The study, “Therapeutic Effect of Bifidobacterium Administration on Experimental Autoimmune Myasthenia Gravis in Lewis Rats,” was published in the journal Frontiers in Immunology.
The immune system defends the body from invaders such as bacteria, yet billions of bacteria live in the body without triggering an immune response. It has recently become clear that interactions between the immune system and these bacteria can have far-reaching immunological effects, which are only beginning to be understood.
Understanding these interactions may open new avenues for treating autoimmune diseases such as MG, because they are caused by the immune system behaving irregularly. Previous research suggested that treating rats with probiotic bacteria can alleviate symptoms, but these mechanisms aren’t fully understood.
To examine this further, researchers attempted to replicate the previous results by feeding female rats that had clinical features similar to MG one of two types of probiotic bacteria — bifidobacteria or lactobacilli. After several weeks, rats fed either probiotic had significantly lower clinical scores than those fed a control diet.
Rats given bifidobacteria — but not lactobacilli — had a significant decrease in levels of autoantibodies targeting the acetylcholine receptor, a major driver of MG. These rats also had significantly higher levels of transforming growth factor beta, a signaling molecule limiting inflammation.
“[T]hese data further confirm our previous study on the efficacy of preventive probiotic treatment in the rat [MG] model,” the researchers wrote.
These effects were not seen if the bacteria were pre-treated with heat, suggesting that live bacteria are needed for a therapeutic effect.
Researchers analyzed how the probiotic bacteria interacted with the cells in the rats’ immune systems. They found the bacteria present in Peyer’s Patches, which are small immunological organs in the gut, suggesting the bacteria’s direct interaction with immune cells.
To further test this idea, the researchers explored the effect of bifidobacteria exposure on two types of rat immune cells: T-cells and dendritic cells (DCs). T-cells kill other cells, and DCs can help activate them to do so.
When rat DCs were put together with bifidobacteria in dishes, the two types of cells physically interacted, as evidenced by both visualization and changes in the expression of receptors that DCs use to recognize bacteria.
When the DCs were put together with T-cells, the researchers measured the movement of the T-cells. T-cells move a lot until activated, when they become less mobile. They classified the T-cells as either motile or stationary, depending on how much they moved.
A significantly greater proportion of T-cells that were put with bifidobacteria-exposed DCs were motile than those put with unexposed DCs (63.7% vs. 27.3%). The motile cells were also moving faster on average (18.2 vs. 8.1 micrometer/minute). These data suggest that bifidobacteria exposure of DCs ultimately resulted in lower T-cell activation, likely contributing to these observed therapeutic effects.
Researchers also performed genetic analysis on the bacteria living in the rats’ guts to determine changes in the makeup of different bacterial species following disease and treatment. Several bacterial types went through a large number of changes following the experimentally induced onset of MG, and over the course of the disease.
Some of these changes were partially alleviated by bifidobacteria treatment, suggesting that the probiotic could help normalize the composition of gut microbes. This may be mechanistically related to the observed therapeutic effect, and further research will be needed to fully understand both the induced changes in gut bacteria and their consequences.
“[T]he selection and characterization of probiotic strains with immunomodulatory properties could be of relevance for MG and other autoimmune diseases,” the researchers wrote.