Fructooligosaccharides benefits on glucose homeostasis upon high-fat diet feeding require type 2 conventional dendritic cells

Adélaïde Gélineau, Geneviève Marcelin, Melissa Ouhachi, Sébastien Dussaud, Lise Voland, Raoul Manuel, Ines Baba, Christine Rouault, Laurent Yvan-Charvet, Karine Clément, Roxane Tussiwand, Thierry Huby and Emmanuel L. Gautier ()
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Adélaïde Gélineau: Hôpital de la Pitié-Salpêtrière
Geneviève Marcelin: NutriOmics
Melissa Ouhachi: Hôpital de la Pitié-Salpêtrière
Sébastien Dussaud: Hôpital de la Pitié-Salpêtrière
Lise Voland: NutriOmics
Raoul Manuel: Hôpital de la Pitié-Salpêtrière
Ines Baba: Hôpital de la Pitié-Salpêtrière
Christine Rouault: NutriOmics
Laurent Yvan-Charvet: Fédération Hospitalo-Universitaire (FHU) Oncoage
Karine Clément: NutriOmics
Roxane Tussiwand: National Institutes of Health
Thierry Huby: Hôpital de la Pitié-Salpêtrière
Emmanuel L. Gautier: Hôpital de la Pitié-Salpêtrière

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Diet composition impacts metabolic health and is now recognized to shape the immune system, especially in the intestinal tract. Nutritional imbalance and increased caloric intake are induced by high-fat diet (HFD) in which lipids are enriched at the expense of dietary fibers. Such nutritional challenge alters glucose homeostasis as well as intestinal immunity. Here, we observed that short-term HFD induced dysbiosis, glucose intolerance and decreased intestinal RORγt+ CD4 T cells, including peripherally-induced Tregs and IL17-producing (Th17) T cells. However, supplementation of HFD-fed male mice with the fermentable dietary fiber fructooligosaccharides (FOS) was sufficient to maintain RORγt+ CD4 T cell subsets and microbial species known to induce them, alongside having a beneficial impact on glucose tolerance. FOS-mediated normalization of Th17 cells and amelioration of glucose handling required the cDC2 dendritic cell subset in HFD-fed animals, while IL-17 neutralization limited FOS impact on glucose tolerance. Overall, we uncover a pivotal role of cDC2 in the control of the immune and metabolic effects of FOS in the context of HFD feeding.

Date: 2024
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DOI: 10.1038/s41467-024-49820-x

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