Obesity-induced hyperglycemia impairs oral tolerance induction and aggravates food allergy

Lícia Torres, Mariana Camila Gonçalves Miranda, Vinícius Dantas Martins, Felipe Caixeta, Mariana de Almeida Oliveira, Luísa Martins Trindade, Helder Carvalho de Assis, Valbert Nascimento, Natália Pinheiro Rosa, Eliane Gomes, Sophia Oliveira Almeida, Florian Marquet, Laurent Genser, Genevieve...

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Nota geral Agradecimentos: We thank Dr. Judith Aron-Wisnewsky, and Prof Christine Poitou (nutrition department, Pitié-Salpêtrière hospital, Paris) for patients’ recruitment, and Dr Florence Marchelli for patients’ data management. Leda Quercia Vieira, Leonardo Vaz, and Ana Elisa Nolasco for the use of her... Ver mais Agradecimentos: We thank Dr. Judith Aron-Wisnewsky, and Prof Christine Poitou (nutrition department, Pitié-Salpêtrière hospital, Paris) for patients’ recruitment, and Dr Florence Marchelli for patients’ data management. Leda Quercia Vieira, Leonardo Vaz, and Ana Elisa Nolasco for the use of her laboratory’s equipment. Ilda Marçal and Hermes Ribeiro for mice facility care. Adaliene de Matos Versiane Ferreira to coordinate the Capes-COFECUB program. This work was supported by research grants from Fundação de Apoio à Pesquisa do Estado de Minas Gerais - FAPEMIG ((APQ 00704-14, RED 00140-16) and Pro-Reitoria de Pesquisa (PRPq) UFMG. LT, VMD, MAO, and LMT are recipients of scholarships, and TUM, MR, and AMCF are fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). NPR and HC are recipients of scholarships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). We acknowledge the Fondation pour la Recherche Medicale, the French National Agency of Research (Captor program), the European Foundation for the Study of Diabetes, the research program CAPES (Coordenação de Aperfeiçooamento de Pessoal de Nível Superior)/COFECUB (Comité Français d'Évaluation de la Coopération Universitaire et Scientifique avec le Brésil), as well as Novo Nordisk foundation (Jacobaus prize to KC) Ver menos

Resumo Abstract: Obesity and type 2 diabetes (T2D) have been found to be associated with abnormalities in several organs, including the intestine. These conditions can lead to changes in gut homeostasis, compromising tolerance to luminal antigens and increasing susceptibility to food allergies. The... Ver mais Abstract: Obesity and type 2 diabetes (T2D) have been found to be associated with abnormalities in several organs, including the intestine. These conditions can lead to changes in gut homeostasis, compromising tolerance to luminal antigens and increasing susceptibility to food allergies. The underlying mechanisms for this phenomenon are not yet fully understood. In this study, we investigated changes in the intestinal mucosa of diet-induced obese mice and found that they exhibited increased gut permeability and reduced Treg cells frequency. Upon oral treatment with ovalbumin (OVA), obese mice failed to develop oral tolerance. However, hyperglycemia treatment improved intestinal permeability and oral tolerance induction in mice. Furthermore, we observed that obese mice exhibited a more severe food allergy to OVA, and this allergy was alleviated after treatment with a hypoglycemic drug. Importantly, our findings were translated to obese humans. Individuals with T2D had higher serum IgE levels and downregulated genes related to gut homeostasis. Taken together, our results suggest that obesity-induced hyperglycemia can lead to a failure in oral tolerance and to exacerbation of food allergy. These findings shed light on the mechanisms underlying the relationship among obesity, T2D, and gut mucosal immunity, which could inform the development of new therapeutic approaches Ver menos

Nota de informação sobre financiamento

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAIS - FAPEMIG

APQ 00704-14; RED 00140-16

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ

COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES

Direito de acesso

Aberto

Assuntos

Mucosa intestinal

Obesidade

Hiperglicemia

Hipersensibilidade alimentar