Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation

This study aims to uncover how specific bacteria and bile acids (BAs) contribute to steatosis induced by diet and farnesoid X receptor (FXR) deficiency in both genders. A control diet (CD) and Western diet (WD), which contains high fat and carbohydrate, were used to feed wild type (WT) and FXR knock...

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Published in:	Scientific reports 2017-05, Vol.7 (1), p.1748-12, Article 1748
Main Authors:	Sheng, Lili, Jena, Prasant Kumar, Liu, Hui-Xin, Kalanetra, Karen M, Gonzalez, Frank J, French, Samuel W, Krishnan, Viswanathan V, Mills, David A, Wan, Yu-Jui Yvonne
Format:	Article
Language:	eng
Subjects:	Acids Animals Bile Bile acids Bile Acids and Salts - metabolism Cholic acid Diet, Western Dysbiosis - pathology Fatty liver Fatty Liver - genetics Fatty Liver - metabolism Fatty Liver - pathology Female Gender differences Gene Expression Regulation Glucose Tolerance Test Homeostasis - genetics Insulin Insulin Resistance Intestinal microflora Lipid Metabolism - genetics Lipids Liver - metabolism Liver cancer Male Metabolic disorders Mice, Inbred C57BL Mice, Knockout Microbiota - genetics Phenotype Phenotyping Receptors, Cytoplasmic and Nuclear - deficiency Receptors, Cytoplasmic and Nuclear - metabolism Rodents Serum lipids Sex Characteristics Sex differences Statistics, Nonparametric Steatosis Taurine
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Summary:	This study aims to uncover how specific bacteria and bile acids (BAs) contribute to steatosis induced by diet and farnesoid X receptor (FXR) deficiency in both genders. A control diet (CD) and Western diet (WD), which contains high fat and carbohydrate, were used to feed wild type (WT) and FXR knockout (KO) mice followed by phenotyping characterization as well as BA and microbiota profiling. Our data revealed that male WD-fed FXR KO mice had the most severe steatosis and highest hepatic and serum lipids as well as insulin resistance among the eight studied groups. Gender differences in WD-induced steatosis, insulin sensitivity, and predicted microbiota functions were all FXR-dependent. FXR deficiency enriched Desulfovibrionaceae, Deferribacteraceae, and Helicobacteraceae, which were accompanied by increased hepatic taurine-conjugated cholic acid and β-muricholic acid as well as hepatic and serum lipids. Additionally, distinct microbiota profiles were found in WD-fed WT mice harboring simple steatosis and CD-fed FXR KO mice, in which the steatosis had a potential to develop into liver cancer. Together, the presented data revealed FXR-dependent concomitant relationships between gut microbiota, BAs, and metabolic diseases in both genders. Gender differences in BAs and microbiota may account for gender dissimilarity in metabolism and metabolic diseases.
ISSN:	2045-2322 2045-2322