Study finds altered gut bacteria in people with relapsing NMOSD
Gut microbiome normalizes for patients in remission after treatment
The composition of bacteria in the gut is altered in neuromyelitis optica spectrum disorder (NMOSD) patients experiencing disease relapses compared with healthy people in the same household, a study reports.
Following treatment, however, the gut bacterial profiles of NMOSD patients in remission resembled those of healthy people.
“The results of this study provide evidence that the changes in the gut microbiome are associated with the [development] of NMOSD,” researchers wrote.
The study, “Perturbed microbial ecology in neuromyelitis optica spectrum disorder: Evidence from the gut microbiome and fecal metabolome,” was published in Multiple Sclerosis and Related Disorders.
The human digestive system is home to billions of bacteria and other microorganisms, collectively called the gut microbiome. The gut microbiome has profound effects on health that are only beginning to be understood.
Gut microbiome changes linked to changes in immune activity, brain biology
Increasing research suggests that gut microbiome changes are linked to changes in immune activity and brain biology, contributing to the development of some autoimmune and neurological diseases.
Some studies have also reported significant changes in gut microbiota in people with NMOSD, an autoimmune disorder marked by abnormal inflammatory attacks that damage healthy cells in the brain and spinal cord.
While underlying mechanisms are unclear, it’s thought that an unbalanced gut microbiome produces more of certain molecules that may prime immune cells to mount inflammatory responses.
In the new study, a team of scientists in China set out to further explore the potential connection between changes in gut microbiome and NMOSD development.
In a first set of experiments, the researchers used fecal samples to analyze the composition of the gut microbiome in people with or without NMOSD. The team assessed samples from 25 NMOSD patients who were in an acute phase of the disease, or experiencing a relapse (a flare-up of symptoms), 11 NMOSD patients who were in remission, and 24 healthy family members who lived with patients.
NMOSD patients in acute disease phase had changes in gut microbiome
Results showed that, compared with healthy controls, patients in the acute phase showed significant changes in gut microbiome species diversity, as well as richness at the level of species and genus, a biological classification comprising species marked by common features.
For example, the relative abundance of Streptococcus — a bacterial genus that’s been linked to several autoimmune diseases — was higher in NMOSD patients in the acute phase.
Previous studies have reported that an increased Streptococcus abundance is linked to more severe NMOSD. In addition, this genus can promote inflammation by increasing levels of inflammatory molecules, such as IL-6 and IL-17, and promoting the maturation of inflammatory immune cells, including Th17 cells, which are known to contribute to NMOSD.
For NMOSD patients in remission, the gut microbiome was largely similar to what was seen in healthy controls.
“Compared with NMOSD patients in the acute phase, for NMOSD patients in the remission phase … diversity and richness at the species and genus levels were similar to those of the [healthy control] group, indicating that [the altered gut microbiota] of NMOSD patients improved with drug treatment,” the researchers wrote.
Analyses of gut microbiome metabolic pathways yielded comparable results: NMOSD patients in the acute phase showed marked changes compared with patients in remission and healthy controls.
‘Gut microbiome plays an important role in disease exacerbation’
All these findings suggest “the gut microbiome plays an important role in disease exacerbation,” the team wrote.
In a second set of experiments, the researchers took fecal samples from healthy people and people with acute NMOSD and transplanted them into the guts of mice. The scientists then looked at how these gut microbiome transplants affected the mice’s immune systems.
Results showed that mice given gut bacteria from relapsing NMOSD patients had significantly increased levels of the pro-inflammatory molecules IL-6, IL-17A, and IL-2 relative to those that received samples from healthy controls. Meanwhile, levels of an anti-inflammatory signaling molecule called IL-10 were decreased in animals given the NMOSD samples.
Consistent with the changes in signaling molecules, mice given gut bacteria from patients with active NMOSD showed increased counts of Th17 cells, and decreased counts of anti-inflammatory immune cells called regulatory T-cells.
These data “suggest that the NMOSD microbiome may also functionally contribute to NMOSD-like immune alterations in mice,” the researchers wrote.
Overall, the findings indicate “gut microbiome imbalances, including a decrease in intestinal [friendly] bacteria and an increase in opportunistic [disease-causing bacteria], may be involved in the development of NMOSD through the regulation of various inflammatory [molecules],” the team wrote. “In-depth studies are needed to determine whether this differential abundance in gut bacteria is a risk factor for NMOSD or, more precisely, a result of the disease process.”
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