Propionic Acid modulates gastric rhythms and cortical excitability in Multiple Sclerosis

Abstract

Multiple Sclerosis (MS) is a neurological disease characterized by systemic neuroinflammation and immune dysregulation. Reduced levels of Propionic Acid (PA), a gut-derived metabolite known for its immune-modulating effects, have been observed in MS patients. However, its impact on neurophysiological measures such as gastric rhythmicity and cortical excitability remain unknown. In this study, 21 MS patients (Verum N = 14; Placebo N = 7) underwent simultaneous magnetoencephalography (MEG) and electrogastrography (EGG). We analyzed the effects of PA on the aperiodic 1/f slope (20–45 Hz) and gastric slow-wave dynamics across baseline and post-supplementation sessions. At baseline, patients exhibited gastric dysrhythmia, with mean normogastria at 39%, substantially below the 70% healthy standard. After 90 days of PA supplementation, the verum group showed directional improvements in gastric function. While these changes did not reach formal statistical significance, they yielded consistent moderate effect sizes for improved normogastria (Hedges’ g = 0.53), increased rhythmic stability (g = −0.41), and enhanced contractile power (g = 0.58). On a neural level, a Bayesian hierarchical model revealed a credible, uniform flattening of the aperiodic slope (Posterior Mean = −0.11, 95% HDI: [−0.17, −0.05]). This shift toward increased cortical excitability was consistent across individuals and was not exclusive to certain brain networks. Lastly, a logistic regression classifier was trained and successfully identified the treatment condition based on the individual change in aperiodic slope with 58.8% accuracy. Our findings suggest that PA acts as a stabilizer for gastric rhythmicity and cortical excitability in MS. The widespread flattening of the 1/f slope indicates that PA may counter the increased neural inhibition typically observed in MS populations. By directionally modulating both visceral and cortical dynamics, PA offers a novel therapeutic pathway for stabilizing the gut-brain axis and neurophysiological function.submitted by: Niklas David Jocher, BScEnthält Literaturverzeichnis auf Seite 28-35Masterarbeit University of Salzburg 202