Multiple sclerosis (MS) patients' gut bacterial compositions differ significantly from those of healthy people, according to a global research team lead by UC San Francisco researchers, as do MS patients who are taking various pharmacological treatments.
Intestinal bacteria have been linked in recent years to a variety of illnesses, not simply those affecting the gut, such as diabetes and rheumatoid arthritis. Advances in DNA sequencing in the early 2010s gave researchers a clearer image of the bacteria found in stool, blood, mucosal tissue, and skin samples, which greatly expanded the area of microbiome studies.
Multiple sclerosis is a chronic disease that affects the central nervous system, which is the brain, spinal cord, and optic nerves. Scientists have now discovered that multiple sclerosis patients have a distinct gut microbiota compared to healthy people.
Up until recently, studies on mice had provided the majority of the experimental data supporting a connection between gut microbes and MS. Smaller sample sizes and a failure to account for how the environment affects a person’s microbiome were two reasons why studies in humans have produced inconsistent results.
The bacteria that reside in our bodies depend greatly on where we live, whether it be in the city or the country, adjacent to an oil refinery or on a mountain top.
The International Multiple Sclerosis Microbiome Study (IMSMS) collaboration of scientists recruited a sizable number of MS patients from three continents and selected genetically unrelated controls from the same homes as the patients in order to get around these restrictions. This methodology had never before been applied to such a sizable investigation.
The study compares the gut microbiota patterns of 576 patients and an equivalent number of household controls in the US, the UK, Spain, and Argentina. It was published in Cell in September 2022. The research could result in brand-new treatments that entail dietary changes or microbiota manipulation.
“This is the reference study that will be used by the field for years to come,” said Sergio Baranzini, Ph.D., the Heidrich Family and Friends Endowed Chair in Neurology and member of the UCSF Weill Institute for Neurosciences, who is the lead author on the new study. With their innovative protocol, Baranzini and his colleagues were able to identify dozens of new bacteria species associated with MS and confirm other species that had previously only been associated with the disease. “We were surprised by the number of species that were differentially present in MS when compared to controls,” said Baranzini.
Additionally, they discovered that the participants’ geographic location was the main contributor to the variance in bacteria species, supporting the significance of geography and regional dietary variations for the gut microbiome. The researchers had anticipated that a participant’s disease condition would be the second biggest cause of variation.
The research was the second in a series being carried out by iMSMS, an international cooperative founded in 2015 with the goal of figuring out how gut bacteria affect MS disease risk, progression, and therapeutic response. The initial investigation established the validity of the household control methodology and demonstrated that it improves statistical power in population-based microbiome research.
“Knowing which genes from which species we are able to identify in cases and controls, we can now start to reconstruct which potential pathways are active in patients and controls,” said Baranzini.
Additionally, the short-chain fatty acid concentrations in the faeces of MS patients treated with interferon beta-1a, the oldest treatment for MS, were shown to be lower than those in the blood.
This shows that interferon functions by enhancing the transfer of these molecules from the gut to the blood stream, which Baranzini suggested could be one of the modes of action of interferon. Short-chain fatty acids are renowned for their anti-inflammatory characteristics.
Until the cohort reaches 2000 members altogether, the iMSMS group will continue to recruit patients, expanding to Germany and Canada.