Dozens of gut bacteria linked to multiple sclerosis

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Graphic abstract. attributed to him: cell (2022). DOI: 10.1016 / j.cell.2022.08.021

An international research consortium led by UCSF scientists has shown significant differences between the gut bacteria profiles of MS patients and healthy individuals, as well as between MS patients receiving different drug treatments. While some of these changes have been reported before, most of them have been reported for the first time. The group also revealed new mechanisms by which these bacteria may influence disease progression and response to treatment.

In recent years, scientists have increasingly made connections between the gut bacteria And a number of diseases — not just bowel diseases — including diabetes and arthritis. The field of microbiome studies really opened up with advances in DNA sequencing in the early 2010s that allowed scientists to get a detailed picture of what bacteria were in samples of stool, blood, mucosal tissue, and skin.

Until recently, most experimental evidence suggesting a link between gut bacteria and MS came from research in mice. Studies in humans have provided inconsistent results – in part because there were fewer participants, and a failure to rule out the effects of the environment on an individual’s microbiome. Where a person – rural or urban, on top of a mountain or next to an oil refinery – plays a large role in the bacteria that harbor our bodies.

To overcome these limitations, the Consortium of Scientists involved in the International Multiple Sclerosis Microbiome Study (IMSMS) recruited a large number of MS patients from three continents and selected genetically unrelated controls from the same households of patients. This was the first time that this methodology had been used in such a large study.

The study, which was published in cell 15 September 2022 describes the differences between the gut microbiome profiles of 576 patients and an equal number of home controls in the United States, United Kingdom, Spain and Argentina. The findings could lead to new treatments that involve either microbiome manipulation or dietary interventions.

“This is the reference study that the field will use for years to come,” said Sergio Baranzini, PhD, Heydrich Family and Friends Chair in Neurology and a member of the UCSF Weill Institute for Neurosciences. Lead author of the new study.

Thanks to their innovative protocol, Baranzini and colleagues were able to identify dozens of new bacteria species associated with MS and only confirm others previously associated with the disease. “We were surprised by the number of species that were present differently in MS when compared to controls,” Baranzini said.

They also found that the largest source of variation in bacteria types was related to the participants’ geographic location, confirming the importance of location and local differences in diet for the gut microbiome. The second largest source of difference was the disease status of one of the participants, which the researchers expected.

This study was the second in a series conducted by iMSMS, an international consortium founded in 2015 for the purpose of determining the role of gut bacteria in MS susceptibility, development, and response to treatment. The first study validated the family control protocol, showing that it increases statistical power in population-based microbiome studies.

Baranzini acknowledges that the results of the study are primarily descriptive. “When looking at the microbiome, there are two questions that are usually asked,” he said. The “first is” who’s there? That’s what we’re trying to answer in this paper. The second is, “What do they do?”

Answering the second question requires mechanistic studies with individual bacteria to understand their metabolic profiles. However, the researchers got some hints about what the bacteria do by studying the potential pathways these bacteria encode.

“By knowing which genes of which species we can identify in cases and controls, we can now begin to reconstruct potential pathways that are active in patients and controls,” Baranzini said.

For example, some of the bacteria the team found linked to MS appear to play a role in helping humans process fibers from plants, whose metabolites tend to be present in increased concentrations in MS patients. Other species appear to have an effect on inflammation and the cell’s energy production mechanism.

The researchers also found that patients treated with an immunomodulator known as interferon beta-1a, the oldest treatment for MS, had lower concentrations of short-chain fatty acids in their stool and higher concentrations in their blood. short series fatty acids Known for their anti-inflammatory properties, so this suggests that interferon works by increasing the transport of these molecules from the gut into the bloodstream, which Baranzini said could be one of the mechanisms of interferon action.

The iMSMS cohort will continue to recruit patients, expanding into Germany and Canada, until the total number of cohort participants reaches 2,000. Beginning this fall, they will also follow a subset of patients over two years to see how their gut microbiota changes in response to treatment, Lifestyle change and disease progression. All data from these studies will be publicly available.

“This is an example of how big science can only be achieved collaboratively,” he added. “In the iMSMS, we’ve already assembled the best and brightest researchers in the microbiome and multiple sclerosis research field, all headed toward the same goal.”


Decoding dynamics of the gut microbiome in response to dietary fiber


more information:
Xiaoyuan Zhou et al, The gut microbiome of multiple sclerosis patients and dual home health controls reveals association with disease risk and of course, cell (2022). DOI: 10.1016 / j.cell.2022.08.021

Journal information:
cell


the quote: Dozens of Gut Bacteria Associated with Multiple Sclerosis (2022, September 15) Retrieved September 15, 2022 from

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