Title :

High-dose dietary supplementation with zinc prevents gut inflammation: investigation of the role of metallothioneins and beyond by transcriptomic and metagenomic studies

Author(s) :

Foligne, Benoit [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
George, Fanny [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Standaert, Annie [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Garat, Anne [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Poiret, Sabine [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Peucelle, Véronique [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Ferreira, Stephanie [Auteur]
Sobry, Helene [Auteur]
Muharram, Ghaffar [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Lucau, Anca [Auteur]
Institut Charles Viollette (ICV) - ULR 7394
Daniel, Catherine [Auteur]

Journal title :

FASEB journal . official publication of the Federation of American Societies for Experimental Biology

Abbreviated title :

FASEB J.

Publication date :

2020-07-30

ISSN :

1530-6860

Keyword(s) :

metallothionein
colitis
microbiota
mouse
transcriptomics
dietary zinc

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Although it is known that zinc has several beneficial roles in the context of gut inflammation, the underlying mechanisms have not been extensively characterized. Zinc (Zn) is known to be the primary physiological inducer ...
Show more >Although it is known that zinc has several beneficial roles in the context of gut inflammation, the underlying mechanisms have not been extensively characterized. Zinc (Zn) is known to be the primary physiological inducer of the expression of the metallothionein (MT) superfamily of small stress-responsive proteins. The expression of MTs in various tissues is induced or enhanced (including the gastrointestinal tract (GIT)) by a variety of stimuli, including infection and inflammation. However, the MTs' exact role in inflammation is still subject to debate. In order to establish whether or not MTs are the sole vectors in the Zn-based modulation of intestinal inflammation, we used transcriptomic and metagenomic approaches to assess the potential effect of dietary Zn, the mechanisms underlying the MTs' beneficial effects, and the induction of previously unidentified mediators. We found that the expression of endogenous MTs in the mouse GIT was stimulated by an optimized dietary supplementation with Zn. The protective effects of dietary supplementation with Zn were then evaluated in mouse models of chemically induced colitis. The potential contribution of MTs and other pathways was explored via transcriptomic analyses of the ileum and colon in Zn-treated mice. The microbiota's role was also assessed via fecal 16S rRNA sequencing. We found that high-dose dietary supplementation with Zn induced the expression of MT-encoding genes in the colon of healthy mice. We next demonstrated that the Zn diet significantly protected mice in the two models of induced colitis. When comparing Zn-treated and control mice, various genes were found to be differentially expressed in the colon and the ileum. Finally, we found that Zn supplementation did not modify the overall structure of the fecal microbiota, with the exception of (i) a significant increase in endogenous Clostridiaceae, and (ii) some subtle but specific changes at the family and genus levels. Our results emphasize the beneficial effects of excess dietary Zn on the prevention of colitis and inflammatory events in mouse models. The main underlying mechanisms were driven by the multifaceted roles of MTs and the other potential molecular mediators highlighted by our transcriptomic analyses although we cannot rule out contributions by other factors from the host and/or the microbiota.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
CNRS
Inserm
Institut Pasteur de Lille
Université de Lille

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
• IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2021-07-06T12:47:49Z
2022-11-29T09:35:01Z