劉瑞雪,李勇超,張 波(北京聯(lián)合大學(xué)功能食品科學(xué)技術(shù)研究院,應(yīng)用文理學(xué)院,北京100191)
腸道菌群微生態(tài)平衡與人體健康的研究進(jìn)展
劉瑞雪,李勇超,張 波*
(北京聯(lián)合大學(xué)功能食品科學(xué)技術(shù)研究院,應(yīng)用文理學(xué)院,北京100191)
人體腸道微生物種類(lèi)繁多且數(shù)量龐大。正常腸道菌群作為人體的天然屏障,對(duì)維持人體健康起著重要的作用。機(jī)體內(nèi)外環(huán)境的變化可影響腸道菌群的結(jié)構(gòu),造成腸道菌群失衡,繼而引發(fā)或加重疾病,影響人體健康。通過(guò)膳食補(bǔ)充益生菌和益生元,選擇性地剌激和調(diào)節(jié)腸道菌群的數(shù)量和組成,保持腸道菌群的微生態(tài)平衡,是預(yù)防和治療疾病,促進(jìn)人體健康的有效措施。本文綜述了國(guó)內(nèi)外關(guān)于腸道菌群的組成及功能、與相關(guān)疾病及治療的關(guān)系以及維持腸道微生態(tài)平衡的措施。
腸道菌群,疾病,微生態(tài)平衡
人體腸道內(nèi)存在著數(shù)量龐大、種類(lèi)繁多的微生物,約1000~1150種,超過(guò)100萬(wàn)億個(gè)細(xì)菌,是人體細(xì)胞數(shù)量的10倍。人體腸道菌群從嬰兒出生開(kāi)始就與人類(lèi)相伴,組成了人體不可或缺的功能強(qiáng)大的微生態(tài)系統(tǒng),在人類(lèi)營(yíng)養(yǎng)、代謝、疾病等各個(gè)方面發(fā)揮著巨大的作用,影響著人類(lèi)的發(fā)育和健康。因此,人體腸道的結(jié)構(gòu)和功能是當(dāng)今生命科學(xué)和醫(yī)學(xué)研究的主要熱點(diǎn)。
人類(lèi)的腸道菌群是一個(gè)復(fù)雜的生態(tài)系統(tǒng),主要為細(xì)菌(總數(shù)超過(guò)1014,約1.5 kg)還包括一些其他微生物,如真菌、寄生蟲(chóng)、病毒和古細(xì)菌。而這些微生物所攜帶的基因大約是人類(lèi)基因組的150倍[1-2]。大量腸道細(xì)菌主要位居于結(jié)腸和遠(yuǎn)端小腸,其密度分布隨著從腸道遠(yuǎn)端向近端、從腸腔內(nèi)向腸腔外兩個(gè)方向遞減,同時(shí)腸道菌群菌多樣性也同向遞減。其中腸道專(zhuān)性厭氧菌占絕對(duì)優(yōu)勢(shì),腸道兼性厭氧或需氧的革蘭陰性細(xì)菌只占細(xì)菌總數(shù)的0.11%。個(gè)體腸道菌群的組成在種水平上具有很大的差異,但在門(mén)水平上具有一定的穩(wěn)定性和保守性。大量研究發(fā)現(xiàn)[3-4],人體內(nèi)重要的細(xì)菌種類(lèi)主要包括擬桿菌門(mén)(Bacteroidetes)、厚壁菌門(mén)(Firmicutes)、變形菌門(mén)(Proteobacteria)、放線菌門(mén)(Actinobacteria)、梭桿菌(Fusobacteria)和疣微菌門(mén)(Verrucomicrobia),而這些細(xì)菌中,厚壁菌門(mén)(Firmicutes)和擬桿菌門(mén)(Bacteroidetes)也是數(shù)量上最占優(yōu)勢(shì)的。
人類(lèi)從出生開(kāi)始通過(guò)多種方式獲得腸道菌群。新生兒體內(nèi)的微生物主要來(lái)源于母體產(chǎn)道、糞便以及體表的微生物,在嬰兒出生后一些兼性厭氧微生物如大腸桿菌、金黃色葡萄球菌和鏈球菌等通過(guò)分娩移植到新生兒腸道中并不斷增殖,造成新生兒腸道的厭氧環(huán)境,從而有利于厭氧微生物如擬桿菌和雙歧桿菌的生長(zhǎng)繁殖[5-6]。母乳喂養(yǎng)是嬰兒出生后母體的菌群向嬰兒體內(nèi)轉(zhuǎn)移的一種重要方式,母乳喂養(yǎng)使母體微生物包括金黃色葡萄球菌、鏈球菌、雙歧桿菌以及乳酸桿菌等不斷向嬰兒腸道轉(zhuǎn)移并加速腸道菌群的增殖和成熟[7-8]。特別重要的是母乳中含有低聚糖等益生元使雙歧桿菌等益生菌大量增殖,益生菌和益生元共同調(diào)節(jié)嬰兒腸道的菌群,建立平衡的微生態(tài)環(huán)境,抑制病原微生物的增殖、調(diào)節(jié)腸道黏膜屏障功能及免疫功能[9-10]。母乳喂養(yǎng)的嬰兒1周歲時(shí)腸道菌群的發(fā)育已經(jīng)比較完善,3周歲時(shí)腸道菌群基本接近成年人[11-12]。因此,嬰幼兒期腸道菌群的定植和發(fā)育十分關(guān)鍵,將對(duì)嬰兒以致對(duì)成年以后的代謝與免疫疾病產(chǎn)生重要的影響。進(jìn)入成年期后的腸道菌群比較穩(wěn)定,但當(dāng)進(jìn)入老年期時(shí),一些生理功能包括免疫系統(tǒng)功能的改變將顯著影響腸道菌群的組成[13]。
食物經(jīng)由胃和小腸分解、消化后進(jìn)入大腸。腸道菌群利用人體未完全消化的食物成分、部分代謝產(chǎn)物以及腸道粘液等進(jìn)行新陳代謝活動(dòng)并維持自身的數(shù)量平衡,通過(guò)自身的各項(xiàng)生理活動(dòng)在多個(gè)方面影響宿主的健康。
2.1 腸道菌群對(duì)腸道的保護(hù)作用
正常的腸道菌群通過(guò)構(gòu)建機(jī)械屏障、生物屏障和免疫屏障抵御外來(lái)病原微生物的入侵,維持腸道內(nèi)環(huán)境的穩(wěn)定和微生態(tài)平衡。人腸道中厭氧菌占絕對(duì)優(yōu)勢(shì)(99%以上),大量繁殖的腸道菌群消耗了絕大部分腸道微環(huán)境中細(xì)菌生長(zhǎng)繁殖所必需的營(yíng)養(yǎng)物,尤其是鐵離子,從外部入侵的致病菌由于其載鐵體遠(yuǎn)不如正常菌群發(fā)達(dá)因而無(wú)法競(jìng)爭(zhēng)生長(zhǎng),減少了其在腸道的定植[14]。此外,腸道菌群在代謝過(guò)程中產(chǎn)生揮發(fā)性脂肪酸、乳酸以及乙酸、丙酸、細(xì)菌素等,降低腸道內(nèi)的pH,促進(jìn)酸對(duì)大腸桿菌、沙門(mén)氏菌的抑制和殺傷,抑制外籍菌的生長(zhǎng)和繁殖,從而減少這些細(xì)菌產(chǎn)生的毒性物質(zhì)的形成,使結(jié)腸中的潛在致癌物的形成數(shù)量減少[15]。另外,厭氧菌和腸道黏膜上皮細(xì)胞緊密結(jié)合形成生物膜-菌群復(fù)合結(jié)構(gòu),對(duì)腸上皮組織起著重要的占位保護(hù)作用[16]。
2.2 腸道菌群與物質(zhì)能量代謝
定植于人體腸道的微生物群為宿主提供了多種人體自身所不具備的酶與生化途徑,能夠分解人體不易消化的多糖、寡聚糖以及糖蛋白質(zhì)等,生成短鏈脂肪酸為宿主提供能量以及為腸道菌群生長(zhǎng)繁殖提供營(yíng)養(yǎng)物質(zhì)[15]。除此之外,腸道菌群還能合成多種維生素包括B族維生素、維生素K、維生素C、生物素以及葉酸等,如大腸桿菌能合成維生素K,而人無(wú)法從食物中獲取。除此之外,腸道菌群還能通過(guò)與宿主發(fā)生共代謝作用,通過(guò)肝腸循環(huán)等多條代謝途徑參與藥物及其他外來(lái)化合物的分解代謝,膽汁酸及脂肪等的代謝便是其中最為典型的例子[17]。
2.3 腸道菌群與機(jī)體的免疫功能
腸道菌群通過(guò)細(xì)菌本身或細(xì)胞壁成分刺激宿主免疫系統(tǒng)使免疫細(xì)胞活化,通過(guò)增加抗體含量、調(diào)節(jié)淋巴細(xì)胞的吞噬作用以及增加干擾素的分泌等作用提高機(jī)體的免疫力。大量實(shí)驗(yàn)結(jié)果表明,無(wú)菌動(dòng)物的腸系膜淋巴結(jié)較小且數(shù)量也少于正常動(dòng)物,抗體分泌水平也明顯低于正常動(dòng)物[18]。粘膜免疫系統(tǒng)的主要功能是通過(guò)產(chǎn)生分泌型免疫球蛋白A(sIgA)阻止微生物在粘膜上皮定植和繁殖。Sjogren等[19]的研究發(fā)現(xiàn),初生嬰兒糞便中雙歧桿菌的數(shù)量與黏膜分泌型免疫球蛋白A(sIgA)的濃度呈顯著正相關(guān),表明雙歧桿菌能促進(jìn)粘膜免疫系統(tǒng)的sIgA的成熟及分泌。
3.1 腸道菌群與炎癥性腸病
炎癥性腸?。╥nflammatory bowel disease,IBD)是發(fā)生于胃腸道的慢性復(fù)發(fā)性疾病,克羅恩病(CD)和潰瘍性結(jié)腸炎(UC)為其兩種主要表現(xiàn)形式,其致病因素及發(fā)病機(jī)制至今尚未完全闡明,但目前普遍認(rèn)為IBD是由遺傳因素、免疫功能紊亂、腸道屏障功能障礙和腸道菌群改變等多因素所致。越來(lái)越多的研究表明[20-21],腸道菌群失調(diào)是參與IBD發(fā)病的重要因素,主要表現(xiàn)為微生物的組成和豐度的改變及功能的損傷。近年來(lái)人們對(duì)腸道菌群失調(diào)引起免疫損傷進(jìn)而導(dǎo)致炎癥性腸病這一觀點(diǎn)表現(xiàn)出愈發(fā)濃厚的興趣。
大量研究表明,UC患者腸道菌群的豐度與多樣性發(fā)生了明顯的改變[22-23]。Machiels[24]發(fā)現(xiàn)在UC患者中兩種重要的厚壁菌門(mén)產(chǎn)丁酸細(xì)菌人酵母菌(Roseburia hominis),普拉梭菌(F.Prausnitzii)明顯減少。丁酸是腸上皮主要的能源來(lái)源,而且還具有防止病原體侵襲,調(diào)節(jié)免疫系統(tǒng)功能以及抗炎的作用[25]。研究還表明產(chǎn)丁酸細(xì)菌的數(shù)量會(huì)隨疾病的嚴(yán)重程度發(fā)生改變[26]。Varela等[27]發(fā)現(xiàn)F.prausnitzii的數(shù)量在UC緩解期明顯增加,因此認(rèn)為F.pramnitzii對(duì)UC的治療起著重要的作用。此外,研究發(fā)現(xiàn)UC患者體內(nèi)腸道菌群的代謝產(chǎn)物短鏈脂肪酸尤其是具有顯著抗炎活性的乙酸、丙酸、丁酸的含量明顯減少[28]。愈來(lái)愈多的研究認(rèn)為腸道菌群是UC免疫損傷過(guò)程的一個(gè)重要激發(fā)因素,促使致病菌滋生和益生菌缺失,破壞腸粘膜免疫系統(tǒng)對(duì)腸道菌群的耐受性,從而產(chǎn)生過(guò)度且持續(xù)的炎癥反應(yīng)。Vigsnaes等[29]采用熒光定量PCR的方法檢測(cè)UC患者糞便中腸道細(xì)菌的數(shù)量,發(fā)現(xiàn)UC患者乳酸桿菌的減少十分顯著。Pilarczyk-Zurek等[30]對(duì)30例活動(dòng)期UC患者的炎癥組織和非炎癥組織的結(jié)腸黏膜進(jìn)行活檢,發(fā)現(xiàn)病變腸段大腸埃希菌明顯增多,提示腸道大腸埃希菌和乳酸桿菌均與UC的發(fā)病有一定的關(guān)系。雖然到目前為止還不能確定腸道菌群紊亂與UC之間是原發(fā)性還是繼發(fā)性關(guān)系,但有一點(diǎn)可以肯定腸道菌群在抗炎與調(diào)節(jié)免疫方面發(fā)揮著重要的作用,調(diào)節(jié)腸道菌群對(duì)UC有一定的輔助治療作用[22-31]。大量研究發(fā)現(xiàn),益生菌對(duì)潰瘍性結(jié)腸炎具有明顯的緩解和治療作用,通過(guò)PI3K/Akt和NF-kB信號(hào)通路,降低促炎因子TNF-a、IL-1β等的水平,升高抗炎因子IL-10的分泌,UC癥狀明顯緩解[32-34]。另外,糞便菌群移植(FMT)技術(shù)治療UC也正逐漸成為研究的熱點(diǎn)[35]。
3.2 腸道菌群與肥胖
隨著人們生活水平的提高,肥胖的發(fā)病率日益增加,現(xiàn)已成為嚴(yán)重困擾世界各國(guó)的公共衛(wèi)生問(wèn)題。肥胖的病因至今尚未完全明確,一般認(rèn)為肥胖是在遺傳因素與環(huán)境因素兩方面共同作用的結(jié)果。目前許多研究表明腸道菌群在肥胖的發(fā)病過(guò)程中起到重要的作用[36-37]。腸道細(xì)菌最重要的代謝功能是能夠通過(guò)編碼大量的糖苷水解酶,從而發(fā)酵食物中宿主自身不能消化的多糖,將其轉(zhuǎn)化為單糖以及代謝終產(chǎn)物短鏈脂肪酸。Bjursell等[38]的研究顯示,缺失短鏈脂肪酸受體的小鼠體重明顯輕于野生型小鼠。Dinq等[39]的研究顯示,無(wú)菌小鼠在一定程度上可以抵抗飲食導(dǎo)致的肥胖,這在一定程度上證明了腸道菌群與肥胖的關(guān)系。腸道菌群不僅能夠促進(jìn)宿主吸收更多的能量,而且還與慢性系統(tǒng)炎癥的發(fā)生有一定聯(lián)系。研究發(fā)現(xiàn)高脂飲食可以改變腸道菌群結(jié)構(gòu),增加革蘭陰性菌的比例,導(dǎo)致脂多糖產(chǎn)生增多,菌群比例的失調(diào)還可通過(guò)抑制腸道上皮細(xì)胞間緊密連接蛋白的表達(dá),增加腸道上皮通透性,促使脂多糖進(jìn)入血液引起代謝性?xún)?nèi)毒素血癥并誘發(fā)肥胖[40-42]。Muccioli等[43]發(fā)現(xiàn),脂多糖可使內(nèi)源性大麻素活性增強(qiáng),增加大麻素受體在結(jié)腸及脂肪組織中的表達(dá),使腸道通透性增加以及脂肪儲(chǔ)存增多,而增加的腸道通透性又促使脂多糖進(jìn)入血液,引發(fā)炎癥并進(jìn)一步加重肥胖的進(jìn)程。因此,改善腸道微生態(tài)可能是調(diào)整肥胖個(gè)體能量平衡的有效措施。
3.3 腸道菌群與肝臟疾病
慢性肝臟疾病與腸道菌群的改變息息相關(guān)。近10年來(lái),由于對(duì)腸-肝軸認(rèn)識(shí)的逐步深入,腸道菌群在慢性肝病發(fā)病過(guò)程中的作用備受關(guān)注[44]。正常情況下,肝臟可清除來(lái)自腸道的內(nèi)毒素、氨、吲哚、酚類(lèi)等各種毒素。但是腸道微生態(tài)的改變使腸道屏障功能受損,各種代謝產(chǎn)物大量進(jìn)入腸外器官,過(guò)度激活機(jī)體免疫系統(tǒng),引起異常免疫反應(yīng),導(dǎo)致肝細(xì)胞凋亡及壞死。大量研究還表明,慢性肝臟疾病患者存在不同程度的腸道菌群失調(diào),雙歧桿菌、乳酸桿菌等厭氧菌的數(shù)量減少,革蘭陰性細(xì)菌過(guò)度生長(zhǎng)繁殖,并釋放大量?jī)?nèi)毒素引發(fā)或加重慢性肝臟疾病。
對(duì)非酒精性脂肪性肝炎以及酒精性肝病患者腸道菌群的分析發(fā)現(xiàn),腸道菌群失調(diào)、腸桿菌比例明顯高于健康人群,說(shuō)明腸道菌群異常在一定程度上促進(jìn)肝病的發(fā)展??刂颇c道菌群失調(diào)可明顯改善臨床癥狀[45-50]。
通過(guò)膳食調(diào)節(jié)腸道微生態(tài)平衡的措施主要是補(bǔ)充益生菌和益生元。益生菌(probiotics)是一類(lèi)通過(guò)改善腸道菌群組成從而發(fā)揮有益作用的活性微生物;益生元(prebiotics)是一些不被消化或難以被消化的食物成分,通常為低聚糖類(lèi),這些成分通過(guò)選擇性的剌激結(jié)腸內(nèi)細(xì)菌的增殖、活性,從而對(duì)宿主的健康產(chǎn)生有益作用。
4.1 益生菌
腸道中的益生菌,有序地定植于腸道黏膜形成生物屏障,減少病原微生物的侵染和定植,起著占位、爭(zhēng)奪營(yíng)養(yǎng)和拮抗的作用,保護(hù)機(jī)體免受病原菌入侵。某些益生菌可產(chǎn)生具有廣譜抗菌作用的物質(zhì)如細(xì)菌素等,抑制腸道內(nèi)的大腸埃希菌、沙門(mén)氏菌和鏈球菌等的生長(zhǎng)繁殖。益生菌還可以通過(guò)產(chǎn)生胞外糖苷酶阻止致病菌對(duì)腸黏膜細(xì)胞的侵襲。
通過(guò)膳食補(bǔ)充的益生菌主要是兩大類(lèi)乳酸菌群:一類(lèi)為雙歧桿菌如嬰兒雙歧桿菌、長(zhǎng)雙歧桿菌、短雙歧桿菌以及青春雙歧桿菌等。另一類(lèi)為乳桿菌如嗜酸乳桿菌、干酪乳桿菌、鼠李糖乳桿菌、植物乳桿菌和羅伊氏乳桿菌等。研究表明通過(guò)膳食補(bǔ)充雙歧桿菌和乳酸桿菌,可抑制病原菌對(duì)腸粘膜的粘附作用,穩(wěn)定微生物群落結(jié)構(gòu),改善胃黏膜的完整性和屏障功能,從而改善肥胖、炎癥性疾病以及代謝性并發(fā)癥[51]。普拉梭菌(Faecalibacterium prausnitzii)是人體腸道菌群中含量最豐富的細(xì)菌,占細(xì)菌總數(shù)的5%。F.pramnitzii代謝腸道中未吸收的糖類(lèi)產(chǎn)生大量丁酸,是腸道中產(chǎn)生丁酸的主要細(xì)菌,對(duì)腸道健康起著重要的作用,其失調(diào)與多種疾病如特應(yīng)性皮炎、慢性特發(fā)性腹瀉、急性闌尾炎以及結(jié)直腸癌等的發(fā)生發(fā)展均存在相關(guān)性[52]。F.prausnitzii與炎癥性腸病關(guān)系的研究也是近幾年研究的熱點(diǎn)。2013年,Varela等[53]應(yīng)用實(shí)時(shí)定量PCR技術(shù)對(duì)116例處于緩解期的UC患者和16例健康人的糞便細(xì)菌進(jìn)行了研究,發(fā)現(xiàn)UC患者F.prausnitzii細(xì)菌的定植明顯減少。且口服F.pramnitzii對(duì)緩解期UC患者有一定的治療作用[53-54]。動(dòng)物實(shí)驗(yàn)也表明F.pramnitzii培養(yǎng)上清液對(duì)2,4,6-三硝基苯磺酸誘導(dǎo)的小鼠結(jié)腸炎具有緩解作用。F.pramnitzii可能會(huì)作為一種新型的益生菌進(jìn)行開(kāi)發(fā)利用。
4.2 益生元
益生元主要指功能性低聚糖,包括各種寡糖類(lèi)物質(zhì)(Oligosaccharides)或稱(chēng)低聚糖(由2~10個(gè)單糖分子組成,如低聚木糖、低聚果糖、低聚半乳糖、水蘇糖、異麥芽糖、乳果糖和乳酮糖等)。由于人體胃腸道內(nèi)沒(méi)有代謝此類(lèi)低聚糖的β-半乳糖苷酶系,當(dāng)其通過(guò)消化道時(shí)不能被其中的酸和酶分解,不被小腸消化吸收,直接進(jìn)入大腸而被大腸中廣泛存在的微生物菌群所利用。近年來(lái),國(guó)內(nèi)外對(duì)低聚糖調(diào)節(jié)腸道功能的研究十分活躍,如殼寡糖、低聚半乳糖以及低聚果糖通過(guò)激活動(dòng)物腸上皮細(xì)胞、保護(hù)腸道緊密連接功能以及調(diào)節(jié)結(jié)腸上皮的杯狀細(xì)胞的分泌功能等機(jī)制保護(hù)腸道的屏障功能,預(yù)防結(jié)腸炎甚至結(jié)腸癌的發(fā)生[55-61]。國(guó)內(nèi)學(xué)者也對(duì)一些重要中藥多糖、植物多糖及其水解產(chǎn)物改善腸道的功能及機(jī)理進(jìn)行了研究。如國(guó)內(nèi)學(xué)者對(duì)大黃多糖及水解物,魔芋多糖及其低聚糖調(diào)節(jié)腸道功能的作用進(jìn)行了研究,結(jié)果表明大黃多糖及水解物,魔芋多糖及其低聚糖等可降低結(jié)腸黏膜MPO水平以及TNF-α表達(dá)量;提高結(jié)腸中雙歧桿菌和乳桿菌的數(shù)量并降低大腸桿菌及腸球菌的數(shù)量,改善腸道菌群失調(diào);提高結(jié)腸中短鏈脂肪酸(SCFA)的產(chǎn)量,從而治療和緩解TNBS誘導(dǎo)的結(jié)腸炎[62-66]。
綜上所述,腸道菌群和人體有著密不可分的互利共生關(guān)系,直接影響著每個(gè)人的健康,他們?cè)谌梭w消化、免疫和疾病防治等方面均起著重要的作用,并參與了多種非感染性疾病,特別是慢性代謝疾病的發(fā)生發(fā)展過(guò)程,同時(shí)也表明適當(dāng)?shù)恼{(diào)節(jié)腸道菌群可能成為疾病的一種潛在治療方式。年齡、生活方式、腸道動(dòng)力異常、免疫功能障和抗生素的使用等一系列貫穿整個(gè)生命過(guò)程的復(fù)雜的、動(dòng)態(tài)的交互因素均會(huì)引起腸道菌群的變化。日前膳食結(jié)構(gòu)對(duì)人體腸道菌群的影響也引起國(guó)內(nèi)外學(xué)術(shù)界的廣泛關(guān)注。合理地膳食補(bǔ)充益生菌和益生元可能會(huì)成為保持腸道菌群的微生態(tài)平衡,預(yù)防和治療疾病,促進(jìn)宿主健康的新措施。然而,由于腸道菌群結(jié)構(gòu)和功能的復(fù)雜性,目前對(duì)于腸道菌群參與機(jī)體代謝、與機(jī)體相互作用的機(jī)制仍不明確,有待更深入的研究。
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Research progress on gut microbiota homeostasis and human health
LIU Rui-xue,LI Yong-chao,ZHANG Bo*
(Research Institute for Science and Technology of Functional Food,College of Arts and Science,Beijing Union University,Beijing 100191,China)
The human gut was colonized by a wide diversity of micro-organisms,which were known to play a key role in the human host.It will not only lead to intestinal dysbacteriosis but also induce and aggravate various diseases when the balance of the intestinal flora was disturbed by host and external environment change.Supplementing probiotics and prebiotics by nutritional management could stimulate the amount and composition of intestinal bacteria which considered as an effective method to prevent diseases and promote human health.Here was to make a review of the research progress in function,related diseases and therapeutic,homeostasis of gut microbiota.
gut microbiota;diseases;microbiota homeostasis
TS201.3
A
1002-0306(2016)06-0383-06
10.13386/j.issn1002-0306.2016.06.068
2015-06-30
劉瑞雪(1987-),女,碩士研究生,研究方向:生物活性物質(zhì)的功能與毒理,E-mail:liuruixue871024@163.com。
張波(1962-),女,教授,研究方向:生物活性物質(zhì)的功能與毒理,E-mail:zhangbo_wl@buu.edu.cn。
“十二五”國(guó)家科技支撐計(jì)劃課題(2012BAD33B06)。