Gut-derived lipopolysaccharides increase post-prandial oxidative stress via Nox2 activation in patients with impaired fasting glucose tolerance: effect of extra-virgin olive oil

Eur J Nutr. 2019 Mar;58(2):843-851. doi: 10.1007/s00394-018-1718-x. Epub 2018 May 16.

Abstract

Purpose: Post-prandial phase is characterized by enhanced oxidative stress but the underlying mechanism is unclear. We investigated if gut-derived lipopolysaccharide (LPS) is implicated in this phenomenon and the effect of extra virgin olive oil (EVOO) in patients with impaired fasting glucose (IFG).

Methods: This is a randomized cross-over interventional study including 30 IFG patients, to receive a lunch with or without 10 g of EVOO. Serum LPS, Apo-B48, markers of oxidative stress such as oxidized LDL (oxLDL) and soluble Nox2-derived peptide (sNox2-dp), a marker of nicotinamide-adenine-dinucleotide-phosphate oxidase isoform Nox2 activation, and plasma polyphenols were determined before, 60 and 120 min after lunch.

Results: In patients not given EVOO oxidative stress as assessed by sNox2-dp and oxLDL significantly increased at 60 and 120 min concomitantly with an increase of LPS and Apo-B48. In these patients, changes of LPS were correlated with Apo-B48 (Rs = 0.542, p = 0.002) and oxLDL (Rs = 0.463, p = 0.010). At 120 min, LPS (β - 15.73, p < 0.001), Apo-B48 (β - 0.14, p = 0.004), sNox2-dp (β - 5.47, p = 0.030), and oxLDL (β - 42.80, p < 0.001) significantly differed between the two treatment groups. An inverse correlation was detected between polyphenols and oxLDL (R - 0.474, p < 0.005). In vitro study showed that LPS, at the same concentrations found in the human circulation, up-regulated Nox2-derived oxidative stress via interaction with Toll-like receptor 4.

Conclusions: Post-prandial phase is characterized by an oxidative stress-related inflammation potentially triggered by LPS, a phenomenon mitigated by EVOO administration.

Keywords: Extra-virgin olive oil; Lipopolysaccharide; Oxidative stress.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Cross-Over Studies
  • Fasting
  • Female
  • Glucose Intolerance / metabolism*
  • Humans
  • Intestinal Mucosa / metabolism*
  • Lipopolysaccharides / metabolism*
  • Male
  • Middle Aged
  • NADPH Oxidase 2 / metabolism*
  • Olive Oil / administration & dosage
  • Olive Oil / pharmacology*
  • Oxidative Stress / physiology*
  • Postprandial Period / physiology

Substances

  • Lipopolysaccharides
  • Olive Oil
  • NADPH Oxidase 2