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

被引:6
作者
Fagundes, Raphael R. [1 ]
Bravo-Ruiseco, Gabriela [2 ]
Hu, Shixian [1 ]
Kierans, Sarah J. [3 ,4 ]
Weersma, Rinse K. [1 ]
Taylor, Cormac T. [3 ,4 ]
Dijkstra, Gerard [1 ]
Harmsen, Hermie J. M. [2 ]
Faber, Klaas Nico [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol & Infect Prevent, Groningen, Netherlands
[3] Univ Coll Dublin, Sch Med & Med Sci, Dublin, Ireland
[4] Univ Coll Dublin, Conway Inst, Dublin, Ireland
关键词
HIF1; alpha; IL-18; intestine; epithelial-bacteria interaction; HoxBan in vitro coculture system; Faecalibacterium; IBD; INFLAMMATORY-BOWEL-DISEASE; INDUCIBLE FACTOR-I; BARRIER FUNCTION; HYPOXIA; HIF; EXPRESSION; RECEPTOR; BUTYRATE; PERMEABILITY; REPRESSION;
D O I
10.3389/fmicb.2023.1298304
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 1 alpha (HIF1 alpha) 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 HIF1 alpha 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 HIF1 alpha pathway activation in patients with IBD. HIF1 alpha-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 HIF1 alpha-dependent manner that may aid in mucosal healing in IBD.
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页数:15
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