Epigallocatechin Gallate Protects Mice against Methionine–Choline-Deficient-Diet-Induced Nonalcoholic Steatohepatitis by Improving Gut Microbiota To Attenuate Hepatic Injury and Regulate Metabolism

Epigallocatechin
gallate (EGCG) has been regarded as a protective
bioactive polyphenol in green tea against nonalcoholic steatohepatitis
(NASH), but the mechanism remains poorly deciphered. Herein, we assessed
the role and mechanism of EGCG on gut microbiota and the metabolism
in NASH development. Forty-eight male C57BL/6J mice were fed with
either a methionine–choline-sufficient diet or a methionine–choline-deficient
(MCD) diet with or without EGCG administration for 4 weeks. Liver
injury, inflammation, lipid accumulation, and iron overload were examined.
16S ribosomal RNA sequencing was used to detect the fecal microbiome.
In our research, we observed that EGCG notably improved MCD-diet-derived
gut microbiota dysbiosis, as proved by a distinctively clustered separation
from that of the MCD group and by the decrease of the Oxalobacter, Oscillibacter, Coprococcus_1, and Desulfovibrio genera and enrichment of norank_f__Bacteroidales_S24_7_group, Alloprevotella, and Bacteroides. Spearman-correlation heatmap analysis
indicated that Bacteroides and Alloprevotella induced by EGCG were strongly negatively
correlated with lipid accumulation. Functional enzymes of the gut
microbiome were predicted by PICRUSt based on the operation classification
unit. The results revealed that 1468 enzymes were involved in various
metabolic pathways, and 371 enzymes showed distinct changes between
untreated and EGCG-treated mice. Long-chain-fatty-acid-CoA ligase
ACSBG played a distinct role in fatty acid metabolism and ferroptosis
and was significantly negatively correlated with Bacteroides. Altogether, the salutary effect of EGCG on NASH might be via shifting
gut flora and certain enzymes from genera. Our study thus takes a
step toward NASH prevention and therapy.