Endocannabinoids, endocannabinoid-like molecules and their precursors in human small intestinal lumen and plasma: does diet affect them?

Silvia Tagliamonte, Chris IR Gill, L. Kirsty Pourshahidi, Mary Slevin, RK Price, Rosalia Ferracane, Roger Lawther, Gloria O'Connor, Paola Vitaglione

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To determine the small intestinal concentration of endocannabinoids (ECs), N-acylethanolamines (NAEs) and their precursors N-acylphosphatidylethanolamines (NAPEs) in humans. To identify relationships between those concentrations and habitual diet composition as well as individual inflammatory status.
An observational study was performed involving 35 participants with an ileostomy (18W/17M, aged 18–70 years, BMI 17–40 kg/m 2). Overnight fasting samples of ileal fluid and plasma were collected and ECs, NAEs and NAPEs concentrations were determined by LC-HRMS. Dietary data were estimated from self-reported 4-day food diaries.
Regarding ECs, N-arachidonoylethanolamide (AEA) was not detected in ileal fluids while 2-arachidonoylglycerol (2-AG) was identified in samples from two participants with a maximum concentration of 129.3 µg/mL. In contrast, mean plasma concentration of AEA was 2.1 ± 0.06 ng/mL and 2-AG was 4.9 ± 1.05 ng/mL. NAEs concentrations were in the range 0.72–17.6 µg/mL in ileal fluids and 0.014–0.039 µg/mL in plasma. NAPEs concentrations were in the range 0.3–71.5 µg/mL in ileal fluids and 0.19–1.24 µg/mL in plasma being more abundant in participants with obesity than normal weight and overweight. Significant correlations between the concentrations of AEA, OEA and LEA in biological fluids with habitual energy or fat intakes were identified. Plasma PEA positively correlated with serum C-reactive protein.
We quantified ECs, NAEs and NAPEs in the intestinal lumen. Fat and energy intake may influence plasma and intestinal concentrations of these compounds. The luminal concentrations reported would allow modulation of the homeostatic control of food intake via activation of GPR119 receptors located on the gastro-intestinal mucosa. 

Clinical trial registry number and website: NCT04143139; www.clinicaltrials.gov.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalEuropean Journal of Nutrition
Early online date26 Oct 2020
Publication statusPublished online - 26 Oct 2020

Bibliographical note

Funding Information:
Open access funding provided by Università degli Studi di Napoli Federico II within the CRUI-CARE Agreement. We acknowledge funding from the Western Health and Social Care Trust, and Ulster University. The funders had no role in design, implementation, analysis and interpretation of data in this study. Data described in the manuscript will be made available upon request. Acknowledgements

Publisher Copyright:
© 2020, The Author(s).

Copyright 2020 Elsevier B.V., All rights reserved.


  • Gastrointestinal receptors
  • Ileal fluids
  • Ileostomists
  • Lipid mediators
  • N-acylethanolamines
  • Nutrient sensing


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