The short-chain fatty acid propionic acid influences the intestine-mediated immune regulation in people with multiple sclerosis (MS). The application of propionic acid in addition to MS medication reduced the relapse rate and the risk of disability progression in the long term. Moreover, initial Magnetic Resonance Imaging studies indicated that propionic acid may reduce brain atrophy as a sign of neuronal cell death. The results were published in the journal Cell .

The gut microbiome, i.e. the entire bacterial colonisation of the intestine, plays an important role not only for the healthy organism, but its association with chronic diseases, such as multiple sclerosis has been recently appreciated. Within the gut, the interaction between dietary components, microbiota, their metabolites, and the immune system takes place in the intestinal wall. "This is how intestinal bacteria can directly and indirectly affect anatomically distant structures such as the brain," explains the se

In the current study, the researchers successfully transferred the results previously shown in the cell culture dish and the experimental model to their MS patients: short-chain fatty acids such as propionic acid (PA) or its salt propionate increased the differentiation and function of regulatory T cells in the gut. "These cells stop excessive inflammatory processes and reduce auto-immune cells in autoimmune diseases like MS," says another author.

In their study, the researchers showed that the microbiome composition is altered in MS patients. Moreover, they demonstrated a deficiency of propionic acid in the feces and serum of MS patients, which was most pronounced in the earliest phases of the disease.

The authors supplemented PA to therapy-naive MS patients and as an add-on to MS immunotherapy. After 2 weeks of PA intake, they observed a significant and sustained increase of functionally competent regulatory T (Treg) cells, whereas Th1 and Th17 cells decreased significantly.

Post-hoc analyses revealed a reduced annual relapse rate, disability stabilization, and reduced brain atrophy after 3 years of PA intake. Functional microbiome analysis revealed increased expression of Treg-cell-inducing genes in the intestine after PA intake. The increased function of these cells was due to their improved energy utilisation through an altered function of the mitochondria.

The short-chain fatty acids represent only a fraction of the metabolites of intestinal bacteria that are generated from the diet. "Further research into this largely unknown organ and the knowledge gained from it will enable us to develop innovative dietary measures to complement the known therapeutics in the future," says the senior author.

https://news.rub.de/english/press-releases/2020-03-11-neurology-diet-has-impact-multiple-sclerosis-disease-course

https://www.cell.com/cell/fulltext/S0092-8674(20)30212-9