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. 2025 Jul 1:372:123624.
doi: 10.1016/j.lfs.2025.123624. Epub 2025 Apr 7.

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

Vanessa Fernandes Rodrigues  1 , Jefferson Elias-Oliveira  2 , Ítalo Sousa Pereira  2 , Jéssica Assis Pereira  2 , Sara Cândida Barbosa  2 , Melissa Santana Gonsalez Machado  2 , Jhefferson Barbosa Guimarães  2 , Thaílla Cristina Faria Pacheco  2 , Jonatã Bortolucci  3 , Lívia Soares Zaramela  4 , Vânia Luiza Deperon Bonato  5 , João Santana Silva  6 , Flaviano Santos Martins  7 , José Carlos Alves-Filho  8 , Luiz Gustavo Gardinassi  9 , Valeria Reginatto  3 , Daniela Carlos  10
Affiliations

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

Vanessa Fernandes Rodrigues et al. Life Sci. .

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-α+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.

Keywords: Akkermansia muciniphila; Immunoregulation; Regulatory T cells; Tolerogenic dendritic cells; Type 1 diabetes.

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Conflict of interest statement

Declaration of competing interest The authors declare that the research was conducted without commercial or financial relationships that could be interpreted as potential conflicts of interest.

MeSH terms

Supplementary concepts