Intestinal mucosal mannose-containing glycoconjugates

Intestinal mucosal mannose-containing glycoconjugates are a diverse group of glycoproteins and glycolipids located on the surface of the intestinal epithelium that feature terminal mannose residues. These structures serve as critical attachment sites for various pathogenic and commensal bacteria, most notably Adherent-Invasive Escherichia coli (AIEC), which utilize the mannose-binding lectin FimH to colonize the gut mucosa (Barnich et al., 2007, PubMed: 17404304). In conditions like Crohn's disease, the expression of specific mannosylated proteins, such as Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), is significantly upregulated, facilitating increased bacterial adhesion and subsequent inflammation (Boudeau et al., 2001, PubMed: 11560861). Therapeutic strategies targeting this interaction typically involve the use of mannosides or FimH inhibitors, such as Sibofimloc (EB8018), which act as competitive decoys to prevent bacterial attachment (Sivignon et al., 2015, PubMed: 25643271). By blocking the binding of pathogens to these glycoconjugates, these drugs aim to reduce mucosal inflammation and restore intestinal homeostasis without the use of traditional antibiotics. This approach is particularly relevant for patients with ileal Crohn's disease where AIEC colonization is a known driver of pathology. Because these drugs are often designed to be non-systemic, they offer a targeted treatment profile with minimal systemic side effects. The interaction between host mannose and bacterial lectins represents a novel paradigm in treating chronic inflammatory conditions by modulating the gut microbiome's physical interaction with the host.

Other names

Mannosylated host receptorsMannose-containing glycoproteinsHigh-mannose glycansIntestinal mannosidesCarcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6)

Competitive inhibition of bacterial lectin (FimH) binding to host mannose residues to prevent pathogen colonization.