普洱茶調(diào)節(jié)腸道菌群作用的研究進(jìn)展
1(云南大益微生物技術(shù)有限公司,云南 昆明,650217)2(云南省普洱茶發(fā)酵工程研究中心,云南 昆明,650217)3(勐海茶業(yè)有限責(zé)任公司,云南 勐海,666200)
摘 要 普洱茶作為一種風(fēng)味獨(dú)特的后發(fā)酵茶,具有多種保健功能。而腸道菌群直接或間接地影響著人類的代謝健康,正逐漸成為治療疾病的一個(gè)新靶點(diǎn)。普洱茶可通過調(diào)節(jié)腸道菌群改善肥胖、結(jié)腸炎、糖尿病等疾病,但其成分復(fù)雜,功能性成分對(duì)腸道菌群的作用機(jī)制尚不清楚,這阻礙了普洱茶進(jìn)一步開發(fā)利用。該文簡(jiǎn)述了普洱茶調(diào)節(jié)腸道菌群改善疾病的研究現(xiàn)狀,探討了普洱茶中可能調(diào)節(jié)腸道菌群的功能成分,以期為普洱茶促健康功能的機(jī)制研究和產(chǎn)品開發(fā)提供參考。
普洱茶是國(guó)家地理標(biāo)志產(chǎn)品,以云南大葉種茶葉(Camellia sinensis var.assamica)為原料,經(jīng)特定加工工藝制成,具有獨(dú)特品質(zhì)特征。依據(jù)加工工藝的差異,可將普洱茶分為普洱生茶和普洱熟茶[1]。普洱熟茶經(jīng)微生物后發(fā)酵制成,大量的微生物參與,催化形成復(fù)雜而豐富的化學(xué)成分,使普洱茶具有獨(dú)特風(fēng)味和保健作用[2-5]。已有研究發(fā)現(xiàn)普洱茶具有多種保健功能,如降血脂、降血糖、抗肥胖、抗氧化、緩解代謝綜合征等[6-7]。近年來隨著研究的深入,發(fā)現(xiàn)普洱茶保健作用可能是通過茶中功能性成分與腸道微生物相互作用來實(shí)現(xiàn)的[8]。
腸道微生物被視為人類的第二基因組,約有1 000種細(xì)菌生活在人類腸道中,其中大部分屬于厚壁菌門(Firmicutes)和擬桿菌門(Bacteriodetes)[9]。近20年來的研究結(jié)果表明,腸道菌群對(duì)人體宿主的代謝有一定影響,參與調(diào)節(jié)多種常見疾病,包括肥胖、2型糖尿病、非酒精性肝病、腸易激綜合征、心臟代謝性疾病和自身免疫性疾病,這些疾病的發(fā)生均伴隨腸道菌群的紊亂[10-11]。腸道菌群已逐漸成為治療疾病的一個(gè)新靶點(diǎn),尤其在腸道疾病方面,糞便微生物群移植已成為治療的有效手段[12]。同時(shí),研究發(fā)現(xiàn)許多植物及其生物活性成分可以通過影響腸道菌群來預(yù)防和治療人類疾病,如葡萄、漿果、蘋果、姜黃、辣椒、大豆、高粱和大麥等,通過增加腸道菌群多樣性,上調(diào)抗肥胖的腸道菌群豐度,下調(diào)導(dǎo)致肥胖的腸道菌群豐度,起到抗肥胖作用[13],一些生物活性成分如多酚、類黃酮和多糖可通過調(diào)節(jié)腸道菌群來抵抗腸道疾病[14]。
普洱茶作為一種風(fēng)味獨(dú)特的后發(fā)酵茶,促健康作用是其受歡迎的重要原因。近年來已發(fā)表許多普洱茶調(diào)節(jié)腸道菌群改善機(jī)體疾病的研究,但其與腸道菌群相互作用的功能成分與作用機(jī)制仍需加強(qiáng)研究。因此本文對(duì)普洱茶調(diào)節(jié)腸道菌群的文章進(jìn)行綜述,歸納總結(jié)普洱茶通過調(diào)節(jié)腸道菌群發(fā)揮的保健作用和可能的功能成分,以期為普洱茶促健康功能的機(jī)制研究和產(chǎn)品開發(fā)提供新視角。
1 普洱茶通過調(diào)節(jié)腸道菌群發(fā)揮的促健康作用
普洱茶通過改變腸道菌群的構(gòu)成和多樣性來緩解或治療多種代謝性疾病,包括肥胖、結(jié)腸炎、糖尿病、代謝綜合征、慢性飲酒引起的代謝紊亂等,詳情見表1。
1.1 普洱茶通過調(diào)節(jié)腸道菌群改善肥胖
流行病學(xué)研究顯示,肥胖已成為中國(guó)的一項(xiàng)重大公共衛(wèi)生問題,超重和肥胖人數(shù)在過去40年間迅速增加,而肥胖大大增加了患2型糖尿病、非酒精性脂肪肝、高血壓、心肌梗塞、癌癥等疾病的風(fēng)險(xiǎn)[15-16]。因此,預(yù)防或改善肥胖已成為我們面臨的重大挑戰(zhàn)。越來越多的證據(jù)表明,普洱熟茶提取物(Pu-erh tea extract,PTE)可通過調(diào)節(jié)腸道菌群來預(yù)防和改善肥胖。
腸道菌群中厚壁菌門和擬桿菌門的相對(duì)豐度可能是指示肥胖易感性的生物標(biāo)志物,比較肥胖和健康個(gè)體的腸道微生物群,肥胖人群中厚壁菌門和擬桿菌門的比值(F/B)較高[17-18],研究認(rèn)為F/B值增加,可能有利于能量吸收和儲(chǔ)存脂肪,而導(dǎo)致體重增加和肥胖[19]。多項(xiàng)研究發(fā)現(xiàn)普洱茶提取物能逆轉(zhuǎn)由高脂飲食引起的肥胖小鼠腸道菌群F/B值的升高[20-27],而XIA等[28]和GAO等[29]和高曉余[30]的研究則有相反的結(jié)論,這可能是由于檢測(cè)方法和技術(shù)的差異造成,但以上研究均發(fā)現(xiàn)普洱熟茶提取物能顯著改善肥胖小鼠門水平上的腸道菌群,重構(gòu)腸道菌群的組成,提升多樣性,顯著抑制由高脂飲食引起的小鼠體重增加。
在屬水平上,乳酸桿菌屬(Lactobacillus),芽孢桿菌屬(Bacillus),腸球菌屬(Enterococcus),乳球菌屬(Lactococcus),鏈球菌屬(Streptococcus),明串珠菌屬(Leuconostoc)等菌屬與膽鹽水解酶(bile-salt hydrolase,BSH)活性相關(guān),HUANG等[31]研究發(fā)現(xiàn)普洱熟茶中茶褐素可通過抑制這些菌屬生長(zhǎng),從而增加回腸結(jié)合膽汁酸(bile acids,BAs)水平來抑制腸道FXR-FGF15信號(hào)通路,增加BAs肝臟生成和糞便排泄,減少肝臟膽固醇和脂肪生成。而另枝菌屬(Alistipes),阿克曼氏菌屬(Akkermansia),布勞特氏菌屬(Blautia),羅斯氏菌屬(Roseburia)等與肥胖呈負(fù)相關(guān)的菌屬,普洱熟茶可顯著提升其豐度[20,22-23,26]。
在種水平上,嗜黏蛋白阿克曼氏菌(Akkermansia muciniphila)定殖于腸道黏膜層并調(diào)節(jié)基礎(chǔ)代謝,已被證明與超重、肥胖和其他代謝綜合征存在負(fù)相關(guān),通過補(bǔ)充嗜黏蛋白阿克曼氏菌可治療肥胖[32-33]。灌喂普洱茶能顯著提高小鼠中嗜黏蛋白阿克曼氏菌的豐度[20,28-29]。研究顯示,普洱茶是通過提高嗜黏蛋白阿克曼氏菌等7-去羥基化菌群,使非12-羥基化的膽汁酸增加,從而促進(jìn)白色和褐色脂肪組織的能量代謝[25]。
除了大量的動(dòng)物實(shí)驗(yàn)研究,人體實(shí)驗(yàn)研究發(fā)現(xiàn)普洱茶能改變?nèi)梭w微生物組成,降低志愿者血清中膽固醇、甘油三酯水平和腰圍/臀圍比值,增加糞便中BAs排出量,這表明普洱茶在促進(jìn)脂質(zhì)代謝和調(diào)節(jié)肝臟功能方面具有一定潛力[30-31],但普洱茶是否通過調(diào)節(jié)腸道菌群來調(diào)節(jié)脂質(zhì)代謝從而實(shí)現(xiàn)降脂減肥的功效,還有待進(jìn)一步研究。
1.2 普洱茶通過調(diào)節(jié)腸道菌群改善腸道炎癥
炎癥性腸病(inflammatory bowel disease,IBDs)主要指潰瘍性結(jié)腸炎(ulcerative colitis,UC)和克羅恩病(Crohn’s disease,CD),是一種病因不明的慢性胃腸道疾病,在世界范圍內(nèi)尤其發(fā)達(dá)國(guó)家非常流行。雖然IBDs的確切病因尚不完全清楚,但目前的共識(shí)是,疾病的開始或發(fā)展往往與人類遺傳學(xué)、環(huán)境因素、宿主免疫反應(yīng)和腸道菌群之間的相互作用有關(guān)[34]。近年來,茶對(duì)結(jié)腸炎的預(yù)防和保護(hù)作用得到了極大的關(guān)注和廣泛的研究,有研究表明普洱茶輔助治療葡聚糖硫酸鈉(dextran sulfate sodium, DSS)誘導(dǎo)的小鼠結(jié)腸炎是最有效的[35-36]。HUANG等[37]研究也證明了普洱茶可通過調(diào)節(jié)NF-κB和HIF-1α信號(hào)通路減輕小鼠DSS誘導(dǎo)的結(jié)腸炎。
同時(shí),腸道微生物參與宿主消化和代謝,調(diào)節(jié)上皮屏障、宿主免疫系統(tǒng),以及抵御病原體定植,被認(rèn)為是宿主對(duì)IBDs易感性的關(guān)鍵因素[38]。普洱茶能重塑腸道菌群,降低抑制腸道氧化應(yīng)激介導(dǎo)的炎癥信號(hào)通路,上調(diào)腸道緊密連接蛋白,進(jìn)而改善腸道免疫屏障,且以灌喂普洱茶小鼠的糞便作為供體,通過糞便菌群移植改變了結(jié)腸炎小鼠的腸道菌群組成,降低炎癥反應(yīng)和組織損傷水平,進(jìn)一步證明普洱茶能通過調(diào)節(jié)腸道菌群來改善結(jié)腸炎[39-40]。ZHANG等[41]研究發(fā)現(xiàn)普洱茶顯著促進(jìn)腸道雙歧桿菌屬(Bifidobacterium)和乳酸桿菌屬(Lactobacillus)等益生菌增殖,通過增加益生菌的數(shù)量來緩解腸道紊亂和損傷。在結(jié)腸炎小鼠中腸桿菌科(Enterobacteriaceae),幽門螺桿菌(Helicobacter)和Lachnoclostridium等與胃腸病相關(guān)的菌屬豐度較高,而乳酸桿菌屬、雙歧桿菌屬、阿克曼氏菌屬等有益菌屬豐度較低,普洱茶逆轉(zhuǎn)了這種情況,恢復(fù)了小鼠腸道菌群應(yīng)對(duì)DSS的彈性[40,42]。
1.3 普洱茶通過調(diào)節(jié)腸道菌群改善糖尿病及其它疾病
關(guān)于普洱茶通過抑制α-葡萄糖苷酶和α-淀粉酶降糖的體外研究較多[43],但通過調(diào)節(jié)腸道菌群降糖的研究較少。DING等[44]發(fā)現(xiàn)相較于普洱生茶,普洱熟茶能顯著降低糖尿病大鼠的空腹血糖水平,且呈劑量依賴性,進(jìn)一步研究發(fā)現(xiàn),熟茶可增加擬桿菌門的相對(duì)豐度,降低F/B值,促進(jìn)有益菌屬如乳酸桿菌屬,擬普雷沃菌屬(Alloprevotella)和普雷沃菌屬(Prevotella)的富集。YUE等[45-46]研究證明腸道微生物與血清代謝物、肥胖和胰島素抵抗之間存在較強(qiáng)的相關(guān)性,普洱茶主要通過靶向調(diào)節(jié)腸道微生物繁殖,如富集多形擬桿菌(Bacteroides thetaiotaomicron),鼠乳桿菌(Lactobacillus murinus),狄氏副擬桿菌(Parabacteroides distasonis),產(chǎn)酸擬桿菌(Bacteroides acidifaciens)等與膽汁分泌、甘油磷脂代謝相關(guān)的菌株,從而改善大鼠糖脂代謝。
除了改善肥胖、結(jié)腸炎、糖尿病以外,近年的研究還發(fā)現(xiàn),普洱茶通過調(diào)節(jié)腸道菌群可以改善慢性飲酒引起的代謝紊亂、晝夜節(jié)律紊亂和延緩衰老,這些疾病通常都伴隨著氧化應(yīng)激、器官炎癥、糖脂代謝紊亂以及腸道微生物改變,普洱茶能從不同的途徑修復(fù)損傷,減少炎癥發(fā)生,逆轉(zhuǎn)疾病引起的菌群改變,抑制有害菌如幽門螺桿菌的富集[47-49]。
2 普洱茶調(diào)節(jié)腸道菌群可能的功能性成分
普洱茶具有調(diào)節(jié)腸道菌群改善機(jī)體疾病的作用,目前多以普洱茶水提物為研究對(duì)象,針對(duì)水提物中明確活性成分的研究較少,一定程度上限制了相關(guān)功能性產(chǎn)品的開發(fā)。關(guān)于其他茶類(如綠茶)調(diào)節(jié)腸道菌群的功能性成分研究主要集中在茶多酚、茶多糖、茶皂素等[50]。由于后發(fā)酵這一獨(dú)特的加工方式,使普洱茶具有不同于其他茶的風(fēng)味口感,也使其所含的化學(xué)物質(zhì)有所改變,包括兒茶素類成分和氨基酸的減少,茶多糖、沒食子酸和咖啡因的明顯增加,一些新物質(zhì)(如普洱茶素puerins)的形成[4,22]。這些化學(xué)物質(zhì)的改變?yōu)槠涔δ芴峁┝宋镔|(zhì)基礎(chǔ)。結(jié)合現(xiàn)有文獻(xiàn)分析,普洱茶中發(fā)揮調(diào)節(jié)腸道菌群的功能物質(zhì)可能為茶褐素、茶多酚、茶多糖。
2.1 茶褐素
茶褐素是普洱茶中一類水溶性酚性色素,在發(fā)酵過程中,其顯著增加,被認(rèn)為是普洱茶的特征成分[51-52]。研究表明茶褐素能降低產(chǎn)膽鹽水解酶的腸道細(xì)菌豐度和膽鹽水解酶活性,起到降膽固醇和降脂作用,同時(shí)可通過改變腸道菌群,尤其是增加7-去羥基化菌群如嗜黏蛋白阿克曼氏菌、梭狀芽胞桿菌(Clostridium scindens)和狄氏副擬桿菌(Parabacteroides disasonis),使膽汁酸的生物合成從經(jīng)典途徑轉(zhuǎn)移到替代途徑,從而改善白色和棕色脂肪組織的能量代謝,起到改善肥胖作用[25,31]。此外茶褐素通過調(diào)節(jié)腸道菌群可改善糖尿病、代謝綜合征和衰老[45-46,49],詳見表1。相對(duì)于其他功能物質(zhì),茶褐素調(diào)節(jié)腸道菌群的研究較多,但茶褐素是一種較為復(fù)雜的大分子聚合物,由多糖、酚類物質(zhì)、蛋白質(zhì)、氨基酸等聚合形成,其形成過程復(fù)雜,較難分離純化,確切的組成和結(jié)構(gòu)特征尚不清楚,檢測(cè)方法并不成熟,這可能導(dǎo)致不同研究中的茶褐素性質(zhì)不盡相同[53-54]。
2.2 茶多酚
茶多酚一直被認(rèn)為是茶葉中的主要功能成分,有較強(qiáng)的抗氧化活性,研究發(fā)現(xiàn)約80%以上的茶多酚無法被胃腸道直接吸收,而是到達(dá)結(jié)腸與腸道菌群相互作用[55]。而多酚的結(jié)構(gòu)多樣性,會(huì)影響生物利用度、代謝和生物活性,個(gè)體差異對(duì)多酚的代謝能力也不同[56]。在普洱熟茶中茶多酚含量相較于生茶有所下降,但其構(gòu)成發(fā)生了改變,主要涉及到兒茶素的氧化、大量沒食子酸和短鏈脂肪酸的形成[4],這可能使普洱熟茶有更好的健康作用。GAO等[29]認(rèn)為氧化茶多酚可能是普洱茶的功能成分,氧化的茶多酚能恢復(fù)高脂誘導(dǎo)的小鼠腸道微生物群落結(jié)構(gòu),顯著降低薩特菌(Sutterella spp.)、脫硫弧菌屬(Desulfovibrio spp.)等有害菌,增加嗜黏蛋白阿克曼氏菌和雙歧桿菌(Bifidobacterium spp.)等有益菌,此外氧化的茶多酚能不同程度上恢復(fù)腸道屏障完整性基因Muc2,Occludin和ZO-1的表達(dá)水平,修復(fù)腸道屏障功能。XIA等[28]對(duì)肥胖大鼠盲腸微生物群落進(jìn)行宏基因組和元蛋白質(zhì)組的比較研究顯示,普洱茶茶多酚及其腸道菌群代謝物通過刺激II型和III型分泌系統(tǒng)蛋白、延伸因子Tu和甘油醛-3-磷酸脫氫酶,促進(jìn)了嗜黏蛋白阿克曼氏菌的生長(zhǎng)。而普洱茶多酚是一種復(fù)雜的多酚組合,目前對(duì)于復(fù)雜的多酚組合對(duì)腸道菌群組成和功能的影響研究較少,機(jī)制尚不清楚[57]。
2.3 茶多糖
茶多糖在茶葉加工過程中常與多酚和蛋白質(zhì)結(jié)合形成多糖綴合物,普洱茶陳化時(shí)間的差異和發(fā)酵工藝不同會(huì)導(dǎo)致茶多糖的化學(xué)成分和蛋白質(zhì)結(jié)合的變化,從而影響其生物活性,與其他茶類多糖相比,普洱茶多糖抗氧化和抗糖尿病的活性最好[58-59]。研究證實(shí)同為后發(fā)酵茶的茯磚茶多糖能不被分解地通過消化系統(tǒng),安全到達(dá)大腸,被腸道菌群分解利用,通過降低F/B值,增加普雷沃氏菌(Prevotella)和擬桿菌屬(Bacteroides)的相對(duì)豐度,促進(jìn)短鏈脂肪酸(short-chain fatty acids,SCFAs)的產(chǎn)生來起到改善代謝綜合征的作用[60-62]。茶多糖也能通過調(diào)節(jié)腸道微生物色氨酸代謝,促進(jìn)腸上皮細(xì)胞再生來改善結(jié)腸炎[63]。目前,普洱茶多糖調(diào)節(jié)腸道微生物的研究報(bào)道較少。
2.4 其他
普洱茶中含有一定量的咖啡因[3]??Х纫蛞自谏舷乐苯颖晃?只有極少部分進(jìn)入結(jié)腸,對(duì)其作用于腸道微生物的研究較少[64]。但體外實(shí)驗(yàn)表明咖啡因可抑制非益生菌的生長(zhǎng)[65],GAO等[29]實(shí)驗(yàn)也證明咖啡因可引起小鼠腸道菌群改變,說明即使少量咖啡因也有可能影響腸道菌群,但仍需要更多的研究證實(shí)。
3 討論與展望
腸道菌群與人類疾病息息相關(guān)。普洱茶作為一種獨(dú)特的茶制品,促健康功效已被大眾所熟知,促健康功能也得到了廣泛的研究。普洱茶可通過調(diào)節(jié)腸道菌群改善疾病癥狀,發(fā)揮健康功效,但普洱茶成分復(fù)雜,目前研究多以水提取物為對(duì)象,其功能成分和機(jī)制尚不清楚。且普洱茶品質(zhì)受發(fā)酵工藝的影響[66],這限制了普洱茶可作為益生元被進(jìn)一步開發(fā)利用。
因此,開展普洱茶中何種功能成分及其對(duì)腸道菌群影響的研究是亟待解決的問題。如對(duì)普洱茶茶褐素進(jìn)行更深入的研究,明確其結(jié)構(gòu)和定量方法是非常必要的。普洱茶多酚和多糖均為復(fù)雜的天然成分,可作為益生元被進(jìn)一步研究和開發(fā)。普洱茶素是后發(fā)酵茶中存在的特殊物質(zhì),其功能研究較少,在調(diào)節(jié)腸道菌群方面的研究還是空白,值得進(jìn)一步研究。此外,隨著微生物檢測(cè)技術(shù)、代謝組學(xué)檢測(cè)技術(shù)、宏基因組的發(fā)展,通過多組學(xué)的應(yīng)用使探索普洱茶中功能成分與腸道菌群的相互作用成為可能,這將為普洱茶功能性產(chǎn)品的開發(fā)奠定基礎(chǔ)。
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網(wǎng)址: 普洱茶調(diào)節(jié)腸道菌群作用的研究進(jìn)展 http://m.u1s5d6.cn/newsview616767.html
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