Nan Wang1, Jiazheng Wang2, Tian Zhang3, Liufang Huang1, Weihui Yan4, Lina Lu4, Jie Jia5, Yijing Tao4, Wei Cai6, Ying Wang7. 1. Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 2. Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 3. Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 4. Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. 5. Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China; Department of Nutrition, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 6. Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address: caiw204@sjtu.edu.cn. 7. Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address: wangying02@xinhuamed.com.cn.
Abstract
BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) is a major complication of long-term parenteral nutrition (PN). The pathogenesis of PNALD remains unclear. We investigated the changes in taxonomic and functional composition of gut microbiota and serum bile acid levels in a rat model of PNALD. METHODS: Male 4-week-old Sprague Dawley rats received either total parenteral nutrition or standard chow with 0.9% saline for 7 days. The taxonomic composition of cecal microbiota and its functional composition associated with bile acid metabolism were measured. RESULTS: There were differences in taxonomic composition between the two groups. The abundance of the secondary bile acid biosynthesis pathway was higher in the TPN group (p < 0.05) with an increase in the percentage of bacteria expressing 7-alpha-hydroxysteroid dehydrogenase (p < 0.05). The abundance of enzymes associated with bile salt hydrolase was also higher (p < 0.05) in the TPN group. The TPN group showed a distinct bile acid profile characterized by a higher ratio of secondary bile acids to primary bile acids. CONCLUSIONS: The alteration of bile acid-associated microbiota may lead to increased secondary bile acid production in a rat model of PNALD.
BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) is a major complication of long-term parenteral nutrition (PN). The pathogenesis of PNALD remains unclear. We investigated the changes in taxonomic and functional composition of gut microbiota and serum bile acid levels in a rat model of PNALD. METHODS: Male 4-week-old Sprague Dawley rats received either total parenteral nutrition or standard chow with 0.9% saline for 7 days. The taxonomic composition of cecal microbiota and its functional composition associated with bile acid metabolism were measured. RESULTS: There were differences in taxonomic composition between the two groups. The abundance of the secondary bile acid biosynthesis pathway was higher in the TPN group (p < 0.05) with an increase in the percentage of bacteria expressing 7-alpha-hydroxysteroid dehydrogenase (p < 0.05). The abundance of enzymes associated with bile salt hydrolase was also higher (p < 0.05) in the TPN group. The TPN group showed a distinct bile acid profile characterized by a higher ratio of secondary bile acids to primary bile acids. CONCLUSIONS: The alteration of bile acid-associated microbiota may lead to increased secondary bile acid production in a rat model of PNALD.