摘要
近年来茶多酚与肠道微生物的相互作用逐渐成为食品科学、营养学和生物学的研究热点。茶多酚通过肠道微生物代谢产生的活性物质具有抗氧化、降脂、消炎等作用,而茶多酚又可以通过调节肠道微生物而影响人体健康。本文综述了茶多酚在体内的吸收、肠道微生物对茶多酚的代谢去向、茶多酚对肠道微生物组成的调节及二者的相互作用在降血脂、减少脂肪堆积、维持肠道屏障等方面的研究进展,旨在为茶多酚与肠道微生物的双向作用对人体健康的改善研究提供一定参考。
肠道微生物区系稳态与人体的健康密切相关,肥胖、糖尿病、抑郁症等健康问题都与肠道菌群失调有
茶多酚是茶叶的主要功能成分之一,约占茶叶干质量的18%~36%;儿茶素类是茶多酚的主体成分,约占茶多酚总量70%~80%。由于分子结构的不同,儿茶素又可分为表儿茶素(epicatechin,EC)、表没食子儿茶素(epigallocatechin,EGC)、表儿茶素没食子酸酯(epicatechin-3-gallate,ECG)和表没食子儿茶素没食子酸酯(epigallocatechin-3-gallate,EGCG)4种(

图1 儿茶素的结构
Fig.1 The structure of catechins
多酚在胃部仅被低程度吸收,少部分在小肠被吸收;肠道吸收多酚的方式主要有主动转运和被动扩散2种,以被动扩散为主。例如肠道主要通过被动扩散吸收儿茶素类物质,这是因为儿茶素类物质含羟基较多,无法通过脂质双层,但可经肠上皮细胞的紧密连接被优先吸收进入血
茶多酚在体内的的吸收程度受到分子质量和结构、机体生理状态等多种因素的影响。研究发现,人在饮用绿茶后尿液中EGCG和ECG及其结合物占儿茶素摄入量的11.4%,而EGC和EC排泄量为28.5
大鼠口服4种儿茶素的生物利用度均小于10
茶汤或茶粉在体内经过口腔、胃和肠道消化后可将4种儿茶素逐渐释放出来,释放量达40%~70%,被释放出的物质经消化道进行降解,其中EGCG和ECG经消化后降解产生聚酯型儿茶素A、D及P-
研究表明摄入的多酚90%~95%会直接到达大肠(结肠)后被微生物降
肠道微生物分泌的水解酶、氧化还原酶、裂解酶等可以通过水解、裂解、脱甲基化等反应将未被消化的茶多酚降解成简单的小分子物
肠道微生物对茶多酚的降解受到茶多酚结构组成、菌群种类等多种因素的影响。特定降解菌对(+)-儿茶素和(―)-表儿茶素的降解速率对比结果显示,Eggerthella lenta rK3对两者的C环裂解产物相同,但(+)-儿茶素的裂解速率是(―)-表儿茶素的5
肠道微生物将茶多酚转化成简单的酚酸类物质后,不仅提高了茶多酚的生物利用度,还增加了生物活性。有研究表明,经肠道微生物降解后的代谢产物更易被吸收和利用,如黄烷-3-醇经结肠微生物降解后生物利用度提高到62
肠道微生物可以分解膳食纤维,并代谢产生更加多样化的代谢产物,在调节宿主消化吸收、免疫应答等方面起着重要的作
1)增加肠道有益菌丰度。饮食方式、运动等因素都会改变肠道菌群的组成和结构,而茶多酚的摄入可以影响肠道菌群的生长和代谢,进而调节菌群。经青砖茶提取物处理后,小鼠肠道内的肠杆菌(Enterobacteria)数量减少14.69%、肠球菌减少8.69%,乳杆菌属和双歧杆菌属的数量分别增加10.47%和7.53
2)重塑肠道菌群。茶多酚可以重塑因高脂饮食等导致的肠道菌群紊乱,从而降低肥胖、癌症、糖尿病和炎症等疾病的发生。研究表明,茶多酚处理可显著降低因高脂饮食升高的α多样性指数,说明茶多酚可以重塑肠道菌群的结构;经体外试验进一步验证,茶多酚添加可显著降低厚壁菌门和拟杆菌门的比例,促进拟杆菌属和梭杆菌属(Fusobacterium),抑制肠道炎症致病菌Lachnoclostridium和巨单胞菌属(Megamonas)的生
氧化后的茶多酚对肠道菌群的调节能力不变,但菌群种类和调节程度发生了改变。研究表明茶多酚及其氧化产物都具有调控狄氏副拟杆菌(Parabacteroides distasonis)、双歧杆菌属、普雷沃菌属(Prevotella)和嗜黏蛋白阿克曼菌等肠道菌群的能
3)茶多酚对肠道菌群调节的局限性。茶多酚对肠道菌群的调节作用存在着一定的局限性。茶多酚在调节肠道菌群中显示出了明显的个体差异,EGCG和白藜芦醇组合可显著降低肥胖男性的拟杆菌门和普氏栖粪杆菌的相对丰度,但对女性没有影
血脂中的主要成分为甘油三酯(triglycerides,TG)和胆固醇(total cholesterol,TC)。TG在肝脏中积累会引起简单脂肪变性,诱导非酒精性脂肪肝病,最终可能发展为肝硬化和肝癌。微生物在非酒精性肝病的发生、发展中扮演着重要角色,而茶多酚的摄入可增加乳酸菌的多样性,抑制有害菌,如腐生葡萄球菌的生长,呈剂量依赖的方式减小肝脏脂肪变
茶多酚及其氧化产物还具有良好的调节胆固醇代谢物胆汁酸(bile acid,BAs)的作用,且这种效果是由肠道微生物介导的。茶褐素对胆固醇代谢的影响研究发现,225 mg/(kg·d)茶褐素处理可以抑制小鼠和人体内与胆盐酸水解酶活性相关的微生物生长,增加回肠中结合态BAs的水平,抑制肠道FXR-FGF15信号通路,使BAs的肝脏产生和粪便排泄量增加,从而降低肝脏TC含
肠道微生物与脂肪代谢密切相关。已有研
茶多酚可以通过改变特定菌群的组成和相关基因的表达,抑制脂肪的生成,促进脂肪氧化,调节宿主能量代谢,达到减少脂肪堆积的目的,进而改善肥胖及其并发症。红茶多酚处理可以诱导盲肠厚壁菌门减少和拟杆菌门增加,同时在属水平上降低与体质量呈正相关的双歧杆菌属、布劳特菌属、布兰特菌属(Bryantella)等菌群的比例,提高AMPK磷酸化水平,调节脂质代谢相关基因的表
1)破坏肠道屏障的因素。肠道菌群的改变是破坏肠道屏障的诱因。慢性肠炎患者的厚壁菌门丰度大幅下降,变形菌门和放线菌门的比例上升,产气荚膜菌、脱硫弧菌等有害菌数量增加,直接破坏了肠上皮紧密连接蛋白,导致肠道屏障被破坏,免疫系统紊乱,促炎因子如白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)等大量产生,引起炎症反
2)维持肠道屏障完整的途径。茶多酚作为一种很好的调节剂,可以通过增加有益菌的数量、降低致病菌的丰度来调节肠道菌群的组成,进而维持肠道屏障完整性。已有研究表明绿茶多酚的摄入可以降低拟杆菌门和梭杆菌属的丰度,增加厚壁菌门的丰度,降低炎性因子IL-6、TNF-α和IL-1β的表达,抑制炎症信号通路toll样受体4(toll-like receptor 4,TLR4)的诱导水平,使肠细胞壁得到修
降低肠道氧化应激状态也是维持肠道屏障完整的有效途径。毛螺菌科、拟杆菌属、另枝菌属(Alistipes)和粪杆菌属(Faecalibaculum)等菌群是肠道氧化还原状态的生物标志物,与ROS的产生有关,对盲肠细菌进行16S rRNA基因测序并采用LEfSe和CCA分析茶多酚、肠道微生物和肠道氧化应激状态的关系,得出茶多酚的摄入可以调节相关菌群的组成,进而降低肠道氧化应激状
肠道微生物通过合成和分泌神经递质(如5-羟色胺(5-hydroxytryptamine,5-HT))、代谢色氨酸、产生SCFAs,来调节中枢和外周神经系统,诱发大脑功能改变,从而影响肠道分泌等功能,形成肠-脑轴双向作用。人体的某些代谢性疾病是由于昼夜节律紊乱引起的,而肠道菌群和下丘脑均存在昼夜节律振荡,从肠-脑轴角度利用茶多酚调节昼夜节律相关疾病成为未来研究的新方
微生物-肠-脑轴功能障碍是抑郁症等精神障碍疾病的主要病理基础。Pearson相关分析结果揭示精神分裂症的严重程度与琥珀酸弧菌属(Succinivibrio)的丰度呈正相关,与棒状杆菌属(Corynebacterium)的呈负相
茶多酚与肠道微生物的相互作用还可以产生多种有益的影响。对糖尿病前期患者粪便细菌进行16S rRNA基因测序和Pearson相关性分析发现,饮用普洱茶粉可以改变与GLP-1、GLP-2、SCFAs相关的15个菌属丰度,增加糖尿病前期患者的胰岛素敏感性,进而治疗糖尿
尽管茶多酚对健康有诸多好处,但高剂量摄入可能会对机体造成毒害。已有报道表明大鼠口服2 000 mg/kg的EGCG制剂会致死,但口服剂量为200 mg/kg的EGCG对大鼠无毒
综上,茶多酚与肠道微生物的相互作用机制如

图2 茶多酚与肠道微生物的相互作用
Fig.2 Interaction between tea polyphenols and intestinal microorganism
茶多酚的摄入会影响肠道微生物的多样性,反之肠道微生物可以降解茶多酚并产生多种活性代谢产物,这种双向作用在维持肠道屏障、降低氧化应激、调节脂质代谢、增强免疫能力等方面具有重要作用,还可以有效预防和缓解肥胖及其并发症、炎症和抑郁症等疾病,改善宿主健康状况。
鉴于目前对茶多酚与肠道微生物的研究大多在体外和动物模型中进行,未运用在临床上,今后的研究可以从以下三方面进行:一是明确茶多酚与肠道微生物的因果关系,明确哪些是茶多酚的直接效应,哪些是肠道微生物的介导效应;二是明确茶多酚及其氧化产物的有效调节剂量范围及对具体菌群的调节程度,重视个体差异带来的影响,制定针对个体的有效给药方案;三是明确产生活性代谢产物的菌株以及具体产生途径,以便更好地预防和治疗疾病。
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