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Endocannabinoids and endocannabinoid-like molecules are present in foods, blood and ileal fluids from ileostomy subjects: insight into possible metabolic implications
- Silvia Tagliamonte, Chris I R. Gill, Laura Kirsty Pourshahidi, Mary Slevin, Roger Lawther, Gloria O'Connor, Rosalia Ferracane, Paola Vitaglione
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- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E487
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The endocannabinoid system is a lipid signalling system with several regulatory functions throughout the body including regulation of appetite, food intake, macronutrient metabolism, pain sensation, blood pressure, mood, cognition and immunity. It consists of endocannabinoids (ECs), their receptors and enzymes involved in their synthesis and degradation. The two best-characterized endocannabinoids are N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). They are ligands of cannabinoid receptors CB1 and CB2 which are located in the central nervous system (CNS) but also in in the enteric nervous system, in the liver and in the adipose tissue.
Several structural congeners of ECs including N-acylethanolamines (NAEs) such as oleoylethanolamine (OEA), linoleyethanolamine (LEA), and palmitoyletahanolamine (PEA), show similar mechanisms of action, tissue distribution as well as pathways of formation and breakdown. They are considered “endocannabinoid-like” molecules acting through receptors that are located both in CNS and in the gastro-intestinal tract mucosa such as the G-protein coupled receptor 119 (GPR119) and peroxisome proliferator-activated receptors (PPARs). NAEs display EC50 values for human GPR119 and PPAR-α between 65 ng/mL and 1000 ng/mL. Some evidence indicated that NAEs, their phosphorylated precursors N-acylphosphatidylethanolamines (NAPEs) and ECs are also present in food. Thus, we developed a food database of these molecules and we calculated the daily dietary intake in a healthy population.
This study aimed to evaluate whether the concentrations of NAPEs, NAEs and ECs in the human intestinal lumen may support their activity through the receptors lining in the gastro-intestinal tract and if they correlated with those in plasma.
The observational study (16/NI/0267, Ulster University) involved 35 ileostomists (18F/17M, aged 18–70 y, BMI 17–40 kg/m2) who collected overnight fasting samples of ileal fluid and plasma. The concentrations of NAEs, NAPEs and ECs in biological samples were determined by LC-HRMS.
Data showed that NAEs and NAPEs were present in ileal fluids and plasma from all subjects ranging between 46851.0–104742.8 ng/mL and 0.3–59.6 ng/mL in ileal samples and 1159.4–3985.7 ng/mL and 0.19–1.24 ng/mL in plasma, respectively. Contrarily, no ECs in ileal fluids were found except 2-AG in two ileal samples whereas they ranged between 1.6–22.3 ng/mL in plasma. Differences between genders and associations of plasma levels with individual energy intakes were found.
Altogether, the data demonstrated that NAEs in the intestinal lumen are sufficient to elicit metabolic responses through the gastro-intestinal receptors.
Wild strawberry polyphenols exhibit gut-protective bioactivity following in vivo digestion
- Chris Gill, Cheryl Latimer, Nigel Ternan, Kirsty Pourshahidi, Massimilano Fontana, Roger Lawther, Gloria O'Connor, Lorenzo Conterno, Francesca Fava, Kieran Tuohy
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- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E120
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Berries are one of the most commonly consumed sources of bioactive polyphenols and these compounds may exert protective effects against initiation of colorectal cancer (CRC) by reducing DNA damage. The inverse correlation between fruit and vegetable consumption and the incidence of CRC is well established, hence the role of berry derived bioactive phytochemicals in promotion of gut health is of interest. Ileostomy studies provide a unique insight into food digestion, allowing identification of physiologically relevant dietary phytochemicals and their metabolites. Here, we hypothesised that physiologically relevant levels of Italian wild strawberry metabolites exiting the ileum would be both bioavailable and would in turn exert positive effects on gut health markers.
Five ileostomists completed a wild strawberry feeding study (11/NI/0112), ileal fluid was collected pre (0 h) and post (8 h) consumption of strawberries (225 g) and assessed for phytochemical composition by LCMSn. We simulated the interaction of the ileal fluids with colonic microbiota over a 24 h period (0, 5,10, 24 hr) using in vitro gut fermenter models. Nutri-kinetic analysis using LCMSn demonstrated significant increases in the concentration of gut microbiota-mediated polyphenolic metabolites over time, including 3-(4hydroxyphenyl) propionic acid, 3-(3-hydroxyphenyl) propanoic acid, hydroxybenzoic acid and urolithin A. While changes in the bacterial composition of the gut fermenter model(s) were monitored using fluorescent in situ hybridisation analysis (FISH) with validated probes for Total bacteria, Bifidobacterium genus, Clostridium histolyticum/perfringens group, Faecalibacterium prausnitzii, Eubacterium rectale group, Bacteroides, Lactobacilli and Enterobacteria; limited changes were observed.
Bioactivity of the post-berry consumption ileal fermentates was assessed on two colonocyte cell lines (HT29 and CCD841 CON (normal)) using the oxidative challenge COMET assay. Post-berry ileal fermentate (24 h) from all five ileostomists significantly (p < 0.01) decreased DNA damage (expressed as %Tail DNA) in both HT29 cells (~45%) and CCD841 cells (~25%) compared to untreated controls.
To conclude, strawberry phytochemicals were available for colonic fermentation following ileal digestion and human microbiota-mediated fermentation which subsequently increased overall levels of polyphenolic metabolites, the post berry fermentates were demonstrated to reduce DNA damage in colonocytes.