Bacteria in the small intestines can travel to other organs and trigger an autoimmune response, a new Yale study indicates. The researchers also found that the autoimmune reaction can be suppressed with an antibiotic or vaccine designed to target the bacteria.
The findings suggest promising new approaches for treating chronic autoimmune conditions, including systemic lupus and autoimmune liver disease.
[caption id=“attachment_94728” align=“alignleft” width=“300”] Confocal image of the small intestine of animals colonized only with E. gallinarum.
Credit: Manfredo Vieira et al., Science (2018)[/caption]
Gut bacteria have been linked to a range of diseases, including autoimmune conditions characterized by immune system attack of healthy tissue.
To shed light on this link, a Yale research team investigated Enterococcus gallinarum, a bacterium they discovered is able to spontaneously “translocate” outside of the gut to lymph nodes, the liver, and spleen.
Immune System Effects
In models of genetically susceptible mice, the researchers saw that in tissues outside the gut, E. gallinarum initiated the production of auto-antibodies and inflammation — hallmarks of the autoimmune response. They confirmed the same mechanism of inflammation in cultured liver cells of healthy people, and the presence of this bacterium in livers of patients with autoimmune disease.
[caption id=“attachment_94727” align=“aligncenter” width=“680”] Credit: Martin Kriegel[/caption]
Through further experiments, the research team found that they could suppress autoimmunity in mice with an antibiotic or a vaccine aimed at E. gallinarum. With either approach, the researchers were able to suppress growth of the bacterium in the tissues and blunt its effects on the immune system.
“When we blocked the pathway leading to inflammation, we could reverse the effect of this bug on autoimmunity. The vaccine against E. gallinarum was a specific approach, as vaccinations against other bacteria we investigated did not prevent mortality and autoimmunity,"
said senior author Martin Kriegel, M.D.
The vaccine was delivered through injection in muscle to avoid targeting other bacteria that reside in the gut.
While Kriegel and his colleagues plan further research on E. gallinarum and its mechanisms, the findings have relevance for systemic lupus and autoimmune liver disease, they said.
S. Manfredo Vieira, M. Hiltensperger, V. Kumar, D. Zegarra-Ruiz, C. Dehner, N. Khan, F. R. C. Costa, E. Tiniakou, T. Greiling, W. Ruff, A. Barbieri, C. Kriegel, S. S. Mehta, J. R. Knight, D. Jain, A. L. Goodman, M. A. Kriegel Translocation of a gut pathobiont drives autoimmunity in mice and humans Science 09 Mar 2018: Vol. 359, Issue 6380, pp. 1156-1161 DOI: 10.1126/science.aar7201
Image: gut commensal E. gallinarum translocated into the liver tissue of autoimmune mice. Orange dots represent the bacterium. Credit: Manfredo Vieira et al., Science (2018)