BMC MICROBIOL:预防结直肠癌,要从娃娃抓起!致结直肠癌相关大肠杆菌可经母婴传播

2021-09-18 MedSci原创 MedSci原创

能产生致CRC毒素的clb +大肠杆菌或早在新生儿早期阶段就通过母婴密切接触从母亲传播到新生儿,因此如果能减少大肠杆菌从成人传播到婴儿,或许就能降低CRC在人群中的发病率。

结直肠癌(CRC)是世界上第三大常见癌症,也是第二大癌症死亡原因。据预测,到2030年大约有220万将患上、并有110万人将死于CRC。为了减少CRC的发病率和死亡率,识别和减轻导致CRC发病的危险因素来源至关重要。某些携带基因簇clb(也称为pks) 的大肠杆菌菌株与可能致结直肠癌的基因毒素colibactin的生物合成有关,了解这种大肠杆菌菌株的特性和colibactin致癌的分子机制,可以为我们提供早期诊断或预防结肠直肠癌的机会。

众所周知,新生儿在出生后与母亲阴道和皮肤微生物接触时,开始形成自己的肠道微生物群。一项基于大鼠模型的研究表明,共生大肠杆菌菌株可从母亲传播给新生儿其中新生儿肠道中基因毒性大肠杆菌的早期定植可能会影响成年后的肠道稳态,从而增加罹患结直肠癌和其他免疫介导疾病的风险。本研究旨在clb+大肠杆菌是否会从母亲或密切照顾者传播给婴儿,如果是的话,是通过什么来源和媒介传递给婴儿的。

之前的研究检验了日本东京都市区的223名健康成人的粪便样本,其中60名参与者(26.9%)clb +大肠杆菌阳性。而本次研究检查了51名婴儿(25名男性,26名女性),在研究对象出生时或出生后2-3天内收集一组粪便,出生后一个月收集另一组粪便,并采用PCR检测样品中是否存在clbB基因。其中51例新生儿中有8例(15.7%)的检测样本在出生后立即携带clb +大肠杆菌。在出生后一个月,51例新生儿有16例(31.4%)clb +大肠杆菌阳性(图1 b,车道7、10、17、18日,22日,25日,26日,27日,28日,29日,31日,34岁,35岁,45岁,47岁,49岁,图2),提示有8名(15.7%)新生儿在出生后一个月内获得 clb +大肠杆菌菌株定植。clb +大肠杆菌阳性率从15.7%上升到第1月末的31.4%,与健康成人检测出的26.9%水平相当。

婴儿粪便标本中存在clb +大肠杆菌的PCR分析

新生儿clb +和clb -的检出率

围产期传播可能发生在子宫内、产道或母乳喂养时。由于大肠杆菌在健康妊娠中的宫内传播并不常见,本研究调查了分娩方法与新生儿的clb阳性比率的相关性。由于预计分娩方法只会影响新生儿与几天大婴儿的clb阳性比率,因此我们没有使用出生后一个月收集的数据。关于产道传播,通过自然分娩出生的婴儿中有7 / 8(87.5%)检出clb +大肠杆菌,相比之下8例剖宫产婴儿中只有1例(12.5%)clb阳性。

51例接受检查的婴儿中,clb +大肠杆菌感染频率与其分娩方式的相关性,婴儿人数(n = 51)

关于母乳喂养的传播,本研究探讨了婴儿喂养方式与clb阳性率的相关性。我们筛查了43名出生时至出生后几天内被确定为clb阴性的婴儿。一个月后,43例clb阴性婴儿中有8例clb阳性,其余35例(81.4%)通过粪便标本PCR检测未受影响)。总共有26名婴儿接受单独的母乳,17名婴儿是配方奶和母乳的混合喂养。在8例clb阳性婴儿中,7例严格母乳喂养超过一个月,只有1名新生儿在一个月内接受了配方奶粉和母乳的混合喂养。仅母乳喂养的婴儿中有26.9%clb阳性,而混合喂养的婴儿中只有5.9%clb阳性。

在出生时或出生后2 - 3天检测为阴性的新生儿中,clb +与clb -的诊断频率与提供一个月的混合喂养或仅母乳喂养之间的相关性

为了检查看护者喂养或处理食品是否在向婴儿传播大肠杆菌方面发挥作用,本研究对从食品中收集58个不同样本进行筛查。除了牛胃样本都未能检测出大肠杆菌然而在牛胃样本中发现的菌株属于植物群B1,而迄今为止从人类受试者中分离出的所有大肠杆菌菌株都属于B2。最后,在这项研究中,我们没有观察到婴儿出生时或出生后一个月之间大肠杆菌感染率有任何差异。

采用PCR方法对日本58份常见食品样品进行clb +大肠杆菌筛查

总的来说,在所研究的一个月大婴儿中大肠杆菌的感染率为31.4%,与健康成年人的感染率相似。自然分娩出生的婴儿比剖腹产婴儿的阳性率高,严格母乳喂养比混合喂养的孩子表现出更高的阳性率。但混合喂养中也含有母乳,说明母乳本身并不是clb +大肠杆菌的来源。而对日本人常用食物的简单调查表明,clb +大肠杆菌可能不是通过喂养者处理的受污染的食物传播的。相反,潜在致癌性大肠杆菌株感染的最可能途径似乎是通过母亲和婴儿之间的直接皮肤对皮肤接触,或母乳喂养中的皮肤对嘴接触。分娩方法也是如此,自然分娩的婴儿与母亲的皮肤直接接触的频率比剖腹产的婴儿高得多。

综上,clb +大肠杆菌可能在新生儿早期阶段就通过母婴密切接触从母亲传播到新生儿,因此如果能减少大肠杆菌从成人传播到婴儿,或许就能降低CRC在人群中的发病率。例如,我们能据此开发出早期预防CRC的措施,包括预防分娩期间感染,向准夫妻提供咨询帮助他们了解病情,测试阴道定植菌群并进行干预,选择剖腹产帮助分娩等。当然,如果未来的研究能够建立根除clb +大肠杆菌的安全方法,就可以在怀孕前或怀孕稳定期进行以减少clb +大肠杆菌的母婴传播。

 

原文来源:

Tsunematsu et al.Mother-to-infant transmission of the carcinogenic colibactin-producing bacteria.BMC Microbiology (2021) 21:235
https://doi.org/10.1186/s12866-021-02292-1

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    2022-05-01 sunylz
  4. 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    2021-10-21 xjy02
  5. 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  6. 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  7. 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createdAvatar=https://img.medsci.cn/20211015/8d56d5fcf5414c569fbb9517e4db6199/10eae43200f34453a94bd30c453d4254.jpg, createdBy=e2255212929, createdName=14763726m01暂无昵称, createdTime=Sat Sep 18 17:55:40 CST 2021, time=2021-09-18, status=1, ipAttribution=)]
    2021-09-19 zhouqu_8
  8. [GetPortalCommentsPageByObjectIdResponse(id=1767865, encodeId=3c851e67865ba, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Thu Nov 18 10:06:16 CST 2021, time=2021-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1975120, encodeId=1edf19e51201c, content=<a href='/topic/show?id=f145355379' target=_blank style='color:#2F92EE;'>#BMC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3553, encryptionId=f145355379, topicName=BMC)], attachment=null, authenticateStatus=null, 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  9. 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    2021-09-18 14763726m01暂无昵称

    学习

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