Remodeling of the maternal gut microbiome during pregnancy is shaped by parity

Abstract

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.

Taxonomic and functional shifts in the perinatal gut microbiome of rhesus macaques

“…Our data indicate that the maternal microbiome was less rich (lower observed ASVs) but more heterogeneous (increased within group dissimilarity, beta diversity) during pregnancy. This increase in beta-diversity with pregnancy is in line with data from multiple human and animal studies, particularly late in pregnancy (18)(19)(20)37). On the other hand, previous clinical studies have reported a drop, an increase, or no change in the alpha diversity of the maternal microbiome (18,19,35) likely due to the high heterogeneity within the healthy human microbiome (36).…”

“…The gut microbiome plays critical roles in vitamin production (11), immune homeostasis (12), and metabolism of indigestible substrates among others (13). This community stabilizes in adulthood (14), but sensitive to environmental factors such as dietary shifts (15), antibiotic use (16), and other shifts in host physiology such as pregnancy (18). Early studies found that the pregnancy gut microbiome is less diverse, more variable, and harbors an increased abundance of Proteobacteria (19).…”

The early life microbiota mediates maternal effects on offspring growth in a nonhuman primate

“…Second, the correlation between maternal parity and maternal age raises the question of whether the relationships described here may reflect age, rather than parity, effects. Because our hypotheses were centered on the effects of successive reproductions on maternal communities, and because prior work has shown that parity, not age, shapes the maternal microbiota ( Berry et al., 2021 ), we did not include maternal age in our analyses to avoid issues of multicollinearity. Instead, we focused on parity because successive reproductions (independent of maternal age) shape the morphology of both the mammary gland ( Rovai et al., 1999 ) and variation in milk production across mammalian species (e.g., Lang et al., 2012 ; Sevi et al., 2000 ), suggesting that similar effects may be found in maternal milk and infant gut microbiota.…”

“…More broadly, the maternal environment may program the infant gut microbiota for enhanced milk utilization via vertical microbial transmission. Thus far, parity effects on maternal microbiota have been demonstrated in agricultural species ( Berry et al., 2021 ; Bogado Pascottini et al., 2021 ), and more recently in humans ( Kervinen et al., 2021 ; Lopez Leyva et al., 2021 ). However, in pigs, parity effects extend to the infant gut microbiota, suggesting that such effects may be vertically transmitted from maternal reservoirs ( Berry et al., 2021 ).…”

“…Thus far, parity effects on maternal microbiota have been demonstrated in agricultural species ( Berry et al., 2021 ; Bogado Pascottini et al., 2021 ), and more recently in humans ( Kervinen et al., 2021 ; Lopez Leyva et al., 2021 ). However, in pigs, parity effects extend to the infant gut microbiota, suggesting that such effects may be vertically transmitted from maternal reservoirs ( Berry et al., 2021 ). Large-scale investigations into maternal vertical transmission have identified the maternal gut as the largest source of colonizing bacteria to the infant gut ( Bäckhed et al., 2015 ; Ferretti et al., 2018 ; Makino et al., 2013 ; Maqsood et al., 2019 ).…”