Multiple sclerosis is an autoimmune disease where the immune system attacks the nervous system, and alterations in gut bacteria are linked to increased harmful immune cells in people with the condition. Now, researchers have found that reduced levels of gut microbiota-produced bile acids in the guts of multiple sclerosis patients may contribute to immune dysregulation by increasing the number of harmful immune cells. 

The findings, published in Cell Reports Medicine, suggest that gut microbiota-produced bile acids can be used as therapeutic targets for multiple sclerosis. “Our data highlight the key role of immune regulatory [bile acid metabolites] for the prevention of central nervous system autoimmunity,” the researchers say.

Scientists have known that gut bacteria produce metabolites that help control immune responses by promoting protective immune cells and suppressing harmful ones. These metabolites also affect immune cells outside the gut, but their role in multiple sclerosis is still unclear.

Martina Antonini Cencicchio at IRCCS San Raffaele Scientific Institute in Milan and her colleagues set out to investigate the role of gut microbiota-produced bile acids in regulating immune responses by analyzing samples from people with multiple sclerosis and a mouse model of the condition.

Immune system dysfunction

The researchers examined the gut microbiota and the levels of secondary bile acids in the guts of people with multiple sclerosis. 

Compared to healthy individuals, those with multiple sclerosis have an imbalance in their gut bacteria, which may contribute to immune system dysfunction. Multiple sclerosis patients have fewer bacteria that produce beneficial bile acid metabolites such as deoxycholic acid (DCA) and lithocholic acid (LCA). 

This reduction in bile acid metabolites was linked to an increase in immune cells, called Th17 cells, that are known to drive multiple sclerosis progression. Further experiments showed that gut bacteria from people with multiple sclerosis boosted the growth of Th17 cells, but adding DCA reversed this effect. 

Protecting the brain

Giving DCA and LCA to mice with autoimmune encephalomyelitis, a model for multiple sclerosis, reduced disease symptoms and nerve damage. DCA alone also provided protection, but it was less effective than the combination of DCA and LCA. 

DCA and LCA appeared to reduce gut inflammation by lowering the levels of pro-inflammatory molecules and controlling the expansion of harmful immune cells. In mice with autoimmune encephalomyelitis, treatment with gut microbiota-derived bile acids reduced inflammatory immune cells and increased protective ones outside the gut. These mice also had fewer damaging immune cells in their brains and spinal cords.

The findings suggest that microbiota-produced bile acids help prevent the immune system from attacking the nervous system by modifying how specific immune cells develop and function, the authors say. However, they add, “additional experiments

are necessary to clarify the mechanisms responsible for [bile acid metabolites] mediated modulation of autoimmunity in the [central nervous system].”