Dataset Information

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

ABSTRACT:

Introduction

Intestinal 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).

Methods

Mucosal 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.

Results

Mucosal 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.

Conclusion

Butyrate-producing gut bacteria like F. prausnitzii regulate mucosal IL18 expression in a HIF1α-dependent manner that may aid in mucosal healing in IBD.

SUBMITTER: Fagundes RR

PROVIDER: S-EPMC10755969 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

<i>Faecalibacterium prausnitzii</i> promotes intestinal epithelial IL-18 production through activation of the HIF1α pathway.

Fagundes Raphael R RR Bravo-Ruiseco Gabriela G Hu Shixian S Kierans Sarah J SJ Weersma Rinse K RK Taylor Cormac T CT Dijkstra Gerard G Harmsen Hermie J M HJM Faber Klaas Nico KN

Frontiers in microbiology 20231214

<h4>Introduction</h4>Intestinal 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 <i>IL18</i> expression in inflammatory bowel disease (IBD).<h4>Methods</h4>Mucosal samples from patients with IBD (<i>n</i> = 760) were analyzed for bacterial composition, <i>IL18</i> levels and HIF1α pathway activation. Wild-type Caco- ...[more]

PMID: 38163085

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