Delivery Mode Affects Stability of Early Infant Gut Microbiota

Caroline M Mitchell, Chiara Mazzoni, Larson Hogstrom, Allison Bryant, Agnes Bergerat, Avital Cher, Shawna Pochan, Penelope Herman, Maureen Carrigan, Karen Sharp, Curtis Huttenhower, Eric S Lander, Hera Vlamakis, Ramnik J Xavier, Moran Yassour, Caroline M Mitchell, Chiara Mazzoni, Larson Hogstrom, Allison Bryant, Agnes Bergerat, Avital Cher, Shawna Pochan, Penelope Herman, Maureen Carrigan, Karen Sharp, Curtis Huttenhower, Eric S Lander, Hera Vlamakis, Ramnik J Xavier, Moran Yassour

Abstract

Mode of delivery strongly influences the early infant gut microbiome. Children born by cesarean section (C-section) lack Bacteroides species until 6-18 months of age. One hypothesis is that these differences stem from lack of exposure to the maternal vaginal microbiome. Here, we re-evaluate this hypothesis by comparing the microbial profiles of 75 infants born vaginally or by planned versus emergent C-section. Multiple children born by C-section have a high abundance of Bacteroides in their first few days of life, but at 2 weeks, both C-section groups lack Bacteroides (primarily according to 16S sequencing), despite their difference in exposure to the birth canal. Finally, a comparison of microbial strain profiles between infants and maternal vaginal or rectal samples finds evidence for mother-to-child transmission of rectal rather than vaginal strains. These results suggest differences in colonization stability as an important factor in infant gut microbiome composition rather than birth canal exposure.

Keywords: infant gut microbiota, caesarean delivery, Bacteroides, delivery mode, transmission of maternal strains.

Conflict of interest statement

C.M.M. receives grant funding from Merck and has served as a consultant for Scynexis. C.H. is a member of the Seres Therapeutics, Empress Therapeutics, and ZOE Nutrition scientific advisory boards. E.S.L. serves on the board of directors for Codiak BioSciences and on the scientific advisory board of F-Prime Capital Partners and Third Rock Ventures; he is also affiliated with several non-profit organizations, including serving on the board of directors of the Innocence Project, Count Me In, and the Biden Cancer Initiative, and the board of trustees for the Parker Institute for Cancer Immunotherapy. He has served and continues to serve on various federal advisory committees. R.J.X. is a consultant to Nestlé.

© 2020 The Author(s).

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Cohort Description and Key Differential Taxa across Delivery Modes (A) Cohort information about delivery mode, feeding practices, and sampling. Women presenting to Labor and Delivery at term (≥37 weeks) with singleton gestation were enrolled and had a rectal and vaginal sample collected before delivery. A stool sample was collected from the infants’ diaper daily while in the hospital, and parents sent a single stool sample from home at 2 weeks of life. Feeding practices were abstracted from inpatient charts for week 1 and obtained from parent questionnaires for week 2. (B) Impact of delivery mode on early life microbial composition. Multivariate linear regression was used to identify taxa that were enriched in vaginally delivered versus C-section-delivered (CS) infants and pre- versus post-labor CS (using the results of 16S rRNA sequencing). Analyses were adjusted for feeding practices in the week of interest. A positive coefficient represents a taxon more abundant in vaginally delivered infants. Only associations with absolute coefficients ≥0.015, and FDR corrected q value Bacteroides colonization in CS-delivered infants. Maximal abundance of Bacteroides in week 1 (i.e., the sample with the highest relative abundance) versus week 2 samples by 16S sequencing was compared within delivery mode using the t test. (D) Differences in patterns of Bacteroides colonization by delivery mode. The Bacteroides colonization phenotype was assigned based on detection at ≥0.1% in week 1 samples only (early-only), week 2 only (late-only), both week 1 and week 2 (persistent), or neither (absent). Results are presented for the 67 infants with samples available from both time points.
Figure 2
Figure 2
Shared Species and Strain between Maternal Rectal and Infant Stool Samples Using Metagenomic Sequencing (A) Comparison of Bacteroides species prevalence across delivery modes, among infants with detectable Bacteroides in week 1 samples (≥0.1%, n = 67). (B) Mother-infant dyads with shared species between maternal rectal swabs and infant stool samples in either week 1 or week 2 samples (≥0.1%, n = 18 vaginal delivery, n = 22 CS delivery). (C) Mother-infant dyads with shared Bacteroides species. (D) Detailed view of shared species and matched strains in mother-infant dyads by delivery mode and week of sampling. A total of 10 dyads (9 vaginal, 1 CS) demonstrated evidence of shared strains between maternal rectal and infant stool samples.

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