Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn’s disease

GD and AWW receive core funding support from the Scottish Government’s Rural and Environmental Science and Analytical Services (RESAS) Division. JW was funded by the Wellcome Trust [Grant No. 098051]. JVL is funded by MRC New Investigator Grant (MR/P002536/1) and ERC Starting Grant (715662). JK is funded by NIHR: II-OL-1116-10027, NIH: R01-CA204403-01A1, Horizon H2020: ITN GROWTH. Imperial Biomedical Research Centre, SAGES research grant. Infrastructure support for this research was provided by the NIHR Imperial biomedical Research Centre (BRC). Microbiota analyses were carried out using the Maxwell computer cluster at the University of Aberdeen. We thank the Illumina MiSeq team at the Wellcome Sanger Institute for their assistance. This work was partially described in the Ph.D. thesis of KD (Retrieved 2020, Pediatric inflammatory bowel disease Monitoring, nutrition and surgery, https://pure.uva.nl/ws/files/23176012/Thesis_complete_.pdf).Peer reviewedPublisher PD

The PPARγ Agonist Rosiglitazone Impairs Colonic Inflammation in Mice with Experimental Colitis

Various animal models showed that peroxisome proliferator-activated receptor (PPAR)γ agonists, when given as a gavage shortly preceding colitis induction, protect against inflammatory bowel disease (IBD). We have examined the effects of 16 days rosiglitazone treatment via the diet prior to dextran sodium sulphate (DSS)-induced colitis in mice. After 7 days DSS in the drinking water, rosiglitazone-fed mice had lost significantly more weight than control mice. Rosiglitazone-treated mice had more diarrhea, weight of colon and spleen were increased, and length of colon was decreased. Histology showed that rosiglitazone-treated mice had more severe colitis, mainly caused by more ulceration, crypt loss, and edema. Immunofluorescence showed a loss of tight junction structure Zonula Occludens protein 1 (ZO-1) in colons of rosiglitazone-treated mice as compared to control mice. Also, serum amyloid P component (SAP) concentrations in plasma were increased. However, concentrations of tumor necrosis factor (TNF)-α and interferon (IFN)-γ in colon homogenates, and TNF-α in spleen homogenates were significantly decreased, whereas interleukin (IL)-10 in spleen homogenates was increased. Other cytokines (IL-2, IL-4, IL-6, IL-12p70 and monocyte chemotactic protein (MCP)-1) and myeloperoxidase (MPO) concentrations showed no differences. In conclusion, 16 days pretreatment with rosiglitazone impaired DSS-induced colitis in mice

Two Major Medicinal Honeys Have Different Mechanisms of Bactericidal Activity

Honey is increasingly valued for its antibacterial activity, but knowledge regarding the mechanism of action is still incomplete. We assessed the bactericidal activity and mechanism of action of Revamil® source (RS) honey and manuka honey, the sources of two major medical-grade honeys. RS honey killed Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa within 2 hours, whereas manuka honey had such rapid activity only against B. subtilis. After 24 hours of incubation, both honeys killed all tested bacteria, including methicillin-resistant Staphylococcus aureus, but manuka honey retained activity up to higher dilutions than RS honey. Bee defensin-1 and H2O2 were the major factors involved in rapid bactericidal activity of RS honey. These factors were absent in manuka honey, but this honey contained 44-fold higher concentrations of methylglyoxal than RS honey. Methylglyoxal was a major bactericidal factor in manuka honey, but after neutralization of this compound manuka honey retained bactericidal activity due to several unknown factors. RS and manuka honey have highly distinct compositions of bactericidal factors, resulting in large differences in bactericidal activity

Severe COVID-19: NLRP3 Inflammasome Dysregulated

SARS-CoV-2 might directly activate NLRP3 inflammasome resulting in an endogenous adjuvant activity necessary to mount a proper adaptive immune response against the virus. Heterogeneous response of COVID-19 patients could be attributed to differences in not being able to properly downregulate NLRP3 inflammasome activation. This relates to the fitness of the immune system of the individual challenged by the virus. Patients with a reduced immune fitness can demonstrate a dysregulated NLRP3 inflammasome activity resulting in severe COVID-19 with tissue damage and a cytokine storm. We sketch the outlines of five possible scenarios for COVID-19 in medical practice and provide potential treatment options targeting dysregulated endogenous adjuvant activity in severe COVID-19 patients

Critical appraisal of the current practice in murine TNBS-induced colitis

There is no standard practice in the induction of colitis by 2,4,6-trinitrobenzene sulfonic acid. In this review the current practice in 2,4,6-trinitrobenzene sulfonic acid colitis is studied using 20 recently published articles. We compare the different protocols, discuss the mechanism of disease and give recommendations for the future use of the mode

Apoptosis as a therapeutic paradigm in inflammatory bowel diseases

Evidence is increasing that a defect in apoptosis is involved in the pathogenesis of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). CD seems to be the cause of an intrinsic defect in the apoptotic pathway of (autoreactive) T cells, resulting in excessive T cell responses. In UC, an increased rate of apoptosis of epithelial cells is observed. In this review we will describe apoptotic mechanisms and their association to IBD. In addition, we will review how specific therapeutic approaches interact at different levels with the apoptotic pathwa

Analysis of cytokines and chemokines produced by whole blood, peripheral mononuclear and polymorphonuclear cells

Cytokines are immunomodulating proteins involved in cellular communication. The levels of different cytokines reflect the immune capabilities of a person. In literature both whole blood and peripheral blood mononuclear cells (PBMCs) are used, which might lead to different results. The choice between these different sources is not always explained. The goal of our experiments is to determine the cytokine response of whole blood, PBMCs and polymorphonuclear cells (PMNs) after stimulation with lipopolysaccharide (LPS). We used a multiplex analysis to determine a difference in cytokine secretion patterns. In general, PBMCs demonstrated the highest cytokine production and PMNs have an overall low cytokine production. CCL11 and interleukin-23 (IL-23) (and IL-12p40) were exclusively expressed in whole blood. IL-20, VEGF and GM-CSF were expressed only by PBMCs. This difference in expression could be explained by the bioactive components in serum, presence and interaction with granulocytes or platelets in whole blood, the anticoagulant heparin in whole blood and others. The expression of cytokines by cells is dependent on the microenvironment. Different conditions lead to different results. We recommend a thorough examination of the conditions before performing experiment