Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity

Background: Recent evidence suggests a role for the gut–brain axis in the pathophysiology of multiple sclerosis (MS). Materials and methods: We studied biomarkers of intestinal permeability in 126 people with MS (57 relapsing-remitting multiple sclerosis (RRMS) and 69 progressive MS) and in a group...

Full description

Saved in:
Bibliographic Details
Published in:Multiple sclerosis 2020-10, Vol.26 (11), p.1340-1350
Main Authors: Camara-Lemarroy, Carlos R, Silva, Claudia, Greenfield, Jamie, Liu, Wei-Qiao, Metz, Luanne M, Yong, V Wee
Format: Article
Language:English
Subjects:
Biomarkers
Blood-brain barrier
Digestive system
Dysbacteriosis
Fatty acid-binding protein
Gastrointestinal tract
Inflammation
Intestine
Lactic acid
Lipopolysaccharides
Magnetic resonance imaging
Multiple sclerosis
Neuroimaging
Permeability
Proteins
Tight junctions
Zonula occludens-1 protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background: Recent evidence suggests a role for the gut–brain axis in the pathophysiology of multiple sclerosis (MS). Materials and methods: We studied biomarkers of intestinal permeability in 126 people with MS (57 relapsing-remitting multiple sclerosis (RRMS) and 69 progressive MS) and in a group of healthy controls for comparison. Serum/plasma concentrations of zonulin (a regulator of enterocyte tight junctions), tight junction proteins (ZO-1 and occludin), intestinal fatty acid binding protein (IFABP)/ileal bile acid binding protein (IBABP), D-lactate, and lipopolysaccharide (LPS) binding protein were measured. Results: Zonulin concentrations were significantly higher when a concurrent magnetic resonance imaging (MRI) confirmed the presence of blood–brain barrier (BBB) disruption (Gad+ RRMS) and were correlated with tight junction proteins. IBABP and D-lactate were elevated in people with RRMS compared to controls, but did not discriminate between Gad+ and Gad– subgroups. Baseline zonulin concentrations were associated with 1-year disease progression in progressive MS. Conclusions: People with MS have altered biomarkers of intestinal barrier integrity. Zonulin concentrations are associated with 1-year disease progression in progressive MS and closely mirror BBB breakdown in RRMS. Zonulin may mediate breakdown of both the intestinal barrier and the BBB in gut dysbiosis through the regulation of tight junctions. This could explain how the gut–brain axis modulates neuroinflammation in MS.
ISSN:1352-4585
1477-0970
DOI:10.1177/1352458519863133