Plasma Metabolomics Analysis of Aspirin Treatment and Risk of Colorectal Adenomas

Abstract

Despite substantial observational and experimental evidence that aspirin use can provide protection against the development of colorectal neoplasia, our understanding of the molecular mechanisms involved is inadequate and limits our ability to use this drug effectively and safely for chemoprevention. We employed an untargeted plasma metabolomics approach using liquid chromatography with high-resolution mass spectroscopy to explore novel metabolites that may contribute to the chemopreventive effects of aspirin. Associations between levels of metabolic features in plasma and aspirin treatment were investigated among 523 participants in a randomized placebo-controlled clinical trial of two doses of aspirin (81 or 325 mg/day) and were linked to risk of colorectal adenoma occurrence over 3 years of follow-up. Metabolic pathways that were altered with aspirin treatment included linoleate and glycerophospholipid metabolism for the 81-mg dose and carnitine shuttle for both doses. Metabolites whose levels increased with 81 mg/day aspirin treatment and were also associated with decreased risk of adenomas during follow-up included certain forms of lysophosphatidylcholine and lysophosphatidylethanolamine as well as trihydroxyoctadecenoic acid, which is a derivative of linoleic acid and is upstream of cyclooxygenase inhibition by aspirin in the linoleate and arachidonic acid metabolism pathways. In conclusion, our findings regarding lysophospholipids and metabolites in the linoleate metabolism pathway may provide novel insights into the chemopreventive effects of aspirin in the colorectum, although they should be considered hypothesis-generating at this time. Prevention Relevance: This research used metabolomics, an innovative discovery-based approach, to identify molecular changes in human blood that may help to explain how aspirin use reduces the risk of colorectal neoplasia in some individuals. Ultimately, this work could have important implications for optimizing aspirin use in the prevention of colorectal cancer.

Plasma Instead of Serum Avoids Critical Confounding of Clinical Metabolomics Studies by Platelets

“…This was suggested by the drug-induced upregulation of serotonin, aspartic acid and taurine (Figure C), in addition to an alteration in the fatty acid composition of triacylglycerols (Figure ). These observations are not novel, but in accordance with existing literature. ,,, However, the functional significance of these findings remains to be investigated in more detail.…”

“…These observations are not novel, but in accordance with existing literature. 15,40,43,46 However, the functional significance of these findings remains to be investigated in more detail.…”

Chemopreventive effect of a milk whey by-product derived from Buffalo (Bubalus bubalis) in protecting from colorectal carcinogenesis

“…In this case, the control group is separated from the treated samples along PC-2, while all treated groups cluster together except for a subgroup spreading along PC-1, due to biological variability. Metabolic pathways altered by DMW treatment included glycerophospholipid metabolism, which is associated with colorectal cancer risk [ 39 , 40 ]. The predominant alterations observed in AOM + DMW involved the choline-containing phospholipids, namely phosphatidylcholines and lysophosphatidylcholines, with down-regulation of glycerophosphocholine and up-regulation of lysophosphatidylcholine (1-palmitoyl-sn-glycero-3-phosphocholine, 1-octadecenoyl-sn-glycero-3-phosphocholine, 1-eicosapentaenoyl-glycero-3-phosphocholine, and 1-docosahexaenoyl-glycero-3-phosphocholine).…”

Microencapsulated essential oils alleviate diarrhea in weaned piglets by modulating the intestinal microbial barrier as well as not inducing antibiotic resistance: a field research

“…In agreement with this, we found that the MEO group displayed increases in linoleic acid metabolism and elevated end products including 9,12,13-and 9,10,13-trihydroxy-10-octadecenoic acid. This metabolism typically takes place in eosinophils in pigs and contributes to skin barrier health but also has implications in colorectal cancer diagnostics and therapy (50,51).…”