Calcium-sensing receptor alleviates gut damage caused by endotoxemia by regulating gut microbiota

Transl Pediatr. 2023 Dec 26;12(12):2179-2190. doi: 10.21037/tp-23-327. Epub 2023 Dec 20.

Abstract

Background: Growing evidence points to an association between the gut microbiota and neonatal diseases. Calcium-sensing receptor (CaSR) is a major modulator of tissue responses associated with calcium homeostasis and is highly expressed in the mammalian gut. CaSR may affect the composition and balance of the intestinal microenvironment.

Methods: Neonatal rats were randomized to the control, lipopolysaccharide (LPS), CaSR agonist, and CaSR inhibitor groups. The intestinal contents of neonatal rats were collected within 24 hours or 7 days after intervention. Then, 16S rRNA short amplicon sequencing was used to analyze biological information and the richness and diversity of individual taxa.

Results: LPS aggravated intestinal injury. The CaSR agonist alleviated injury, and the inhibitor further enhance intestinal injury. Activation of CaSR enhanced the diversity of the gut microbiota and the abundance of Lactobacillus. The lowest abundance of Firmicutes and the highest abundance of Bacteroidetes were found in the agonist group. CaSR impacted the bacterial species in rats with endotoxemia, and Akkermansia had the greatest effect on the differences among groups.

Conclusions: Activation of CaSRs could enhance the species richness and β-diversity of the gut microbiota and alter the abundance of many taxa. This could attenuate LPS-induced gut injury by modulating the gut microbiota.

Keywords: Gut microbiota; calcium-sensing receptor (CaSR); endotoxemia; high-throughput sequencing; lipopolysaccharide (LPS).