Abstract
Inflammatory bowel disease is associated with intestinal dysbiosis and with elevated antibody production toward microbial epitopes. The underlying processes linking the gut microbiota with inflammation are still unclear. Considering the constant induction of antibodies by gut microbial glycans, the aim of this study was to address whether the repertoire of carbohydrate-specific antibodies is altered in Crohn’s disease or ulcerative colitis. IgG and IgM reactivities to oligosaccharides representative of mucosal glycans were tested in blood serum from 20 healthy control subjects, 17 ulcerative colitis patients, and 23 Crohn’s disease patients using glycan arrays. An increased IgG and IgM reactivity toward fucosylated oligosaccharides was detected in Crohn’s disease but not in ulcerative colitis. To address the antibody reactivity to the gut microbiota, IgG binding to members of a complex intestinal microbiota was measured and observed to be increased in sera of patients with Crohn’s disease. Based on the elevated reactivity to fucosylated oligosaccharides, gut bacteria were tested for recognition by the fucose-binding Aleuria aurantia lectin. Bacteroides stercoris was detected in IgG- and lectin-positive fractions and reactivity of A. aurantia lectin was demonstrated for additional Bacteroides species. IgG reactivity to these Bacteroides species was significantly increased in inflammatory bowel disease patients, indicating that the increased reactivity to fucosylated oligosaccharides detected in Crohn’s disease may be induced by fucose-carrying intestinal bacteria. Enhanced antibody response to fucosylated epitopes may have systemic effects by altering the binding of circulating antibodies to endogenous glycoproteins.
Highlights
Inflammatory bowel disease (IBD) encompasses a group of chronic inflammatory diseases of the gastrointestinal tract including the two major types of ulcerative colitis (UC) and Crohn’s disease (CD)
To address whether the repertoire of carbohydrate-specific antibodies is altered in IBD, and whether changes in antibody profiles can be linked to the expansion of specific bacterial taxa, we investigated the reactivity of serum antibodies to mucosal glycans in IBD patients using oligosaccharide arrays
The investigation of carbohydrate-specific antibodies in IBD patients revealed an increased antibody response to oligosaccharides in CD patients, which was mainly reflected by a higher reactivity to fucosylated oligosaccharides
Summary
Inflammatory bowel disease (IBD) encompasses a group of chronic inflammatory diseases of the gastrointestinal tract including the two major types of ulcerative colitis (UC) and Crohn’s disease (CD). IBD is a multifactorial disease associated with abnormal mucosal immune responses combined with altered function of the intestinal barrier and genetic and environmental factors. Despite controversial results on the increase or decrease of specific taxa, studies consistently reported a lower abundance of Firmicutes in IBD (Manichanh et al, 2006; Frank et al, 2007; Nishida et al, 2018). IBD is associated with an increase of potentially inflammatory bacteria, such as adherent-invasive Escherichia coli (Martin et al, 2004; Nishida et al, 2018), and a decrease of bacteria with anti-inflammatory characteristics, such as Faecalibacterium prausnitzii (Fujimoto et al, 2013; Machiels et al, 2014; Takahashi et al, 2016). A higher abundance of Bacteroidetes and Proteobacteria, including Enterobacteriaceae (Seksik et al, 2003; Gophna et al, 2006), has been reported, even though there are studies that showed a decrease of Bacteroidetes (Frank et al, 2007)
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