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Mucus Barriers to Microparticles and Microbes are Altered in Hirschsprung's Disease

“…[11] The observed differences in passive diffusion between WT and Ednrb -/could also be related to differences in MUC2 concentration and density of negatively charged glycoproteins in mucus. [9,[30][31][32][33] Mucins, such as MUC2, the main gel-forming intestinal mucin, have different oligosaccharide side chains which impart their neutral or acidic nature (i.e., sulfomucins or sialomucins). [34] An increased ratio of neutral mucins: acidic mucins, as seen in HD, [13] would correspond to a relative negative charge decrease, which could diminish electrostatic repulsive forces between the microspheres and mucin fibers ( Figure 6), leading to slower particle diffusion and reduced predicted penetration in Ednrb -/mucus as compared to WT (Figure 3).…”

“…A lowered concentration of sulphomucins reported to be associated with HD would result in a reduced resistance to bacterial mucin-degrading enzymes and potential increase of bacterial penetration and onset of enterocolitis. [29,34] However, HD patients also display heightened sialomucin secretion, [33] especially in the proximal colon, [34] suggesting an increased degree of bacterial adhesion to mucus. Lower average microbe speeds in the Ednrb -/proximal section compared to WT could be due to increased sialomucin binding ( Figure 6).…”