欢迎访问中南医学期刊社系列期刊网站!

湖北省期刊发展扶持资金资助期刊

美国化学文摘社(CAS)数据库收录期刊

中国学术期刊网络出版总库收录期刊

中国核心期刊(遴选)数据库收录期刊

中文科技期刊数据库收录期刊

《中国学术期刊影响因子年报》统计源期

首页 在线期刊 2024年 第37卷,第10期 详情

肠道微生态在膳食多酚防治肥胖中作用的研究进展

发表时间:2024年11月01日阅读:1176次 下载:187次 下载 手机版

作者: 杨雪巍 1 熊延乐 2 康超 3

作者单位: 1. 四川省疾病预防控制中心疫苗中心(成都 610041) 2. 成都中医药大学公共卫生学院(成都 611137) 3. 中国人民解放军西部战区总医院营养科(成都 610083)

关键词: 肠道微生态 膳食多酚 肥胖

DOI: 10.12173/j.issn.1004-4337.202405190

基金项目: 四川省科技厅应用基础研究项目(2021YJ0209);四川省卫生健康委员会普及应用项目(21PJ070)

引用格式: 杨雪巍, 熊延乐, 康超. 肠道微生态在膳食多酚防治肥胖中作用的研究进展[J]. 数理医药学杂志, 2024, 37(10): 786-798. DOI: 10.12173/j.issn.1004-4337.202405190.

Yang XW, Xiong YL, Kang C. Reserch progress of the role of gut microbiota in the prevention and treatment of obesity by dietary polyphenols[J]. Journal of Mathematical Medicine, 2024, 37(10): 786-798. DOI: 10.12173/j.issn.1004-4337.202405190.[Article in Chinese]

摘要| Abstract

近年来,全球肥胖问题日益严重,大量研究表明膳食中的多酚类化合物有助于体重控制。然而,多酚类化合物在人体的生物吸收效率较低,小部分可在小肠吸收,而大部分在结肠内被肠道菌群利用,进而发挥其生物学作用。由肠道菌群及其代谢物为主要组成的肠道微生态是膳食多酚发挥减重作用的关键因素,本文综述了肠道微生态参与多酚防治肥胖的研究进展。

全文| Full-text

近年来,全球肥胖率急剧攀升,据世界卫生组织统计,2022年全球有25亿成年人超重,其中8.9亿人肥胖,此外超过3.9亿5~19岁的儿童处于超重或肥胖[1]。肥胖会增加各种疾病的风险,包括2型糖尿病、心血管疾病、代谢综合征、慢性肾脏病、高脂血症、高血压等,对人们的健康和生命构成巨大威胁[2]。目前,肥胖的防治首选生活方式干预,包括营养、运动和认知行为治疗,当患者具有明显胰岛素抵抗或其他相关代谢异常时,考虑采用药物治疗,司美格鲁肽、奥利司他、氯卡色林和利拉鲁肽等药物被证实具有减重作用,但目前仅奥利司他作为肥胖治疗的处方药,且上述药物可能引发厌食、心悸等副作用[3]。因此,研究人员致力于寻找副作用更小的膳食成分或天然化合物,通过膳食营养途径达到减重目的。

膳食多酚是一种广泛存在于植物中的多功能化合物,具有显著的抗炎、抗氧化等生物学作用,能有效预防心血管疾病、糖尿病和肥胖等代谢综合征[4]。然而,膳食多酚在人体内的生物利用率较低,仅有约5%~10%的多酚可在小肠中被降解,其余90%~95%在结肠中被肠道菌群利用,因此肠道可能是多酚发挥生物活性的重要环节[5]。肠道微生态被证实对肥胖及其相关疾病的发展至关重要,成为预防和治疗肥胖的新靶点,靶向肠道微生态的干预策略在减重治疗中具有广阔的应用前景[6]。膳食多酚能促进肠道有益菌生长,抑制致病菌繁殖,并影响肠道菌群代谢物,同时肠道菌群参与膳食多酚体内代谢过程,影响其生物学活性。本文将系统综述肠道微生态与膳食多酚的相互作用及其在体重控制领域的研究进展,为肥胖防治提供新视角和新思路。

1 膳食多酚概述

多酚是一类富含酚羟基的植物化合物,广泛存在于可可、咖啡、茶、葡萄酒及多种水果和蔬菜中,是人类日常饮食中不可或缺的部分。从化学结构上看,多酚类化合物是指至少有一个苯甲酸环带有一个或多个羟基的化合物。多酚是由氨基酸苯丙氨酸经特定酶的作用下生物合成而来,依据芳香环数量,主要分为非黄酮和黄酮类化合物两大类,非黄酮类化合物包括酚酸、木质素类和芪类等[7];黄酮类化合物是多酚的主要类型,数量约占所有多酚种类的2/3,根据碳环结构,又可分为花青素、黄酮、黄酮醇、黄烷醇、异黄酮、二氢黄酮醇等[8]。多数食物含有多种膳食多酚成分,如槲皮素(黄酮醇类化合物)广泛存在于几乎所有的植物性膳食中,而柚皮素(二氢黄酮醇类化合物)、染料木黄酮(异黄酮类化合物)等仅存在于某些特定的食物中,因此,膳食多酚的健康效应往往表现为多种多酚类物质的协同作用。

1.1 茶多酚

茶是全球最流行的饮品,根据色泽和加工方法,可分为红茶、绿茶、青茶、黄茶、黑茶和白茶。茶提取物的关键活性成分是茶多酚(tea polyphenols,TPs),占茶叶干重的1/4,主要由儿茶素、类黄酮、花青素和酚酸等组成。绿茶中儿茶素占比最大,每1 L绿茶中含有1.0 g左右的儿茶素。常见儿茶素类型包括表没食子儿茶素(epigallocatechin,EGC)、表儿茶素没食子酸酯(epicatechin gallate,ECG)、表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)、没食子儿茶素没食子酸酯(gallocatechin gallate,GCG)和表儿茶素(epicatechin,EC)[9]。茶多酚具有抗氧化、抗肿瘤、抗炎、抗菌和降脂等生物活性[10]。中国西南地区的藤茶由葡萄科蛇葡萄属显齿蛇葡萄(Ampelopsis grossedentata)嫩茎叶制成,中医古籍记载其能清热、利尿、促进血液循环并通络。藤茶中二氢杨梅素(dihydromycetin,DHM)含量高达30%以上,是主要的黄酮类化合物,具有抗氧化、抗菌和抗炎作用,且能被肠道微生物代谢产生潜在药效[11-12]。流行病学研究显示,去咖啡因的绿茶多酚可延迟肥胖女孩的性早熟,改善其肥胖相关表型[13]。一项Meta分析结果显示,持续补充绿茶8周以上、剂量超过1  000 mg/天可以降低肥胖人群的体重,尤其对肥胖或超重女性而言,不仅体重下降,其体重指数(body mass index,BMI)和腰围也呈下降趋势[14]。

1.2 葡萄多酚

葡萄酒是世界上消费量最大的饮品之一,其中膳食多酚在红酒中约为50~400 mg·L-1,花青素、黄烷醇、黄酮醇、酚酸和白藜芦醇等多酚类化合物对红酒的品质和香气至关重要,且与人体健康密切相关,目前大量研究已证实红酒多酚对心血管疾病、肿瘤和糖尿病等具有预防和改善作用[15- 16]。Vidot等的研究发现,相较于不喝酒人群,长期摄入红酒的人群发生代谢综合征的风险更低 [17]。研究显示,针对40名超重或肥胖人群予以白葡萄酒或葡萄果汁干预3个月后,其体重、体脂百分比、腰围和血压等均显著下降[18]。

1.3 异黄酮类

豆类及其制品是亚洲国家经常食用的食物,富含优质蛋白、脂类、多种微量营养素,是许多健康膳食模式的重要组成。豆类多酚主要为异黄酮类化合物,绝大多数为染料木黄酮(genistein)和大豆苷元(daidzein),分别占所有异黄酮类化合物的60%和30%[19]。豆类中的异黄酮类化合物作为植物雌激素,可与体内雌激素受体(estrogen,ER)结合发挥弱雌激素作用(与雌二醇一样可与ER结合,但亲和力更低),具有预防肥胖、心血管疾病及激素敏感肿瘤等多种生物学功能 [20- 21]。一项针对中国人群的大规模膳食调查发现,膳食大豆异黄酮摄入越多,肥胖发生风险越低,尤其是对于绝经后女性,相关性更为显著[22]。一项Meta分析纳入了22项针对亚洲肥胖和超重人群的随机对照试验,发现豆类制品可降低体重、BMI、体脂含量及腰围[23]。

1.4 其他

花青素(黄酮类化合物)在葡萄和蓝莓等浆果类食物中含量丰富,具有抗癌、抗氧化和抗炎等多种生物学活性[24-25]。单宁是广泛存在于浆果中的多酚,具有抗炎、抗氧化、抗癌和抗菌特性[26-27]。可可及衍生物(黑巧克力等)在全世界广泛种植和食用,含有丰富的膳食多酚,主要为黄酮类化合物,具有抗炎和抗氧化等多种作用[28]。柑橘类水果是黄烷酮的良好来源, 可降低疾病发生风险[29]。绿原酸是中药制剂中的常见成分,作为一种高效天然酚类抗氧化剂,具有降血糖和降血脂的功效[30-31]。总之,多酚具有相当大的结构多样性,是日常饮食中重要的功能性食物,对人类健康产生积极影响。

2 多酚对肠道菌群的直接调控作用

肠道菌群对维持人体健康,保护肠粘膜至关重要。它们提供必需的维生素、酶等营养物质,并协助防御病原体。人体肠道菌群主要包括五个门的细菌,其中拟杆菌门和厚壁菌门占多数[32]。肥胖人群的肠道菌群相较于健康人群存在显著差异,表现为多样性与丰富性降低,菌群结构紊乱,致病菌丰度上升,厚壁菌门与拟杆菌门(Firmicutes to Bacteroidetes ratio,F/B)比例失调[33-34]。

膳食多酚可以促进肠道有益菌生长,遏制病原菌增殖,扮演益生元角色。膳食多酚能显著提升肠道微生物多样性(α和β多样性),增强乳酸菌、双歧杆菌和阿克曼菌等有益菌的相对丰度,有助于维护肠道屏障完整性,并改变F/B比例[35]。多酚对肠道菌群的调控主要有两种方式:一是参与调整微生物生态平衡,可能通过促进某些菌种生长而间接影响其他菌群的生长;二是选择性地促进特定微生物生长。此外,多酚的胺或糖基结构能为细菌提供氮或可发酵糖作为营养来源。然而,过量的多酚可能抑制结肠有益菌的生长[36]。

膳食多酚能抑制肠道致病菌的生长,如白藜芦醇对沙门氏菌、粪肠球菌和大肠杆菌等具有抗菌效果[37]。多酚的抗菌机制取决于多酚类型和细菌种类,首先,多酚可以与细菌蛋白结合,降低或抑制其酶活性;其次,多酚还可以抑制细菌DNA合成,进而阻断其生长;除此之外,多酚还能破坏细菌细胞膜并抑制细胞壁的形成 [38]。表1列举了膳食多酚及常见食物来源与肠道菌群相关研究。

2.1 茶多酚与肠道菌群

茶多酚可通过调节肠道菌群达到减重效果,特别在高脂饮食诱导的肥胖中发挥显著作用。茶多酚能影响肠道微生态的平衡,如改善肠道氧化应激、强化屏障功能和调控微生物代谢途径[57]。茯砖茶多酚能有效减轻高脂饮食诱导的肥胖表型,调节肠道菌群,提高肠道菌群多样性,降低F/B的比例[39]。F/B比例的改变,尤其是拟杆菌门相对减少,是高脂饮食引发肠道菌群紊乱的标志,可能与短链脂肪酸(short chain fatty acid,SCFA)代谢失调和能量增加有关[58]。绿茶、红茶、茯砖茶、柑普茶和普洱茶等茶多酚均能调节肠道菌群中F/B的比例,见表1,而厚壁菌门产短链脂肪酸菌群如Faecalibaculum、Prevotella等可促进肠道SCFA的产生。研究显示,茶多酚可增加粘液降解菌Akkermansia muciniphila的相对丰度,该益生菌在维持肠道屏障功能、降低体内慢性炎症水平方面具有保护效应[59]。DIRECT-PLUS是一项纳入294名腹型肥胖或脂代谢异常的随机对照试验,在地中海膳食模式下额外补充3~4杯绿茶的膳食干预18个月后,肠道Prevotella显著增加,受试者的体重和肝脏脂肪蓄积得到明显改善 [44- 45]。此外,绿茶多酚还能改变大鼠肠道微生物的代谢途径,如三羧酸循环、胆汁酸代谢和氨基酸等,从而降低能量和脂肪的肠道吸收,提高能量转化效率[60]。上述结果表明,茶多酚在维护肠道健康和对抗肥胖中具有潜在作用。研究发现,DHM可以显著改变肠道微生物群落组成,通过增加乳酸菌、普拉梭菌、双歧杆菌属和多形拟杆菌等有益菌的相对丰度,抑制肠道中的某些致病菌,如肠杆菌科和脆弱拟杆菌,从而改变肠道微生物群落组成,并进一步调节肠道中的胆汁酸代谢,表明DMH可能通过调节肠道菌群组成来发挥生物活性[46, 61-62]。

  • 表格1 膳食多酚干预对肥胖人群或动物模型中肠道菌群的影响
    Table 1.Effects of dietary polyphenol intervention on intestinal flora in obese people or animal models
    注:HFD,high fat diet,高脂饮食;BW,body weight,体重。

2.2 葡萄多酚与肠道菌群

红酒多酚通过增加有益菌(如阿克曼菌)的相对丰度,调节肠道菌群组成,并抑制肠道病原菌的生长,从而达到减重效果[63]。Belda等的研究发现,摄入适量葡萄酒的高葡萄酒多酚代谢者,其粪便样本中阿克曼菌等有益菌的丰度显著增加,葡萄酒多酚能促进SCFA,特别是丙酸和乙酸的生成[64]。一项小样本的随机对照交叉试验发现,摄入红酒可增加乳球菌和产丁酸菌群的相对丰度,降低产LPS菌群的相对丰度(大肠杆菌等),并改善代谢综合征人群的糖脂代谢水平[47]。Nunes等的研究发现,红酒多酚能保护肠上皮细胞免受大肠杆菌270的黏附和毒素影响,显著减少细胞死亡,具有维护肠道黏膜的作用[65],提示红酒多酚在调节肠道微生物和健康中具有显著作用。

红酒多酚也富含白藜芦醇,肠道菌群可以显著影响白藜芦醇在体内的生物利用度,反之,白藜芦醇及其代谢产物又能影响肠道菌群的多样性和组成[66]。Wang等的研究表明,白藜芦醇能通过修复肠黏膜,增强肠道屏障功能。它能调节肠道细菌组成,表现为有害菌如脱硫弧菌和另枝菌属的减少,同时促进产生SCFA(如异杆菌属和拟杆菌属)的细菌丰度增加[67]。高脂诱导的肥胖小鼠补充白藜芦醇后,肠道产丁酸菌群显著增加,介导了其发挥减重和改善胰岛素敏感性的作用[48]。一项针对37名超重或肥胖人群的随机对照试验显示,使用白藜芦醇联合表儿茶素可降低肠道拟杆菌门水平,男性受试者肠道普氏栖粪杆菌的相对丰度降低[49]。上述研究表明,白藜芦醇可以调控肠道菌群,对宿主健康产生积极影响。

2.3 异黄酮与肠道菌群

大豆异黄酮具有显著的减重作用,研究显示,肠道菌群是大豆异黄酮发挥其减重作用的重要靶点,大豆异黄酮可抑制有害菌的生长及肥胖相关细菌的繁殖,促进肠道益生菌的生长[68]。一项针对104名美国人(含29名肥胖人群)的横断面研究显示,特定肠型的人群摄入豆类越多,其血压越低,同时高摄入豆类人群的肠道菌群小杆菌属和普雷沃氏菌属的相对丰度较低[69]。Luo等发现补充大豆异黄酮可逆转肥胖模型大鼠体内促炎细胞因子的表达、改善肠道的免疫功能和通透性、降低氧化应激损伤状态,肠道内产SCFA的有益菌群比例增加,有害细菌显著减少[51]。Guevara- Cruz等针对45名肥胖受试者的随机对照试验结果显示,染料木黄酮在改善受试者胰岛素抵抗水平的同时,能增加Akkermansia等肠道有益菌种的相对丰度[52]。

2.4 其他主要膳食多酚及食物来源

2.4.1 浆果多酚与肠道菌群

浆果类食物包括蓝莓、蔓越莓、覆盆子和草莓等,富含花青素,这种化合物具有抗炎、抗氧化等生物学活性。研究发现,花青素可影响肠道菌群的结构和功能,保护肠上皮屏障,降低体内慢性炎症水平,最终达到减肥的目的[70]。Liu等发现高脂饮食诱导的肥胖小鼠模型在补充蓝莓和蔓越莓中的花青素提取物后,体内血浆脂多糖(lipopolysaccharide,LPS)含量降低,理研菌属、链球菌科等致病菌的相对丰度减少,花青素可以促进拟杆菌门细菌生长,并增加SCFA的产生[53]。富含多种浆果类的北欧浆果促进肠道Akkermansia的相对丰度,该益生菌具有减重效果 [54]。金银花果多酚可以减少肠道葡萄球菌等致病菌的相对丰度,进而缓解高脂诱导的小鼠体内炎症水平[55]。

2.4.2 可可多酚与肠道菌群

可可多酚虽在肠道吸收有限,但其代谢产物具有生物活性,可被人体利用,作为益生元影响肠道微生态。这些化合物能促进肠道有益菌(如乳酸杆菌和双歧杆菌)增殖,同时抑制肠道有害菌(如产气荚膜梭菌)的相对丰度。另外,具有生物活性的可可代谢物对肠道健康有益,具有抗炎和抗氧化作用,能增强免疫力,降低患病风险,尤其在防治肥胖方面效果显著[71]。Weikart等的研究发现,对高脂诱导的肥胖小鼠补充可可粉能降低体重,维持肠道屏障功能,减少血清炎症因子水平,同时降低肠道F/B比值[56]。

3 多酚对肠道菌群代谢产物的影响

3.1 短链脂肪酸

肠道菌群参与体内多种代谢过程,包括膳食碳水化合物和蛋白质在胃肠道的消化、发酵和吸收等生物学过程,同时为宿主提供必需的维生素和氨基酸。肠道菌群代谢物包括SCFA(主要有甲酸盐、乙酸盐、丙酸盐、丁酸盐、异丁酸盐)、支链氨基酸(brand chain amino acid, BCAA)、胆汁酸(bile acids, BAs)、三甲胺-N-氧化物(trimethylamino oxide, TMAO)等,对人体健康具有显著影响。目前产SCFA细菌包括嗜黏蛋白阿克曼菌、普雷沃氏菌属、瘤胃球菌、粪球菌、普拉梭菌、真杆菌和罗氏菌等[72]。乙酸是肠道糖酵解的主要产物,有降低食欲的作用。丙酸是肠道拟杆菌门的主要发酵产物之一,可抑制人体内脂肪酸的产生,也可作为肠道中慢性低度炎症的抑制剂。丁酸是肠道厚壁菌门的主要发酵产物之一,也是结肠上皮细胞的主要能量来源[73-74]。SCFA在改善肠道、肝脏和体内血糖稳态方面具有积极作用,并在基因组、转录组和蛋白组等多个水平上影响体内脂代谢和脂肪组织蓄积,调节体内能量稳态和影响食欲[75]。膳食多酚可通过改变肠道菌群的组成和功能来促进SCFA的产生。Zhang等的研究发现,在HFD诱导肥胖小鼠模型中,补充茶多酚可增加瘤胃菌科(包括普拉梭菌属)和罗氏菌属等产丁酸盐菌群的相对丰度[76]。EGCG培养物中的总SCFA浓度显著高于对照组,其中甲酸、乙酸、丙酸和丁酸的浓度均显著增加。Wang等的研究发现,高碳水化合物喂养的小鼠补充苹果多酚后可显著激活结肠中游离脂肪酸受体2和3的表达[77]。同时,苹果多酚能显著抑制厚壁菌门相对丰度,并以剂量依赖性方式显著促进疣微菌门和变形菌门等的相对丰度,而疣微菌门的某些菌群可显著增加肠道内SCFA的含量。

3.2 胆汁酸

BAs是一组异质的两亲性甾体酸,与肠道菌群存在双向调节机制,影响宿主脂质和葡萄糖代谢[78]。BAs主要作为信号分子,发挥生物活性作用,其合成和代谢与疾病的发生发展密切相关,包括肥胖、脂肪肝和糖尿病等代谢综合征[79]。膳食多酚作为天然抗氧化剂,可直接或间接调控法尼醇X受体(farnesoid X receptor, FXR)和G蛋白偶联胆汁酸受体5(takeda-G-protein-receptor-5,TGR5),以及影响肠道菌群次级BAs的合成[80-81]。FXR和TGR5是两种主要的BAs受体[82],在胆汁酸、脂质和葡萄糖代谢中发挥重要作用[83-85]。肠道菌群产生胆盐水解酶(bile salt hydrolase,BSH),发挥7α-脱羟基作用参与修饰从胆囊释放到肠道的BAs,产生非共轭的BAs和次级BAs。富含BSHs的菌群包括拟杆菌属、真杆菌属和梭状芽孢杆菌属等[86]。肠道菌群紊乱影响BSH活性,导致非结合型BAs在结肠中富集,包括去氧胆酸(deoxycholic acid,DCA)、石胆酸(lithocholic acid,LCA)等次级BAs,与炎症和肿瘤的发生发展密切相关。补充膳食多酚(DHM、姜黄素等)可显著增加产BSH酶的肠道菌群,影响次级BAs的合成。此外,多酚可以调控肠肝循环中FXR和TGR5的活化和抑制,影响肥胖和炎症等代谢性疾病的发生发展[81]。DHM可以调节肝脏和回肠中FXR介导的通路以改善BAs代谢,促进BAs结合和肝脏中的转运,抑制回肠中BAs的再吸收,减少肝脏脂肪蓄积[46]。

3.3 支链氨基酸

BCAA是必需氨基酸,必须通过食物或膳食补充剂摄入。肠道菌群在BCAA的生物合成、转运和代谢中发挥重要作用[87]。体内BCAA水平的升高与炎症、肥胖和糖尿病等疾病的发生发展密切相关[88]。通过宏基因组学和代谢组学方法,证实了普雷沃氏菌和普通拟杆菌是导致体内BCAA水平升高的主要菌种,而乳酸菌是参与氨基酸降解的主要细菌[89]。膳食多酚可以通过调节肠道特定菌群影响体内支链氨基酸的水平,从而抑制肥胖的发生发展。绿茶提取物和柑橘类的膳食多酚调节与支链氨基酸降解相关的肠道细菌[90]。小檗碱富含多酚化合物和植物生物碱,可减少链球菌科、梭状芽胞杆菌科和普雷沃氏菌科等产生BCAA的菌群,从而预防和治疗肥胖[91]。

3.4 氧化三甲胺

肠道菌群可将膳食中的左旋肉碱、胆碱和卵磷脂代谢为三甲胺(trimethylamine,TMA),然后在人体肝脏中通过黄素-单氧酶3(monooxygenase isoform,FMO3)转化为TMAO,而TMAO水平升高与心血管疾病和全因死亡风险有关[92]。此外,TMAO的循环水平还与肥胖之间存在剂量依赖关系[93]。多酚类化合物在TMA-FMO3-TMAO通路中发挥着关键作用,血浆TMAO浓度与普雷沃氏菌属、胃球菌科和梭状芽胞杆菌呈正相关关系,而与普氏粪杆菌呈负相关关系[87],因此,多酚类化合物可以通过调节肠道菌群中相关菌种的组成或功能,抑制TMA转化TMAO,最终减少TMAO的形成。白藜芦醇可以调节产TMA的细菌,Chen等的研究发现,膳食补充白藜芦醇可增加肠道乳酸杆菌、双歧杆菌属、普雷沃氏菌属、幽门螺杆菌属和拟杆菌属的相对丰度[94]。

4 肠道菌群对多酚体内代谢的影响

多酚在人体内的生物利用度相对较低,仅有不到10%的膳食多酚可以被小肠吸收,未被吸收的多酚多在大肠中蓄积[95]。膳食多酚及其微生物代谢物先后经过肠道和肝脏的I期和II期代谢,到达各个靶器官,最终通过尿液排泄[96]。多酚受到肠道菌群酶的催化,包括C环裂解、脱羧、脱羟基化和去甲基化[37],被代谢成更小的低分子量酚类代谢物,被人体利用。DMH可以通过还原和脱羟基途径被肠道菌群代谢,其中脱羟基代谢物占主导地位[62]。相比与原始化合物,多酚的肠道次生代谢产物具有许多优势,如具有更高的生物活性和生物利用度。肠道中Eggerthella、Adlercreutzia、Asaccharobacter、Slackia和Lactococcus菌群可对大豆苷元进行水解、羟基化、脱氧等一系列代谢后,转化为雌马酚(Equol),雌马酚被认为是大豆异黄酮类化合物众多成分中活性最高的成分[97]。研究发现,羟基苯乙酸和3-羟基苯丙酸(白藜芦醇的两种肠道微生物衍生物)可以显著改善脂质代谢[98]。细枝真杆菌、普氏梭杆菌和巴氏梭菌菌株能代谢槲皮素,从而促使SCFA、紫杉叶素和3,4-二羟基苯乙酸的形成[37]。因此,酚类物质和肠道微生物群之间存在相互作用,发挥防治肥胖的作用。

5 小结

膳食多酚作为一组具有显著活性的天然产物,广泛存在于植物性食物中,但其体内生物利用度不高。膳食多酚在肠道内的代谢过程中可与肠道菌群发生相互作用,参与多酚体内生物转化与吸收代谢过程,也能影响肠道菌群组成及其代谢物的产生。膳食多酚因其广泛的生物学活性受到越来越多的重视,但是众多多酚活性物质发挥作用的机制及参与代谢的途径尚未明确,需要进一步探究其健康作用。本文纳入的多酚与肠道菌群的大部分研究结果来源于动物实验,基于人群的数据相对较少,人群研究的结果存在较大异质性,其原因是多方面的,如纳入人群的种族、年龄、性别等,干预周期、干预剂量等因素存在差异,尤其是个体肠道菌群具有特异性,均对结果产生不同影响。未来的研究应当基于人群肠道菌群特征,如肠型、肠道菌群基因丰度等对纳入人群区分亚组,获得更为精准的结果;基于人群对多酚干预的反应差异区分亚组,即敏感组和迟滞组,比较组间肠道菌群差异,得到关键基石菌种,进而定位到菌株水平,阐明肠道微生态在多酚减重作用的因果关系,最终应用于超重或肥胖人群,获得确切减重效果。随着对肠道菌群和多酚的双向调节机制的深入研究,越来越多的研究结果提示基于肠道微生态的膳食多酚精准干预模式是防治肥胖的重要方法,具有广阔的应用前景。

参考文献| References

1.World Health Organisation. Obesity and overweight[EB/OL]. (2024-03-01). https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight.

2.Lin X, Li H. Obesity: epidemiology, pathophysiology, and therapeutics[J]. Front Endocrinol (Lausanne), 2021, 12: 706978. DOI: 10.3389/fendo.2021,706978.

3.Chao AM, Tronieri JS, Amaro A, et al. Semaglutide for the treatment of obesity[J]. Trends Cardiovasc Med, 2023, 33(3): 159-166. DOI: 10.1016/j.tcm.2021.12.008.

4.Williamson G. The role of polyphenols in modern nutrition[J]. Nutr Bull, 2017, 42(3): 226-235. DOI: 10.1111/nbu.12278.

5.Cardona F, Andrés-Lacueva C, Tulipani S, et al. Benefits of polyphenols on gut microbiota and implications in human health[J]. J Nutr Biochem, 2013, 24(8): 1415-1422. DOI: 10.1016/j.jnutbio.2013.05.001.

6.Geng J, Ni Q, Sun W, et al. The links between gut microbiota and obesity and obesity related diseases[J]. Biomed Pharmacother, 2022, 147: 112678. DOI: 10.1016/j.biopha.2022.112678.

7.Kanner J. Food polyphenols as preventive medicine[J]. Antioxidants (Basel), 2023, 12(12): 2103. DOI: 10.3390/antiox12122103.

8.Rudrapal M, Rakshit G, Singh RP, et al. Dietary polyphenols: review on chemistry/sources, bioavailability/metabolism, antioxidant effects, and their role in disease management[J]. Antioxidants (Basel), 2024, 13(4): 429. DOI: 10.3390/antiox13040429.

9.Li H, Guo H, Luo Q, et al. Current extraction, purification, and identification techniques of tea polyphenols: an updated review[J]. Crit Rev Food Sci Nutr, 2023, 63(19): 3912-3930. DOI: 10.1080/10408398.2021.1995843.

10.Chen Y, Cheng S, Dai J, et al. Molecular mechanisms and applications of tea polyphenols: a narrative review[J]. J Food Biochem, 2021, 45(10): e13910. DOI: 10.1111/jfbc.13910.

11.Carneiro RCV, Ye L, Baek N, et al. Vine tea (Ampelopsis grossedentata): a review of chemical composition, functional properties, and potential food applications[J]. J Funct Foods, 2021, 76: 104317. DOI: 10.1016/j.jff.2020. 104317.

12.Zhang Q, Zhao Y, Zhang M, et al. Recent advances in research on vine tea, a potential and functional herbal tea with dihydromyricetin and myricetin as major bioactive compounds[J]. J Pharm Anal, 2021, 11(5): 555-563. DOI: 10.1016/j.jpha.2020.10.002.

13.Xie L, Tang Q, Yao D, et al. Effect of decaffeinated green tea polyphenols on body fat and precocious puberty in obese girls: a randomized controlled trial[J]. Front Endocrinol (Lausanne), 2021, 12: 736724. DOI: 10.3389/fendo.2021.736724.

14.Zhang Y, Tang N, Xia W, et al. The effect of green tea supplementation on the anthropometric outcomes in overweight and obese women: a time and dose-response meta-analysis of randomized controlled trials[J]. Crit Rev Food Sci Nutr, 2023, 10: 1-10. DOI: 10.1080/10408398.2023.2220796.

15.Naumovski N, Panagiotakos DB, D'Cunha NM. Untangling the 2-way relationship between red wine polyphenols and gut microbiota[J]. Gastroenterology, 2020, 158(1): 48-51. DOI: 10.1053/j.gastro.2019.10.015.

16.Buljeta I, Pichler A, Šimunović J, et al. Beneficial effects of red wine polyphenols on human health: comprehensive review[J]. Curr Issues Mol Biol, 2023, 45(2): 782-798. DOI: 10.3390/cimb45020052.

17.Vidot DC, Stoutenberg M, Gellman M, et al. Alcohol consumption and metabolic syndrome among Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos[J]. Metab Syndr Relat Disord, 2016, 14(7): 354-362. DOI: 10.1089/met.2015.0171.

18.Flechtner-Mors M, Biesalski HK, Jenkinson CP, et al. Effects of moderate consumption of white wine on weight loss in overweight and obese subjects[J]. Int J Obes Relat Metab Disord, 2004, 28(11): 1420-1426. DOI: 10.1038/sj.ijo.0802786.

19.Gómez-Zorita S, González-Arceo M, Fernández-Quintela A, et al. Scientific evidence supporting the beneficial effects of isoflavones on human health[J]. Nutrients, 2020, 12(12): 3853. DOI: 10.3390/nu12123853.

20.Kim IS. Current perspectives on the beneficial effects of soybean isoflavones and their metabolites for humans[J]. Antioxidants (Basel), 2021, 10(7): 1064. DOI: 10.3390/antiox10071064.

21.Nakai S, Fujita M, Kamei Y. Health promotion effects of soy isoflavones[J]. J Nutr Sci Vitaminol (Tokyo), 2020, 66(6): 502-507. DOI: 10.3177/JNSV.66.502.

22.Zhu J, Zhao Q, Qiu Y, et al. Soy isoflavones intake and obesity in Chinese Adults: a cross-sectional study in Shanghai, China[J]. Nutrients, 2021, 13(8): 2715. DOI: 10.3390/nu13082715.

23.Mu Y, Kou T, Wei B, et al. Soy products ameliorate obesity-related anthropometric indicators in overweight or obese asian and non-menopausal women: a meta-analysis of randomized controlled trials[J]. Nutrients, 2019, 11(11): 2790. DOI: 10.3390/nu11112790.

24.Verediano TA, Stampini Duarte Martino H, Dias Paes MC, et al. Effects of anthocyanin on intestinal health: a systematic review[J]. Nutrients, 2021, 13(4): 1331. DOI: 10.3390/nu13041331.

25.Qi Q, Chu M, Yu X, et al. Anthocyanins and proanthocyanidins: chemical structures, food sources, bioactivities, and product development[J]. Food Reviews International, 2022, 39(7): 4581-4609. DOI: 10.1080/87559129.2022.2029479.

26.Sllva AS, Nabavi SF, Saeedi M, et al. Recent advances in natural products analysis[M]. Leiden: Elsevier, 2020: 132-146.

27.Sallam IE, Abdelwareth A, Attia H, et al. Effect of gut microbiota biotransformation on dietary tannins and human health implications[J]. Microorganisms, 2021, 9(5): 965. DOI: 10.3390/microorganisms9050965.

28.Sorrenti V, Ali S, Mancin L, et al. Cocoa polyphenols and gut microbiota interplay: bioavailability, prebiotic effect, and impact on human health[J]. Nutrients, 2020, 12(7): 1908. DOI: 10.3390/nu12071908.

29.Tang R, Yu H, Ruan Z, et al. Effects of food matrix elements (dietary fibres) on grapefruit peel flavanone profile and on faecal microbiota during in vitro fermentation[J]. Food Chem, 2022, 371: 131065. DOI: 10.1016/j.foodchem.2021.131065.

30.Miao M, Xiang L. Pharmacological action and potential targets of chlorogenic acid[J]. Adv Pharmacol, 2020, 87: 71-88. DOI: 10.1016/bs.apha.2019.12.002.

31.Yan Y, Zhou X, Guo K, et al. Use of chlorogenic acid against diabetes mellitus and its complications[J]. J Immunol Res, 2020, 2020: 9680508. DOI: 10.1155/2020/ 9680508.

32.Pushpanathan P, Mathew GS, Selvarajan S, et al. Gut microbiota and its mysteries[J]. Indian J Med Microbiol, 2019, 37(2): 268-277. DOI: 10.4103/ijmm.IJMM_19_373.

33.Cani PD, Van Hul M. Gut microbiota in overweight and obesity: crosstalk with adipose tissue[J]. Nat Rev Gastroenterol Hepatol, 2024, 21(3): 164-183. DOI: 10.1038/s41575-023-00867-z.

34.Duan M, Wang Y, Zhang Q, et al. Characteristics of gut microbiota in people with obesity[J]. PLoS One, 2021, 16(8): e0255446. DOI: 10.1371/journal.pone.0255446.

35.Hervert-Hernández D, Goñi I. Dietary polyphenols and human gut microbiota: a review[J]. Food reviews international, 2011, 27(2): 154-169. DOI: 10.1080/ 87559129.2010.535233.

36.Cheng H, Zhang D, Wu J, et al. Interactions between gut microbiota and polyphenols: a mechanistic and metabolomic review[J]. Phytomedicine, 2023, 119: 154979. DOI: 10.1016/j.phymed.2023.154979.

37.Corrêa TAF, Rogero MM, Hassimotto NMA, et al. The two-way polyphenols-microbiota interactions and their effects on obesity and related metabolic diseases[J]. Front Nutr, 2019, 6: 188. DOI: 10.3389/fnut.2019.00188.

38.Makarewicz M, Drożdż I, Tarko T, et al. The interactions between polyphenols and microorganisms, especially gut microbiota[J]. Antioxidants (Basel), 2021, 10(2): 188. DOI: 10.3390/antiox10020188.

39.Zhou F, Li YL, Zhang X, et al. Polyphenols from Fu brick tea reduce obesity via modulation of gut microbiota and gut microbiota-related intestinal oxidative stress and barrier function[J]. J Agric Food Chem, 2021, 69(48): 14530-14543. DOI: 10.1021/acs.jafc.1c04553.

40.Ushiroda C, Naito Y, Takagi T, et al. Green tea polyphenol (epigallocatechin-3-gallate) improves gut dysbiosis and serum bile acids dysregulation in high-fat diet-fed mice[J]. J Clin Biochem Nutr, 2019, 65(1): 34-46. DOI: 10.3164/jcbn.18-116.

41.Liao Y, Wang C, Gao Z, et al. Anti-obesity mechanism of Ganpu tea revealed by microbiome, metabolome and transcriptome analyses[J]. Food Chem, 2023, 412: 135048. DOI: 10.1016/j.foodchem.2022.135048.

42.Liu Z, Chen Q, Zhang C, et al. Comparative study of the anti-obesity and gut microbiota modulation effects of green tea phenolics and their oxidation products in high-fat-induced obese mice[J]. Food Chem, 2022, 367: 130735. DOI: 10.1016/j.foodchem.2021.130735.

43.Ye J, Zhao Y, Chen X, et al. Pu-erh tea ameliorates obesity and modulates gut microbiota in high fat diet fed mice[J]. Food Res Int, 2021, 144: 110360. DOI: 10.1016/j.foodres.2021.110360.

44.Yaskolka Meir A, Rinott E, Tsaban G, et al. Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial[J]. Gut, 2021, 70(11): 2085-2095. DOI: 10.1136/gutjnl-2020-323106.

45.Rinott E, Meir AY, Tsaban G, et al. The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial[J]. Genome Med, 2022, 14(1): 29. DOI: 10.1186/s13073-022-01015-z.

46.Song Y, Sun L, Ma P, et al. Dihydromyricetin prevents obesity via regulating bile acid metabolism associated with the farnesoid X receptor in ob/ob mice[J]. Food Funct, 13(5): 2491-2503. DOI: 10.1039/d1fo03971g.

47.Moreno-Indias I, Sánchez-Alcoholado L, Pérez-Martínez P, et al. Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients[J]. Food Funct, 2016, 7(4): 1775-1787. DOI: 10.1039/c5fo00886g.

48.Wang P , Li D, Ke W, et al. Resveratrol-induced gut microbiota reduces obesity in high-fat diet-fed mice[J]. Int J Obes (Lond), 2020, 44(1): 213-225. DOI: 10.1038/s41366-019-0332-1.

49.Most J, Penders J, Lucchesi M, et al. Gut microbiota composition in relation to the metabolic response to 12-week combined polyphenol supplementation in overweight men and women[J]. Eur J Clin Nutr, 2017, 71(9): 1040-1045. DOI: 10.1038/ejcn.2017.89.

50.Huang L, Zheng T, Hui H, et al. Soybean isoflavones modulate gut microbiota to benefit the health weight and metabolism[J]. Front Cell Infect Microbiol, 2022, 12: 1004765. DOI: 10.3389/fcimb.2022.1004765.

51.Luo Q, Cheng D, Huang C, et al. Improvement of colonic immune function with soy isoflavones in high-fat diet-induced obese rats[J]. Molecules, 2019, 24(6): 1139. DOI: 10.3390/molecules24061139.

52.Guevara-Cruz M, Godinez-Salas ET, Sanchez-Tapia M, et al. Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects[J]. BMJ Open Diabetes Res Care, 2020, 8(1): e000948. DOI: 10.1136/bmjdrc-2019-000948.

53.Liu J, Hao W, He Z, et al. Blueberry and cranberry anthocyanin extracts reduce bodyweight and modulate gut microbiota in C57BL/6 J mice fed with a high-fat diet[J]. Eur J Nutr, 2021, 60(5): 2735-2746. DOI: 10.1007/s00394-020-02446-3.

54.Huang F, Marungruang N, Kostiuchenko O, et al. Identification of nordic berries with beneficial effects on cognitive outcomes and gut microbiota in high-fat-fed middle-aged C57BL/6J mice[J]. Nutrients, 2022, 14(13): 2734. DOI: 10.3390/nu14132734.

55.Wu S, Hu R, Nakano H, et al. Modulation of gut microbiota by Lonicera caerulea L. berry polyphenols in a mouse model of fatty liver induced by high fat diet[J]. Molecules, 2018, 23(12): 3213. DOI: 10.3390/molecules23123213.

56.Weikart DK, Indukuri VV, Racine KC, et al. Effect of processing on the anti-inflammatory efficacy of cocoa in a high fat diet-induced mouse model of obesity[J]. J Nutr Biochem, 2022, 109: 109117. DOI: 10.1016/j.jnutbio.2022.109117.

57.Zhang Z, Liu C, Fang W, et al. Research progress on the lipid-lowering and weight loss effects of tea and the mechanism of its functional components[J]. J Nutr Biochem, 2023, 112: 109210. DOI: 10.1016/j.jnutbio.2022.109210.

58.Stojanov S, Berlec A, Štrukelj B. The influence of probiotics on the firmicutes/bacteroidetes ratio in the treatment of obesity and inflammatory bowel disease[J]. Microorganisms, 2020, 8(11): 1715. DOI: 10.3390/microorganisms8111715.

59.Cani PD, Depommier C, Derrien M, et al. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms[J]. Nat Rev Gastroenterol Hepatol, 2022, 19(10): 625-637. DOI: 10.1038/s41575-022-00631-9.

60.Zhou J, Tang L, Shen CL, et al. Green tea polyphenols boost gut-microbiota-dependent mitochondrial TCA and urea cycles in Sprague-Dawley rats[J]. J Nutr Biochem, 2020, 81: 108395. DOI: 10.1016/j.jnutbio.2020.108395.

61.Zhang Y, Kang C, Wang XL, et al. Dietary factors modulate colonic tumorigenesis through the interaction of gut microbiota and host chloride channels[J]. Mol Nutr Food Res, 2018, 62(5): 1700554. DOI: 10.1002/mnfr.201700554.

62.Fan L, Zhao X, Tong Q, et al. Interactions of dihydromyricetin, a flavonoid from vine tea (Ampelopsis grossedentata) with gut microbiota[J]. J Food Sci, 2018, 83(5): 1444-1453. DOI: 10.1111/1750-3841.14128.

63.Nash V, Ranadheera CS, Georgousopoulou EN, et al. The effects of grape and red wine polyphenols on gut microbiota-a systematic review[J]. Food Res Int, 2018, 113: 277-287. DOI: 10.1016/j.foodres.2018.07.019.

64.Belda I, Cueva C, Tamargo A, et al. A multi-omics approach for understanding the effects of moderate wine consumption on human intestinal health[J]. Food Funct, 2021, 12(9): 4152-4164. DOI: 10.1039/d0fo02938f.

65.Nunes C, Figueiredo R, Laranjinha J, et al. Intestinal cytotoxicity induced by Escherichia coli is fully prevented by red wine polyphenol extract: mechanistic insights in epithelial cells[J]. Chem Biol Interact, 2019, 310: 108711. DOI: 10.1016/j.cbi.2019.06.024.

66.Chaplin A, Carpéné C, Mercader J. Resveratrol, metabolic syndrome, and gut microbiota[J]. Nutrients, 2018, 10(11): 1651. DOI: 10.3390/nu10111651.

67.Wang P, Wang J, Li D, et al. Targeting the gut microbiota with resveratrol: a demonstration of novel evidence for the management of hepatic steatosis[J]. J Nutr Biochem, 2020, 81: 108363. DOI: 10.1016/j.jnutbio.2020.108363.

68.Chen P, Sun J, Liang Z, et al. The bioavailability of soy isoflavones in vitro and their effects on gut microbiota in the simulator of the human intestinal microbial ecosystem[J]. Food Res Int, 2022, 152: 110868. DOI: 10.1016/j.foodres.2021.110868.

69.Shah RD, Tang ZZ, Chen G, et al. Soy food intake associates with changes in the metabolome and reduced blood pressure in a gut microbiota dependent manner[J]. Nutr Metab Cardiovasc Dis, 2020, 30(9): 1500-1511. DOI: 10.1016/j.numecd.2020.05.001.

70.Coutinho-Wolino KS, Melo MFS, Mota JC, et al. Blueberry, cranberry, raspberry, and strawberry as modulators of the gut microbiota: target for treatment of gut dysbiosis in chronic kidney disease? From current evidence to future possibilities[J]. Nutr Rev, 2024, 82(2): 248-261. DOI: 10.1093/nutrit/nuad048.

71.Sorrenti V, Ali S, Mancin L, et al. Cocoa polyphenols and gut microbiota interplay: bioavailability, prebiotic effect, and impact on human health[J]. Nutrients, 2020, 12(7): 1908. DOI: 10.3390/nu12071908.

72.Kumari M, Kozyrskyj AL. Gut microbial metabolism defines host metabolism: an emerging perspective in obesity and allergic inflammation[J]. Obes Rev, 2017, 18(1): 18-31. DOI: 10.1111/obr.12484.

73.Lin S, Wang Z, Lam KL, et al. Role of intestinal microecology in the regulation of energy metabolism by dietary polyphenols and their metabolites[J]. Food Nutr Res, 2019, 63. DOI: 10.29219/fnr.v63.1518.

74.Murugesan S, Nirmalkar K, Hoyo-Vadillo C, et al. Gut microbiome production of short-chain fatty acids and obesity in children[J]. Eur J Clin Microbiol Infect Dis, 2018, 37(4): 621-625. DOI: 10.1007/s10096-017-3143-0.

75.Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism[J]. Gut Microbes, 2016, 7(3): 189-200. DOI: 10.1080/19490976.2015.1134082.

76.Zhang X, Zhu XL, Sun YK, et al. Fermentation in vitro of EGCG, GCG and EGCG3"Me isolated from Oolong tea by human intestinal microbiota[J]. Food Research International, 2013, 54(2): 1589-1595. DOI: 10.1016/j.foodres.2013.10.005.

77.Wang X, Liu F, Cui Y, et al. Apple polyphenols extracts ameliorate high carbohydrate diet-induced body weight gain by regulating the gut microbiota and appetite[J]. J Agric Food Chem, 2022, 70(1): 196-210. DOI: 10.1021/acs.jafc.1c07258.

78.Tveter KM, Mezhibovsky E, Wu Y, et al. Bile acid metabolism and signaling: emerging pharmacological targets of dietary polyphenols[J]. Pharmacol Ther, 2023, 248: 108457. DOI: 10.1016/j.pharmthera.2023.108457.

79.Chambers KF, Day PE, Aboufarrag HT, et al. Polyphenol effects on cholesterol metabolism via bile acid biosynthesis, CYP7A1: a review[J]. Nutrients, 2019, 11(11): 2588. DOI: 10.3390/nu11112588.

80.Naumann S, Haller D, Eisner P, et al. Mechanisms of interactions between bile acids and plant compounds-a review[J]. Int J Mol Sci, 2020, 21(18): 6495. DOI: 10.3390/ijms21186495.

81.Liu Y, Huang K, Zhang Y, et al. Dietary polyphenols maintain homeostasis via regulating bile acid metabolism: a review of possible mechanisms[J]. Food Func, 2023, 14(21): 9486-9505. DOI: 10.1039/d3fo02471g.

82.Jiang L, Zhang H, Xiao D, et al. Farnesoid X receptor (FXR): structures and ligands[J]. Comput Struct Biotechnol J, 2021, 19: 2148-2159. DOI: 10.1016/j.csbj.2021.04.029.

83.Stofan M, Guo GL. Bile acids and FXR: novel targets for liver diseases[J]. Front Med (Lausanne), 2020, 7: 544. DOI: 10.3389/fmed.2020.00544.

84.Clifford BL, Sedgeman LR, Williams KJ, et al. FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption[J]. Cell Metab, 2021, 33(8): 1671-1684. DOI: 10.1016/j.cmet.2021. 06.012.

85.Merlen G, Bidault-Jourdainne V, Kahale N, et al. Hepatoprotective impact of the bile acid receptor TGR5[J]. Liver Int, 2020, 40(5): 1005-1015. DOI: 10.1111/liv.14427.

86.Bourgin M, Kriaa A, Mkaouar H, et al. Bile salt hydrolases: at the crossroads of microbiota and human health[J]. Microorganisms, 2021, 9(6): 1122. DOI: 10.3390/microorganisms9061122.

87.Man AWC, Zhou Y, Xia N, et al. Involvement of gut microbiota, microbial metabolites and interaction with polyphenol in host immunometabolism[J]. Nutrients, 2020, 12(10): 3054. DOI: 10.3390/nu12103054.

88.Anhê FF, Varin TV, Le Barz M, et al. Gut microbiota dysbiosis in obesity-linked metabolic diseases and prebiotic potential of polyphenol-rich extracts[J]. Curr Obes Rep, 2015, 4(4): 389-400. DOI: 10.1007/s13679-015-0172-9.

89.Xia F, Wen LP, Ge BC, et al. Gut microbiota as a target for prevention and treatment of type 2 diabetes: mechanisms and dietary natural products[J]. World J Diabetes, 2021, 12(8): 1146-1163. DOI: 10.4239/wjd.v12.i8.1146.

90.Zhu M, Ouyang J, Zhou F, et al. Polysaccharides from Fu brick tea ameliorate obesity by modulating gut microbiota and gut microbiota-related short chain fatty acid and amino acid metabolism[J]. J Nutr Biochem, 2023, 118: 109356. DOI: 10.1016/j.jnutbio.2023.109356.

91.Wang Z, Zeng M, Wang Z, et al. Food phenolics stimulate adipocyte browning via regulating gut microecology[J]. Crit Rev Food Sci Nutr, 2023, 63(19): 4026-4052. DOI: 10.1080/10408398.2021.1997905.

92.Angiletta CJ, Griffin LE, Steele CN, et al.Impact of short-term flavanol supplementation on fasting plasma trimethylamine N-oxide concentrations in obese adults[J]. Food Funct, 2018, 9(10): 5350-5361. DOI: 10.1039/c8fo00962g.

93.Dehghan P, Farhangi MA, Nikniaz L, et al. Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) potentially increases the risk of obesity in adults: an exploratory systematic review and dose-response Meta- analysis[J]. Obes Rev, 2020, 21(5): e12993. DOI: 10.1111/obr.12993.

94.Chen ML, Yi L, Zhang Y, et al. Resveratrol attenuates trimethylamine-N-oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via remodeling of the gut microbiota[J]. mBio, 2016, 7(2): e02210-e2215. DOI: 10.1128/mBio.02210-15.

95.Catalkaya G, Venema K, Lucini L, et al. Interaction of dietary polyphenols and gut microbiota: microbial metabolism of polyphenols, influence on the gut microbiota, and implications on host health[J]. Food Frontiers, 2020, 1(2): 109-133. DOI: 10.1002/fft2.25.

96.Cardona F, Andrés-Lacueva C, Tulipani S, et al. Benefits of polyphenols on gut microbiota and implications in human health[J]. J Nutr Biochem, 2013, 24(8): 1415-1422. DOI: 10.1016/j.jnutbio.2013.05.001.

97.Peirotén Á, Bravo D, Landete JM. Bacterial metabolism as responsible of beneficial effects of phytoestrogens on human health[J]. Crit Rev Food Sci Nutr, 2020, 60(11): 1922-1937. DOI: 10.1080/10408398.2019.1622505.

98.Wang TQ, Wu QM, Zhao TQ. Preventive effects of kaempferol on high-fat diet-induced obesity complications in C57BL/6 mice[J]. Biomed Res Int, 2020, 2020: 4532482. DOI: 10.1155/2020/4532482.