When friend becomes foe: gut bacteria triggers autoimmunity in mice and humans

The history of medicine and epidemiology is full of “bad bug” stories—bacteria have a reputation for causing many horrible diseases like cholera and tuberculosis. More recently, however, research efforts like the Human Microbiome Project have turned to investigating the role that “ good bacteria” plays in everyday health. The human microbiome is complex, and consists of a diverse collection of commensal bacteria—naturally existing and harmless—all throughout our bodies, but particularly in the gut. Barriers within the gut keep the microbes in place where they help to regulate many metabolic processes that keep our healthy bodies in homeostasis. However, when these “healthy” bacteria leave the gut barrier, they can potentially trigger autoimmune responses that may be detrimental to the processes keeping our bodies in good health.

A recent study published in Science identified the gut bacterium Enterococcus gallinarum is associated with the development of autoimmunity similar to systemic lupus erythematosus (SLE). Humans with SLE often have genetic risk factors that cause several immune responses: oversignalling of RNA-sensing Toll-like receptor 7 (TLR7), the secretion of type I interferons (IFNs), and the production of  anti–double-stranded DNA (dsDNA), anti–ERV gp70 (endogenous retrovirus), and anti-phospholipid antibodies, among others. Therefore, this systemic response of autoimmunity can have an effect on multiple target organs with varying severity.

The researchers found that E. gallinarum is able to translocate out of the gut and move into other systemic organs like the liver, lymph nodes, and the spleen in the lupus mouse model. This translocation is an effect of the weakening of the gut barrier, due to the dysregulation of the immune system. E. gallinarum translocation was also observed in an analysis of stool and liver biopsies from human SLE patients.

To study the effects of E. gallinarum on autoimmune function, bacteria isolated from the livers of (NZW × BXSB)F1 hybrid mice (a standard lupus model) was co-cultured in vitro with primary hepatocytes. The presence of the bacterium induced expression of anti–ERV gp70 and anti-β2GPI phospholipid, as well as type I IFN and other proinflammatory cytokines. Similar findings were observed in healthy liver cells co-cultured with E. gallinarum.

When the (NZW × BXSB)F1 hybrid mice were treated with antibiotics—either vancomycin or ampicillin—autoimmune symptoms, antibody production, and mortality outcomes were reduced, and translocation of bacteria was inhibited as well. However, antibiotic treatments are not a feasible long term treatment in humans. First of all, antibiotics will affect all of the bacterial population in the microbiome and does not target a specific strain. Secondly, antimicrobial resistance is a growing concern, with once treatable diseases that are now resistant because of the evolution of “superbugs”. Therefore, Manfredo-Vieira et al. proposed a method of vaccination by using heat-killed E. gallinarum. This method of vaccination ensures that the bacteria (or virus) cannot replicate, but it is still able to elicit an immune response from the host. In (NZW × BXSB)F1 hybrid mice, the vaccination prevented bacterial translocation and also reduced autoantibody responses and autoimmune outcomes.

The microbiome is complex, and there is still much to be discovered about the delicate relationship between commensal bacteria and host cells. With further study, the understanding of how gut bacteria influence immunity can help lead to better therapeutic treatments that can help improve the quality of life for those who suffer from autoimmune disorders.


Manfredo Vieira et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science. 2018 Mar 9;359(6380):1156-1161. doi: 10.1126/science.aar7201.


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