Mucosal Protection by Phosphatidylcholine

Abstract

The colonic mucus serves a first barrier towards invasion of commensal bacteria in stools to prevent inflammation. One essential component of intestinal mucus is phosphatidylcholine (PC) which represents more than 90% of the phospholipids in mucus indicative for a selective transport of PC into this compartment. It is arranged in lamellar structures as surfactant-like particles which provide a hydrophobic surface on top of the hydrated mucus gel to prevent the invasion of bacteria from intestinal lumen. In ulcerative colitis (UC), the mucus PC content is reduced by 70%, irrespective of the state of inflammation. Thus, it could represent an intrinsic primary pathogenetic condition predisposing to bacterial invasion and the precipitation of inflammation. Since PC was shown to be mainly secreted by the ileal mucosa from where it is assumed to move distally to the colon, the PC content along the colonic wall towards the rectum gradually thins, with the least PC content in the rectum. This explains the start of the clinical manifestation of UC in the rectum and the expansion from there to the upper parts of the colon. In three clinical trials, when missing mucus PC in UC was supplemented by an oral, delayed release PC preparation, the inflammation improved and even resolved after a 3-month treatment course. The data indicate the essential role of the mucus PC content for protection against inflammation in colon.

Phospholipase A₂ of Microbiota as Pathogenetic Determinant to Induce Inflammatory States in Ulcerative Colitis: Therapeutic Implications of Phospholipase A₂ Inhibitors

“…It was shown to restore the mucus PC content, which reestablished the barrier against microbiotic invasion and, thus, fighting mucosal inflammation [5,[22][23][24]. Assuming that genetically low mucus PC content is capable of maintaining barrier function up to a borderline concentration of 30% compared to normal subjects [2,20], it could be postulated that a drop below this critical level allows bacterial invasion with consequent mucosal inflammation. Accordingly, inflammatory episodes in UC require an impaired mucosal barrier -low mucus PC content -and the invasion of bacteria: the double-edged sword for the pathogenesis of UC.…”

“…We postulated that an intrinsic low mucus PC constitutes a risk factor for bacterial invasion [20]. Accordingly, predominance of ectophospholipase carrying bacteria in stool can critically reduce the PC barrier.…”

Anti-Cytokine Strategies beyond Anti-Tumour Necrosis Factor-α Therapy: Pathophysiology and Clinical Implications

“…A barrier defect is frequently seen as the first pathophysiological relevant problem [33,34] . This barrier defect may be caused by a reduction of phosphatidylcholine incorporation into the mucus layer of the mucosa [35][36][37] . Stremmel et al [37] have shown that the mucus layer in UC patients is decreased in thickness [38] .…”

“…This barrier defect may be caused by a reduction of phosphatidylcholine incorporation into the mucus layer of the mucosa [35][36][37] . Stremmel et al [37] have shown that the mucus layer in UC patients is decreased in thickness [38] . This has stimulated new developments for a phosphatidylcholine substitution therapy as a new therapeutic approach in UC [39][40][41][42] .…”

The Detergent Effect of Mesalazine Interferes with Phosphatidylcholine Binding to Mucin 2

“…As recently described, there is a substantial amount of phosphatidylcholine (PC) secreted into the distal ileum for incorporation into the mucus to serve as a hydrophobic barrier towards the stool microbiota [7][8][9]. PC is believed to incorporate mainly into mucin 2 which is secreted by goblet cells and constitutes the main structural scaffold of the outer layer of the mucus [10].…”