Background: The maternal microbiome has emerged as an important factor in gestational health and outcome and is associated with risk of preterm birth and offspring morbidity. Epidemiological evidence also points to successive pregnancies - referred to as maternal parity - as a risk factor for preterm birth, infant mortality, and impaired neonatal growth. Despite the fact that both the maternal microbiome and parity are linked to maternal-infant health, the impact of parity on the microbiome remains largely unexplored, in part due to the challenges of studying parity in humans. Results: Using synchronized pregnancies and dense longitudinal monitoring of the microbiome in pigs, we describe a microbiome trajectory during pregnancy and determine the extent to which parity modulates this trajectory. We show that the microbiome changes reproducibly during gestation and that this remodeling occurs more rapidly as parity increases. At the time of parturition, parity was linked to the relative abundance of several bacterial species, including Treponema bryantii, Lactobacillus amylovorus, and Lactobacillus reuteri. Strain tracking carried out in 18 maternal-offspring "quadrads" - each consisting of one mother sow and three piglets - linked maternal parity to altered levels of Akkermansia muciniphila, Prevotella stercorea, and Campylobacter coli in the infant gut 10 days after birth. Conclusions: Collectively, these results identify parity as an important environmental factor that modulates the gut microbiome during pregnancy and highlight the utility of a swine model for investigating the microbiome in maternal-infant health. In addition, our data show that the impact of parity extends beyond the mother and is associated with alterations in the community of bacteria that colonize the offspring gut early in life. The bacterial species we identified as parity-associated in the mother and offspring have been shown to influence host metabolism in other systems, raising the possibility that such changes may influence host nutrient acquisition or utilization. These findings, taken together with our observation that even subtle differences in parity are associated with microbiome changes, underscore the importance of considering parity in the design and analysis of human microbiome studies during pregnancy and in infants.

中文翻译：

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孕期母体肠道微生物组的重塑受胎次影响

背景：孕产妇微生物组已成为影响妊娠健康和结局的重要因素，并与早产和后代发病风险相关。流行病学证据还指出，连续怀孕-被称为产妇平价-是早产，婴儿死亡率和新生儿生长受损的危险因素。尽管事实上孕产妇的微生物组和均等都与孕产妇的健康有关，但对孕产妇的微生物组的影响仍未得到充分探索，部分原因是研究人类均等的挑战。结果：使用同步妊娠和猪中微生物组的密集纵向监测，我们描述了妊娠期间的微生物组轨迹，并确定了奇偶校验调节该轨迹的程度。我们显示，微生物组在妊娠期间可重复发生变化，并且随着胎次增加，这种重塑发生得更快。在分娩时，胎次与几种细菌的相对丰度有关，这些细菌包括布鲁氏螺旋体，淀粉乳杆菌和罗伊氏乳杆菌。在出生后十天的婴儿肠道中，对18个母－子“ quadrads”（每个由一只母猪和3头小猪组成）进行了应变追踪，将母本与胎盘中Akkermansia muciniphila，stervopreella和弯曲杆菌水平的变化联系起来。结论：总体而言，这些结果确定了胎次是在怀孕期间调节肠道微生物组的重要环境因素，并突出了猪模型在调查母婴健康中的效用。此外，我们的数据表明，对等的影响超出了母亲，并且与生命早期定居后代肠道的细菌群落的变化有关。我们发现在母亲和后代中被确定为同等相关的细菌物种会影响其他系统中的宿主代谢，从而增加了这种变化可能影响宿主营养素获取或利用的可能性。这些发现，加上我们的观察结果，即即使是均等的微小差异也与微生物组的变化有关，这凸显了在怀孕期间和婴儿中进行人类微生物组研究的设计和分析中考虑均等的重要性。我们的数据表明，均等的影响超出了母亲，并且与生命早期定居后代肠道的细菌群落的变化有关。我们发现在母亲和后代中被确定为同等相关的细菌物种会影响其他系统中的宿主代谢，从而增加了这种变化可能影响宿主营养素获取或利用的可能性。这些发现，加上我们的观察结果，即即使是均等的微小差异也与微生物组的变化有关，这凸显了在怀孕期间和婴儿中进行人类微生物组研究的设计和分析中考虑均等的重要性。我们的数据表明，均等的影响超出了母亲，并且与生命早期定居后代肠道的细菌群落的变化有关。我们发现在母亲和后代中被确定为同等相关的细菌物种会影响其他系统中的宿主代谢，从而增加了这种变化可能影响宿主营养素获取或利用的可能性。这些发现，加上我们的观察结果，即即使是均等的微小差异也与微生物组的变化有关，这凸显了在怀孕期间和婴儿中进行人类微生物组研究的设计和分析中考虑均等的重要性。增加了这种变化可能影响宿主营养素获取或利用的可能性。这些发现，加上我们的观察结果，即即使是均等的微小差异也与微生物组的变化有关，这凸显了在怀孕期间和婴儿中进行人类微生物组研究的设计和分析中考虑均等的重要性。增加了这种变化可能影响宿主营养素获取或利用的可能性。这些发现，加上我们的观察结果，即即使是均等的微小差异也与微生物组的变化有关，这凸显了在怀孕期间和婴儿中进行人类微生物组研究的设计和分析中考虑均等的重要性。