Akkermansia muciniphila restrains type 1 diabetes onset by eliciting cDC2 and Treg cell differentiation in NOD and STZ-induced experimental models

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Rodrigues, Vanessa Fernandes ; Elias-Oliveira, Jefferson ; Pereira, Italo Sousa ; Pereira, Jessica Assis ; Barbosa, Sara Candida ; Machado, Melissa Santana Gonsalez ; Guimaraes, Jhefferson Barbosa ; Pacheco, Thailla Cristina Faria ; Bortolucci, Jonata ; Zaramela, Livia Soares ; Bonato, Vania Luiza Deperon ; Silva, Joao Santana ; Martins, Flaviano Santos ; Alves-Filho, Jose Carlos ; Gardinassi, Luiz Gustavo ; Reginatto, Valeria ; Carlos, Daniela

• Document type: Journal article
• Source: Life Sciences; v. 372, p. 21-pg., 2025-04-14.

Abstract

Aims: Akkermansia muciniphila (A. muciniphila), a Gram-negative anaerobic mucus-layer-degrading bacterium found in the intestinal mucosa, exhibits potential as a probiotic, showing promise in mitigating autoimmune and chronic inflammatory diseases. This study aims to investigate whether A. muciniphila supplementation might confer protection against type 1 diabetes (T1D) and to elucidate the immunological pathways through which it exerts its beneficial effects. Materials and methods: Non-obese diabetic (NOD) mice and streptozotocin (STZ)-induced type 1 diabetes (T1D) models were used to evaluate the protective effects of A. muciniphila during T1D course. Body weight, blood glucose levels, and T1D incidence were monitored. Immune responses in the pancreas, pancreatic (PLN) and cecal lymph nodes (CLN) and bone marrow-derived dendritic cells (BMDC) were evaluated by flow cytometry and ELISA. Key findings: Viable A. muciniphila supplementation conferred protection against T1D onset in STZ-induced T1D and NOD mouse models. T1D modulation by A. muciniphila in the STZ model was independent of the gut microbiota, and it was associated with increased tolerogenic type-2 dendritic cells (SIRP-alpha+CD11b+CD103+) and regulatory T (Treg) cells in PLN and pancreas. BMDC differentiated in the presence of A. muciniphila exhibited a tolerogenic profile and induced Treg cell generation in vitro. A. muciniphila-induced protection in T1D outcome was abrogated in FOXP3-DTR mice depleted of Treg cells, indicating that its mechanism of action is dependent on the CD4+Foxp3+ Treg cells. Significance: A. muciniphila supplementation attenuates T1D development in mice by modulating the tolerogenic immune response and is a promising new therapeutic tool for this autoimmune disease. (AU)

• 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
• FAPESP's process: 20/08554-9 - Establishment of an experimental and computational platform to study host-microbes interactions promoted by sialic acids
• Grantee: Lívia Soares Zaramela
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/05514-6 - Evaluation of the immunomodulatory potential of the Akkermansia muciniphila probiotic as preventive/therapeutic strategy in T1D
• Grantee: Vanessa Fernandes Rodrigues
• Support Opportunities: Scholarships in Brazil - Post-Doctoral