Infection and Drug Resistance (Aug 2023)
Calcium-Sensitive Receptors Alters Intestinal Microbiota Metabolites Especially SCFAs and Ameliorates Intestinal Barrier Damage in Neonatal Rat Endotoxemia
Abstract
Yan Sun,1,* Jiayu Song,2,* Xue Lan,1 Fei Ma,2 Mingyu Jiang,3 Chunming Jiang1,2 1Department of Neonatology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China; 2Department of Neonatology, Zhuhai Women and Children’s Hospital, Zhuhai, Guangdong, 519060, People’s Republic of China; 3Department of Pediatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunming Jiang, Department of Neonatology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, People’s Republic of China, Tel +86-13303601657, Fax +86 0451-53670428, Email [email protected]: The calcium-sensing receptor (CaSR) acts as a major modulator of tissue responses related to calcium homeostasis and expresses highly in the mammalian intestine. Endotoxemia tends to impair intestinal barrier function and poses significant obstacles in clinical treatment. This work is designed to decipher whether CaSR can protect lipopolysaccharide (LPS)-induced intestinal barrier dysfunction in neonatal rats by targeting intestinal metabolites.Patient and Methods: In this study, we utilized gas chromatography (GC) combined with liquid chromatography-mass spectrometry (LC-MS) to quantitatively analyze SCFAs and metabolites in fecal samples of 24 neonatal rats with LPS induced endotoxemia.Results: Our results showed that CaSR alleviated endotoxin damage to the intestinal tight junction structure and upregulated the levels of butyric acid, propionic acid, valeric acid, and isovaleric acid in short-chain fatty acids (SCFAs). Non-targeted metabolomics analysis indicated that CaSR improved intestinal metabolic disorders by regulating glycerophospholipid metabolism, α-linolenic acid metabolism, as well as sphingolipids metabolism.Conclusion: CaSR can alter intestinal microbiota metabolites, especially SCFAs, and improve intestinal barrier damage in neonatal rat endotoxemia.Keywords: calcium-sensing receptor, lipopolysaccharide, endotoxemia, short chain fatty acids, metabolomics
