A translational model for in vivo intestinal permeability assessment in pigs.

Abstract

Background: Several non-communicable diseases in humans are associated with increases in intestinal permeability, which can be modulated by dietary factors. To investigate diet-induced changes in intestinal permeability, relevant translational models are required. Pigs are relevant models for nutrition research, gastro-intestinal tract health and intestinal permeability, but intestinal permeability assessment in pigs needs optimization.

Objective: The aim of this study was to develop and optimize protocols to induce and quantify intestinal permeability in pigs as a translational model.

Methods: We treated pigs (age 10.9 - 13.5 weeks) with indomethacin (3 experiments) or dextran sodium sulfate (DSS, 2 experiments) and assessed intestinal permeability via urinary recovery (baseline to 120h) of orally administered sucralose (SL), erythritol (E) and Co-EDTA. Faecal inflammatory biomarkers and consistency were investigated at baseline, during treatment and during treatment washout. Body weight and villus and crypt dimensions in intestinal tissue were investigated at the end of the experiment.

Results: Indomethacin increased intestinal permeability as evidenced by increased cumulative excretion of SL from 332.7±64.2 to 559.8±98.6 mg (p<0.001) and Co-EDTA from 356.2±84.6 to 572.0±82.6 mg (p<0.001) in 120h urine. SL:E ratios increased 1.83 fold and Co-EDTA:E ratios 1.79 fold. Faecal consistency scores and faecal S100-A12 as a biomarker for intestinal inflammation increased while width of duodenal villi decreased from 191.9±10.8 to 166.7±10.1 μm (p =0.014). DSS treatment did not alter intestinal permeability but increased faecal S100-A12 and colon crypt depth from 507.1±33.7 to 657.9±364 76.8 μm (p=0.012) and decreased duodenum villi width from 191.5±17.5 to 154.5±9.8μm (p=0.022).

Conclusions: We successfully developed a model to disrupt intestinal health in pigs and optimized methods to assess intestinal permeability and health. We provided recommendations on intestinal permeability assessment protocols relevant for future implementation in pigs and humans. Our model can be used to study the effects of food (components) on intestinal permeability and health.