with increased risk of initiation of biologic therapy, while age > 40 years was associated with decreased risk.

Conclusion: A high proportion of patients had ileal disease and inflammatory behavior at diagnosis. Still, nearly 40% started biologic therapy within the 1-year follow-up, while only 5% required intra-abdominal surgery.

Background and aims: Transmural healing, including as assessed by magnetic resonance enterography (MRE) has been associated with long-term favorable outcomes in Crohn's Disease (CD), but data concerning MRE improvement and normalization with therapy are sparse. We performed a prospective longitudinal study utilizing the recently developed pediatric MRE-based multi-item measure of inflammation (PICMI) to examine the efficacy of adalimumab (ADA) and immunomodulator (IM) in attaining improvement of transmural inflammation of the small intestine.

Methods: Pediatric patients with CD involving small bowel and initiating ADA or IM were prospectively enrolled and followed with repeat MRE at 1 year. A single radiologist provided global assessment (RGA) and scored PICMI items (wall thickness, wall diffusion restriction, mural ulcers, comb sign, mesenteric edema) blinded to clinical information and to the timing of MRE. The primary outcome was mild improvement in PICMI at one year without a change in therapy.

Results: Sixty-two eligible patients were enrolled, 26 receiving ADA and 36 IM. On intent to treat basis, a decline in PICMI score of >20 points without change of therapy was observed more frequently in ADA versus IM-treated patients (54% vs 31%, P = .01). By RGA, 71% improved with ADA vs 42% with IM (P = .03). MRE normalization was rare with both treatments (9% vs 6%, P = .62). A change in PICMI of >20 points was confirmed as the best cut off for MRE improvement as assessed by RGA also for the small bowel.

Conclusions: ADA therapy was associated with objective improvement in MRE findings of inflammation more frequently than IM. The low rate of MRE normalization suggests that this is not yet a realistic target with existing therapies.

Strictures in inflammatory bowel disease, especially Crohn's disease (CD), are characterized by increased intestinal wall thickness, which, according to recent accumulating data, is mainly attributed to the expansion of the intestinal smooth muscle layers and to a lesser extent to collagen deposition. In this review, we will discuss the role of intestinal smooth muscle cells (SMCs) as crucial orchestrators of stricture formation. Activated SMCs can synthesize extracellular matrix (ECM), thus contributing to intestinal fibrosis, as well as growth factors and cytokines that can further enhance ECM production, stimulate other surrounding mesenchymal and immune cells, and increase SMC proliferation via paracrine or autocrine signaling. There is also evidence that, in stricturing CD, a phenotypic modulation of SMC toward a myofibroblast-like synthetic phenotype takes place. Moreover, the molecular mechanisms and signaling pathways that regulate SMC hyperplasia/hypertrophy will be extensively reviewed. The understanding of the cellular network and the molecular background behind stricture formation is essential for the design of effective anti-fibrotic strategies, and SMCs might be a promising therapeutic target in the future.