Phospholipid turnover in the inflamed intestinal mucosa: Arachidonic acid-rich phosphatidyl/plasmenyl-ethanolamine in the mucosa in inflammatory bowel disease

Abstract

Cytosolic phospholipase A2 (PLase A2) is activated by low Ca2+ concentrations and translocates from the cytosol to the cell membrane, releasing arachidonic acid; the arachidonic acid cascade then leads to the production of many inflammatory mediators. The aim of this study, accordingly, was to investigate the role of phospholipid metabolism in the intestinal mucosa in inflammatory bowel disease (IBD). Surgically resected specimens from patients with Crohn's disease (CD), ulcerative colitis (UC), and colrectal cancer (non-cancerous tissue; as a control) were submitted to phospholipid analysis and a PLase A2 assay, which measures the degradation of endogenous mucosal phospholipids. A high percentage of plasmenylethanolamine (plas.E) was detected in the glycerophospholipid fraction of CD mucosa. The arachidonic acid content of the phosphatidylethanolamine plus plas.E subfraction was higher in inflamed than in intact mucosa in CD. PLaseA2 activity, resulting in lysophosphatidyl ethanolamine production, was detected only in inflamed mucosa from CD and UC patients, but not in normal mucosa from controls. PLaseA2 activity was highest in moderately inflamed mucosa adjacent to a severely ulcerated area. The PLaseA2 that reacts with endogenous phosphatidylcholine (PC) to form lysoPC was found irrespective of the presence of inflammation. The PLaseA2 that reacts with ethanolamine-containing phospholipids is more closely related to inflammation than other PLaseA2 isoenzymes in IBD mucosa.

The Treatment-Naive Microbiome in New-Onset Crohn’s Disease

“…In a first exploration, we performed a comparison between representative reference genomes for each of these species, generating a view of the differential KEGG pathways (Figure 3). The species increased in CD uniquely contributed pathway components of glycerophospholipid and lipopolysaccharide metabolism, found to instigate inflammation (Morita et al, 1999), and phosphonoacetate hydrolase, providing access to a novel carbon and phosphate source not accessible to most other organisms (Kim et al, 2011). Interestingly, the latter is a zinc-dependent enzyme that might contribute to a mineral deficiency common in newly diagnosed IBD patients.…”

Inferred metagenomic comparison of mucosal and fecal microbiota from individuals undergoing routine screening colonoscopy reveals similar differences observed during active inflammation

“…22 This may be related to alterations in phospholipid turnover that has previously been associated with the inflamed mucosa of IBD patients. 23 The importance of bacterial xenobiotics metabolism in the gut was first highlighted when it was found that xenobiotics exposure induced expression of bacterial genes involved in drug resistance and metabolism. In a more recent study of mouse model colitis, xenobiotics metabolism pathways, particularly benzoate biodegradation, were implicated to promote the growth of Enterobacteriaceae, a family of bacteria enriched during colitis.…”

New insights into the role of fatty acids in the pathogenesis and resolution of inflammatory bowel disease

“…To support the hypothesis that a preferential ω-6 LCFA metabolism occurs in the intestine, increased phospholipid turnover and elevated levels of phospholipase A 2 have been reported in both UC and CD mucosal biopsies, 38 which results in an increase in AA hydrolysis and the downstream generation of proinflammatory oxidized AA lipid mediators. For example, elevations in LTB 4 , as well as the enzymes necessary for its production, have been detected in colonic biopsies of IBD patients.…”