Numerous reports have identified a dysbiosis in the intestinal microbiota in patients suffering from inflammatory bowel diseases (IBD), yet the mechanism(s) in which this complex microbial community initiates or perpetuates inflammation remains unclear. The purpose of this review is to present evidence for one such mechanism that implicates enteric microbial derived proteases in the pathogenesis of IBD. We highlight and discuss studies demonstrating that proteases and protease receptors are abundant in the digestive system. Additionally, we investigate studies demonstrating an association between increased luminal protease activity and activation of protease receptors, ultimately resulting in increased intestinal permeability and exacerbation of colitis in animal models as well as in human IBD. Proteases are essential for the normal functioning of bacteria and in some cases can serve as virulence factors for pathogenic bacteria. Although not classified as traditional virulence factors, proteases originating from commensal enteric bacteria also have a potential association with intestinal inflammation via increased enteric permeability. Reports of increased protease activity in stools from IBD patients support a possible mechanism for a dysbiotic enteric microbiota in IBD. A better understanding of these pathways and characterization of the enteric bacteria involved, their proteases, and protease receptors may pave the way for new therapeutic approaches for these diseases.

Background: Immune modulating therapies are associated with an increased risk of infections and malignancies. This is of particular concern in elderly inflammatory bowel disease patients. This study aims to compare the safety and efficacy of vedolizumab between young and elderly inflammatory bowel disease patients.Methods: A binational, multicentre, retrospective, cohort study was performed from 2015 to 2019. Patients who underwent treatment with vedolizumab and were followed for at least 14 weeks were studied. They were divided according to age into groups: 40 years or less or 60 years or older. Clinical and endoscopic responses at weeks 14 and 52 and infection development were compared between young and elderly inflammatory bowel disease patient groups.Results: There were 144 patients (82 Crohn’s disease and 62 ulcerative colitis) in the elderly cohort and 140 patients (83 Crohn’s disease and 57 ulcerative colitis) in the young cohort. The average age was 70.2 ± 7.3 years and 29.6 ± 5.7 years, respectively. Clinical and endoscopic responses were comparable between the groups (week 52 remission of Crohn’s disease: 40% vs. 35%, P = 0.7; week 52 remission of ulcerative colitis: 48% vs. 51%, P = 0.84). Previous anti‐tumour necrosis factor biological therapy was independently associated with poor clinical remission rates at week 52 (Crohn’s disease: odds ratio 0.23, 95% confidence interval 0.06–0.79; P = 0.02 and ulcerative colitis: odds ratio 0.10 95% confidence interval 0.01–0.74; P = 0.024). There were significantly more infections in the elderly cohort (2% vs. 12%, P = 0.002), none of which were fatal.Conclusions: Vedolizumab is equally effective in elderly and young inflammatory bowel disease patients. The findings of this study demonstrate an increased risk of infections among the elderly treated with vedolizumab, which may be related to their age and underlying diseases.

Heme oxygenase-1 (HO-1) and its enzymatic by-product carbon monoxide (CO) have emerged as important regulators of acute and chronic inflammation. Mechanisms underlying their anti-inflammatory effects are only partially understood. In this addendum, we summarize current understanding of the role of the HO-1/CO pathway in regulation of intestinal inflammation with a focus on innate immune function. In particular, we highlight our recent findings that HO-1 and CO ameliorate intestinal inflammation through promotion of bacterial clearance. Our work and that of many others support further investigation of this global homeostatic pathway in the human inflammatory bowel diseases (IBDs).

(1) Background: Malnutrition is a highly prevalent complication in patients with inflammatory bowel diseases (IBD). It is strongly associated with poor clinical outcomes and quality of life. Screening for malnutrition risk is recommended routinely; however, current malnutrition screening tools do not incorporate IBD specific characteristics and may be less adequate for screening these patients. Therefore, we aimed to identify IBD-related risk factors for development of malnutrition. (2) Methods: A retrospective case-control study among IBD patients attending the IBD clinic of the Tel-Aviv Medical Center for ≥2 consecutive physician consultations per year during 2017–2020. Cases who had normal nutritional status and developed malnutrition between visits were compared to matched controls who maintained normal nutritional status. Detailed information was gathered from medical files, including: demographics, disease phenotype, characteristics and activity, diet altering symptoms and comorbidities, medical and surgical history, annual healthcare utility, nutritional intake and the Malnutrition Universal Screening Tool (MUST) score. Univariate and multivariate analyses were used to identify malnutrition risk factors. The independent risk factors identified were summed up to calculate the IBD malnutrition risk score (IBD-MR). (3) Results: Data of 1596 IBD patients met the initial criteria for the study. Of these, 59 patients developed malnutrition and were defined as cases (n = 59) and matched to controls (n = 59). The interval between the physician consultations was 6.2 ± 3.0 months, during which cases lost 5.3 ± 2.3 kg of body weight and controls gained 0.2 ± 2.3 kg (p < 0.001). Cases and controls did not differ in demographics, disease duration, disease phenotype or medical history. Independent IBD-related malnutrition risk factors were: 18.5 ≤ BMI ≤ 22 kg/m² (OR = 4.71, 95%CI 1.13–19.54), high annual healthcare utility (OR = 5.67, 95%CI 1.02–31.30) and endoscopic disease activity (OR = 5.49, 95%CI 1.28–23.56). The IBD-MR was positively associated with malnutrition development independently of the MUST score (OR = 7.39, 95%CI 2.60–20.94). Among patients with low MUST scores determined during the index visit, identification of ≥2 IBD-MR factors was strongly associated with malnutrition development (OR = 8.65, 95%CI 2.21–33.82, p = 0.002). (4) Conclusions: We identified IBD-related risk factors for malnutrition, highlighting the need for a disease-specific malnutrition screening tool, which may increase malnutrition risk detection.