Summary: Harvard researchers and collaborators identified a novel biological pathway that limits inflammation and damage in the central nervous system (brain and spinal cord). In this study, they demonstrate that they can successfully alter this pathway and reduce inflammation in mice with MS-like disease by feeding them an engineered experimental probiotic. Probiotics have the potential to be a new therapeutic approach to treat MS.
Details: Dr. Francisco Quintana (Harvard Medical School/Brigham and Women’s Hospital) and team examined ‘dendritic cells’, which are key regulators of immune activity. These cells command other immune cells, determining what gets attacked as a foreign invader and what gets deemed harmless and ignored, such as the body’s own tissues. In immune-mediated diseases like MS, dendritic cells may play a role in the inappropriate targeting of the body’s own brain and spinal cord tissues. In this study, the investigators found a key feedback mechanism in dendritic cells that can limit their damaging activity. They also found that lactate, a substance produced by cells when food is turned into energy, is a driver of this feedback mechanism.
The researchers took advantage of recent knowledge pointing to the gut as a source of immune cells that damage the central nervous system and the potential of the bacteria that live in the gut (microbiome) to regulate these cells. They used this knowledge to custom-engineer a probiotic that would activate this feedback mechanism in a mouse model of MS. To develop the probiotic, they manipulated harmless bacteria to make them produce lactate. These bacteria were then fed to mice with MS-like disease as a probiotic, and the bacteria produced lactate in the gut.
Results: The team purposely engineered the probiotic to release lactate gradually rather than just feeding the mice lactate, because having too much lactate build up in the body can cause serious harm. The mice fed the probiotic had less inflammation in the central nervous system than is typical of a mouse model of MS.
Impact: This innovative approach has potential for developing new therapies to reduce immune activity in MS and in other immune-mediated diseases. Further work will be needed to confirm this approach and translate it into new treatments for people. Note that this experimental probiotic is not yet available to the public and has not yet been tested in people to understand its safety and effectiveness.
References:
Article published in Nature on August 9, 2023 - Lactate limits CNS autoimmunity by stabilizing HIF-1a in dendritic cells. Link to article – here.
We acknowledge the National MS Society (USA) and International Progressive MS Alliance for authoring some of the original content in this article.