Short-chain fatty acids are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here, we investigate propionic acid (PA) in multiple sclerosis (MS), an autoimmune and neurodegenerative disease. Serum and feces of subjects with MS exhibited significantly reduced PA amounts compared with controls, particularly after the first relapse. In a proof-of-concept study, we supplemented PA to therapy-naive MS patients and as an add-on to MS immunotherapy. After 2 weeks of PA intake, we 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. Furthermore, PA normalized Treg cell mitochondrial function and morphology in MS. Our findings suggest that PA can serve as a potent immunomodulatory supplement to MS drugs.

ObjectivesCentral nervous system involvement is one important clinical aspect of myotonic dystrophy type 1 and 2 (DM1 and DM2). We assessed CNS involvement DM1 and DM2 by 3T MRI and correlated clinical and neuocognitive symptoms with brain volumetry and voxel-based morphometry (VBM).Methods12 patients with juvenile or classical DM1 and 16 adult DM2 patients underwent 3T MRI, a thorough neurological and neuropsychological examination and scoring of depression and daytime sleepiness. Volumes of brain, ventricles, cerebellum, brainstem, cervical cord, lesion load and VBM results of the patient groups were compared to 33 matched healthy subjects.ResultsClinical symptoms were depression (more pronounced in DM2), excessive daytime sleepiness (more pronounced in DM1), reduced attention and flexibility of thinking, and deficits of short-term memory and visuo-spatial abilities in both patient groups. Both groups showed ventricular enlargement and supratentorial GM and WM atrophy, with prevalence for more GM atrophy and involvement of the motor system in DM1 and more WM reduction and affection of limbic structures in DM2. White matter was reduced in DM1 in the splenium of the corpus callosum and in left-hemispheric WM adjacent to the pre- and post-central gyrus. In DM2, the bilateral cingulate gyrus and subgyral medio-frontal and primary somato-sensory WM was affected.Significant structural-functional correlations of morphological MRI findings (global volumetry and VBM) with clinical findings were found for reduced flexibility of thinking and atrophy of the left secondary visual cortex in DM1 and of distinct subcortical brain structures in DM2. In DM2, depression was associated with brainstem atrophy, Daytime sleepiness correlated with volume decrease in the middle cerebellar peduncles, pons/midbrain and the right medio-frontal cortex.ConclusionGM and WM atrophy was significant in DM1 and DM2. Specific functional-structural associations related morphological changes to cognitive impairment, depression and daytime sleepiness, partly indicating involvement of complex neuronal networks.

Remote health assessments that gather real-world data (RWD) outside of clinic settings require a clear understanding of appropriate methods for data collection, quality assessment, analysis and interpretation. Here, we examine the performance and limitations of smartphones in collecting RWD in the remote mPower observational study of Parkinson's Disease (PD). Within the first six months of study commencement, 960 participants had enrolled and performed at least 5 self-administered active PD symptom assessments (speeded tapping, gait/balance, phonation, or memory). Task performance, especially speeded tapping, was predictive of self-reported PD status (AUC=0.8) and correlated with in-clinic evaluation of disease severity (r =0.71; p<1.8×10 -6 ) when compared with motor MDS-UPDRS). Although remote assessment requires careful consideration for accurate interpretation of RWD, our results support the use of smartphones and wearables in objective and personalized disease assessments.RWD offers the opportunity to improve our understanding and management of health and disease outside of the clinical setting. 1 An increasingly popular method for collecting RWD is the use of remote digital assessments that allow frequent sampling and have been used to aid in the diagnosis, treatment, and monitoring of multiple conditions, including atrial fibrillation and diabetes. 2,3 When used in population-based studies, remote assessment can increase understanding of heterogeneity in disease manifestation, the Bas Bloem currently serves as Editor-in-Chief for the Journal of Parkinson's disease, serves on the editorial board of Practical Neurology and Digital Biomarkers, has received honoraria from serving on the scientific advisory board for Zambon, Biogen, UCB and Walk with Path, has