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Merck
  • An IBD-associated pathobiont synergises with NSAID to promote colitis which is blocked by NLRP3 inflammasome and Caspase-8 inhibitors.

An IBD-associated pathobiont synergises with NSAID to promote colitis which is blocked by NLRP3 inflammasome and Caspase-8 inhibitors.

Gut microbes (2023-01-20)
Raminder Singh, Valerio Rossini, Stephen R Stockdale, Gonzalo Saiz-Gonzalo, Naomi Hanrahan, Tanya D' Souza, Adam Clooney, Lorraine A Draper, Colin Hill, Ken Nally, Fergus Shanahan, Stefan Andersson-Engels, Silvia Melgar
要旨

Conflicting evidence exists on the association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic worsening of inflammatory bowel disease (IBD). We hypothesized that the heterogeneous prevalence of pathobionts [e.g., adherent-invasive Escherichia coli (AIEC)], might explain this inconsistent NSAIDs/IBD correlation. Using IL10-/- mice, we found that NSAID aggravated colitis in AIEC-colonized animals. This was accompanied by activation of the NLRP3 inflammasome, Caspase-8, apoptosis, and pyroptosis, features not seen in mice exposed to AIEC or NSAID alone, revealing an AIEC/NSAID synergistic effect. Inhibition of NLRP3 or Caspase-8 activity ameliorated colitis, with reduction in NLRP3 inflammasome activation, cell death markers, activated T-cells and macrophages, improved histology, and increased abundance of Clostridium cluster XIVa species. Our findings provide new insights into how NSAIDs and an opportunistic gut-pathobiont can synergize to worsen IBD symptoms. Targeting the NLRP3 inflammasome or Caspase-8 could be a potential therapeutic strategy in IBD patients with gut inflammation, which is worsened by NSAIDs.

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Sigma-Aldrich
オルトバナジン酸ナトリウム, 99.98% trace metals basis
Sigma-Aldrich
エチレンジアミン四酢酸 二ナトリウム塩 溶液, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
Sigma-Aldrich
Anti-goat IgG (H+L)-Peroxidase antibody produced in donkey, affinity isolated antibody, lyophilized powder