首頁(yè) 資訊腸道菌群對(duì)人體健康的作用及其應(yīng)用

腸道菌群對(duì)人體健康的作用及其應(yīng)用

來(lái)源：泰然健康網(wǎng) 時(shí)間：2024年12月15日 02:38

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摘要

人類(lèi)腸道菌群復(fù)雜多樣，在與人類(lèi)長(zhǎng)期的共同進(jìn)化過(guò)程中，具備了調(diào)節(jié)人體免疫應(yīng)答、影響疾病發(fā)展的作用。這種免疫調(diào)節(jié)作用與腸道菌群本身的多樣性和關(guān)鍵菌種的存在與否具有緊密聯(lián)系。然而腸道菌群結(jié)構(gòu)和功能的特性在很大程度上受到腸道菌群宿主的飲食結(jié)構(gòu)、年齡和生活環(huán)境等因素的影響。正常的腸道菌群能夠調(diào)節(jié)腸上皮細(xì)胞的通透性，刺激物質(zhì)代謝與免疫反應(yīng)，使腸道微環(huán)境長(zhǎng)期處于穩(wěn)態(tài)；一旦腸道菌群失衡，引起腸道微環(huán)境穩(wěn)態(tài)變化，則會(huì)提高許多疾病的發(fā)生風(fēng)險(xiǎn)，尤其是胃腸代謝疾病，以及免疫和神經(jīng)性疾病。本文主要從腸道菌群與人體健康的關(guān)系、影響腸道菌群組成的因素、功能性食品對(duì)人體健康的影響以及如何維持腸道微生態(tài)平衡等幾個(gè)方面，綜述了人體腸道菌群的當(dāng)前研究現(xiàn)狀和相關(guān)產(chǎn)業(yè)應(yīng)用，期望能夠?yàn)槟c道菌群與人體健康的相互關(guān)系研究及其成果轉(zhuǎn)化提供新的思考。

Abstract

In the coevolutionary journey with humans, the complex and diverse human intestinal flora has evolved to regulate the human immune responses and affect the development of diseases. This immunomodulatory effect is closely related to the diversity of intestinal flora and the presence of key strains. The composition and function of the intestinal flora are greatly influenced by a variety of factors, including the diet, age and living envi‐ ronment of the host. Normal intestinal flora can regulate the permeability of intestinal epithelial cells, stimulate in‐ testinal metabolism and immunoreaction, and maintain local homeostasis in the intestinal microenvironment. When the intestinal flora is imbalanced and the intestinal homeostasis is disrupted, the risk of many diseases, such as the gastrointestinal metabolic diseases, as well as the immune and neurological diseases, will increase. Here we reviewed the current research progress and therapeutic applications of human intestinal flora in the following sec‐ tions: the relationship between intestinal flora and human health, the factors affecting the composition of intestinal flora, the impact of functional foods on human health, and how to maintain intestinal microecological balance. Hopefully this review will provide new thinking for future studies on the interaction between intestinal flora and human health and the related translational applications.

1 腸道菌群與人體健康

人類(lèi)腸道菌群復(fù)雜多樣，在維護(hù)人體健康和體內(nèi)微生態(tài)平衡方面發(fā)揮著重要作用[1]。腸道菌群的結(jié)構(gòu)組成具有明顯的地域?qū)傩院蛡€(gè)體特異性，已有研究表明，腸道菌群的特異性和人類(lèi)的年齡、居住環(huán)境的氣候、生活飲食、基因表達(dá)等的差異具有密切相關(guān)性[2, 3]。盡管存在差異，但核心腸道菌群（某物種健康個(gè)體的腸道內(nèi)、長(zhǎng)期與宿主互利共生并保持種群穩(wěn)定的非特異性類(lèi)群，如放線菌、擬桿菌、厚壁菌、變形菌等）一般比較保守[4]，而且這些核心微生物群與個(gè)體的年齡沒(méi)有明顯的相關(guān)性，只是在不同的時(shí)間階段其物種豐度存在小范圍、有規(guī)律的波動(dòng)，這或許能夠有利于腸道菌群與人類(lèi)健康建立起一種微妙的平衡關(guān)系[5]。但也有研究指出，核心腸道菌群的“保守性”實(shí)際上具有一定的相對(duì)性，該類(lèi)群依然受到特定且穩(wěn)定的微生物家族基因、代謝途徑等因素的調(diào)節(jié)，同時(shí)指出這對(duì)維持宿主腸道微生態(tài)環(huán)境的穩(wěn)定性具有重要意義[6]。

在人體腸道中，生活著數(shù)以百萬(wàn)計(jì)的微生物動(dòng)態(tài)群落，它們一般通過(guò)自身細(xì)胞壁表面的纖毛等附著于腸上皮細(xì)胞表面[6, 7]，且伴隨著人體組織差異，局部區(qū)域的微生物呈現(xiàn)相對(duì)特異性[8]。例如在人體結(jié)腸中菌體個(gè)數(shù)達(dá)到峰值，單位質(zhì)量（g）內(nèi)容物中細(xì)菌個(gè)體數(shù)可達(dá)1013以上。從功能上看，腸道中的絕大多數(shù)微生物和參與轉(zhuǎn)化食物組分的酶相關(guān)。食物經(jīng)過(guò)腸道菌群的生物轉(zhuǎn)化后，生成小分子的碳水化合物、有機(jī)酸和對(duì)人體健康、維持機(jī)體內(nèi)穩(wěn)態(tài)具有重要作用的微生物特異性代謝產(chǎn)物——維生素和短鏈脂肪酸（Short-Chain Fatty Acids，SCFAs）等[8]。但是，腸道菌群的代謝產(chǎn)物因人而異，且與人類(lèi)年齡、飲食、居住環(huán)境、壓力、精神狀態(tài)等因素具有一定的相關(guān)性。研究表明，當(dāng)腸道菌群穩(wěn)態(tài)被打破時(shí)，腸道菌群物種多樣性及其豐度變化顯著，這會(huì)導(dǎo)致功能基因的表達(dá)、代謝相關(guān)酶等物質(zhì)的水平發(fā)生顯著變化，從而誘發(fā)腸道代謝紊亂，情況嚴(yán)重的則會(huì)引起炎癥性腸病、結(jié)直腸癌等代謝疾病[6]。另外，盡管抗生素對(duì)治療腸道疾病具有良好效果，但是面對(duì)抗生素的無(wú)差別攻擊，部分有益微生物的豐度也會(huì)在抗生素的作用下大幅下降。因此，基于飲食調(diào)節(jié)的功能性食品的開(kāi)發(fā)為改善人體腸道健康、維持腸道菌群與宿主之間的平衡提供了良好機(jī)會(huì)。

2 影響腸道菌群組成的因素

2.1 飲食

飲食對(duì)腸道菌群結(jié)構(gòu)的調(diào)節(jié)具有至關(guān)重要的作用，直接影響了腸道菌群的優(yōu)勢(shì)物種及其代謝主要組分[9]。對(duì)于新生兒來(lái)說(shuō)，飲食是塑造腸道菌群的關(guān)鍵驅(qū)動(dòng)力，例如母乳喂養(yǎng)的新生兒表現(xiàn)出放線菌優(yōu)勢(shì)和厚壁菌門(mén)、變形菌門(mén)劣勢(shì)，從代謝物的角度上整體表現(xiàn)出SCFAs水平增加，加強(qiáng)了免疫系統(tǒng)反應(yīng)，使IgG表達(dá)量升高[10, 11]。隨著新生兒年齡的增長(zhǎng)，飲食成為影響腸道菌群結(jié)構(gòu)、多樣性發(fā)展的重要因素。飲食中膳食纖維的攝入能夠確保腸道黏膜的完整性，在很大程度上降低了腸道疾病發(fā)生的風(fēng)險(xiǎn)[12]，富含纖維的飲食結(jié)構(gòu)也能夠改善人體血糖水平，促進(jìn)人體健康代謝循環(huán)[13]。高蛋白的飲食結(jié)構(gòu)能夠使得腸道中的擬桿菌、嗜雙胞桿菌大量增殖，這可能導(dǎo)致人體免疫力降低，增加疾病風(fēng)險(xiǎn)（包括代謝疾?。14, 15]。

2.2 年齡

年齡是影響腸道菌群組成的另一個(gè)主要因素。新生兒出生后，變形菌等需氧型細(xì)菌首先定植在人體腸道中，隨著腸道局部部位氧濃度的變化，厚壁菌門(mén)、擬桿菌門(mén)等細(xì)菌逐漸定植于氧濃度更低的腸道部位[16]。研究表明，新生兒腸道菌群的多樣性最低，但隨著年齡的增長(zhǎng)，其物種多樣性逐漸提高[17]。青春期時(shí)腸道菌群代謝物中葉酸和維生素B12的合成量顯著升高，這表明某些腸道菌可能參與了人體的生長(zhǎng)發(fā)育過(guò)程[18]。成年人腸道菌群以厚壁菌門(mén)、擬桿菌門(mén)的細(xì)菌為主，放線菌和變形菌的豐度相對(duì)較低[19]。而在老年人的腸道菌群中，多樣性降低，兼性厭氧菌、梭桿菌、芽孢桿菌等的豐度相對(duì)較高，雙歧桿菌、類(lèi)桿菌等豐度降低[20]，SC‐ FAs表達(dá)量相對(duì)較低[21]。

2.3 其他因素

除了飲食和年齡能夠顯著影響腸道菌群的結(jié)構(gòu)與功能外，運(yùn)動(dòng)、抗生素藥物、生活環(huán)境等也能在一定程度上影響腸道菌群功能的發(fā)揮。Hughes等研究表明，規(guī)律的運(yùn)動(dòng)習(xí)慣能夠豐富有益菌群的豐度和多樣性[22]。與非運(yùn)動(dòng)員相比，運(yùn)動(dòng)員的腸道菌群顯示出豐度更高的厚壁菌、乳桿菌和雙歧桿菌等，SCFAs和丁酸鹽等有益代謝產(chǎn)物的表達(dá)水平也顯著高于非運(yùn)動(dòng)員的平均水平[23]，梭狀芽胞桿菌、玫瑰芽孢桿菌等的豐度也在有益代謝產(chǎn)物的作用下明顯提高，其他類(lèi)群物種豐度均有不同程度的降低[22]?？股厮幬镒鳛椴≡w滅活劑在進(jìn)行病原體殺傷過(guò)程中具有“無(wú)差別”效應(yīng)，即在殺滅病原菌的同時(shí)也能對(duì)腸道有益微生物進(jìn)行滅活，從而導(dǎo)致腸道菌群代謝紊亂[24]。Dethlefsen等研究發(fā)現(xiàn)，抗生素對(duì)腸道菌群的影響主要取決于抗生素種類(lèi)和給藥時(shí)長(zhǎng)[25]。例如萬(wàn)古霉素能夠降低擬桿菌、煙曲霉菌和糞腸球菌的豐度，提高變形菌的豐度[26]，環(huán)丙沙星對(duì)乳球菌的抑制效果能夠達(dá)到6個(gè)月以上，而克拉霉素滅活幽門(mén)螺桿菌的過(guò)程中，放線菌的豐度顯著降低[27]。此外，基于氣候、遺傳、飲食等生活方式的不同，腸道菌群的結(jié)構(gòu)功能也表現(xiàn)出一定的差異性[28]。有研究顯示，在飲食結(jié)構(gòu)相對(duì)接近的條件下，相比于發(fā)展中國(guó)家，工業(yè)化程度更高的西方發(fā)達(dá)國(guó)家人群的腸道菌群中，厚壁菌和擬桿菌的比例似乎更高[29]。

3 功能性食品對(duì)人體健康的作用

功能性食品是一類(lèi)不僅能夠提供多種營(yíng)養(yǎng)物質(zhì)，還能夠提高人體健康水平、降低某些疾病風(fēng)險(xiǎn)的食物[30]，通常作為人類(lèi)生長(zhǎng)代謝調(diào)節(jié)劑，主要包括益生元、益生菌、膳食纖維、天然抗氧化劑和生物活性肽等[31]。已有研究表明，功能性食品中對(duì)人體有益的組分不僅僅局限于食物中活菌的補(bǔ)充，也包括這些有益菌的代謝產(chǎn)物。另外，我們個(gè)人的飲食結(jié)構(gòu)對(duì)于有益菌的類(lèi)群、代謝產(chǎn)物具有相當(dāng)?shù)臎Q定作用[32]。為此，我們有必要了解功能性食品的代謝與人體健康之間的關(guān)系。

3.1 降低腸道病原菌的感染風(fēng)險(xiǎn)

飲食作為最容易造成腸道菌群個(gè)體差異性的因素，已成為當(dāng)下研究腸道菌群代謝變化的主要熱點(diǎn)之一。在飲食組分中，益生元等功能性食品有利于小腸和結(jié)腸的功能穩(wěn)定[33]，腸道菌群對(duì)這些物質(zhì)的代謝可以改善胃腸功能和屏障穩(wěn)態(tài)，增強(qiáng)人體的礦物質(zhì)吸收能力，調(diào)節(jié)能量代謝以及降低腸道病原菌的感染風(fēng)險(xiǎn)等[34]。相反，體內(nèi)缺乏益生元?jiǎng)t會(huì)引起體內(nèi)生長(zhǎng)因子多樣性消失，導(dǎo)致糖尿病、結(jié)腸癌、心血管疾病等的發(fā)病風(fēng)險(xiǎn)增高，這一點(diǎn)在西方國(guó)家尤為明顯[35]。

益生元作為功能性食品的常見(jiàn)形式進(jìn)入人體后，能夠通過(guò)自身的新陳代謝作用產(chǎn)生有機(jī)酸，降低腸道中的酸堿度，從而達(dá)到抑制病原菌生長(zhǎng)的目的[34]。Vulevic等研究發(fā)現(xiàn)，65歲老年人每日服用低聚半乳糖5.5g，其自然殺傷性細(xì)胞和吞噬細(xì)胞的生物活性顯著增強(qiáng)[36]。動(dòng)物實(shí)驗(yàn)研究發(fā)現(xiàn)，膳食纖維可通過(guò)代謝產(chǎn)生酸性物質(zhì)等以降低結(jié)腸微環(huán)境的酸堿度，從而達(dá)到預(yù)防致病菌感染的目的[37]。因此，攝入益生元等功能性食品有益于調(diào)節(jié)人體腸道功能，維持腸道微生態(tài)穩(wěn)定，避免病原菌在腸道表面粘附、增殖、移位等。

3.2 改善礦物質(zhì)吸收能力

在礦物質(zhì)吸收方面，功能性食品也發(fā)揮了良好作用。研究顯示，低聚糖、低聚半乳糖和糖醇等對(duì)改善維生素、抗氧化化合物、礦物質(zhì)等微量元素的吸收能力具有良好效果[38]。這些物質(zhì)被代謝后所產(chǎn)生的SCFAs等能刺激結(jié)合蛋白的表達(dá)，利于礦物復(fù)合物的降解，提高腸道對(duì)礦物小分子的吸收效率并改善腸道微環(huán)境[39]，這些小分子也被充當(dāng)為輔因子參與到代謝循環(huán)中。另外，某些礦物質(zhì)在特定的環(huán)境下具有抗菌特性，表現(xiàn)出利于預(yù)防腸道感染的特性[40]。

SCFAs作為益生元常見(jiàn)的降解產(chǎn)物，能夠通過(guò)調(diào)節(jié)腸道內(nèi)的酸堿平衡以促進(jìn)腸上皮細(xì)胞對(duì)鈣的溶解與吸收[34]。Abrams等已經(jīng)證明，青少年每日補(bǔ)充適量的果聚糖（約8g）能夠有效提高鈣的吸收，每日鈣吸收量超過(guò)250mg的人群達(dá)到65%以上。 Whisner等研究發(fā)現(xiàn)，低聚半乳糖也能通過(guò)腸道菌群的代謝產(chǎn)生SCFAs，進(jìn)而促進(jìn)腸上皮細(xì)胞對(duì)鈣的吸收，同時(shí)腸道菌群中雙歧桿菌的豐度顯著升高[41]，他們?cè)趧?dòng)物實(shí)驗(yàn)中得到了相似的結(jié)論。這些結(jié)果表明，益生元等功能性食品在經(jīng)過(guò)腸道菌群的代謝后產(chǎn)生的小分子物質(zhì)能夠有效的調(diào)節(jié)腸道微環(huán)境的穩(wěn)態(tài)，同時(shí)能夠影響腸道菌群的多樣性變化。

3.3 改善免疫調(diào)節(jié)

益生元對(duì)免疫調(diào)節(jié)的影響涉及多種代謝通路。通過(guò)微生物群的作用，益生元大部分被降解為SCFAs，通過(guò)腸上皮細(xì)胞的吸收，SCFAs參與到機(jī)體的代謝循環(huán)中，從而影響了抗炎細(xì)胞因子的基因表達(dá)[42]。已有研究表明，機(jī)體中的SCFAs水平同炎癥性腸?。↖nflammatory Bowel Disease，IBD）、糖尿病和動(dòng)脈粥樣硬化等疾病的發(fā)生具有一定的相關(guān)性[43]。

研究表明，SCFAs能夠依賴(lài)丁酸鹽結(jié)合樹(shù)突細(xì)胞的GPR41、GPR43和GPR109A組分，并通過(guò)誘導(dǎo)組蛋白H3乙?；?、醛基脫氫酶的表達(dá)來(lái)促進(jìn)結(jié)腸Treg細(xì)胞的產(chǎn)生[44]，間接影響了相關(guān)細(xì)胞免疫因子對(duì)免疫系統(tǒng)的調(diào)節(jié)。動(dòng)物實(shí)驗(yàn)研究表明，SCFAs的水平降低和疾病的嚴(yán)重程度具有密切相關(guān)性。人們?cè)谂R床研究中發(fā)現(xiàn)，高產(chǎn)SCFAs的菌群豐度的降低能夠顯著提高腸炎的發(fā)生風(fēng)險(xiǎn)[45]。由此可見(jiàn)，結(jié)腸中SCFAs的產(chǎn)生是調(diào)節(jié)并維持天然免疫系統(tǒng)和適應(yīng)性免疫系統(tǒng)正常功能的關(guān)鍵因素[40]。

3.4 抗癌效果

影響細(xì)胞癌變的因素有很多，但其中最主要的是基因與環(huán)境（尤其是腸道微環(huán)境）的相互作用[46]。在癌癥中，由腸炎引起的結(jié)直腸癌發(fā)病率長(zhǎng)期居高不下，已有研究證明，結(jié)直腸癌的發(fā)病與腸道菌群的失衡有直接關(guān)系[40]。Femia等通過(guò)動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn)，乳雙歧桿菌和鼠李糖乳桿菌混合物能夠提高腸道丁酸鹽水平，降低癌變細(xì)胞的增殖、直腸癌發(fā)生相關(guān)酶的活性，從而降低大鼠的結(jié)腸癌發(fā)病率[47]。后續(xù)研究表明，長(zhǎng)鏈果聚糖和短鏈果糖能夠通過(guò)調(diào)節(jié)腸道的酸堿度來(lái)間接影響結(jié)腸腫瘤的發(fā)病率[48]。

Raman等研究發(fā)現(xiàn)，盲腸、結(jié)腸和糞便中腸道菌基因表達(dá)的改變，增加了結(jié)腸中微量營(yíng)養(yǎng)素的吸收，同時(shí)能夠調(diào)節(jié)異種代謝酶的活性和免疫應(yīng)答[49]。益生元在腸道菌群的作用下能夠產(chǎn)生SCFAs，從而表現(xiàn)出一定的抗癌活性[40, 50]，而常規(guī)的低碳水化合物的飲食結(jié)構(gòu)不僅會(huì)降低腸道內(nèi)SCFAs的水平，還會(huì)提高潛在有害代謝物（如支鏈脂肪酸、亞硝基化合物、硫化物和吲哚化合物等）的水平，導(dǎo)致細(xì)胞組織出現(xiàn)毒性或促炎性，引起慢性疾?。ㄈ缃Y(jié)直腸癌）的發(fā)展[40]。相比于SCFAs，丁酸鹽更能促進(jìn)結(jié)腸區(qū)域的代謝活動(dòng)，降低細(xì)胞癌變風(fēng)險(xiǎn)，能夠誘導(dǎo)結(jié)腸癌細(xì)胞的凋亡并抑制其增殖[51]。此外，乳酸、某些糖蛋白、膽汁酸等微生物胞外代謝物也對(duì)腸道菌群的代謝活性及特異性生理功能產(chǎn)生影響[52]。

4 腸道微生態(tài)平衡的維持策略

現(xiàn)今，關(guān)于維持腸道微生態(tài)平衡的方法有很多，比較成熟的有益生菌、糞菌移植和噬菌體策略。

4.1 益生菌

益生菌是一類(lèi)可定植在人體內(nèi)，通過(guò)調(diào)節(jié)宿主黏膜與系統(tǒng)免疫功能或腸道菌群的、對(duì)宿主有益的活性微生物。在日常生活中適當(dāng)攝入益生菌對(duì)延長(zhǎng)宿主壽命具有一定積極影響。目前已有研究證明，腸道中的益生菌對(duì)腸道微環(huán)境的穩(wěn)定具有一定的調(diào)節(jié)作用，同時(shí)對(duì)腸道病原菌的防御也具有一定的促進(jìn)作用[49]。目前最常用的益生菌主要有雙歧桿菌、乳酸桿菌和酵母菌等，其應(yīng)用范圍廣泛，涉及制藥、乳制品發(fā)酵、非乳制品添加劑等領(lǐng)域[53]。

益生菌的功能靈活多樣，能夠通過(guò)產(chǎn)生SCFAs以調(diào)節(jié)腸道環(huán)境的酸堿平衡，也能夠產(chǎn)生多種維生素（如維生素K），還能產(chǎn)生細(xì)菌素或其他具有抗菌活性的物質(zhì)。另外，益生菌在代謝過(guò)程中，還能夠調(diào)節(jié)巨噬細(xì)胞活性，細(xì)胞因子、免疫球蛋白水平以激活免疫反應(yīng)，或者通過(guò)調(diào)節(jié)腸上皮細(xì)胞的通透性來(lái)間接激活免疫系統(tǒng)[54]。研究表明，益生菌對(duì)預(yù)防過(guò)大的精神壓力以及某些慢性疾?。ㄈ鐒?dòng)脈粥樣硬化損傷、糖尿病等）也有一定的作用[55]，因此有針對(duì)性地開(kāi)發(fā)以益生菌為基礎(chǔ)的治療藥物已經(jīng)成為熱點(diǎn)之一，該研究方向主要聚焦于劑量、藥效時(shí)長(zhǎng)和菌株選擇等方面[56]。

當(dāng)前，已經(jīng)有研究表明益生菌對(duì)癌癥具有預(yù)防作用。益生菌在宿主體內(nèi)的代謝過(guò)程能產(chǎn)生與細(xì)胞誘變劑結(jié)合的小分子，它們能促進(jìn)這些潛在致癌因子的降解和代謝，避免正常細(xì)胞向癌細(xì)胞轉(zhuǎn)化。與此同時(shí)，產(chǎn)生的SCFAs等分子能刺激抗炎因子的分泌，為適當(dāng)?shù)拿庖邞?yīng)答[57] 做好準(zhǔn)備。另外，也有研究證實(shí)益生菌能夠減緩腹瀉、肥胖等疾病癥狀[55]，對(duì)Ⅱ型糖尿病、心血管疾病等也有良好的預(yù)防效果[58]。盡管益生菌在調(diào)節(jié)腸道微生物穩(wěn)態(tài)、人體免疫等方面具有很大潛力，但其實(shí)際應(yīng)用仍然受到臨床診斷等的多方阻礙。因此，基于多組學(xué)技術(shù)系統(tǒng)性地研究益生菌在人體代謝中的功能作用機(jī)制，是解決當(dāng)下應(yīng)用困境的主要方法。

4.2 糞菌移植

糞菌移植（Fecal Microbiota Transplantation， FMT），指的是將健康人的腸道菌移植到腸道感染者體內(nèi)，以恢復(fù)患者腸道菌群結(jié)構(gòu)及其功能的過(guò)程[59]。目前的研究及臨床應(yīng)用均已證明，F(xiàn)MT對(duì)炎癥性腸病、腸易激綜合征、結(jié)腸癌等腸道疾病導(dǎo)致的微生態(tài)失衡具有結(jié)構(gòu)與功能的重建作用[60]。此外，F(xiàn)MT也已經(jīng)廣泛應(yīng)用于對(duì)腹瀉、過(guò)敏性疾病、腫瘤等疾病的治療[61, 62]。

然而，F(xiàn)MT具體是如何影響腸道菌的結(jié)構(gòu)與功能，它治療某些疾病的具體機(jī)制是什么，這些問(wèn)題仍有待進(jìn)一步探究。比較容易接受的觀點(diǎn)是FMT在腸道中基于自身的代謝，產(chǎn)生了許多有益的小分子（如有機(jī)酸、醇、醛等）和活性肽，這些物質(zhì)一方面調(diào)節(jié)了腸道微環(huán)境的酸堿性，另一方面通過(guò)刺激宿主產(chǎn)生免疫反應(yīng)，加快了腸道微生物結(jié)構(gòu)與功能的恢復(fù)[63]。從實(shí)驗(yàn)室研究和臨床的初步應(yīng)用中可以判斷，F(xiàn)MT對(duì)某些腸道疾病的治療是有利的，但是在實(shí)際應(yīng)用中往往存在許多瓶頸和問(wèn)題。例如，如何規(guī)避FMT供體中病原菌的轉(zhuǎn)移，如何降低與腸道菌群有關(guān)的疾病（糖尿病、心血管疾病等）產(chǎn)生的風(fēng)險(xiǎn)。由此可見(jiàn)，對(duì)FMT治愈目標(biāo)疾病的具體機(jī)制的研究，將有助于開(kāi)發(fā)和應(yīng)用更加安全可靠有效的FMT藥劑。

4.3 噬菌體策略

在人類(lèi)疾病的產(chǎn)生中，病原菌并非是唯一的原因，噬菌體也是影響人類(lèi)健康的重要類(lèi)群[64]。噬菌體在人體中廣泛存在，它能顯著地影響腸道微生物的結(jié)構(gòu)和功能。因此在理論上，我們可以通過(guò)影響噬菌體來(lái)間接影響腸道微生物的多樣性及其功能的發(fā)揮，以達(dá)到維持腸道微環(huán)境“穩(wěn)態(tài)”的目的[64]。然而，人們?cè)谂R床指標(biāo)中發(fā)現(xiàn)，給藥后往往呈現(xiàn)噬菌體數(shù)量指數(shù)級(jí)擴(kuò)增的現(xiàn)象，且在動(dòng)力學(xué)的角度分析發(fā)現(xiàn)，噬菌體擴(kuò)增規(guī)律是非恒定的，但與給藥劑量、給藥時(shí)間、宿主免疫反應(yīng)強(qiáng)度具有密切相關(guān)性[65]。由于這種復(fù)雜的相關(guān)性，目前關(guān)于噬菌體介導(dǎo)的腸道微生物調(diào)節(jié)也僅停留在實(shí)驗(yàn)室研究階段。

5 展望

近年來(lái)，人們對(duì)腸道菌群的研究愈發(fā)廣泛和深入。腸道菌群能影響宿主的新陳代謝、生理和免疫系統(tǒng)。腸道菌群的組成受到多種因素的影響，如飲食、年齡、藥物和生活方式等。腸道菌群結(jié)構(gòu)和功能的改變直接影響人體的健康，對(duì)多種疾病的發(fā)生和發(fā)展起著重要作用。因此，對(duì)腸道菌群和宿主之間的關(guān)系進(jìn)行進(jìn)一步系統(tǒng)性的研究是非常必要的。此外，在臨床應(yīng)用中，如益生元輔助的食療和糞菌移植等手段在腸道疾病的治療過(guò)程中具有巨大潛力。結(jié)合不同學(xué)科的研究技術(shù)和方法，深入探究腸道菌群與人體健康的相互關(guān)系，開(kāi)發(fā)應(yīng)用基于腸道菌群功能的食品和藥物，對(duì)胃腸道疾病的預(yù)防與治療具有重要意義。

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基本信息

中圖分類(lèi)號(hào): R333.3
文獻(xiàn)標(biāo)識(shí)碼: A
DOI: 10.13885/j.issn.2096-8965.20210206
文章編號(hào): 2096-8965(2021)02-0039-07

基金信息

蘭州大學(xué)第二醫(yī)院萃英科技創(chuàng)新計(jì)劃 (2020QN-08)；

引用信息

稿件歷史

收稿日期: 2020-11-25