Multiple sclerosis (MS) is a disease where the immune system attacks the protective covering around nerve cells, called myelin, in the brain. The relationship between diet, the gut microbiota and MS is not well understood. While environmental risk factors such as low levels of sunlight exposure/vitamin D and infection with Epstein-Barr virus (EBV) have been studied at length, these alone are not sufficient to cause MS. In the general population, the Mediterranean diet has consistently been associated with better health outcomes, including a reduced risk of several chronic diseases (including neurological) and mortality. Emerging studies suggest that a disrupted gut microbiota and some aspects of diet could alter a person’s susceptibility to MS; however, the relationship behind how diet and gut bacteria are linked to MS is mostly unexplored.

 A trivariate analysis is a method of measuring 3 variables and is useful in determining relationships and analyzing patterns. Here, the researchers investigated the 3-way relationship between diet, the types of bacteria within the gut, and the link to MS in young people using stool samples from youth with MS and without. Specific measurements of diet included the Mediterranean diet score and specific components of the diet, as well as fibre, iron, and whole-grains consumption. The researchers also looked for gut microbiota taxa (a ranking of groups of organisms with similarities) that moderate the association between diet and risk of MS.

 Studying the gut microbiota of children and youth with MS offers a window closer to MS disease onset than is often not  possible in adults. This ability to study the gut microbiome very early in MS when fewer exposures have happened, like use of many medications, may allow clearer insight into the interaction of diet, the gut microbiota and MS.

 Diet, gut microbiota analysis and MS risk relationship

 The researchers found that a diet richer in fibre and Mediterranean foods were less common in those with MS compared to those without. This dietary pattern was linked to differences in the gut bacteria. Furthermore, a higher Mediterranean diet score and eating more fibre and iron was associated with reduced likelihood of having MS. For example, an increase of 1-point in the Mediterranean diet score was associated with 37% reduced odds of MS and a 1-gram increase in fibre was associated with 13% lower odds of MS.

 Significant differences in gut bacteria were found between those with MS and those without. Among the gut bacteria, Methanobrevibacter was the highest in those with MS compared to those without. Its presence in the gut microbiome was associated with a significantly higher (23-fold) likelihood of having MS. Methanobrevibacter produces methane and is associated with constipation, a common complaint in MS. Furthermore, the MS group were depleted of certain short chain fatty acids producing bacteria—products of fibre fermentation. Short chain fatty acids can defend the central nervous system (brain and spinal cord) against damage.

 Importantly, this study links MS-associated bacteria to the Mediterranean diet score and fibre intake, which in turn were associated with a lower risk of MS. Both the Mediterranean diet and having MS were associated with different amounts of specific gut microbiota—these bacteria potentially play a role in the protective associations of a healthier diet.

 Higher Mediterranean diet score may protect against MS

 This study is unique in that it links dietary measurements such as the Mediterranean diet score and dietary fibre to MS-associated bacteria. Diet is known to have a significant effect on gut bacteria. Participants with a high Mediterranean diet score and diets high in fibre had distinct microbiota composition compared to those with lower scores; the variation in gut microbiota between participants was associated with diet—not MS.

 A higher Mediterranean diet score, and higher intakes of fibre and iron were significantly linked to a reduced likelihood of paediatric-onset MS. Furthermore, a protective relationship was seen between the changes in the gut microbiota associated with diets rich in fibre, whole-grains and adequate iron—all found in a Mediterranean diet. A distinct diet-microbiota-MS (trivariate) relationship was identified. Together, these findings suggest, but cannot prove, that diet may help prevent MS by influencing gut bacteria. Recent evidence suggests that the Mediterranean diet may help modify symptoms and the course of MS. This study opens the door to further studies examining how diet can impact MS through gut bacteria.     

Mirza, A.I., Zhu, F., Knox, N. et al. Mediterranean diet and associations with the gut microbiota and pediatric-onset multiple sclerosis using trivariate analysis. Commun Med 4, 148 (2024). https://doi.org/10.1038/s43856-024-00565-0