Intestinal villi. Small finger-like projections that extend into the lumen of the small intestine surrounded by gut bacteria, which can be manipulated by probiotic treatments to treat diseases like multiple sclerosis.
Credit: ChrisChrisW/Getty Images

An engineered probiotic could be one answer to treating autoimmunity in the brain in multiple sclerosis (MS) patients, suggests research led by Brigham and Women’s Hospital and Harvard University.

“Engineered probiotics could revolutionize the way we treat chronic diseases,” said lead investigator Francisco Quintana, a professor at Harvard and a researcher at the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, in a press statement.

“When a drug is taken, its concentration in the bloodstream peaks after the initial dose, but then its levels go down. However, if we can use living microbes to produce medicine from within the body, they can keep producing the active compound as its needed, which is essential when we consider lifelong diseases that require constant treatment.”

Dendritic cells are a type of immune cell found predominantly in the gastrointestinal tract and around the brain and neurological system. They are involved in the development and activation of self-reactive pathogenic T cells.

As described in Nature, in this study the researchers analyzed these cells in mice to better understand the role they play in autoimmune diseases such as MS. The results revealed that there is a signaling loop in dendritic cells designed to limit excessive immune activation like that seen in autoimmune disease.

A protein called NDUFA4L2 limits production of mitochondrial reactive oxygen molecules that eventually trigger the activation of pathogenic autoimmune T cells. Lactate is produced by a number of cells in the body and this boosts the expression of the NDUFA4L2 protein through hypoxia-inducible factor 1α (HIF-1α).

Quintana and team created a probiotic that produces lactate and can activate the natural anti-autoimmunity pathway in dendritic cells.

“Probiotics are nothing new—we’ve all seen them sold as supplements and marketed as a way to promote health,” said Quintana. “By using synthetic biology to get probiotic bacteria to produce specific compounds relevant to diseases, we can take the benefits and amp them up to the max.”

When the team tested their probiotic in a mouse model of MS, they found that brain inflammation and symptoms were reduced in the animals. These results are not yet in humans, but the researchers think their probiotic could be helpful for patients with diseases such as MS in the future.

“We’ve learned in recent decades that the microbes of the gut have a significant impact on the central nervous system,” said Quintana. “One of the reasons we focused on multiple sclerosis in this study was to determine whether we can leverage this effect in treating autoimmune diseases of the brain. The results suggest we can.”

Also of Interest