Frontiers in Microbiology (Dec 2023)

Faecalibacterium prausnitzii promotes intestinal epithelial IL-18 production through activation of the HIF1α pathway

  • Raphael R. Fagundes,
  • Gabriela Bravo-Ruiseco,
  • Shixian Hu,
  • Sarah J. Kierans,
  • Rinse K. Weersma,
  • Cormac T. Taylor,
  • Gerard Dijkstra,
  • Hermie J. M. Harmsen,
  • Klaas Nico Faber

DOI
https://doi.org/10.3389/fmicb.2023.1298304
Journal volume & issue
Vol. 14

Abstract

Read online

IntroductionIntestinal epithelial cells produce interleukin-18 (IL-18), a key factor in promoting epithelial barrier integrity. Here, we analyzed the potential role of gut bacteria and the hypoxia-inducible factor 1α (HIF1α) pathway in regulating mucosal IL18 expression in inflammatory bowel disease (IBD).MethodsMucosal samples from patients with IBD (n = 760) were analyzed for bacterial composition, IL18 levels and HIF1α pathway activation. Wild-type Caco-2 and CRISPR/Cas9-engineered Caco-2-HIF1A-null cells were cocultured with Faecalibacterium prausnitzii in a “Human oxygen-Bacteria anaerobic” in vitro system and analyzed by RNA sequencing.ResultsMucosal IL18 mRNA levels correlated positively with the abundance of mucosal-associated butyrate-producing bacteria, in particular F. prausnitzii, and with HIF1α pathway activation in patients with IBD. HIF1α-mediated expression of IL18, either by a pharmacological agonist (dimethyloxallyl glycine) or F. prausnitzii, was abrogated in Caco-2-HIF1A-null cells.ConclusionButyrate-producing gut bacteria like F. prausnitzii regulate mucosal IL18 expression in a HIF1α-dependent manner that may aid in mucosal healing in IBD.

Keywords