Akkermansia mono-colonization modulates microglia and astrocytes in a strain specific manner

Area of Science:

• Neuroimmunology
• Microbiome Research
• Glial Cell Biology

Background:

• Microglia and astrocytes are key glial cells in the central nervous system (CNS).
• Gut microbiota composition influences CNS health, but specific bacterial roles remain unclear.
• Previous studies suggest microbiota regulate CNS glia, but strain-specific effects are not well-defined.

Purpose of the Study:

• To investigate the impact of specific gut bacteria, Akkermansia muciniphila (type strain and a novel strain H3) and Bacteroides cellulosilyticus, on microglia and astrocyte gene expression.
• To explore strain-specific effects of A. muciniphila on glial cells.
• To examine the influence of these bacteria on peripheral immune cells and short-chain fatty acid production.

Main Methods:

• Germ-free mice were colonized with specific bacterial strains: Akkermansia muciniphila (type strain and H3) and Bacteroides cellulosilyticus.
• RNA sequencing was used to analyze gene expression changes in microglia and astrocytes.
• Flow cytometry was employed to assess splenic γδ-T cells and CD4+ T cell IFNγ production.
• Intestinal short-chain fatty acids were measured using gas chromatography.

Main Results:

• Akkermansia species downregulated genes related to antigen presentation and cell migration in microglia.
• Akkermansia H3 uniquely altered histone/protein binding and ion transport genes in microglia.
• Akkermansia H3 induced astrocyte proliferation pathways and altered cytoskeletal gene expression.
• Bacterial colonization increased splenic γδ-T cells and CD4+ T cell IFNγ production.
• A. muciniphila produced primarily propionate, while B. cellulosilyticus produced acetate, propionate, and isovalerate.

Conclusions:

• Specific intestinal bacteria, including Akkermansia muciniphila strains, modulate gene expression in CNS microglia and astrocytes.
• Strain-specific effects of Akkermansia were observed on glial cell pathways.
• Gut microbiota composition influences peripheral immune cell populations and function.
• Short-chain fatty acids and peripheral immune signaling may mediate the observed effects of the gut microbiota on the CNS.