SAN FRANCISCO, Sept. 17 (Xinhua) -- Researchers at the University of California, San Francisco, or UCSF, have found that gut microbes may play a role in the neurodegeneration that characterizes multiple sclerosis (MS).
By identifying specific gut microbes associated with MS in human patients and showing that these microbes take part in regulating immune responses in mouse models of the disease, the researchers hope to understand the origins of MS and potentially lead to treatments.
An autoimmune neurodegenerative disorder that affects approximately 2.5 million people worldwide with progressive loss of vision, weakness and tremors, and problems with coordination and balance, MS is caused when the immune system attacks the layers of insulation that surround nerve cells.
While suspected environmental contributors to MS, such as history of smoking, diet, and environmental exposures, are hard to pin down and associate with a biological impact on patients, a growing number of studies demonstrating that gut microbes can directly influence the function of the human immune system.
"The intestine is actually the most intimate connection between the outside world and the immune system," explained Sergio Baranzini, a professor of neurology at UCSF and the senior author on the new study published in the National Academy of Sciences (PNAS).
The researchers analyzed the gut microbiome composition of 71 MS patients and 71 healthy control subjects, identified specific species of bacteria that were either more or less common in people with multiple sclerosis than the general population, then turned to investigating how these differences might influence the immune system's attack on myelin in MS.
They exposed human immune cells in laboratory dishes to blended extracts of each bacterial species, and found that two species of bacteria that were more common in people with MS, namely Akkermansia muciniphila and Acinetobacter calcoaceticus, triggered the cells to become pro-inflammatory, while another species found at lower than usual levels in MS patients, namely Parabacteroides distasonis, triggered immune-regulatory responses.
They introduced each of these three species into mice who otherwise lacked a microbiome to simulate overgrowth of these strains relative to other strains and found that they had a similar effect: A. muciniphila and A. calcoaceticus triggered inflammatory immune responses, while P. distasonis tamped down inflammation.
To answer the question how the complex microbial ecosystems of MS patients might impact neurodegeneration, the team performed fecal transplants on mice with an experimentally induced form of MS and found that replacing the microbiomes of these mice with the microbiomes of patients with MS caused the animals to lose key immune-regulatory cells and to develop more serious neurodegeneration, suggesting that the microbiome alone could contribute to the progression of MS.
"To be clear, we don't think the microbiome is the only trigger of MS," Egle Cekanaviciute, a postdoctoral researcher in the Baranzini lab, was quoted as saying in a news release. "But it looks like these microbes could be making the disease progression worse or better - pushing someone with genetic predisposition across the threshold into disease or keeping them safe."
The findings may lead to treatments such as dietary changes or drugs based on microbial byproducts that could improve the course of the disease.