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. 2019 Jul;65(1):34-46.
doi: 10.3164/jcbn.18-116. Epub 2019 Apr 6.

Green tea polyphenol (epigallocatechin-3-gallate) improves gut dysbiosis and serum bile acids dysregulation in high-fat diet-fed mice (VSports在线直播)

Chihiro Ushiroda  1 , Yuji Naito  1 , Tomohisa Takagi  1 , Kazuhiko Uchiyama  1 , Katsura Mizushima  1 , Yasuki Higashimura  2 , Zenta Yasukawa  3 , Tsutomu Okubo  3 , Ryo Inoue  4 , Akira Honda  5 , Yasushi Matsuzaki  5 , Yoshito Itoh  1
Affiliations

Green tea polyphenol (epigallocatechin-3-gallate) improves gut dysbiosis and serum bile acids dysregulation in high-fat diet-fed mice

Chihiro Ushiroda et al. J Clin Biochem Nutr. 2019 Jul.

Abstract

Gut microbiota have profound effects on bile acid metabolism by promoting deconjugation, dehydrogenation, and dehydroxylation of primary bile acids in the distal small intestine and colon. High-fat diet-induced dysbiosis of gut microbiota and bile acid dysregulation may be involved in the pathology of steatosis in patients with non-alcoholic fatty liver disease. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic catechin in green tea, has been widely investigated for its inhibitory or preventive effects against fatty liver. The aim of the present study was to investigate the effects of EGCG on the abundance of gut microbiota and the composition of serum bile acids in high-fat diet-fed mice and determine the specific bacterial genera that can improve the serum bile acid dysregulation associated with EGCG anti-hepatic steatosis action. Male C57BL/6N mice were fed with the control diet, high-fat diet, or high-fat diet + EGCG at a concentration of 0. 32% for 8 weeks. EGCG significantly inhibited the increases in weight, the area of fatty lesions, and the triglyceride content in the liver induced by the high-fat diet. Principal coordinate analysis revealed significant differences in microbial structure among the groups. At the genus level, EGCG induced changes in the microbiota composition in high-fat diet-fed mice, showing a significantly higher abundance of Adlercreutzia, Akkermansia, Allobaculum and a significantly lower abundance of Desulfovibrionaceae. EGCG significantly reversed the decreased population of serum primary cholic acid and β-muricholic acid as well as the increased population of taurine-conjugated cholic acid, β-muricholic acid and deoxycholic acid in high-fat diet-fed mice VSports手机版. Finally, the correlation analysis between bile acid profiles and gut microbiota demonstrated the contribution of Akkermansia and Desulfovibrionaceae in the improvement of bile acid dysregulation in high-fat diet-fed mice by treatment with EGCG. In conclusion, the present study suggests that EGCG could alter bile acid metabolism, especially taurine deconjugation, and suppress fatty liver disease by improving the intestinal luminal environment. .

Keywords: Akkermansia; dysbiosis; epigallocatechin-3-gallate; high-fat diet; taurine-conjugated bile acids V体育安卓版. .

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Conflict of interest statement

YN received scholarship funding from EA Pharma Co. , Ltd. and collaboration research funding from Fujifilm Medical Co. , Ltd. and has been paid lecture fees by Janssen Pharma K. K. , Mylan EPD Co. , Takeda Pharma. Co. , Ltd. , Mochida Pharma. Co. , Ltd. , EA Pharma Co. , Ltd. , Otsuka Pharma V体育ios版. Co. , Ltd. , Astellas Pharma Inc. and Miyarisan Pharma. Co. , Ltd. ZY and TO are having the limited stock ownership as an employee of the company. No further financial interest is stated. The research was partly funded by these funds. Neither the funding agency nor any outside organization has participated in study design or have any competing of interest. These pharmaceutical companies had final approval of the manuscript. YI has an affiliation with a donation-funded department from Nichinichi Pharmaceutical Co. , Ltd. The other authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Inhibitory effect of EGCG on the HFD-induced obese phenotype and hepatic triacylglycerol accumulation. (A) Time-course of mouse body weight. Body weight of male mice receiving an EGCG-containing diet for 8 weeks. (B) Liver weight. (C) Hematoxylin-eosin (HE)-stained liver sections. (D) Area of fatty lesions in the liver. (E) Hepatic triacylglycerol (TG) content. C57BL/6N mice were fed a CE-2 diet (control), a high-fat diet (HFD), or an HFD supplemented with 0.32% EGCG (HFD + EGCG) for 8 weeks. Values are expressed as the means and SEM of eight mice in each group. Significant differences compared with the control group are denoted * (p<0.05), and those with the HFD group are denoted † (p<0.05). Photographs are of HE staining of liver sections from representative mice of each group (scale bar = 500 µm).
Fig. 2
Fig. 2
Effects of EGCG administration on gut microbiota in α and β diversity indices. (A) Principal coordinate analysis (PCoA) plot of unweighted UniFrac data. (B) PCoA plot of weighted UniFrac data. (C) The Chao 1 index (OTU richness estimation). (D) The Shannon index (OTU evenness estimation). C57BL/6N mice were fed with the control CE-2 diet (control), a high-fat diet (HFD), or the HFD supplemented with 0.32% EGCG (HFD + EGCG) for eight weeks. The composition of cecal content was analyzed using Illumina-based 16S rRNA sequencing. Values are expressed as the means and SEM of six mice in each group. Significant differences compared with the control group are denoted * (p<0.05), and those with the HFD group are denoted † (p<0.05).
Fig. 3
Fig. 3
Effects of EGCG administration on gut microbiota at the phylum level. (A) The microbial composition at the phylum level. (B) At the phylum level of microbiota (calculated as the percentage of total microbiota). (C) Firmicutes/Bacteroidetes ratio. C57BL/6N mice were fed with the control CE-2 diet (control), a high-fat diet (HFD), or the HFD supplemented with 0.32% EGCG (HFD + EGCG) for eight weeks. The composition of cecal content was analyzed using Illumina-based 16S rRNA sequencing. Values are expressed as the means and SEM of six mice in each group. Significant differences compared with the control group are denoted * (p<0.05), and those with the HFD group are denoted † (p<0.05).
Fig. 4
Fig. 4
Effects of EGCG administration on gut microbiota at the genus level. (A) The microbial composition at the genus level. (B) Heat map of 16S rRNA gene sequencing analysis of cecal content at the genus level. The scale reflects the data as follows: violet indicates high values whereas white indicates low values for the percentage of reads that were classified at that rank. C57BL/6N mice were fed with the control CE-2 diet (control), a high-fat diet (HFD), or the HFD supplemented with 0.32% EGCG (HFD + EGCG) for eight weeks. The composition of cecal content was analyzed using Illumina-based 16S rRNA sequencing. Significant differences compared with the control group are denoted * (p<0.05), and those with the HFD group are denoted † (p<0.05).
Fig. 5
Fig. 5
Determination of BA profile and calculation of BA transformation activities by gut microbiota. (A) Deconjugation. (B) Taurine-conjugated BAs. (C) 7α-Dehydroxylation. C57BL/6N mice were fed with the control CE-2 diet (control), a high-fat diet (HFD), or the HFD supplemented with 0.32% EGCG (HFD + EGCG) for eight weeks. Values are expressed as the means and SEM of six mice in each group. Significant differences compared with the control group are denoted * (p<0.05), and those with the HFD group are denoted † (p<0.05). CA, free cholic acid; Tauro-CA, taurine-conjugated cholic acid; β-MCA, free β-muricholic acid; Tauro-β-MCA, taurine-conjugated β-muricholic acid; DCA, free deoxycholic acid; Tauro-DCA, taurine-conjugated deoxycholic acid; BA, bile acid; LCA, free lithocholic acid; CDCA, free chenodeoxycholic acid.
Fig. 6
Fig. 6
A heat map generated by Spearman’s correlation analysis reveals the relationship between the abundance of gut microbiota at the genus level and BA profile. Correlation heat map demonstrating the association between the indicated gut microbiota taxonomic genera and BAs. Red denotes a positive association, blue a negative association, and white no association. C57BL/6N mice were fed with a high-fat diet (HFD), or a HFD supplemented with 0.32% EGCG (HFD + EGCG) for eight weeks.
Fig. 7
Fig. 7
Correlation heat map demonstrating the association between the indicated gut microbiota taxonomic genera and BA composition. Red denotes a positive association, blue a negative association, and white no association. CA, free cholic acid; Tauro-CA, taurine-conjugated cholic acid; β-MCA, free β-muricholic acid; Tauro-β-MCA, taurine-conjugated β-muricholic acid; DCA, free deoxycholic acid; Tauro-DCA, taurine-conjugated deoxycholic acid; LCA, free lithocholic acid; CDCA, free chenodeoxycholic acid.
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