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Glutamate attenuates lipopolysaccharide induced intestinal barrier injury by regulating corticotropin-releasing factor pathway in weaned pigs

  • Guo, Junjie (Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University) ;
  • Liang, Tianzeng (Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University) ;
  • Chen, Huifu (Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University) ;
  • Li, Xiangen (Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University) ;
  • Ren, Xiaorui (Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University) ;
  • Wang, Xiuying (Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University) ;
  • Xiao, Kan (Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University) ;
  • Zhao, Jiangchao (Department of Animal Science, Division of Agriculture, University of Arkansas) ;
  • Zhu, Huiling (Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University) ;
  • Liu, Yulan (Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University)
  • Received : 2021.10.19
  • Accepted : 2022.01.29
  • Published : 2022.08.01

Abstract

Objective: The purpose of this study was to evaluate the protection of glutamate (GLU) against the impairment in intestinal barrier function induced by lipopolysaccharide (LPS) stress in weaned pigs. Methods: Twenty-four weaned pigs were divided into four treatments containing: i) non-challenged control, ii) LPS-challenged control, iii) LPS+1.0% GLU, and iv) LPS+2.0% GLU. On day 28, pigs were treated with LPS or saline. Blood samples were collected at 0, 2, and 4 h post-injection. After blood samples collection at 4 h, all pigs were slaughtered, and spleen, mesenteric lymph nodes, liver and intestinal samples were obtained. Results: Dietary GLU supplementation inhibited the LPS-induced oxidative stress in pigs, as demonstrated by reduced malondialdehyde level and increased glutathione level in jejunum. Diets supplemented with GLU enhanced villus height, villus height/crypt depth and claudin-1 expression, attenuated intestinal histology and ultrastructure impairment induced by LPS. Moreover, GLU supplementation reversed intestinal intraepithelial lymphocyte number decrease and mast cell number increase induced by LPS stress. GLU reduced serum cortisol concentration at 4 h after LPS stress and downregulated the mRNA expression of intestinal corticotropin-releasing factor signal (corticotrophin-releasing factor [CRF], CRF receptor 1 [CRFR1], glucocorticoid receptor, tryptase, nerve growth factor, tyrosine kinase receptor A), and prevented mast cell activation. GLU upregulated the mRNA expression of intestinal transforming growth factor β. Conclusion: These findings indicate that GLU attenuates LPS-induced intestinal mucosal barrier injury, which is associated with modulating CRF signaling pathway.

Keywords

Acknowledgement

This research was financially supported by the projects of Wuhan Science and Technology Bureau (No. 201802040101 1304), the Project of Natural Science Foundation of Hubei Province (No. 2019CFB831), the open Project of Hubei Key Laboratory of Animal Nutrition and Feed Science (No. 201901), the National Natural Science Foundation of China (No. 31772615), and the Project of Innovative Research Groups of the Natural Science Foundation of Hubei Province (No. 2019CFA015).

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