Systemic Evaluation of Administered FITC-Dextran or Evans Blue Dye to Determine Intestinal Barrier Permeability in Nonhuman Primates

Abstract

Background: Microbial translocation is a key contributor to chronic immune activation during HIV infection. Current methods of measuring microbial translocation are limited in sensitivity and are largely indirect, underscoring the need for more precise and direct techniques that can be followed longitudinally. We aimed to address this gap by applying modalities commonly employed in mouse models of intestinal permeability. 

Methods: We explored whether oral FITC-Dextran or suppository-delivered Evans blue dye in nonhuman primates could be leveraged to approximate intestinal barrier disruption in healthy and SIV-infected rhesus macaques.

Results: After administration, FITC-Dextran was detected at comparable concentrations in the plasma of healthy and chronically infected animals, whereas healthy animals had greater concentrations of Evans blue dye as compared to chronically infected animals. Evans blue was reliably detected in phagocytic cells across tissue types, with detection often highest in the rectum, liver, and spleen biopsies. Exogenous uracil modulated an increase in intestinal barrier permeability observed through standard markers, which was not reliably reflected on Evans blue uptake.

Conclusion: These data demonstrate that dye-based measurements of intestinal permeability routinely used in murine models are not sufficient in nonhuman primates, and that common biomarkers and/or sugar permeability and immunohistochemical approaches are still preferred.