早期婴儿肠道微生物群与母亲的高脂饮食有关
新的研究证据表明，子宫内环境并非像以前所推测的那样无菌。在小鼠身上的研究表明，共生细菌在怀孕期间从母亲传播到胎儿，尽管目前还不清楚是什么调节了这一过程。
作者之前在非人类灵长类动物身上发现，孕期和哺乳期的母体高脂饮食会持续地塑造幼年肠道微生物群。本研究中，作者在人类纵向队列中探究了母亲的高脂饮食是否同样改变了新生儿和婴儿早期肠道微生物群。
The early infant gut microbiome varies in association with a maternal high-fat diet
Chu et al. Genome Medicine (2016)
DOI 10.1186/s13073-016-0330-z
论文摘要
Background: Emerging evidence suggests that the in utero environment is not sterile as once presumed. Work in the mouse demonstrated transmission of commensal bacteria from mother to fetus during gestation, though it is unclear what modulates this process. We have previously shown in the nonhuman primate that, independent of obesity, a maternal high-fat diet during gestation and lactation persistently shapes the juvenile gut microbiome. We therefore sought to interrogate in a population-based human longitudinal cohort whether a maternal high-fat diet similarly alters the neonatal and infant gut microbiome in early life.
Methods: A representative cohort was prospectively enrolled either in the early third trimester or intrapartum (n = 163), with a subset consented to longitudinal sampling through the postpartum interval (n = 81). Multiple body site samples, including stool and meconium, were collected from neonates at delivery and by 6 weeks of age. A rapid dietary questionnaire was administered to estimate intake of fat, added sugars, and fiber over the past month (National Health and Examination Survey). DNA was extracted from each infant meconium/stool sample (MoBio) and subjected to 16S rRNA gene sequencing and analysis.
Results: On average, the maternal dietary intake of fat ranged from 14.0 to 55.2 %, with an average intake of 33. 1 % (σ = 6.1 %). Mothers whose diets significantly differed from the mean (±1 standard deviation) were separated into two distinct groups, a control group (n = 13, μ = 24.4 %) and a high-fat group (n = 13, μ = 43.1 %). Principal coordinate analysis revealed that the microbiome of the neonatal stool at birth (meconium) clustered differently by virtue of maternal gestational diet (PERMANOVA p = 0.001). LEfSe feature selection identified several taxa that discriminated the groups, with a notable relative depletion of Bacteroides in the neonates exposed to a maternal high-fat gestational diet (Student’s t-test, p < 0.05) that persisted to 6 weeks of age.
Conclusions: Similar to the primate, independent of maternal body mass index, a maternal high-fat diet is associated with distinct changes in the neonatal gut microbiome at birth which persist through 4–6 weeks of age. Our findings underscore the importance of counseling pregnant mothers on macronutrient consumption during pregnancy and lactation.
研究对象：孕晚期妇女及其婴儿。
入组标准：18岁或以上、妊娠>28周的孕妇；排除过去6个月内已知有HIV或丙型肝炎感染、免疫抑制性疾病、使用细胞因子或免疫抑制剂、除局部切除所管理的皮肤鳞状细胞癌或基底细胞癌之外的癌症史、治疗或怀疑曾发生过中毒性休克综合征、或过去5年中除胆囊切除术或阑尾切除术以外的胃肠道疾病大手术。
实验方法：每个母亲回答膳食筛查者问卷(DSQ)，该问卷由国家健康和检查调查(NHANES)计划(2009-2010)制定和验证。DSQ是一个由26个问题组成的快速膳食筛选器，可以在一次访问中完成，并要求被调查者提供普通食物的食用频率；产后24-48小时内从第一张尿布获得新生儿胎粪；第二个粪便样本是从4-6周大的婴儿中收集的；粪便样本收集后马上置于冰上，-80℃保存至DNA提取。
检测方法：16S rRNA基因测序和分析
研究结论：
孕期母亲的高脂饮食与新生儿出生时的微生物群的显著变化独立相关，并且这种变化持续到新生儿4-6周，这种变化并不依赖于肥胖（BMI）。这些发现对完善妊娠期饮食建议有直接意义；
暴露于母体高脂饮食与肠球菌的富集以及拟杆菌的相对耗竭显著相关，拟杆菌是一种已知的共生体，有助于粘膜免疫的成熟；
显著增加的膳食脂肪摄入量（超过医学研究所推荐限制的35％）对后代微生物有持久的影响；
尽管肥胖和妊娠期体重增加在短期内对患者来说可能难以解决，但是在怀孕期间建立健康的饮食习惯可能更容易实现，对母亲和孩子都有显著的长期益处。
Figure 1. Specific taxa in the neonatal meconium significantly associated with maternal gestational diet. Heatmap of taxa in the neonatal meconium identified by LEfSe feature selection that were significantly associated with either a maternal high-fat or maternal control diet during pregnancy
图 1. 新生儿胎粪中的特定分类群与孕期饮食显著相关。通过LEfSe特征选择鉴定的新生儿胎粪中分类群的热图，这些特征选择与孕期母体高脂饮食或母体对照饮食显著相关
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