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:10.3389/fmicb.2023.1298304

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^*

^*Corresponding author voor dit werk

Onderzoeksoutput › Academic › peer review

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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.

Originele taal-2	English
Artikelnummer	1298304
Aantal pagina's	15
Tijdschrift	Frontiers in Microbiology
Volume	14
DOI's	https://doi.org/10.3389/fmicb.2023.1298304
Status	Published - 14-dec.-2023

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@article{d43787df21934bd9ba740db3374b7124,

title = "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. ",

author = "Fagundes, {Raphael R} and Gabriela Bravo-Ruiseco and Shixian Hu and Kierans, {Sarah J} and Weersma, {Rinse K} and Taylor, {Cormac T} and Gerard Dijkstra and Harmsen, {Hermie J M} and Faber, {Klaas Nico}",

note = "Copyright {\textcopyright} 2023 Fagundes, Bravo-Ruiseco, Hu, Kierans, Weersma, Taylor, Dijkstra, Harmsen and Faber.",

year = "2023",

month = dec,

day = "14",

doi = "10.3389/fmicb.2023.1298304",

language = "English",

volume = "14",

journal = "Frontiers in Microbiology",

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T1 - Faecalibacterium prausnitzii promotes intestinal epithelial IL-18 production through activation of the HIF1α pathway

AU - Fagundes, Raphael R

AU - Bravo-Ruiseco, Gabriela

AU - Hu, Shixian

AU - Kierans, Sarah J

AU - Weersma, Rinse K

AU - Taylor, Cormac T

AU - Dijkstra, Gerard

AU - Harmsen, Hermie J M

AU - Faber, Klaas Nico

PY - 2023/12/14

Y1 - 2023/12/14

N2 - 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.

AB - 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.

U2 - 10.3389/fmicb.2023.1298304

DO - 10.3389/fmicb.2023.1298304

M3 - Article

C2 - 38163085

SN - 1664-302X

VL - 14

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

M1 - 1298304

ER -

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

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