Summary: A new study reveals changes in the gut microbiomes of untreated and treated multiple sclerosis patients.

Source: Bingham and Women’s Hospital.

Study finds alterations in the gut microbiomes of treated and untreated MS patients.

A connection between the bacteria living in the gut and immunological disorders such as multiple sclerosis have long been suspected, but for the first time, researchers have detected clear evidence of changes that tie the two together. Investigators from Brigham and Women’s Hospital (BWH) have found that people with multiple sclerosis have different patterns of gut microorganisms than those of their healthy counterparts. In addition, patients receiving treatment for MS have different patterns than untreated patients. The new research supports recent studies linking immunological disorders to the gut microbiome and may have implications for pursuing new therapies for MS.

“Our findings raise the possibility that by affecting the gut microbiome, one could come up with treatments for MS – treatments that affect the microbiome, and, in turn, the immune response,” said Howard L. Weiner, MD, director of the Partners MS Center and co-director of the Ann Romney Center for Neurologic Disease at Brigham Women’s Hospital, . “There are a number of ways that the microbiome could play a role in MS and this opens up a whole new world of looking at the disease in a way that it’s never been looked at before.”

Weiner and colleagues conducted their investigations using data and samples from subjects who are part of the CLIMB (Comprehensive Longitudinal Investigation of Multiple Sclerosis) study at Brigham and Women’s Hospital. The team analyzed stool samples from 60 people with MS and 43 control subjects, performing gene sequencing to detect differences in the microbial communities of the subjects.

Samples from MS patients contained higher levels of certain bacterial species – including Methanobrevibacter and Akkermansia – and lower levels of others – such as Butyricimonas – when compared to healthy samples. Other studies have found that several of these microorganisms may drive inflammation or are associated with autoimmunity. Importantly, the team also found that microbial changes in the gut correlated with changes in the activity of genes that play a role in the immune system. The team also collected breath samples from subjects, finding that, as a result of increased levels of Methanobrevibacter, patients with MS had higher levels of methane in their breath samples.

The researchers also investigated the gut microbe communities of untreated MS patients, finding that MS disease-modifying therapy appeared to normalize the gut microbiomes of MS patients. The researchers note that further study will be required to determine the exact role that these microbes may be playing in the progression of disease and whether or not modifying the microbiome may be helpful in treating MS. They plan to continue to explore the connection between the gut and the immune system in a larger group of patients and follow changes over time to better understand disease progression and interventions.

“This work provides a window into how the gut can affect the immune system which can then affect the brain,” said Weiner, who is also a professor of Neurology at Harvard Medical School. “Characterizing the gut microbiome in those with MS may provide new opportunities to diagnose MS and point us toward new interventions to help prevent disease development in those who are at risk.”

Funding: Funding support for this work included grants from the NIH/NINDS, The National Multiple Sclerosis Society and from The Harvard Digestive Disease Center.

Source: Haley Bridger – Bingham and Women’s Hospital
Image Source: This NeuroscienceNews.com image is credited to Howard Weiner, Brigham and Women’s Hospital.
Original Research: Full open access research for “Alterations of the human gut microbiome in multiple sclerosis” by Sushrut Jangi, Roopali Gandhi, Laura M. Cox, Ning Li, Felipe von Glehn, Raymond Yan, Bonny Patel, Maria Antonietta Mazzola, Shirong Liu, Bonnie L. Glanz, Sandra Cook, Stephanie Tankou, Fiona Stuart, Kirsy Melo, Parham Nejad, Kathleen Smith, Begüm D. Topçuolu, James Holden, Pia Kivisäkk, Tanuja Chitnis, Philip L. De Jager, Francisco J. Quintana, Georg K. Gerber, Lynn Bry and Howard L. Weiner in Nature Communications. Published online June 28 2016 doi:10.1038/ncomms12015

Abstract

Alterations of the human gut microbiome in multiple sclerosis

The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis.

“Alterations of the human gut microbiome in multiple sclerosis” by Sushrut Jangi, Roopali Gandhi, Laura M. Cox, Ning Li, Felipe von Glehn, Raymond Yan, Bonny Patel, Maria Antonietta Mazzola, Shirong Liu, Bonnie L. Glanz, Sandra Cook, Stephanie Tankou, Fiona Stuart, Kirsy Melo, Parham Nejad, Kathleen Smith, Begüm D. Topçuolu, James Holden, Pia Kivisäkk, Tanuja Chitnis, Philip L. De Jager, Francisco J. Quintana, Georg K. Gerber, Lynn Bry and Howard L. Weiner in Nature Communications. Published online June 28 2016 doi:10.1038/ncomms12015