Phosphatidylcholine in Intestinal Mucus Protects against Mucosal Invasion of Microbiota and Consequent Inflammation

Abstract

Intestinal mucus serves as the first line barrier within the mucosa to protect against microbiota attack due to its water-repellent properties, which are the result of the high abundance of phosphatidylcholine bound to mucins. A deficiency of mucus phosphatidylcholine predisposes it to mucosal inflammation by the attack of commensal microbiota, as it is intrinsically low in ulcerative colitis. However, for precipitation of an acute inflammatory episode, mucus phosphatidylcholine has to fall below the critical level required for mucosal protection. Bacterial ectophospholipase could be a candidate for further thinning of the mucus phosphatidylcholine shield as shown, for example, with the ectophospholipase containing Helicobacter pylori bacterium. Despite supporting evidence for this mechanism in the intestine, the responsible ectophospholipase-carrying bacteria species are still to be defined. Applying phosphatidylcholine to the lumen can serve to fill up empty mucin-binding sites in ulcerative colitis as well as provide a substrate for the ectophospholipase-carrying bacteria preventing their attacks on the mucus phosphatidylcholine layer. Evidence supporting this concept comes from clinical trials in humans with ulcerative colitis as well as from colitis mouse models where phosphatidylcholine was substituted in the lumen. An alternative strategy could involve adding non-absorbable phospholipase inhibitors to the intestinal lumen, which has been shown to be effective in a mouse model of ulcerative colitis. Bacterial phospholipase should be considered a pathogenetic factor of the intestinal microbiota and therapeutic strategies should be developed to prevent their hyperactivity for clinical improvement of intestinal inflammation.

Keywords

• phospholipase
• phosphatidylcholine
• microbiota
• mucus
• ulcerative colitis
• genetic mouse models