A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) are chronic intestinal disorders often characterized by a dysregulation of T cells, specifically T helper (Th) 1, 17 and T regulatory (Treg) repertoire. Increasing evidence demonstrates that dietary polyphenols from Mangifera indica L. extract (MIE, commonly known as mango) mitigate intestinal inflammation and splenic Th17/Treg ratio. In this study, we aimed to dissect the immunomodulatory and anti-inflammatory properties of MIE using a reverse translational approach, by initially using blood from an adult IBD inception cohort and then investigating the mechanism of action in a preclinical model of T cell-driven colitis. Of clinical relevance, MIE modulates TNF-α and IL-17 levels in LPS spiked sera from IBD patients as an ex vivo model of intestinal barrier breakdown. Preclinically, therapeutic administration of MIE significantly reduced colitis severity, pathogenic T-cell intestinal infiltrate and intestinal pro-inflammatory mediators (IL-6, IL-17A, TNF-α, IL-2, IL-22). Moreover, MIE reversed colitis-induced gut permeability and restored tight junction functionality and intestinal metabolites. Mechanistic insights revealed MIE had direct effects on blood vascular endothelial cells, blocking TNF-α/IFN-γ-induced up-regulation of COX-2 and the DP2 receptors. Collectively, we demonstrate the therapeutic potential of MIE to reverse the immunological perturbance during the onset of colitis and dampen the systemic inflammatory response, paving the way for its clinical use as nutraceutical and/or functional food.

Proposed pathway for therapeutic drug monitoring and dose escalation of vedolizumab.

Vedolizumab is a gut-selective monoclonal antibody approved for the management of Crohn's disease and ulcerative colitis. The available data demonstrate a favourable response to dose escalation in patients with primary non-response or secondary loss of response to vedolizumab. While therapeutic drug monitoring has a proven clinical utility for tumour necrosis factor antagonists, the available guidance for therapeutic drug monitoring and dose escalation of vedolizumab is rather limited. The present review proposes a practical algorithm to use vedolizumab trough levels in the management of treatment failure. Therapeutic drug monitoring can differentiate underexposed patients from those with mechanistic failure. Underdosed patients can respond to dose escalation instead of unnecessarily switching to other treatment modalities. We also review the safety and potential cost-effectiveness of vedolizumab dose escalation, the role of antidrug antibodies and the possible applicability of this strategy to subcutaneous vedolizumab.

COVID-19-related health anxieties and impact of specific interventions in patients with inflammatory bowel disease in the UK.

OBJECTIVE: Health-related concerns brought on by the COVID-19 pandemic and the impact of specific local and national interventions have not been explored in patients with inflammatory bowel disease (IBD) in the UK. We evaluated perspectives of patients with IBD on the pandemic and effectiveness of information dissemination in addressing concerns. METHODS: We prospectively conducted a survey among patients with IBD during the COVID-19 pandemic to assess concerns, information-seeking behaviours, risk perception, compliance and effect of specific interventions. RESULTS: A total of 228 patients were interviewed of whom 89% reported being concerned about the impact of COVID-19 on their health. Access to at least one IBD-specific clinical interaction during the pandemic (COVID-19 information letter from IBD team, interaction with IBD team or general practitioner, Crohn and Colitis UK website visit) was significantly associated with alleviating concerns (OR 2.66; 95% CI 1.35 to 5.24; p=0.005). Seeking health information solely through unofficial channels (search engines or social media) was less likely to ease concerns (OR 0.15; 95% CI 0.03 to 0.61; p=0.008). A quarter of patients disagreed with their assigned risk groups, with majority perceiving higher-risk profiles. This discordance was greatest in patients within the moderate-risk group and constituted immunosuppression use. Nearly 40% of patients had ongoing concerns with regard to their medications of whom a third felt their concerns were not addressed. CONCLUSION: IBD-specific clinical interactions are associated with alleviation of COVID-19 health concerns. These findings have wider implications and emphasise importance of innovative solutions that facilitate effective communication with patients without overburdening current services.