Gut Immunity and Microbiota Dysbiosis Are Associated with Altered Bile Acid Metabolism in LPS-Challenged Piglets.

Xiao Xiao,Jie Fu,Mingliang Jin,Zeqing Lu,Yizhen Wang,Xin Zong,Fengqin Wang,Yuanzhi Cheng,Si Qin

doi:10.1155/2021/6634821

Abstract

Bacterial infections are among the major factors that cause stress and intestinal diseases in piglets. Lipopolysaccharide (LPS), a major component of the Gram-negative bacteria outer membrane, is commonly employed for inducing an immune response in normal organisms for convenience. The association between LPS stimulation and gut immunity has been reported. However, the effects of gut immunity on microbial homeostasis and metabolism of host, especially bile acid and lipid metabolism in piglets, remain unclear. Hence, in the current study, we elucidated the effect of gut immunity on microbial balance and host metabolism. Twenty-one-day-old healthy piglets (male) were randomly assigned into the CON and LPS groups. After 4 hours of treatment, related tissues and cecal contents were obtained for further analysis. The obtained results showed that stimulated LPS considerably damaged the morphology of intestinal villi and enhanced the relative expression of proinflammatory cytokines. Besides, LPS partially changed the microbial structure as indicated by β-diversity and increased operational taxonomic units (OTUs) related to Oxalobacter and Ileibacterium. Furthermore, bile acid, a large class of gut microbiota metabolites, was also assessed by many proteins related to the enterohepatic circulation of bile acids. It was also revealed that LPS markedly inhibited the mRNA and protein expression of TGR5 and FXR (bile acid receptors) in the ileum, which expressed negative feedback on bile acid de novo synthesis. Additionally, results indicated upregulated mRNA of genes associated with the production of bile acid in the liver tissues. Moreover, LPS reduced the expression of bile acid transporters in the ileum and liver tissues and further disturbed the normal enterohepatic circulation. Taken together, gut immunity and microbial dysbiosis are associated with altered bile acid metabolism in LPS-challenged piglets, which provided theoretical basis for revealing the potential mechanism of intestinal inflammation in swine and seeking nutrients to resist intestinal damage.

Highlights

The gastrointestinal tract of neonatal piglets is vulnerable to external stimuli, such as weaning, diarrhea, pathogens infection, and hostile environmental condition during the early life period [1,2,3]
The gut microbiota and metabolites considerably contribute to the crosstalk between microbiota and host homeostasis, which leads to their participation in the occurrence and development of cardiovascular diseases, host metabolism, immune responses, and energy expenditure [9,10,11,12,13]
To the best of our knowledge, bile acids have been synthesized from cholesterol in the liver [21, 25, 37], further metabolized by the gut microbiota, and moved through enterohepatic circulation [24, 38]

Summary

Introduction

The gastrointestinal tract of neonatal piglets is vulnerable to external stimuli, such as weaning, diarrhea, pathogens infection, and hostile environmental condition during the early life period [1,2,3]. Gut microbiota in the enteric cavity is important for the protection of the host intestine against damage [4]. The host intestine and gut microbiota remain in a steady-state condition under normal physiological conditions. Dysregulation or imbalance of gut microbiota leads to metabolic syndrome and many other diseases, affecting the host health negatively for the long term [7, 8]. The gut microbiota and metabolites considerably contribute to the crosstalk between microbiota and host homeostasis, which leads to their participation in the occurrence and development of cardiovascular diseases, host metabolism, immune responses, and energy expenditure [9,10,11,12,13]

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Discussion

Conclusion