1. Butyrate mediates anti-inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through Dact3
- Author
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Sead Chadi, Marion Lenoir, Pamela González-Dávila, Harry Sokol, Philippe Langella, Luis G. Bermúdez-Humarán, Florian Chain, Rebeca Martín, Edgar Torres-Maravilla, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Vitagora Competitive Cluster, French Fond Unique Interministériel, n°F1010012D, Fonds Européen de Développement Régional (Bourgogne: 34606), Burgundy Region, the Conseil Général 21, and the Grand Dijon., Merck Médication Familiale (Dijon, France), Biovitis, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Tâche, Roselyne
- Subjects
Commensal bacteria ,signaling pathway ,0301 basic medicine ,Microbiology (medical) ,[SDV]Life Sciences [q-bio] ,Faecalibacterium prausnitzii ,Butyrate ,Gut flora ,Microbiology ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,inflammatory bowel disease ,transcriptomic analysis ,lcsh:RC799-869 ,biology ,Effector ,Gastroenterology ,Wnt signaling pathway ,biology.organism_classification ,3. Good health ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,Infectious Diseases ,lcsh:Diseases of the digestive system. Gastroenterology ,030211 gastroenterology & hepatology ,Signal transduction - Abstract
International audience; The commensal bacterium Faecalibacterium prausnitzii plays a key role in inflammatory bowel disease (IBD) pathogenesis and serves as a general health biomarker in humans. However, the host molecular mechanisms that underlie its anti-inflammatory effects remain unknown. In this study we performed a transcriptomic approach on human intestinal epithelial cells (HT-29) stimulated with TNF-α and exposed to F. prausnitzii culture supernatant (SN) in order to determine the impact of this commensal bacterium on intestinal epithelial cells. Moreover, modulation of the most upregulated gene after F. prausnitzii SN contact was validated both in vitro and in vivo. Our results showed that F. prausnitzii SN upregulates the expression of Dact3, a gene linked to the Wnt/JNK pathway. Interestingly, when we silenced Dact3 expression, the effect of F. prausnitzii SN was lost. Butyrate was identified as the F. prausnitzii effector responsible for Dact3 modulation. Dact3 upregulation was also validated in vivo in both healthy and inflamed mice treated with either F. prausnitzii SN or the live bacteria, respectively. Finally, we demonstrated by colon transcriptomics that gut microbiota directly influences Dact3 expression. This study provides new clues about the host molecular mechanisms involved in the anti-inflammatory effects of the beneficial commensal bacterium F. prausnitzii.
- Published
- 2020