Farnesoid X receptor blockade attenuates morphological damage, intestinal secretion, and prevents mucus loss induced by SARS-CoV-2 spike protein in the mouse intestine.

INTRODUCTION

The SARS-CoV-2 spike protein has been implicated as an important pathogenic factor, including in intestinal disorders. The farnesoid X receptor (FXR), a nuclear receptor highly expressed in the intestine, has been highlighted in several studies investigating its role in different intestinal dysfunctions.

OBJECTIVES

This study evaluated whether FXR blockade attenuates spike-induced morphological alterations and intestinal dysfunction.

METHODS

Balb/c mice were divided into three groups (PBS, Spike, and DY268-antagonist). A 2-3 cm jejunal loop was surgically prepared, and different substances were inoculated into the loops (200 μl of PBS or 200 μl containing 10 μg of spike protein or 100 μl of DY268 at μmol + 100 μl of spike), followed by 4-h resting period before euthanasia. Chloride (Cl-) was measured, and tissue samples were collected for histomorphometry analysis, mucin and MUC2 evaluation, Paneth cell assessment, malondialdehyde (MDA), and glutathione (GSH) levels.

KEY FINDINGS: FXR antagonism attenuated alterations in all histomorphometric parameters, maintained mucin expression and Paneth cells and their granules, and reduced MDA levels, while restoring GSH in the intestinal loop. However, further studies are needed to understand the mechanisms by which FXR blockade modulates spike-induced intestinal effects.

CONCLUSIONS

These findings may provide insights into novel targeted strategies for the management of intestinal disorders.