What is already known
Several studies have linked the gut microbiota to multiple sclerosis, an autoimmune disorder that leads to muscle weakness, blindness and even death. However, such studies were typically small in size. What’s more, confounding factors, such as the genetic background and the geographic location of participants, abound.
What this research adds
Researchers recruited more than 570 patients with multiple sclerosis from the United States, the United Kingdom, Spain and Argentina, and selected genetically unrelated, healthy controls from the same households as the patients. Compared to healthy people, those with multiple sclerosis had higher levels of Akkermansia muciniphila, Ruthenibacterium lactatiformans, Hungatella hathewayi and Eisenbergiella tayi as well as decreased amounts of Faecalibacterium prausnitzii and Blautia. In people with multiple sclerosis, the researchers also found high levels of microbial genes associated with biological processes such as inflammation and the processing of plant fiber.
Conclusions
The findings shed light on the mechanisms by which gut bacteria influence the development and progression of multiple sclerosis.
Multiple sclerosis is an autoimmune disorder that leads to muscle weakness, blindness and even death. New research provides additional evidence of a link between the condition and the gut microbiota.
The findings, published in Cell, shed light on the mechanisms by which gut bacteria influence disease development and progression. “This is the reference study that will be used by the field for years to come,” says study senior author Sergio Baranzini at the University of California, San Francisco, who leads the International Multiple Sclerosis Microbiome Study — an international project that aims to understand the role of gut bacteria in multiple sclerosis.
Past studies have uncovered a potential role for gut microbes in the condition, but they were small in size. What’s more, confounding factors, such as the genetic background and the geographic location of participants, abound.
To get around these limitations, Baranzini and his colleagues studied the gut microbiota of more than 1,100 people, half of whom had multiple sclerosis.
Microbial pathways
The researchers recruited more than 570 patients with multiple sclerosis from the United States, the United Kingdom, Spain and Argentina, and selected genetically unrelated, healthy controls from the same households as the patients. Nearly 40% of people with multiple sclerosis were untreated.
Compared to healthy people, those with multiple sclerosis had higher levels of Akkermansia muciniphila, Ruthenibacterium lactatiformans, Hungatella hathewayi and Eisenbergiella tayi as well as decreased amounts of Faecalibacterium prausnitzii and Blautia.
In people with multiple sclerosis, the researchers also found high levels of microbial genes associated with biological processes such as inflammation and the processing of plant fiber. Byproducts of plant fiber tend to be found at high concentrations in people with multiple sclerosis. “We can now start to reconstruct which potential pathways are active in patients and controls,” Baranzini says.
Therapeutic activity
The researchers found that patients who were given interferon-beta, an immune molecule that is typically used to treat multiple sclerosis, had lower concentrations of short-chain fatty acids in their feces and higher concentrations in their blood compared to untreated patients.
Short-chain fatty acids are known to dampen inflammation, so these findings suggest that the therapeutic activity of interferon is in part associated with boosting the transport of short-chain fatty acids from the gut to the blood.
Next, the team plans to recruit more patients and follow some of them for two years to see how their gut microbiotas change in response to treatment, lifestyle changes and disease progression.
