The gut bacteria of people with multiple sclerosis vary with disease activity

Diet and lifestyle 26. feb 2023 3 min Professor of Human Metabolism, Chief Research Physician, Specialist of Endocrinology Oluf Borbye Pedersen Written by Kristian Sjøgren

New research suggests that certain gut bacteria may be able to keep multiple sclerosis (MS) at bay. The researchers think that the scientific community should now carry out large randomised controlled trials investigating whether people with MS who eat a plant-based diet experience fewer attacks with aggravated symptoms and, if so, why.

A new study shows that the composition and function of the gut bacteria of people with MS vary depending on whether disease is active or not.

The results indicate that healthy composition and function of gut bacteria, bioactive bacterial molecules or a predominantly plant-based diet may keep MS at bay, so that people with MS do not experience the dreaded periodic attacks when it flares up.

Previous research has shown that the composition of the gut bacteria differs between people with and without MS, but in the new study the researchers went a step further and also identified a difference in the gut viruses.

“Our results suggest that when the disease is inactive, bacteria are present in the gut of people with MS that produce anti-inflammatory compounds that keep the immune response calm and counteract the autoimmune attacks. Conversely, we also found an increased quantity of the bacteria that produce inflammatory hormones in the gut bacteria of the people who experience attacks, and these may influence the development of MS. We also found a difference in the composition of the gut viruses but do not yet know the significance of this,” explains an initiator of the research project, Oluf Borbye Pedersen, Professor and Research Leader, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

The research has been published in Genome Medicine.

In-depth investigation

The researchers used DNA technology to examine the composition and function of the gut bacteria and viruses in stool samples from 148 people with MS and 148 controls.

MS was in remission among 100 of the people with MS, and 48 experienced activity in the form of autoimmune attacks.

The researchers used advanced genetic engineering tools to create a complete map of the bacterial genes in the stool samples and thereby identified the bacteria and their functions.

“We especially focused on how the composition and function of gut bacteria differed between people with MS in remission and those who experienced attacks,” says Oluf Borbye Pedersen.

Attacks linked with unhealthy gut bacteria

The results show that the profile and function of gut bacteria differ between people with and without MS but also between people with MS in remission versus in relapse.

The people who experienced attacks had more gut bacteria that produce pro-inflammatory cytokines, including interleukin 17A, interleukin 22, interferon-beta and tumour necrosis factor-alpha.

Inflammation plays a role in developing MS, because it activates the immune system, and an overactive immune system in the brain and spinal cord helps to attack the myelin sheaths of the nerve fibres early in the course of MS.

Conversely, the researchers found that people with MS in remission had more special bacteria such as Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens.

These bacteria are known to produce health-promoting compounds such as butyric acid, propionic acid and urolithin. In experiments with animals, these health-promoting compounds dampen an overactive immune system so that it does not attack everything around it, including the body’s own cells.

“This suggests some interesting clinical perspectives,” explains Oluf Borbye Pedersen.

Next-generation probiotics might keep MS at bay

The discovery may pave the way for future clinical trials with the aim of keeping MS at bay.

Oluf Borbye Pedersen sees an opportunity to use Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens as next-generation probiotics that can re-establish a composition of gut bacteria that does not promote disease.

“The usual probiotics comprise lactic acid bacteria and bifidobacteria, and they do not prevent chronic disease. In contrast, we are talking about some recently mapped anaerobic bacteria in the human gut. These next-generation probiotics have been shown to benefit people’s immune system and metabolism. So far, in addition to the bacteria mentioned, a handful of other next-generation probiotics have been identified and are likely to be marketed within the next decade. In future interventions in MS, the effect of these probiotics should be tested to supplement existing biological drug treatments,” explains Oluf Borbye Pedersen.

Dietary changes may also improve MS

The results also suggest that dietary changes may help to keep MS at bay.

Oluf Borbye Pedersen says that diet can influence both the composition and function of the gut bacteria, thereby nudging it in a direction that seems to be associated with keeping MS in remission rather than in relapse with attacks.

A predominantly plant-based diet rich in isoflavones, found mainly in beans and other legumes, can encourage health-promoting bacteria.

Isoflavones stimulate the growth of beneficial bacteria, including bacteria that produce anti-inflammatory compounds.

Pilot studies have already indicated that eating more plants may have other effects on MS.

In a trial in Italy, researchers gave participants with MS either a predominantly plant-based diet or a standard Western diet. Twenty people participated, with half following one diet and half the other diet for 1 year. Those who ate the predominantly plant-based diet experienced fewer autoimmune attacks.

“The scientific community should now carry out large randomised controlled trials with people with MS to investigate whether a natural isoflavone-enriched diet together with state-of-the-art drug treatment can keep MS at bay,” concludes Oluf Borbye Pedersen.

The gut microbiota in multiple sclerosis varies with disease activity” has been published in Genome Medicine and is the result of a collaboration between the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen; other departments of the University of Copenhagen; the Danish Multiple Sclerosis Center at Rigshospitalet, Copenhagen; the Technical University of Denmark, Kongens Lyngby; and the French National Research Institute for Agriculture, Food and Environment, Paris.

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