Stool Phospholipid Signature is Altered by Diet and Tumors

Abstract

Intake of saturated fat is a risk factor for ulcerative colitis (UC) and colon cancer. Changes in the microbiota have been implicated in the development of UC and colon cancer. The host and the microbiota generate metabolites that may contribute to or reflect disease pathogenesis. We used lipid class specific quantitative mass spectrometry to assess the phospholipid (PL) profile (phosphatidylcholine [PC], phosphatidylethanolamine [PE], phosphatidylinositol [PI], phosphatidylserine [PS]) of stool from mice fed a high fat (HFD) or control diet with or without induction of colitis-associated tumors using azoxymethane and dextran sodium sulfate. The microbiota was assessed using qPCR for several bacterial groups. Colitis-associated tumors were associated with reduced bulk PI and PE levels in control diet fed mice compared to untreated mice. Significant decreases in the relative quantities of several PC species were found in colitis-associated tumor bearing mice fed either diet. Statistical analysis of the PL profile revealed distinct clustering by treatment group. Partial least squares regression analysis found that the relative quantities of the PS class profile best predicted bacterial abundance of Clostridium leptum and Prevotella groups. Abundance of selected PL species correlated with bacterial group quantities. Thus, we have described that a HFD and colitis-associated tumors are associated with changes in phospholipids and may reflect host-microbial interactions and disease states.

Fecal metabolome of the Hadza hunter-gatherers: a host-microbiome integrative view

“…Specifically, Treponema genomes harbor homologues of CDP-choline pathway for PC biosynthesis, likely using choline as a building block in a camouflage strategy, which is released by eukaryotic partners; whether human, animal or plant host 43 . Interestingly, a decreased relative abundance of several PC species has been found in the feces of mice fed a high-fat diet 44 , and similar results have been obtained regarding the PC and lysoPC content of mucosal aliquots from patients with ulcerative colitis (UC) 39 . It is possible that a defective PC layer exerts an impaired barrier function, allowing bacterial binding to the epithelium and contributing to the development of inflammation typical of the so-called Western diseases.…”

Cross sectional evaluation of the gut-microbiome metabolome axis in an Italian cohort of IBD patients

“…The downregulation of phosphocholines, such as PC (16:0/3:1), could reflect a defect of PC synthesis or secretion. It has been known that several pathologies, like IBD or cancer, are correlated to the phospholipids pathways 38 . Cytosolic phospholipase A2 is activated by low concentration of Ca 2+ , and during this activation the lipase is transferred from the cytosol to the cell membrane to initialise the arachidonic acid cascade producing many inflammatory mediators 39 .…”

Intestinal Epithelial Toll-Like Receptor 4 Signaling Affects Epithelial Function and Colonic Microbiota and Promotes a Risk for Transmissible Colitis

“…Genomic DNA was extracted from the lumen and mucosa of the distal colon and ileum with a QIAamp stool and genomic DNA isolation kit (Qiagen, Valencia, CA). The 16S rRNA gene copy number as an estimate of the total bacterial number and individual bacterial groups in the lumen and mucosal samples was determined by qPCR with universal and group-specific primers as described above and previously ( 32 ). Analyses for microbial richness, composition, and diversity were conducted by Second Genome Inc. (San Francisco, CA) as described in the supplemental material.…”