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. CONCLUSION: 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.
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. CONCLUSION: 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.
Entities:
Keywords:
Biomarkers; gut absorption; intestinal permeability; microbiota; relapsing–remitting; twins
Authors: Olga L Rojas; Anne-Katrin Pröbstel; Elisa A Porfilio; Angela A Wang; Marc Charabati; Tian Sun; Dennis S W Lee; Georgina Galicia; Valeria Ramaglia; Lesley A Ward; Leslie Y T Leung; Ghazal Najafi; Khashayar Khaleghi; Beatriz Garcillán; Angela Li; Rickvinder Besla; Ikbel Naouar; Eric Y Cao; Pailin Chiaranunt; Kyle Burrows; Hannah G Robinson; Jessica R Allanach; Jennifer Yam; Helen Luck; Daniel J Campbell; David Allman; David G Brooks; Michio Tomura; Ryan Baumann; Scott S Zamvil; Amit Bar-Or; Marc S Horwitz; Daniel A Winer; Arthur Mortha; Fabienne Mackay; Alexandre Prat; Lisa C Osborne; Clinton Robbins; Sergio E Baranzini; Jennifer L Gommerman Journal: Cell Date: 2019-01-03 Impact factor: 41.582
Authors: M C Buscarinu; S Romano; R Mechelli; R Pizzolato Umeton; M Ferraldeschi; A Fornasiero; R Reniè; B Cerasoli; E Morena; C Romano; N D Loizzo; R Umeton; M Salvetti; G Ristori Journal: Neurotherapeutics Date: 2018-01 Impact factor: 7.620