Microbial and Transcriptomic Profiling Reveals Diet-Related Alterations of Metabolism in Metabolic Disordered Mice

Weize Zhu; Ying Hong; Yue Li; Yan Li; Jing Zhong; Xiaofang He; Ningning Zheng; Lili Sheng; Houkai Li

doi:10.3389/fnut.2022.923377

Microbial and Transcriptomic Profiling Reveals Diet-Related Alterations of Metabolism in Metabolic Disordered Mice

Front Nutr. 2022 Jul 19:9:923377. doi: 10.3389/fnut.2022.923377. eCollection 2022.

Authors

Weize Zhu¹, Ying Hong¹, Yue Li², Yan Li¹, Jing Zhong^{1

3}, Xiaofang He¹, Ningning Zheng¹, Lili Sheng¹, Houkai Li¹

Affiliations

¹ School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Department of Endocrinology, Shanghai Fifth People's Hospital, Shanghai Medical School, Fudan University, Shanghai, China.
³ Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou, China.

Abstract

Metabolic disorders are the prelude of metabolic diseases, which are mainly due to the high-energy intake and genetic contribution. High-fat diet (HFD) or high-sucrose diet is widely used for inducing metabolic disorders characterized by increased body weight, insulin resistance, hepatic steatosis, and alteration of gut microbiome. However, the triangle relationship among diets, gut microbiome, and host metabolism is poorly understood. In our study, we investigated the dynamic changes in gut microbiota, and host metabolism in mice that were fed with either chow diet, HFD, or chow diet with 30% sucrose in drinking water (HSD) for continued 12 weeks. The gut microbiota was analyzed with 16S rDNA sequencing on feces. Hepatic gene expression profile was tested with transcriptomics analysis on liver tissue. The host metabolism was evaluated by measuring body weight, insulin sensitivity, serum lipids, and expression of proteins involved in lipid metabolism of liver. The results showed that HFD feeding affected body weight, insulin resistance, and hepatic steatosis more significantly than HSD feeding. 16S rRNA gene sequencing showed that HFD rapidly and steadily suppressed species richness, altered microbiota structure and function, and increased the abundance of bacteria responsible for fatty acid metabolism and inflammatory signaling. In contrast, HSD had minor impact on the overall bacteria structure or function but activated microbial bile acid biosynthesis. Fecal microbiota transplantation suggested that some metabolic changes induced by HFD or HSD feeding were transferrable, especially in the weight of white adipose tissue and hepatic triglyceride level that were consistent with the phenotypes in donor mice. Moreover, transcriptomic results showed that HFD feeding significantly inhibited fatty acid degradation and increase inflammation, while HSD increased hepatic de novo lipogenesis and inhibited primary bile acid synthesis alternative pathway. In general, our study revealed the dynamic and diversified impacts of HFD and HSD on gut microbiota and host metabolism.

Keywords: gut microbiota; high-energy diet; metabolic syndrome; metabolism; transcriptomic profiling.