Abstract
Individuals with intestinal barrier dysfunction are more prone to autoimmunity. Lipopolysaccharides (LPS) from gut bacteria have been shown to play a role in systemic inflammation, leading to the opening of the gut and blood-brain barrier (BBB). This study aims to measure antibodies against LPS and barrier proteins in samples positive for anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) and compare them with these same antibodies in controls to determine whether a correlation between LPS and barrier proteins could be found. We obtained 94 ASCA- and 94 ANCA-positive blood samples, as well as 188 blood samples from healthy controls. Samples were assessed for antibodies to LPS, zonulin+occludin, S100B, and aquaporin-4 (AQP4). Results show significant elevation in antibodies in about 30% of ASCA- and ANCA-positive sera and demonstrate positive linear relationships between these antibodies. The findings suggest that individuals positive for ASCA and ANCA have increased odds of developing intestinal and BBB permeability compared to healthy subjects. The levels of LPS antibodies in both ASCA- and ANCA-positive and negative specimens showed from low and moderate to high correlation with antibodies to barrier proteins. This study shows that LPS, by damaging the gut and BBBs, contribute to the extra-intestinal manifestation of IBD. We conclude that IBD patients should be screened for LPS antibodies in an effort to detect or prevent possible barrier damage at the earliest stage possible to abrogate disease symptoms in IBS and associated disorders.
Highlights
Inflammatory bowel disease (IBD) is a heterogeneous group of chronic inflammatory disorders of the gastrointestinal (GI) tract that has two main distinguishable forms, Crohn’s disease (CD) and ulcerative colitis (UC) [1]
A total of 376 sera were assessed for levels of IgG, IgM, and IgA isotype antibodies against LPS, zonulin+occludin, the blood-brain barrier (BBB) protein S100B, and the water channel protein AQP4
Setting the specificity at 31%, we found between 0%–9% of controls or anti-neutrophil cytoplasmic antibodies (ANCA)-negative sera showed elevations in IgG, IgM, and IgA antibodies against LPS, zonulin+occludin, S100B and AQP4
Summary
Inflammatory bowel disease (IBD) is a heterogeneous group of chronic inflammatory disorders of the gastrointestinal (GI) tract that has two main distinguishable forms, Crohn’s disease (CD) and ulcerative colitis (UC) [1]. According to the Centers for Disease Control and Prevention, CD can affect any part of the GI tract from the mouth to the anus, but it most often affects the portion of the small intestine before the large intestine/colon; UC, on the other hand, occurs in the large intestine and colon [2]. Another way to differentiate between CD and UC is that anti-Saccharomyces cerevisiae antibodies (ASCA) are associated with and used as biomarkers for CD, while anti-neutrophil cytoplasm antibodies (ANCA) are recognized as markers for UC [3].
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