Yi Wan1, Jihong Yuan2, Jie Li2, Hao Li1, Jingjing Zhang3, Jun Tang1, Yan Ni4, Tao Huang5, Fenglei Wang6, Feng Zhao7, Duo Li8. 1. Department of Food Science and Nutrition, Zhejiang University, Hangzhou, 310058, China. 2. No. 1 Department of Nutrition, Chinese People's Liberation Army General Hospital, Beijing, China. 3. Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310058, China. 4. The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310024, China. 5. Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China. 6. Department of Food Science and Nutrition, Zhejiang University, Hangzhou, 310058, China; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA. 7. Institute of Nutrition and Health, Qingdao University, Qingdao, 266071, China. Electronic address: fengzhao21c@126.com. 8. Department of Food Science and Nutrition, Zhejiang University, Hangzhou, 310058, China; Institute of Nutrition and Health, Qingdao University, Qingdao, 266071, China. Electronic address: duoli@qdu.edu.cn.
Abstract
BACKGROUND & AIMS: Observational studies have shown that diets high in fat and low in dietary fiber, might have an unfavorable impact on bile acid (BA) profiles, which might further affect host cardiometabolic health. In the current study, we aimed to evaluate the effects of dietary fat content on BA profiles and associated gut microbiota, and their correlates with cardiometabolic risk factors. METHODS: In a randomized controlled-feeding trial, healthy young adults were assigned to one of the three diets: a lower-fat diet (fat 20%, carbohydrate 66% and protein 14%), a moderate-fat diet (fat 30%, carbohydrate 56% and protein 14%) and a higher-fat diet (fat 40%, carbohydrate 46% and protein 14%) for 6 months. All the foods were provided during the entire intervention period. The BA profiles, associated gut microbiota and markers of cardiometabolic risk factors were determined before and after intervention. RESULTS: The higher-fat diet resulted in an elevated concentration of total BAs (p < 0.001), and unconjugated BAs (p = 0.03) compared with lower-fat diet. Secondary BAs, such as deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), 12ketolithocholic acid (12keto-LCA), 3β-DCA and taurolithocholic acid (TLCA) (p < 0.05 after FDR correction) were significantly increased in the higher-fat diet group after the 6-month intervention. Consistently, the abundances of gut bacteria (Bacteroides, Clostridium, Bifidobacterium and Lactobacillus) which affect bile salt hydrolase gene expression were significantly increased after higher-fat consumption. The change of DCA was positively associated with the relative abundance of Bacteroides (r = 0.31, p = 0.08 after FDR correction). In addition, the changes of fecal concentrations of DCA and 12keto-LCA were positively associated with serum total cholesterol (r > 0.3, p = 0.02 and p = 0.008 after FDR correction, respectively). In line with these findings, serum fibroblast growth factor 19 (FGF19) was marginally significantly elevated in the higher-fat group after intervention (p = 0.05). CONCLUSIONS: The higher-fat diet resulted in an alteration of BAs, especially unconjugated BAs and secondary BAs, most likely through actions of gut microbiota. These alterations might confer potentially unfavorable impacts on colonic and host cardiometabolic health in healthy young adults. Clinical trial registry number: NCT02355795 listed on NIH website: ClinicalTrials.gov.
RCT Entities:
BACKGROUND & AIMS: Observational studies have shown that diets high in fat and low in dietary fiber, might have an unfavorable impact on bile acid (BA) profiles, which might further affect host cardiometabolic health. In the current study, we aimed to evaluate the effects of dietary fat content on BA profiles and associated gut microbiota, and their correlates with cardiometabolic risk factors. METHODS: In a randomized controlled-feeding trial, healthy young adults were assigned to one of the three diets: a lower-fat diet (fat 20%, carbohydrate 66% and protein 14%), a moderate-fat diet (fat 30%, carbohydrate 56% and protein 14%) and a higher-fat diet (fat 40%, carbohydrate 46% and protein 14%) for 6 months. All the foods were provided during the entire intervention period. The BA profiles, associated gut microbiota and markers of cardiometabolic risk factors were determined before and after intervention. RESULTS: The higher-fat diet resulted in an elevated concentration of total BAs (p < 0.001), and unconjugated BAs (p = 0.03) compared with lower-fat diet. Secondary BAs, such as deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), 12ketolithocholic acid (12keto-LCA), 3β-DCA and taurolithocholic acid (TLCA) (p < 0.05 after FDR correction) were significantly increased in the higher-fat diet group after the 6-month intervention. Consistently, the abundances of gut bacteria (Bacteroides, Clostridium, Bifidobacterium and Lactobacillus) which affect bile salt hydrolase gene expression were significantly increased after higher-fat consumption. The change of DCA was positively associated with the relative abundance of Bacteroides (r = 0.31, p = 0.08 after FDR correction). In addition, the changes of fecal concentrations of DCA and 12keto-LCA were positively associated with serum total cholesterol (r > 0.3, p = 0.02 and p = 0.008 after FDR correction, respectively). In line with these findings, serum fibroblast growth factor 19 (FGF19) was marginally significantly elevated in the higher-fat group after intervention (p = 0.05). CONCLUSIONS: The higher-fat diet resulted in an alteration of BAs, especially unconjugated BAs and secondary BAs, most likely through actions of gut microbiota. These alterations might confer potentially unfavorable impacts on colonic and host cardiometabolic health in healthy young adults. Clinical trial registry number: NCT02355795 listed on NIH website: ClinicalTrials.gov.
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