Gut-brain axis: Genetically engineered probiotics may combat autoimmune diseases, flags study

14 Aug 2023 --- Researchers have designed a probiotic that can suppress autoimmunity in the brain – when the immune system attacks the cells of the central nervous system, resulting in diseases such as multiple sclerosis (MS). The probiotic could target brain inflammation more precisely and with fewer side effects than standard therapies.

The research team, based in Massachusetts, US, studied dendritic cells, an immune cell found in the gut and brain. These cells signal antigens to inform the fight against invasive pathogens while enforcing tolerance to a person’s own and harmless environmental antigens. 

In autoimmune disorders, a person’s natural defense system cannot tell the difference between its cells and foreign cells. Genetic variants associated with dendritic cell function have been linked to these disorders but are challenging to target. 

“Engineered probiotics could revolutionize the way we treat chronic diseases,” says lead author Francisco Quintana, Ph.D., professor of Neurology at Brigham and Women’s Hospital. 

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

The researchers identified a biochemical pathway to stop other immune cells from attacking the body.Biochemical brake 
By analyzing dendritic cells in the central nervous system of mice, the researchers identified a biochemical pathway that dendritic cells use to stop other immune cells from attacking the body. 

“The mechanism we found is like a brake for the immune system,” explains Quintana. “In most of us, it’s activated, but in people with autoimmune diseases, there are problems with this brake system, which means the body has no way to protect itself from its immune system.”

The researchers found that lactate – a molecule involved in metabolic processes – could activate this biochemical brake. They genetically engineered probiotic bacteria by adapting Escherichia coli to produce lactate and thus suppress T cell autoimmunity by activating the signaling of dendritic cells. 

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

Probiotics on the market increasingly go beyond the gut-brain axis, with healthy aging, immunity and beauty-from-within driving innovations in formulations, formats and application of probiotic products. 

Gut-brain axis  
The researchers tested their probiotic in mice with a disease resembling MS and assessed lactate levels in the plasma, small intestine and colon at 1h, 4h and 24h after ingesting it. After administration of the probiotic, lactate levels increased in plasma and the gut. 

Moreover, they found that the bacteria could reduce the disease’s effects on the brain as the lactate-driven activation of gut dendritic cells suppressed inflammation of the central nervous system. 

As the team did not find bacteria in the bloodstream of the mice, they suggest the observed effect was a result of biochemical signaling between gut and brain cells. 

Genetically engineered probiotics could revolutionize the way we treat chronic diseases, says Quintana.“We’ve learned in recent decades that the gut microbes have a significant impact on the central nervous system,” notes Quintana. “One of the reasons we focused on MS in this study was to determine whether we can leverage this effect in treating autoimmune diseases of the brain. The results suggest we can.”

In this space, nutrition brands have highlighted a sustained demand for products that target the gut-brain axis, supported by a growing body of research linking the gut to other health areas. 

The researchers expect their approach could be translated to humans as the strain of bacteria used to create the probiotic has already been tested on humans. They are also modifying their approach for autoimmune diseases that affect the gut, such as inflammatory bowel syndrome.

“The ability to use living cells as a source of medicine in the body has tremendous potential to make more personalized and precise therapies,” concludes Quintana. “If these microbes living in the gut are powerful enough to influence inflammation in the brain, we’re confident we’ll be able to harness their power elsewhere as well.”

By Jolanda van Hal