母乳微生物群

母乳微生物群(Human Milk Microbiota)也稱為母乳益生菌(Human Milk Probiotics, HMP),是在人類母乳乳腺中的微生物群英語Microbiota[1]。以往曾認為母乳無菌英語Asepsis[1][2],不過近來不論透過微生物培養,或是其他的技術,都已確定母乳中含有許多和人類微生物群系不同的細菌[3][4][5]

母乳樣本中的微生物

母乳微生物群可能是嬰兒體內,偏利共生互利共生,或潛在益生菌腸道菌群的來源[2]世界衛生組織(WHO)對益生菌的定義是:「當達到足夠數量時,能對宿主的健康有益的微生物。」[6]

來源

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母乳中的微生物群,以及十種最常見的菌種

母乳是乳酸菌的自然來源,初生嬰兒透過母乳餵養可以獲取乳酸菌,母乳也可視為是共生食物[7]。健康母親的母乳中,正常細菌含量約為每毫升103菌落形成單位(CFU)[8]。母乳中的菌種非常複雜[8]。在所有母乳樣本中可檢測的超過100種可操作的分類單位英語Taxonomy (biology)中,只有9種菌類是所有樣本共有的(鏈球菌葡萄球菌沙雷氏菌屬假單胞菌棒狀桿菌英語Corynebacterium羅爾斯頓菌英語Ralstonia丙酸桿菌鞘氨醇單胞菌英語Sphingomonas慢生根瘤菌科),但個別母體裏的母乳細菌群落多半都是穩定的[9]。母乳是嬰兒腸道中葡萄球菌、鏈球菌、乳酸菌、雙歧桿菌、丙酸桿菌、棒狀桿菌和其他相關革蘭氏陽性菌的來源[2]

成份

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以前科學界都認為母乳是無菌的,後來才從健康女性身上,以衛生方式採集的母乳中發現了乳桿菌[7]。研究指出母乳中的多個菌類,包括乳桿菌屬,葡萄球菌屬,腸球菌屬和雙歧桿菌屬的細菌菌株,會透過母乳餵哺傳到嬰兒體內,因此由母乳餵哺的嬰兒的腸道微生物群成分與其母親的母乳成分相近似.[2]。研究亦指出母乳微生物群及嬰兒腸道微生物群具有相似性,因此認為飲食攝取(包括母乳益生菌)可以幫助建立嬰兒腸道微生物群,也對其免疫發展有益[10]

母乳樣本中常見的菌種有雙歧桿菌屬乳桿菌屬葡萄球菌屬鏈球菌屬擬桿菌屬梭菌屬微球菌屬腸球菌埃希氏菌屬[3][3][5]。有關母乳的元基因組學分析發現其中主要以葡萄球菌屬、擬桿菌屬及緩慢愛德華氏菌英語Edwardsiella為主[11][12]。母乳微生物群會隨族群及女性的個體差異而不同[13],不過在一個以美國女性為基礎的研究中,觀察到在其研究樣本中有相同的九種菌種,因此認為在母乳微生物群中有主要菌種,至少在美國是這樣的情形[8]。人類初乳中的菌種比一般母乳的更加分散[1][14]

在所有母乳細菌當中,乳桿菌為最常見的菌種,並且由於其潛在的益生菌作用而受到關注。在乳桿菌中,可以分離出三種有益生功效的乳桿菌種,分別是發酵乳桿菌英語L. fermentum (CECT 5716)、加氏乳桿菌英語L. gasseri (CECT 5714) 及唾液乳桿菌英語L. salivarius (CECT 5713)[15],其中發酵乳桿菌是人類母乳中最常見的菌類之一[9],它是在1994年從人類糞便樣本分析中發現的,對消化道酸鹼度及膽汁具有極高的耐受性,對於其益生菌作用極為明顯[16]。由於其免疫增強和抗微生物能力,發酵乳桿菌的抗感染特性亦見顯赫[17]。早期有在配方奶粉中加入發酵乳桿菌,宣稱安全,適合一到六個月的嬰兒[18],且適合長期使用[19]

唾液乳桿菌CECT 5713源於一個月大由母乳餵哺嬰孩的糞便樣本中抽取而來,研究指出由母乳餵哺的嬰孩的腸道微生物群反映了其母親的乳汁細菌成分。 經RAPD和PFGE分析顯示,唾液乳桿菌存在於天然母乳中,並會生產乙酸鹽,L-乳酸鹽和過氧化氫,或有助解釋其在研究中對大部分標記生物的抗菌活性功效。 再者,唾液乳桿菌在模擬腸道極端環境下仍有高存活率[20]

加氏乳桿菌 CECT5714從腸道樣本中抽取而來,屬於嗜酸乳桿菌複合物的一種,被廣泛運用於不同的乳製品中,例如奶酪等。 一個雙盲隨機對照研究發現加氏乳桿菌對過敏反應中涉及的免疫參數有其影響,例如減少血漿IgE的數量和增加調節T細胞。 含有加氏乳桿菌的益生菌產品還增強了先天性和特異性免疫參數,可以普遍改善兒童的健康狀況[21]

起源

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有關母乳微生物群的啟源還不完全清楚[1],目前有許多相關的假說。母乳中的微生物群可能是源自乳房的皮膚微生物群英語skin flora[22][23],或是嬰兒的口腔微生物群英語Oral microbiology[8][12][24][25]。在哺乳或是嬰兒吸吮乳頭時的母乳倒流也可能導致乳腺中的細菌形成[26],透過紅外線攝影英語infrared photography發現在哺乳時有一定程度的母乳倒流[27]。另外,微生物群也可能從母親的消化道,透過樹突狀細胞產生的腸-乳途徑(entero-mammary pathway)進入乳腺[2][3][28]

環境因素

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人體母乳益生菌會收到不同因素的影響,例如母親自身的身體質量指數(BMI)、嬰兒性別、生產方式及母乳餵哺模式等等[29][30]。Soto等人的研究表明,在懷孕和哺乳期間未接受任何抗生素治療的婦女的母乳中有更多的乳酸桿菌和雙歧桿菌含量[9]

母乳寡糖英語Human milk oligosaccharide(HMO)是母乳中的主要成份之一,屬於益生元,可以增進有益的雙歧桿菌和擬桿菌的成長[31][32][33]

產婦的健康情形

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產婦的健康情形會影響母乳中的微生物組。身體質量指數較高及比較肥胖的產,其雙歧桿菌和葡萄球菌的數量會不同,細菌的多樣性也會比較少[14][34]乳糜瀉產婦母乳中的擬桿菌和雙歧桿菌含量會比較少[35]。HIV陽性的婦女其母乳中的微生物多樣性較大,而乳桿菌濃度也比較高[36]乳腺炎和母乳中的微生物組的種類較少,微生物分類層級的變化,以及厭氧生物的減少有關[37][38][12]

足月生產及早產的孕婦,其母乳中微生物群的成份也有不同,足月生產的孕婦,其母乳中的腸球菌比早產孕婦要少,雙歧桿菌種類含量也比較高[39]

很少研究去分析母親飲食對母乳微生物群的影響[1],不過可以確定飲食會影響母乳中的成份組成,例如脂質分佈英語lipid profile[40][41],而母乳成份會影響微生物組成[1]。母親飲食中脂肪及醣類的變化會影響母乳微生物群中的分類組成[42]

母乳微生物中的分類組成和多樣程度也依母親的地理位置有很大的不同[1][13][8],不過還需要有更多不同地方婦女參與研究,以瞭解不同地區的差異[1]

產婦在圍產期是否使用抗生素,和母乳中乳酸桿菌,雙歧桿菌,葡萄球菌和真桿菌英語Eubacterium的出現率有關[9][43][44]

中非共和國的研究發現母乳中的微生物多樣性越廣,越會觀察到母嬰二人組英語Dyad (sociology)的社會網絡密度[45]

哺乳階段

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母乳中的微生物群也會隨哺乳階段而不同,初乳中的微生物群多樣性比較高[1][14]。母乳中微生物群的的分類組成也有不同。一開始的母乳,其中的微生物以魏斯氏菌屬明串珠菌屬、葡萄球菌、鏈球菌、及乳酸乳球菌為主[14],後期的母乳的微生物主要是韋榮氏球菌屬普雷沃氏菌屬、纖毛菌、乳桿菌屬、葡萄球菌、雙歧桿菌及腸球菌屬[14][39]

對健康的影響

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一般認為哺乳是建立嬰兒腸道微生物群的重要方式[46]。餵母乳的嬰兒腸道微生物群的種類較少,其中雙歧桿菌及乳桿菌屬的量會比餵配方奶的嬰兒要多,潛在的病原體會比餵配方奶的嬰兒要少[47][48][49]。母乳中的細菌會透過競爭性來排除有害細菌,降低嬰兒感染的風險[50][51],並產生消除病原性菌株的抗菌化合物[52][53][54][50]。有些乳酸桿菌和雙歧桿菌會因為母乳寡糖而促進其成長[55],可以形成嬰兒腸道的健康代謝及免疫機能[56][57][2][58]

對哺乳女性的益處

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乳腺炎是與哺乳有關的常見炎症性疾病。 兩項不同的研究表明,發酵乳桿菌可以改善乳腺炎(哺乳時常出現的疾病),其方式是降低鏈球菌負荷量,一般認為鏈球菌是乳腺炎的危險因子及病因[59]

對嬰兒的益處

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餵母乳的嬰兒受到感染的比例比較低,有可能是因為母乳產生的腸道菌群的調節作用[60]。餵母乳的嬰兒,其腸道菌群中乳酸桿菌及雙歧桿菌的比例比餵配方奶的嬰兒要高,其中致病菌的比例也比較低[61]。Maldonado等人的研究發現,若嬰兒之後喝的配方奶中有較多的發酵乳酸桿菌,其腸道及呼吸道的不適及感染比例可降低72%,因此這類的配方奶可能可以預防新生兒常見的腸道及上呼吸道傳染病[18]

母奶益生菌也可以提高嬰兒體內細菌的定殖益菌的比例,並且支持嬰兒還不成熟的免疫系統[62]。目前已知乳酸桿菌及雙歧桿菌在腸道中定殖,並且和其他細菌競爭養份,可以抑制致病菌(例如傷寒沙門氏菌英語Salmonella Typhimuriumm產氣莢膜梭菌)的成長,避免這些細菌黏沾在腸道上。腸道內偏利共生的定殖也可以維持免疫系統的穩態,這些細菌會刺激輔助型T細胞1反應,並且對抗輔助型T細胞2對新生兒免疫系統的反應,減少發炎反應(例如壞死性小腸結腸炎)的發生率[15]

嬰兒若有哭鬧症狀,有可能是因為腸道中的細菌不平衡,有哭鬧症狀的嬰兒,檢查其糞便檢體,其大腸桿菌會比沒有哭鬧症狀的嬰兒要多,而乳酸桿菌數量會比較少[63]。另一方面,益生菌可以影響腸蠕動英語intestinal motility感覺神經元,也對腸的收縮活動性有幫助,也可以發揮消炎的作用[62]

免疫調節特性

從初生嬰兒首次接觸微生物的時候,便會開始建構嬰兒自身的腸道微生物群,這個建構過程對於免疫系統的發展極為重要。 腸道微生物群的不同成分會影響具有重要免疫組分的某些疾病的發生率,例如過敏或炎症等。益生菌的免疫調節作用在動物病理模型中也得到體現,從人體提取的益生菌種可以有助提升老鼠的天然和獲得性免疫反應[64]。再者,人體母乳益生菌中的加氏乳桿菌及棒狀乳桿菌亦在動物實驗模型中降低了牛乳蛋白過敏的病發率及嚴重性[65]。最近研究指出,發酵乳桿菌在動物實驗模型中對腸道炎症有正面影響,有助減輕炎症反應及減低腸道損傷風險[66]

研究指出,患有絞痛症狀的兒童可能存在腸道微生物群的不平衡,在對糞便樣本的分析發現,與未患絞痛的兒童相比,患有絞痛症狀的嬰兒的大腸菌群計數較高,但乳酸桿菌計數則較低[65]。另一方面,益生菌已被證明可影響腸道運動和感覺神經元,以及腸道的收縮活動,並發揮抗炎作用[67]

抗菌作用

對細菌和病毒感染的保護是益生菌最常見的聲明之一,現時已經有不同的研究解釋了益生菌抗微生物活性的功效。 一些試管研究表明某些益生菌菌株能夠產生對抗微生物的化合物,如過氧化氫和有機酸等,它們可抑制大腸桿菌,沙門氏菌單核細胞增生李斯特菌的生長[68]

研究亦指出母乳中的菌類能夠通過增加粘蛋白產生和降低腸滲透性來改善腸屏障功能,可是與腸道產毒細菌競爭營養物質和上皮細胞腸道受體結合位點才是益生菌主要的抗感染機制。 舉例而言,乳酸桿菌和雙歧桿菌可通過定植於兒童腸道的和與病原微生物競爭營養來抑制病原微生物如鼠傷寒沙門氏菌和產氣莢膜梭菌的生長,從而防止其粘附於腸道中。 共生細菌在腸道定植也對於維持免疫系統的穩定起着至關重要的作用。 這些細菌能刺激TH1反應並抵消新生兒免疫系統TH2反應,從而降低壞死性小腸炎等炎症過程的發生率[69]

對胃腸道的好處

研究指出,添加了母乳益生菌及益生元嬰幼兒配方奶粉,比僅添加了益生元的能減少腸胃疾病感染達71%,當下人們越來越關注腸道微生物群對於改善胃腸功能和營養吸收的運作原理,不同研究亦指出人體母乳益生菌會在腸道定植,因此增加了糞便樣本的乳桿菌數量,從而改變腸道微生物群成分[70]。再者,分子分析亦表明,這些細菌在人體腸道中具有代謝活性,增強了功能性代謝物如丁酸鹽的產生,丁酸鹽是結腸細胞的主要能量來源,在調節腸道功能中起着至關重要的作用,糞便水分和糞便頻率和體積的增加亦可能與丁酸的糞便濃度增加相關。 相似地,在一個兒童臨床實驗中,加氏乳桿菌的使用亦使糞便乳桿菌數量增加。 在同一實驗中,接受了益生菌療程的兒童的糞便水中含有的細胞毒性低於對照兒童的樣本。 另一臨床實驗表面加入了鼠李糖乳桿菌LGG的嬰兒配方奶粉可以改善新生兒的生長模式,同時表明嬰兒營養素的生物利用度亦被提高[71]

相關條目

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參考資料

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