Probiotic-derived molecule may suppress fatal brain inflammation, study shows

The existence of certain microorganisms in the gut microbiome may bolster the immune system's ability to fend off a viral attacks that can cause fatal brain inflammation, according to a new study by researchers at the City of Hope National Medical Center in Duarte, California, and published in the journal Nature Communications.  

The study, conducted in mice, found that a Bacteroides fragilis (B. fragilis) bacterial envelope, capsular polysaccharide A (PSA), brings forth regulatory T and B cells that suppress the immune system from overproducing harmful inflammatory responses triggered by herpes simplex virus infection. PSA reduced brainstem inflammation by promoting the appearance of IL-10 secreting regulatory T and B cells. IL-10 is a strong anti-inflammatory cytokine which creates a protective, anti-inflammatory response that prevents encephalitis.

PSA can temper the immune system so that infection does not result in an uncontrolled, potentially fatal inflammatory response in the brain, according to Ramakrishna Chandran, PhD, author of the study.

"Although herpes simplex encephalitis is a rare brain inflammation disorder,” Chandran said, “the lessons we learned here might, with more research, be applicable to other viral infections such as other herpesviruses, influenza virus, West Nile virus, and maybe even viral respiratory diseases, conditions where inflammation begins to jeopardize the health of your body and brain function."

Herpes simplex encephalitis affects about 2,000 people in the U.S. each year and has a high mortality rate if symptoms are not recognized and patients aren't treated promptly, according to the National Organization for Rare Disorders. Survivors usually have serious neurological conditions, and about 70 percent of untreated individuals die.

The researchers found that mice pretreated with a probiotic, B. fragilis or PSA, survived a lethal herpes simplex virus infection, whereas mice pretreated with a placebo did not survive despite the fact that both groups were given Acyclovir, an antiviral that is the standard of care for herpes simplex virus encephalitis. The finding suggests that the probiotic-derived PSA optimizes the immune system to fight against viruses, especially those that induce damaging inflammation.

The researchers also reported the important role B cells play in extinguishing inflammation. B cells are a type of white blood cell that secretes antibodies. When the scientists depleted mice of their B cells prior to PSA treatment, the mice lost their ability to marshal regulatory T cells and to secrete the anti-inflammatory cytokine IL-10. The researchers showed that B cells bound PSA, and this was crucial for induction of protective regulatory T cells, which secrete the anti-inflammatory cytokine IL-10. Thus, eliminating B cells rendered the immune system weaponless in the fight against fatal herpes simplex virus brain inflammation.

The findings suggest an envelope molecule from B. fragilis might be useful against viral inflammatory diseases, researchers say. The envelope molecule appears to promote protective, anti-inflammatory responses during a viral infection.

"It's possible that consumption of certain prebiotics, probiotics or synbiotics may enhance your body's natural ability to suppress inflammatory diseases," Chandran said in a statement. "Our study provides an exciting proof of principle that needs further research validation, but it seems reasonable that what you decide to eat may affect your overall health and ability to fight off disease."