Altered intestinal permeability in patients with relapsing-remitting multiple sclerosis: A pilot study.
BACKGROUND
Alterations of intestinal permeability (IP) may contribute to the pathophysiology of immune-mediated diseases.


OBJECTIVE
We investigated the possible association between IP changes and multiple sclerosis (MS).


METHODS
We studied 22 patients with relapsing-remitting multiple sclerosis (RRMS) and 18 age- and sex-matched healthy donors (HDs), including five twin pairs (one concordant, and four discordant for disease). Measurement of lactulose (L) and mannitol (M; two non-metabolized sugars) levels in urine samples, after an oral load, allowed to quantify gut dysfunction.


RESULTS
The proportion of participants with increased IP was significantly higher in patients than in HDs (16/22 (73%) versus 5/18 (28%); p = 0.001). Accordingly, the L/M urinary ratio showed significantly higher values in patients than in controls ( p = 0.0284). Urinary mannitol concentration was significantly lower in patients than in controls ( p = 0.022), suggesting a deficit of absorption from intestinal lumen. Such changes did not appear related to patients' clinical-radiological features.


CONCLUSIONS
The relatively high proportion of IP changes in RR-MS patients seems to confirm our work hypothesis and warrants more work to confirm the result on a larger sample, and to understand the implications for related immunological disturbances and intestinal microbiota alterations. Our finding may also have relevance for oral treatments, recently introduced in clinical practice.
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Maria Chiara
MC
Buscarinu
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Benedetta
B
Cerasoli
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Viviana
V
Annibali
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Claudia
C
Policano
Advanced Molecular Diagnostics Unit, IDI-IRCCS, Istituto Dermopatico dell'Immacolata, Rome, Italy.
Luana
L
Lionetto
Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Matilde
M
Capi
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Rosella
R
Mechelli
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Silvia
S
Romano
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Arianna
A
Fornasiero
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Gianluca
G
Mattei
Neuroimmunology Unit, Fondazione Santa Lucia, Rome, Italy.
Eleonora
E
Piras
Neuroimmunology Unit, Fondazione Santa Lucia, Rome, Italy.
Daniela Francesca
DF
Angelini
Neuroimmunology Unit, Fondazione Santa Lucia, Rome, Italy.
Luca
L
Battistini
Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Maurizio
M
Simmaco
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Renato
R
Umeton
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Marco
M
Salvetti
Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Giovanni
G
Ristori
D000328:Adult; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007792:Lactulose / Q000627:therapeutic use*; D008353:Mannitol / Q000627:therapeutic use*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D010539:Permeability / Q000187:drug effects; D010865:Pilot Projects
D005765:Gastrointestinal Agents; D008353:Mannitol; D007792:Lactulose
Biomarkers; gut absorption; intestinal permeability; microbiota; relapsing–remitting; twins