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母乳微生物群

维基百科,自由的百科全书
母乳样本中的微生物

母乳微生物群(Human Milk Microbiota)也称为母乳益生菌(Human Milk Probiotics, HMP),是在人类母乳乳腺中的微生物群英语Microbiota[1]。以往曾认为母乳无菌英语Asepsis[1][2],不过近来不论透过微生物培养,或是其他的技术,都已确定母乳中含有许多和人类微生物群系不同的细菌[3][4][5]

母乳微生物群可能是婴儿体内,偏利共生互利共生,或潜在益生菌肠道菌群的来源[2]世界卫生组织(WHO)对益生菌的定义是:“当达到足够数量时,能对宿主的健康有益的微生物。”[6]

来源

母乳中的微生物群,以及十种最常见的菌种

母乳是乳酸菌的自然来源,初生婴儿透过母乳喂养可以获取乳酸菌,母乳也可视为是共生食物[7]。健康母亲的母乳中,正常细菌含量约为每毫升103菌落形成单位(CFU)[8]。母乳中的菌种非常复杂[8]。在所有母乳样本中可检测的超过100种可操作的分类单位英语Taxonomy (biology)中,只有9种菌类是所有样本共有的(链球菌葡萄球菌沙雷氏菌属假单胞菌棒状杆菌英语Corynebacterium罗尔斯顿菌英语Ralstonia丙酸杆菌鞘氨醇单胞菌英语Sphingomonas慢生根瘤菌科),但个别母体里的母乳细菌群落多半都是稳定的[9]。母乳是婴儿肠道中葡萄球菌、链球菌、乳酸菌、双歧杆菌、丙酸杆菌、棒状杆菌和其他相关革兰氏阳性菌的来源[2]

成分

以前科学界都认为母乳是无菌的,后来才从健康女性身上,以卫生方式采集的母乳中发现了乳杆菌[7]。研究指出母乳中的多个菌类,包括乳杆菌属,葡萄球菌属,肠球菌属和双歧杆菌属的细菌菌株,会透过母乳喂哺传到婴儿体内,因此由母乳喂哺的婴儿的肠道微生物群成分与其母亲的母乳成分相近似.[2]。研究亦指出母乳微生物群及婴儿肠道微生物群具有相似性,因此认为饮食摄取(包括母乳益生菌)可以帮助建立婴儿肠道微生物群,也对其免疫发展有益[10]

母乳样本中常见的菌种有双歧杆菌属乳杆菌属葡萄球菌属链球菌属拟杆菌属梭菌属微球菌属肠球菌埃希氏菌属[3][3][5]。有关母乳的元基因组学分析发现其中主要以葡萄球菌属、拟杆菌属及缓慢爱德华氏菌英语Edwardsiella为主[11][12]。母乳微生物群会随族群及女性的个体差异而不同[13],不过在一个以美国女性为基础的研究中,观察到在其研究样本中有相同的九种菌种,因此认为在母乳微生物群中有主要菌种,至少在美国是这样的情形[8]。人类初乳中的菌种比一般母乳的更加分散[1][14]

在所有母乳细菌当中,乳杆菌为最常见的菌种,并且由于其潜在的益生菌作用而受到关注。在乳杆菌中,可以分离出三种有益生功效的乳杆菌种,分别是发酵乳杆菌英语L. fermentum (CECT 5716)、加氏乳杆菌英语L. gasseri (CECT 5714) 及唾液乳杆菌英语L. salivarius (CECT 5713)[15],其中发酵乳杆菌是人类母乳中最常见的菌类之一[9],它是在1994年从人类粪便样本分析中发现的,对消化道酸碱度及胆汁具有极高的耐受性,对于其益生菌作用极为明显[16]。由于其免疫增强和抗微生物能力,发酵乳杆菌的抗感染特性亦见显赫[17]。早期有在配方奶粉中加入发酵乳杆菌,宣称安全,适合一到六个月的婴儿[18],且适合长期使用[19]

唾液乳杆菌CECT 5713源于一个月大由母乳喂哺婴孩的粪便样本中抽取而来,研究指出由母乳喂哺的婴孩的肠道微生物群反映了其母亲的乳汁细菌成分。 经RAPD和PFGE分析显示,唾液乳杆菌存在于天然母乳中,并会生产乙酸盐,L-乳酸盐和过氧化氢,或有助解释其在研究中对大部分标记生物的抗菌活性功效。 再者,唾液乳杆菌在模拟肠道极端环境下仍有高存活率[20]

加氏乳杆菌 CECT5714从肠道样本中抽取而来,属于嗜酸乳杆菌复合物的一种,被广泛运用于不同的乳制品中,例如奶酪等。 一个双盲随机对照研究发现加氏乳杆菌对过敏反应中涉及的免疫参数有其影响,例如减少血浆IgE的数量和增加调节T细胞。 含有加氏乳杆菌的益生菌产品还增强了先天性和特异性免疫参数,可以普遍改善儿童的健康状况[21]

起源

有关母乳微生物群的启源还不完全清楚[1],目前有许多相关的假说。母乳中的微生物群可能是源自乳房的皮肤微生物群英语skin flora[22][23],或是婴儿的口腔微生物群英语Oral microbiology[8][12][24][25]。在哺乳或是婴儿吸吮乳头时的母乳倒流也可能导致乳腺中的细菌形成[26],透过红外线摄影英语infrared photography发现在哺乳时有一定程度的母乳倒流[27]。另外,微生物群也可能从母亲的消化道,透过树突状细胞产生的肠-乳途径(entero-mammary pathway)进入乳腺[2][3][28]

环境因素

人体母乳益生菌会收到不同因素的影响,例如母亲自身的身体质量指数(BMI)、婴儿性别、生产方式及母乳喂哺模式等等[29][30]。Soto等人的研究表明,在怀孕和哺乳期间未接受任何抗生素治疗的妇女的母乳中有更多的乳酸杆菌和双歧杆菌含量[9]

母乳寡糖英语Human milk oligosaccharide(HMO)是母乳中的主要成分之一,属于益生元,可以增进有益的双歧杆菌和拟杆菌的成长[31][32][33]

产妇的健康情形

产妇的健康情形会影响母乳中的微生物组。身体质量指数较高及比较肥胖的产,其双歧杆菌和葡萄球菌的数量会不同,细菌的多样性也会比较少[14][34]乳糜泻产妇母乳中的拟杆菌和双歧杆菌含量会比较少[35]。HIV阳性的妇女其母乳中的微生物多样性较大,而乳杆菌浓度也比较高[36]乳腺炎和母乳中的微生物组的种类较少,微生物分类层级的变化,以及厌氧生物的减少有关[37][38][12]

足月生产及早产的孕妇,其母乳中微生物群的成分也有不同,足月生产的孕妇,其母乳中的肠球菌比早产孕妇要少,双歧杆菌种类含量也比较高[39]

很少研究去分析母亲饮食对母乳微生物群的影响[1],不过可以确定饮食会影响母乳中的成分组成,例如脂质分布英语lipid profile[40][41],而母乳成分会影响微生物组成[1]。母亲饮食中脂肪及糖类的变化会影响母乳微生物群中的分类组成[42]

母乳微生物中的分类组成和多样程度也依母亲的地理位置有很大的不同[1][13][8],不过还需要有更多不同地方妇女参与研究,以了解不同地区的差异[1]

产妇在围产期是否使用抗生素,和母乳中乳酸杆菌,双歧杆菌,葡萄球菌和真杆菌英语Eubacterium的出现率有关[9][43][44]

中非共和国的研究发现母乳中的微生物多样性越广,越会观察到母婴二人组英语Dyad (sociology)的社会网络密度[45]

哺乳阶段

母乳中的微生物群也会随哺乳阶段而不同,初乳中的微生物群多样性比较高[1][14]。母乳中微生物群的的分类组成也有不同。一开始的母乳,其中的微生物以魏斯氏菌属明串珠菌属、葡萄球菌、链球菌、及乳酸乳球菌为主[14],后期的母乳的微生物主要是韦荣氏球菌属普雷沃氏菌属、纤毛菌、乳杆菌属、葡萄球菌、双歧杆菌及肠球菌属[14][39]

对健康的影响

一般认为哺乳是建立婴儿肠道微生物群的重要方式[46]。喂母乳的婴儿肠道微生物群的种类较少,其中双歧杆菌及乳杆菌属的量会比喂配方奶的婴儿要多,潜在的病原体会比喂配方奶的婴儿要少[47][48][49]。母乳中的细菌会透过竞争性来排除有害细菌,降低婴儿感染的风险[50][51],并产生消除病原性菌株的抗菌化合物[52][53][54][50]。有些乳酸杆菌和双歧杆菌会因为母乳寡糖而促进其成长[55],可以形成婴儿肠道的健康代谢及免疫机能[56][57][2][58]

对哺乳女性的益处

乳腺炎是与哺乳有关的常见炎症性疾病。 两项不同的研究表明,发酵乳杆菌可以改善乳腺炎(哺乳时常出现的疾病),其方式是降低链球菌负荷量,一般认为链球菌是乳腺炎的危险因子及病因[59]

对婴儿的益处

喂母乳的婴儿受到感染的比例比较低,有可能是因为母乳产生的肠道菌群的调节作用[60]。喂母乳的婴儿,其肠道菌群中乳酸杆菌及双歧杆菌的比例比喂配方奶的婴儿要高,其中致病菌的比例也比较低[61]。Maldonado等人的研究发现,若婴儿之后喝的配方奶中有较多的发酵乳酸杆菌,其肠道及呼吸道的不适及感染比例可降低72%,因此这类的配方奶可能可以预防新生儿常见的肠道及上呼吸道传染病[18]

母奶益生菌也可以提高婴儿体内细菌的定殖益菌的比例,并且支持婴儿还不成熟的免疫系统[62]。目前已知乳酸杆菌及双歧杆菌在肠道中定殖,并且和其他细菌竞争养份,可以抑制致病菌(例如伤寒沙门氏菌英语Salmonella Typhimuriumm产气荚膜梭菌)的成长,避免这些细菌黏沾在肠道上。肠道内偏利共生的定殖也可以维持免疫系统的稳态,这些细菌会刺激辅助型T细胞1反应,并且对抗辅助型T细胞2对新生儿免疫系统的反应,减少发炎反应(例如坏死性小肠结肠炎)的发生率[15]

婴儿若有哭闹症状,有可能是因为肠道中的细菌不平衡,有哭闹症状的婴儿,检查其粪便检体,其大肠杆菌会比没有哭闹症状的婴儿要多,而乳酸杆菌数量会比较少[63]。另一方面,益生菌可以影响肠蠕动英语intestinal motility感觉神经元,也对肠的收缩活动性有帮助,也可以发挥消炎的作用[62]

免疫调节特性

从初生婴儿首次接触微生物的时候,便会开始建构婴儿自身的肠道微生物群,这个建构过程对于免疫系统的发展极为重要。 肠道微生物群的不同成分会影响具有重要免疫组分的某些疾病的发生率,例如过敏或炎症等。益生菌的免疫调节作用在动物病理模型中也得到体现,从人体提取的益生菌种可以有助提升老鼠的天然和获得性免疫反应[64]。再者,人体母乳益生菌中的加氏乳杆菌及棒状乳杆菌亦在动物实验模型中降低了牛乳蛋白过敏的病发率及严重性[65]。最近研究指出,发酵乳杆菌在动物实验模型中对肠道炎症有正面影响,有助减轻炎症反应及减低肠道损伤风险[66]

研究指出,患有绞痛症状的儿童可能存在肠道微生物群的不平衡,在对粪便样本的分析发现,与未患绞痛的儿童相比,患有绞痛症状的婴儿的大肠菌群计数较高,但乳酸杆菌计数则较低[65]。另一方面,益生菌已被证明可影响肠道运动和感觉神经元,以及肠道的收缩活动,并发挥抗炎作用[67]

抗菌作用

对细菌和病毒感染的保护是益生菌最常见的声明之一,现时已经有不同的研究解释了益生菌抗微生物活性的功效。 一些试管研究表明某些益生菌菌株能够产生对抗微生物的化合物,如过氧化氢和有机酸等,它们可抑制大肠杆菌,沙门氏菌单核细胞增生李斯特菌的生长[68]

研究亦指出母乳中的菌类能够通过增加粘蛋白产生和降低肠渗透性来改善肠屏障功能,可是与肠道产毒细菌竞争营养物质和上皮细胞肠道受体结合位点才是益生菌主要的抗感染机制。 举例而言,乳酸杆菌和双歧杆菌可通过定植于儿童肠道的和与病原微生物竞争营养来抑制病原微生物如鼠伤寒沙门氏菌和产气荚膜梭菌的生长,从而防止其粘附于肠道中。 共生细菌在肠道定植也对于维持免疫系统的稳定起着至关重要的作用。 这些细菌能刺激TH1反应并抵消新生儿免疫系统TH2反应,从而降低坏死性小肠炎等炎症过程的发生率[69]

对胃肠道的好处

研究指出,添加了母乳益生菌及益生元婴幼儿配方奶粉,比仅添加了益生元的能减少肠胃疾病感染达71%,当下人们越来越关注肠道微生物群对于改善胃肠功能和营养吸收的运作原理,不同研究亦指出人体母乳益生菌会在肠道定植,因此增加了粪便样本的乳杆菌数量,从而改变肠道微生物群成分[70]。再者,分子分析亦表明,这些细菌在人体肠道中具有代谢活性,增强了功能性代谢物如丁酸盐的产生,丁酸盐是结肠细胞的主要能量来源,在调节肠道功能中起着至关重要的作用,粪便水分和粪便频率和体积的增加亦可能与丁酸的粪便浓度增加相关。 相似地,在一个儿童临床实验中,加氏乳杆菌的使用亦使粪便乳杆菌数量增加。 在同一实验中,接受了益生菌疗程的儿童的粪便水中含有的细胞毒性低于对照儿童的样本。 另一临床实验表面加入了鼠李糖乳杆菌LGG的婴儿配方奶粉可以改善新生儿的生长模式,同时表明婴儿营养素的生物利用度亦被提高[71]

相关条目

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