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Open AccessArticle

Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights

1
Univ. Lille, Inserm, CHU Lille, U995—LIRIC—Lille Inflammation Research International Center, F-59000 Lille, France
2
Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019—UMR 8204—CIIL—Center for Infection and Immunity of Lille, F-59000 Lille, France
3
Univ. Lille, Inserm, CHU Lille, CIC 1403, Centre D’Investigation Clinique, F-59000 Lille, France
4
Service des Maladies de L’Appareil Digestif et de la Nutrition, CHU Lille, F-59000 Lille, France
*
Author to whom correspondence should be addressed.
Cells 2019, 8(6), 577; https://doi.org/10.3390/cells8060577
Received: 30 April 2019 / Revised: 29 May 2019 / Accepted: 6 June 2019 / Published: 12 June 2019
An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn’s disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn’s disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules. View Full-Text
Keywords: helminth protein; immunization; inflammatory bowel diseases; fecal microbiota; fecal transplantation; mice; humans helminth protein; immunization; inflammatory bowel diseases; fecal microbiota; fecal transplantation; mice; humans
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Foligné, B.; Plé, C.; Titécat, M.; Dendooven, A.; Pagny, A.; Daniel, C.; Singer, E.; Pottier, M.; Bertin, B.; Neut, C.; Deplanque, D.; Dubuquoy, L.; Desreumaux, P.; Capron, M.; Standaert, A. Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights. Cells 2019, 8, 577.

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