Omega-3 polyunsaturated fatty acids improve intestinal barrier integrity-albeit to a lesser degree than short-chain fatty acids: an exploratory analysis of the randomized controlled LIBRE trial

Eur J Nutr. 2023 Oct;62(7):2779-2791. doi: 10.1007/s00394-023-03172-2. Epub 2023 Jun 15.

Abstract

Purpose: Adherence to the Mediterranean diet is associated with beneficial health effects, including gastrointestinal disorders. Preclinical studies suggest that omega-3 polyunsaturated fatty acids (n-3 PUFAs), found in Mediterranean foods like nuts and fish, improve intestinal barrier integrity. Here, we assessed possible effects of n-3 PUFAs on barrier integrity in a randomized controlled trial.

Methods: We studied 68 women from the open-label LIBRE trial (clinicaltrials.gov: NCT02087592) who followed either a Mediterranean diet (intervention group, IG) or a standard diet (control group, CG). Study visits comprised baseline, month 3, and month 12. Barrier integrity was assessed by plasma lipopolysaccharide binding protein (LBP) and fecal zonulin; fatty acids by gas chromatography with mass spectrometry. Median and interquartile ranges are shown.

Results: Adherence to the Mediterranean diet increased the proportion of the n-3 docosahexaenoic acid (DHA) (IG + 1.5% [0.9;2.5, p < 0.001]/ + 0.3% [- 0.1;0.9, p < 0.050] after 3/12 months; CG + 0.9% [0.5;1.6, p < 0.001]/ ± 0%) and decreased plasma LBP (IG - 0.3 µg/ml [- 0.6;0.1, p < 0.010]/ - 0.3 µg/ml [- 1.1; - 0.1, p < 0.001]; CG - 0.2 µg/ml [- 0.8; - 0.1, p < 0.001]/ ± 0 µg/ml) and fecal zonulin levels (IG - 76 ng/mg [- 164; - 12, p < 0.010]/ - 74 ng/mg [- 197;15, p < 0.001]; CG - 59 ng/mg [- 186;15, p < 0.050]/ + 10 ng/mg [- 117;24, p > 0.050]). Plasma DHA and LBP (R2: 0.14-0.42; all p < 0.070), as well as plasma DHA and fecal zonulin (R2: 0.18-0.48; all p < 0.050) were found to be inversely associated in bi- and multivariate analyses. Further multivariate analyses showed that the effect of DHA on barrier integrity was less pronounced than the effect of fecal short-chain fatty acids on barrier integrity.

Conclusions: Our data show that n-3 PUFAs can improve intestinal barrier integrity.

Trial registration number: The trial was registered prospectively at ClinicalTrials.gov (reference: NCT02087592).

Keywords: Gut barrier; Gut permeability; Intestinal barrier; Mediterranean diet; Omega 3 fatty acids; PUFAs.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Docosahexaenoic Acids / pharmacology
  • Fatty Acids
  • Fatty Acids, Omega-3* / pharmacology
  • Fatty Acids, Volatile
  • Gas Chromatography-Mass Spectrometry
  • Intestines

Substances

  • Fatty Acids, Omega-3
  • Docosahexaenoic Acids
  • Fatty Acids
  • Fatty Acids, Volatile

Associated data

  • ClinicalTrials.gov/NCT02087592