表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)被认为是绿茶发挥诸多生理功能的主要成分,其生物利用率低,能到达肠道与菌群发生相互作用。采用健康C57BL/6J小鼠,探究摄入4周EGCG后肠道菌群结构组成和代谢产物的变化。结果显示,EGCG显著增加了Akkermansia等菌属的丰度,显著降低了Mucispirillum菌属的丰度。对Akkermansia菌的促进作用与过往研究中EGCG在肥胖和结肠炎小鼠中的结果一致,证明了EGCG对Akkermansia菌的促进作用与疾病状态无关。EGCG显著提高了短链脂肪酸中乙酸、丙酸和丁酸的含量。粪便非靶向代谢组分析显示,胸腺嘧啶脱氧核苷、2′-脱氧鸟苷、鸟嘌呤、脱氧腺苷等有益于发挥抗病毒和抗癌生理功能的代谢产物含量提高。此外,根据富集的菌属和代谢通路,EGCG被证明具有改善血糖代谢的能力。研究结果表明,健康小鼠摄入4周EGCG能显著影响肠道菌群及代谢物组成,且具有益生功能。
The health benefits of green tea are largely attributed to the main ingredient catechin, of which epigallocatechin gallate (EGCG) accounts for 50%-70%. EGCG is a flavone-3-ol polyphenol compound with phenolic antioxidant properties. The six o-phenolic hydroxyl groups in the structure make it superior to other catechins in many properties. EGCG has a low bioavailability, digestion and absorption mainly occur in the small intestine, so EGCG can interact with intestinal microbes to affect the composition of bacteria and metabolites. The interactions between intestinal microbes and the host are one of the important ways for substances to exert physiological functions. At present, there are few relevant studies, which only focus on animal disease models such as obesity and colitis. In this study, SPF C57BL/6J healthy mice were selected for a 4-week EGCG supplement experiment. 16S rRNA sequencing, short-chain fatty acid determination, untargeted metabolite analysis, plasma biochemical analysis, and other analytical methods were chosen to explore the changes of intestinal flora and fecal metabolites in healthy mice after EGCG intake and filled the relevant research gaps. Fecal flora 16S rRNA sequencing results showed that EGCG could significantly change the structure and composition of intestinal flora in healthy mice, and increase the abundance of beneficial bacteria such as Akkermansia and Bifidobacterium. Meanwhile, EGCG could inhibit the colonization of harmful bacteria such as Muribaculaceae and promote the health of intestinal flora. Akkermansia was the most obvious changing genus after EGCG intake among those beneficial bacteria. It is worth noting that previous studies have proved that EGCG can promote the increase of Akkermansia abundance in mice with obesity and colitis disease. This study demonstrated that EGCG also could promote the abundance of Akkermansia in healthy mice and combined with a recent in vitro experiment and provided evidence for targeted promotion of Akkermansia abundance. Targeted metabolite analysis, named short-chain fatty acid content determination, showed that EGCG intake increased the contents of acetic acid, propionic acid, and butyric acid significantly, which was associated with the increased abundance of short-chain fatty acid producing bacteria. The results of untargeted metabolite analysis showed that thymidine, 2′-deoxyguanosine, guanine, 2′-deoxyadenosine, and other metabolites related to antiviral and anticancer drugs were increased compared with the control group. Based on the Spearman correlation analysis between differential bacteria and differential metabolites, we speculated that EGCG might promote the increase of 2′-deoxyguanosine, guanine, 2′-deoxyadenosine, and other substances by increasing the proliferation of Romboutsia, Faecalibacterium, and Anaerostipes. These contribute to play EGCG antiviral and anti-cancer physiological functions. Finally, we demonstrated that the physiological functions based on differential bacteria and metabolites, and also proved EGCG could improve the glucose metabolism level of mice significantly. This study provides a scientific basis for the mechanism of EGCG for health benefits and the development of dietary supplement products.
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