Effects of a Mediterranean Diet Intervention on Anti- and Pro-Inflammatory Eicosanoids, Epithelial Proliferation, and Nuclear Morphology in Biopsies of Normal Colon Tissue

Abstract

This randomized trial evaluated the effects of intervention with either a Healthy Eating or a Mediterranean diet on colon biomarkers in 120 healthy individuals at increased colon cancer risk. The hypothesis was that eicosanoids and markers of proliferation would be favorably affected by the Mediterranean diet. Colon epithelial biopsy tissues and blood samples were obtained at baseline and after six months of intervention. Colonic eicosanoid concentrations were evaluated by HPLC-MS-MS, and measures of epithelial proliferation and nuclear morphology were evaluated by image analysis of biopsy sections. There was little change in pro-inflammatory eicosanoids and in plasma cytokine concentrations with either dietary intervention. There was, however, a 50% increase in colonic prostaglandin E3 (PGE3), which is formed from eicosapentanoic acid, in the Mediterranean arm. Unlike PGE2, PGE3, was not significantly affected by regular use of non-steroidal anti-inflammatory drugs at baseline, and normal weight subjects had significantly higher colon PGE3 than overweight or obese subjects. Increased proliferation in the colon at baseline, by Ki67 labeling, was associated with morphological features that defined smaller nuclei in the epithelial cells, lower colon leukotriene concentrations and higher plasma cytokine concentrations. Dietary intervention had little effect on measures of epithelial proliferation or of nuclear morphology. The increase in PGE3 with a Mediterranean diet indicates that in normal colon, diet might affect protective pathways to a greater extent than pro-inflammatory and proliferative pathways. Hence, biomarkers from cancer models might not be relevant in a true prevention setting.

Colonic Saturated Fatty Acid Concentrations and Expression of COX-1, but not Diet, Predict Prostaglandin E2in Normal Human Colon Tissue

“…Here we found that NSAID use reduced PTGS2, but not PTGS1 mRNA expression levels (Table 1). These findings indicate that PTGS2 may contribute at least partially to PGE 2 production in the normal colon since NSAID use significantly decreased colon PGE 2 concentrations in biopsy samples from this study, as we published previously (29). Cholesterol medication use was significantly associated with reduced mRNA expression of PTGES1, and PTGES1 is the synthase that associates with PTGS2 (Table 1).…”

“…In addition to the effects of dietary fat discussed above, the antioxidant effects of higher consumption of fruits and vegetable also may work to reduce production of inflammatory mediators (15). Despite this, we previously reported that a Mediterranean intervention did not significantly affect colon PGE 2 (16). PGE 2 concentrations at the time of biopsy, however, might not reflect the capacity of the tissue to produce PGE 2 since PGE 2 can be rapidly formed and degraded in cells.…”

The Anti-inflammatory Effect of Personalized Omega-3 Fatty Acid Dosing for Reducing Prostaglandin E2 in the Colonic Mucosa Is Attenuated in Obesity

“…Three frozen biopsies were pulverized in liquid nitrogen, and pooled homogenates were prepared in buffered saline containing indomethacin as described previously (20, 21). Deuterated internal standards were added before extraction and analysis of eicosanoids (20). Protein in a portion of the homogenate was determined by the Bradford assay (Bio-Rad).…”

“…Proliferation in colon biopsies was determined as described previously (20) using IHC staining for Ki67 with antibodies from Leica Biosystems. Positive nuclei were visualized with horseradish peroxidase–conjugated streptavidin and 3,3′-diaminobenzidine substrate.…”

Role of Personalized Nutrition in Chronic-Degenerative Diseases

“…The study of the modulation of the inflammatory state through nutrigenomics would seem to identify the MD as preventive for CDDs [125,126]. Some components of the MD, such as ω3, are known to alter the expression of chemical mediators of the inflammatory state [117,127].…”