KJERSTI AAGAARD'S CO-AUTHORED ARTICLES

KJERSTI AAGAARD'S CO-AUTHORED ARTICLES

WoM_logo.JPGMaturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery

Derrick M Chu, Jun Ma, Amanda L Prince, Kathleen M Antony, Maxim D Seferovic & Kjersti M Aagaard

Human microbial communities are characterized by their taxonomic, metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to determine the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites and assess the effect of the mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early third trimester (n = 81) were prospectively enrolled for longitudinal sampling through 6 weeks after delivery, and a second matched cross-sectional cohort (n = 81) was additionally recruited for sampling once at the time of delivery. Samples across multiple body sites, including stool, oral gingiva, nares, skin and vagina were collected for each maternal–infant dyad. Whole-genome shotgun sequencing and sequencing analysis of the gene encoding the 16S rRNA were performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogeneous across all body sites at delivery, with the notable exception of the neonatal meconium. However, by 6 weeks after delivery, the infant microbiota structure and function had substantially expanded and diversified, with the body site serving as the primary determinant of the composition of the bacterial community and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with the cesarean mode of delivery in some body sites (oral gingiva, nares and skin; R2 = 0.038), this was not true for neonatal stool (meconium; Mann–Whitney P > 0.05), and there was no observable difference in community function regardless of delivery mode. For infants at 6 weeks of age, the microbiota structure and function had expanded and diversified with demonstrable body site specificity (P < 0.001, R2 = 0.189) but without discernable differences in community structure or function between infants delivered vaginally or by cesarean surgery (P = 0.057, R2 = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes substantial reorganization, which is primarily driven by body site and not by mode of delivery.

Read the article

 

WoM_logo.JPG
Impact of maternal nutrition in pregnancy and lactation on offspring gut microbial composition and function


Derrick M. Chu, Kristen M. Meyer, Amanda L. Prince & Kjersti M. Aagaard

Evidence supporting the Developmental Origins of Health and Disease Hypothesis indicates that maternal nutrition in pregnancy has a significant impact on offspring disease risk later in life, likely by modulating developmental processes in utero. Gut microbiota have recently been explored as a potential mediating factor, as dietary components strongly influence microbiota abundance, function and its impact on host physiology. A growing body of evidence has additionally indicated that the intrauterine environment is not sterile as once presumed, indicating that maternal-fetal transmission of microbiota may occur during pregnancy. In this article, we will review the body of literature that supports this emerging hypothesis, as well as highlight the work in relevant animal models demonstrating associations with maternal gestational nutrition and the offspring gut microbiome that may influence offspring physiology and susceptibility to disease.

Read the article


WoM_logo.JPG
The early infant gut microbiome varies in association with a maternal high-fat diet


Derrick M. Chu, Kathleen M. Antony, Jun Ma, Amanda L. Prince, Lori Showalter, Michelle Moller and Kjersti M. Aagaard

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.

Read the article


WoM_logo.JPG
The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis


Amanda L. Prince, PhD1; Jun Ma, PhD1; Paranthaman S. Kannan, PhD; Manuel Alvarez, MSc; Tate Gisslen, MD; R. Alan Harris, PhD; Emma L. Sweeney, PhD; Christine L. Knox, PhD; Donna S. Lambers, MD; Alan H. Jobe, MD, PhD; Claire A. Chougnet, PhD; Suhas G. Kallapur, MD; Kjersti M. Aagaard, MD, PhD

Background
Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis.

Objective
In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/ or funisitis using state-of-the-science whole-genome shotgun metagenomics.

Study Design
This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n ¼ 9[1]15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analysed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R.

Results
Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis (permutational multivariate analysis of variance P ¼ .005), there was no observable impact with either betamethasone or antibiotic treatment. In preterm subjects with chorioamnionitis, we found a high abundance of both urogenital and oral commensal bacteria. These alterations in the microbiome were accompanied by significant variation (P < .05) in microbial metabolic pathways important in the glucose-fed pentose phosphate pathway (term subjects), or glycerophopholipid metabolism, and the biosynthesis of the siderophore group nonribosomal peptides (preterm subjects).

Conclusion
Consistent with ours and others previous findings, women who experienced spontaneous PTB harbor placental microbiota that further differed by severity of chorioamnionitis. Integrative metagenomic analysis revealed significant variation in distinct bacterial metabolic pathways, which we speculate may contribute to risk of preterm birth with and without severe chorioamnionitis.

Read the article