A possible new treatment for Lupus by modulating the microbiome

Sweet potatoes are a natural rich source of Vitamin A.

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Lupus is a well-known autoimmune disease that causes inflammation in several organs and can sometimes be fatal.  Its cause is still unknown, but it has recently been implicated with the microbiome, and we have written about it before on this blog.  New research out of Virginia Tech has provided further evidence of this link by showing specific microbiome differences between control and Lupus affected mice.  They also showed that Vitamin A may help improve the the Lupus mice’s conditions.

The researchers tested two groups of mice, one a healthy control group and the other that had a genetic mutation that causes Lupus-like symptoms.  When they studied the microbiomes of these mice they discovered that the Lupus mice had a significant reduction in Lactobacillaceae and increase in Lachnospiraceae.  The researchers then connected the severity of lupus symptoms directly with the levels of these two bacteria (worse symptoms with higher Lachnospiraceae abundance and lower Lactobacillaceae abundance).  Interestingly, Lupus affects almost 10 times more females than males.  These researchers showed that while there was little difference between genders in the control group microbiomes, there was a much higher diversity in the microbiomes of female Lupus mice as compared to male Lupus mice. 

Vitamin A has been shown in humans to relieve the symptoms of Lupus, so the researchers fed the Lupus mice both retinol (pure vitamin A), as well retinoic acid (a metabolite of vitamin A).  While the retinol did not seem to help the Lupus mice, the retinoic acid restored populations of Lactobacillaceae, and relieved symptoms in the Lupus mice.

We know that mice are not a perfect model for humans, but this research shows that the microbiome may be an important factor in Lupus.  As such, it also shows a potential prebiotic, retinoic acid, for the treatment of Lupus.  Lupus is a complex disease, and we do not expect it to be completely understood through the lens of the microbiome, but research like this is important in elucidating possible connections between the two.

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Lupus, Sjögren’s syndrome, and the microbiome

Drawing of the typical 'butterfly rash' found in Lupus.

Sjögren’s syndrome is an autoimmune disorder characterized by the destruction of exocrine glands, like those that produce tears and saliva. Lupus is an autoimmune disease characterized by inflammation of various body tissues. People suffering from both these disorders produce antibodies and mount an immune response against a peptide, Ro60, that occurs naturally in the body. While this autoimmune response may not be the cause of these diseases, it likely contributes to their severity. An article published by Clinical Immunology shows that specific proteins derived from bacteria in the microbiome can activate the production of these self-destructive antibodies, suggesting that the microbiome could play a role in initiating autoimmunity.

Researchers at the University of Virginia used T cell hybridoma activation and epitope mapping to discover which peptides activate the specific Ro60 immune response.  When they compared these molecules with molecules known to be produced by the human microbiome, they found several instances of proteins produced by the microbiome that could potentially activate antibodies against Ro60.

The most potent peptide from the screening was derived from a specific bacterium, Capnocytophaga ochracea, that is commonly found in people’s mouths and is sometimes pathogenic. According to their data, these bacteria should produce a protein that most strongly activates the antibodies against Ro60. After experimentation, they found that the microbe alone was not able to activate the antibodies. However, a synthetically produced version of the protein from C. ochracea, was successful in activating the antibodies.   

This work is important because it suggests that host bacteria may have a strong connection in generating autoimmune responses.  At least in the cases of Lupus and Sjögren’s syndrome, certain bacteria may induce humans to create antibodies against natural body products, and this immune response contributes to the diseases.