Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism

Area of Science:

• Immunology
• Neuroscience
• Microbiome research

Background:

• Short-chain fatty acids (SCFAs) are produced by gut bacteria from dietary fiber and possess immunomodulatory functions.
• Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease with complex pathophysiology.
• Reduced levels of propionic acid (PA) were observed in MS patients compared to controls, particularly after initial relapses.

Purpose of the Study:

• To investigate the role and therapeutic potential of propionic acid (PA) in multiple sclerosis (MS).
• To assess the impact of PA supplementation on immune cell populations and disease markers in MS patients.

Main Methods:

• A proof-of-concept study involving PA supplementation in therapy-naive MS patients and as an adjunct to existing immunotherapy.
• Analysis of serum and fecal PA levels, immune cell profiling (Treg, Th1, Th17), microbiome gene expression, and clinical outcomes (relapse rate, disability, brain atrophy).
• Assessment of Treg cell mitochondrial function and morphology.

Main Results:

• PA supplementation led to a significant increase in regulatory T (Treg) cells and a decrease in Th1 and Th17 cells within 2 weeks.
• Long-term PA intake (3 years) was associated with reduced annual relapse rates, stabilized disability, and decreased brain atrophy.
• PA intake promoted Treg-cell-inducing gene expression in the gut microbiome and normalized Treg cell mitochondrial function and morphology in MS patients.

Conclusions:

• Propionic acid (PA) demonstrates potent immunomodulatory effects relevant to multiple sclerosis (MS).
• PA supplementation can enhance regulatory T cell function and potentially mitigate MS progression.
• PA may serve as a valuable, potent immunomodulatory supplement for MS treatment strategies.