A Translational Model for In Vivo Intestinal Permeability Assessment in Pigs

Abstract

Background: Several noncommunicable 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, gastrointestinal tract health, and intestinal permeability, but intestinal permeability assessment in pigs needs optimization.

Objectives: 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 (aged 10.9-13.5 wk) with indomethacin (3 experiments) or dextran sodium sulfate (DSS, 2 experiments) and assessed intestinal permeability via urinary recovery (baseline to 120 h) of orally administered sucralose, erythritol, and cobalt-disodium ethylenediaminetetraacetate (Co-EDTA). Fecal 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 sucralose 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 120-h urine. Sucralose:erythritol ratios increased 1.83-fold and Co-EDTA:erythritol ratios 1.79-fold. Fecal consistency scores and fecal S100 calcium-binding protein A12 (S100-A12), a biomarker for intestinal inflammation, increased, whereas the 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 fecal 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 ± 9.8 μm (P = 0.022).

Conclusions: We describe a model to disrupt intestinal health in pigs as well as optimized methods to assess intestinal permeability and health. We provide 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.

Keywords: dextran sodium sulfate; indomethacin; intestinal inflammation; intestinal permeability; pig.