Mutual modulation of gut microbiota and the immune system in type 1 diabetes models

Immunological disorders; Metabolic disorders; Molecular biologyTrastorns immunològics; Trastorns metabòlics; Biologia molecularTrastornos inmunológicos; Trastornos metabólicos; Biología MolecularThe transgenic 116C-NOD mouse strain exhibits a prevalent Th17 phenotype, and reduced type 1 diabetes (T1D) compared to non-obese diabetic (NOD) mice. A cohousing experiment between both models revealed lower T1D incidence in NOD mice cohoused with 116C-NOD, associated with gut microbiota changes, reduced intestinal permeability, shifts in T and B cell subsets, and a transition from Th1 to Th17 responses. Distinct gut bacterial signatures were linked to T1D in each group. Using a RAG-2−/− genetic background, we found that T cell alterations promoted segmented filamentous bacteria proliferation in young NOD and 116C-NOD, as well as in immunodeficient NOD.RAG-2−/− and 116C-NOD.RAG-2−/− mice across all ages. Bifidobacterium colonization depended on lymphocytes and thrived in a non-diabetogenic environment. Additionally, 116C-NOD B cells in 116C-NOD.RAG-2−/− mice enriched the gut microbiota in Adlercreutzia and reduced intestinal permeability. Collectively, these results indicate reciprocal modulation between gut microbiota and the immune system in rodent T1D models.This work was supported by the Plan Nacional de I + D + i of the Spanish Ministry of Science and Innovation (PID2019-109302RB-I00), the DiabetesCERO Foundation (Becas Impulso Talento Joven 2022), and CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) that is an initiative from Instituto de Salud Carlos III (Spain). E.R.-M. was supported by predoctoral fellowships from the Generalitat de Catalunya (AGAUR FI-DGR, grant number: 2013FI_B 00585), the Spanish Government (FPU, grant number: FPU13/02045) and the IRBLleida. M.C.-P., B.A., and L.E.-M. were supported by UdL and IRBLleida predoctoral fellowships. F. Y. was supported by a predoctoral fellowship from the Chilean Government (ANID, grant number: 72190278). G.S.-G. was supported by a predoctoral fellowship from VHIR

Changes in protein expression in mussels Mytilus galloprovincialis dietarily exposed to PVP/PEI coated silver nanoparticles at different seasons

Potential toxic effects of Ag NPs ingested through the food web and depending on the season have not been addressed in marine bivalves. This work aimed to assess differences in protein expression in the digestive gland of female mussels after dietary exposure to Ag NPs in autumn and spring. Mussels were fed daily with microalgae previously exposed for 24 hours to 10 µg/L of PVP/PEI coated 5 nm Ag NPs. After 21 days, mussels significantly accumulated Ag in both seasons and Ag NPs were found within digestive gland cells and gills. Two-dimensional electrophoresis distinguished 104 differentially expressed protein spots in autumn and 142 in spring. Among them, chitinase like protein-3, partial and glyceraldehyde-3-phosphate dehydrogenase, that are involved in amino sugar and nucleotide sugar metabolism, carbon metabolism, glycolysis/gluconeogenesis and the biosynthesis of amino acids KEGG pathways, were overexpressed in autumn but underexpressed in spring. In autumn, pyruvate metabolism, citrate cycle, cysteine and methionine metabolism and glyoxylate and dicarboxylate metabolism were altered, while in spring, proteins related to the formation of phagosomes and hydrogen peroxide metabolism were differentially expressed. Overall, protein expression signatures depended on season and Ag NPs exposure, suggesting that season significantly influences responses of mussels to NP exposure.This work has been funded by the Spanish Ministry of Economy and Competitiveness (NanoSilverOmics project MAT2012-39372), Basque Government (SAIOTEK project S-PE13UN142 and Consolidated Research Group GIC IT810-13) and the University of the Basque Country UPV/EHU (UFI 11/37 and PhD fellowship to N.D.). This study had also the support of Fundação para a Ciência e Tecnologia (FCT) from Portugal through the Strategic Project UID/MAH00350/2013 granted to CIMA. The contribution of K. Mehennaoui was possible within the project NanoGAM (AFR-PhD-9229040) and M. Mikolaczyk was supported by a PhD fellowship from the French Ministry of Higher Education and Research.info:eu-repo/semantics/acceptedVersio

Mutual modulation of gut microbiota and the immune system in type 1 diabetes models

Abstract The transgenic 116C-NOD mouse strain exhibits a prevalent Th17 phenotype, and reduced type 1 diabetes (T1D) compared to non-obese diabetic (NOD) mice. A cohousing experiment between both models revealed lower T1D incidence in NOD mice cohoused with 116C-NOD, associated with gut microbiota changes, reduced intestinal permeability, shifts in T and B cell subsets, and a transition from Th1 to Th17 responses. Distinct gut bacterial signatures were linked to T1D in each group. Using a RAG-2−/− genetic background, we found that T cell alterations promoted segmented filamentous bacteria proliferation in young NOD and 116C-NOD, as well as in immunodeficient NOD.RAG-2−/− and 116C-NOD.RAG-2−/− mice across all ages. Bifidobacterium colonization depended on lymphocytes and thrived in a non-diabetogenic environment. Additionally, 116C-NOD B cells in 116C-NOD.RAG-2−/− mice enriched the gut microbiota in Adlercreutzia and reduced intestinal permeability. Collectively, these results indicate reciprocal modulation between gut microbiota and the immune system in rodent T1D models