Lower Intestinal Fatty Acids May Contribute to MS in Women

Certain fat molecules produced by gut microbes, which have protective immune-suppressing effects and may protect against multiple sclerosis (MS), are lower in women than in men, a case-control study has found.

These findings may explain the greater MS susceptibility observed in women, the scientists said.

The study, “Short-chain fatty acids and intestinal inflammation in multiple sclerosis: modulation of female susceptibility by microbial products?” was published in the journal Autoimmunity Highlights.

Molecules called short-chain fatty acids (SCFAs) — which are secreted by microbes in the intestine via fermentation of indigestible dietary fibers — may influence the development of MS. 

Studies in mice show SCFAs can travel through the bloodstream, enter the brain, and directly interact with certain immune T-cells to suppress the autoimmune attack on the myelin sheath, a protective coat around nerve fibers that is damaged in MS. 

Recently, a clinical trial evaluating a microbe-derived SCFA known as propionate demonstrated benefits in MS patients by increasing the numbers of suppressive T-cells, which counteracted the inflammatory response. 

Although evidence indicates that people with MS have an altered gut microbe composition, few studies have investigated SCFAs in these patients’ intestines.

Additionally, the pro-inflammatory protein calprotectin found in fecal matter is an established marker for inflammatory activity in inflammatory bowel disease, and is elevated in other neurological disorders such as Parkinson’s disease, but has not been evaluated in MS. 

Now, researchers based at Saarland University in Germany measured the levels of fecal SCFAs and calprotectin in 41 people with relapsing-remitting MS and compared them to samples from 35 age-matched healthy controls.

Patients were from 22 to 68 years old (median age 48), and 29 were women. All but three were prescribed anti-inflammatory immunotherapies, and none were receiving steroid therapy. 

The analysis showed no significant difference in fecal calprotectin concentrations between MS patients and healthy controls, which were within the normal range in both groups. Among patients, the levels were similar regardless of disease activity, disability, treatment type, or sex.

Overall, the team tested six types of fecal SCFAs across participants: propionate, acetate, butyrate, isobutyrate, valerate, and isovalerate. While MS patients had lower levels of some of these SCFAs — including a 77% reduction in butyrate — the differences did not reach statistical significance in any of them.

However, women in both groups showed significantly lower levels of these compounds than men. An analysis of patients and controls separately found significantly lower acetate, propionate, and butyrate in women over men in the control group. However, among MS patients, there was a trend towards lower levels in women but this was considered not statistically significant.

Finally, for all participants, lower fecal SCFA concentrations were significantly correlated with older age, but this correlation was not significant among MS patients. 

“In our cohort of MS patients, we found no evidence of an active intestinal inflammation,” the investigators concluded. “Yet, the vast majority of the investigated MS patients was under immunotherapy which might have affected the outcome measures.”

“The sex-associated difference in fecal SCFA concentrations might at least partially explain female predominance in MS,” they added. “Large-scale longitudinal studies including drug-naïve MS patients are required to determine the role of SCFAs in MS and to distinguish between disease-immanent effects and those caused by the therapeutic regime.”