Abstract
Antibiotic-caused changes in intestinal flora (dysbiosis) can have various effects on the host. Secondary bile acids produced by intestinal bacteria are ligands for specific nuclear receptors, which regulate glucose, lipid, and drug metabolism in the liver. The present study aimed to clarify the effect of changes in secondary bile acids caused by antibiotic-induced dysbiosis on the host physiology, especially glucose, lipid, and drug metabolism. After oral administration of non-absorbable antibiotics for 5 days, decreased amounts of secondary bile acid-producing bacteria in faeces and a reduction in secondary bile acid [lithocholic acid (LCA) and deoxycholic acid (DCA)] levels in the liver were observed. Serum glucose and triglyceride levels were also decreased, and these decreases were reversed by LCA and DCA supplementation. Quantitative proteomics demonstrated that the expression levels of proteins involved in glycogen metabolism, cholesterol, bile acid biosynthesis, and drug metabolism (Cyp2b10, Cyp3a25, and Cyp51a1) were altered in the liver in dysbiosis, and these changes were reversed by LCA and DCA supplementation. These results suggested that secondary bile acid-producing bacteria contribute to the homeostasis of glucose and triglyceride levels and drug metabolism in the host, and have potential as therapeutic targets for treating metabolic disease.
Highlights
Antibiotics are widely used for the treatment and prevention of bacterial infections; recent studies indicate that antibiotics can have multiple effects on the host physiology, together with changes in the intestinal flora[1,2]
Antibiotics were administered to mice, with, or without, secondary bile acid supplementation (LCA and deoxycholic acid (DCA)), for 5 days and the hepatic expression levels of proteins relating to glucose, lipid and drug metabolism were determined by quantitative proteomic analysis
The present study revealed that serum glucose levels, serum and liver TG levels, and liver weights in conventional mice were decreased by short-term antibiotic administration (5 days) (Fig. 3A–D)
Summary
Antibiotics are widely used for the treatment and prevention of bacterial infections; recent studies indicate that antibiotics can have multiple effects on the host physiology, together with changes in the intestinal flora (dysbiosis)[1,2]. In our previous study, it was revealed that the protein-expression levels of metabolizing enzymes, including cytochrome P450 (cyp) and transporters, were changed in the liver of short-term (5 days) antibiotic-treated mice[10]. As bile acids have been reported to be ligands for FXR, PXR, CAR and VDR16, it has been inferred that changes in secondary bile acids caused by dysbiosis have an influence on the host physiology, such as glucose, lipid, and drug metabolism, via these nuclear receptors. The purpose of the present study was to clarify the effect of changes in secondary bile acids caused by antibiotic-induced dysbiosis on the host physiology, especially glucose, lipid and drug metabolism. Antibiotics were administered to mice, with, or without, secondary bile acid supplementation (LCA and DCA), for 5 days and the hepatic expression levels of proteins relating to glucose, lipid and drug metabolism were determined by quantitative proteomic analysis
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