Inulin prebiotic ameliorates type 1 diabetes dictating regulatory T cell homing via CCR4 to pancreatic islets and butyrogenic gut microbiota in murine model

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Guimaraes, Jhefferson Barbosa ; Rodrigues, Vanessa Fernandes ; Pereira, Italo Sousa ; Manso, Gabriel Martins da Costa ; Elias-Oliveira, Jefferson ; Leite, Jefferson Antonio ; Waldetario, Mariana Camila Goncalves Miranda ; de Oliveira, Sarah ; Gomes, Arilson Bernardo dos Santos Pereira ; Faria, Ana Maria Caetano ; Ramos, Simone Gusmao ; Bonato, Vania L. D. ; Silva, Joao Santana ; Vinolo, Marco Aurelio Ramirez ; Sampaio, Ulliana Marques ; Clerici, Maria Teresa Pedrosa Silva ; Carlos, Daniela

• Document type: Journal article
• Source: Journal of Leukocyte Biology; v. 115, n. 3, p. 14-pg., 2023-11-21.

Abstract

Gut dysbiosis is linked to type 1 diabetes mellitus (T1D). Inulin (INU), a prebiotic, modulates the gut microbiota, promoting beneficial bacteria that produce essential short-chain fatty acids for immune regulation. However, how INU affects T1D remains uncertain. Using a streptozotocin-induced (STZ) mouse model, we studied INU's protective effects. Remarkably, STZ + INU mice resisted T1D, with none developing the disease. They had lower blood glucose, reduced pancreatic inflammation, and normalized serum insulin compared with STZ + SD mice. STZ + INU mice also had enhanced mucus production, abundant Bifidobacterium, Clostridium cluster IV, Akkermansia muciniphila, and increased fecal butyrate. In cecal lymph nodes, we observed fewer CD4+Foxp3+ regulatory T cells expressing CCR4 and more Foxp3+CCR4+ cells in pancreatic islets, with higher CCL17 expression. This phenotype was absent in CCR4-deficient mice on INU. INU supplementation effectively protects against experimental T1D by recruiting CCR4+ regulatory T cells via CCL17 into the pancreas and altering the butyrate-producing microbiota. (AU)

• FAPESP's process: 19/13858-0 - Effect of administration of Bifidobacterium longum, with or without inulin prebiotic, on the production of AGCC and on the immunoregulation of DM1 in an experimental model
• Grantee: Jhefferson Barbosa Guimarães
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/14815-0 - Evaluation of the intestinal microbioma profile and of the therapeutic potential of intervention strategies in the immunopathogeny of type 1 and 2 Diabetes
• Grantee: Daniela Carlos Sartori
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2