The Perturbation of Infant Gut Microbiota Caused by Cesarean Delivery Is Partially Restored by Exclusive Breastfeeding

Yu Liu, Shengtang Qin, Yilin Song, Ye Feng, Na Lv, Yong Xue, Fei Liu, Shuxian Wang, Baoli Zhu, Jingmei Ma, Huixia Yang, Yu Liu, Shengtang Qin, Yilin Song, Ye Feng, Na Lv, Yong Xue, Fei Liu, Shuxian Wang, Baoli Zhu, Jingmei Ma, Huixia Yang

Abstract

Early establishment of the infant gut microbiome has been attributed to various environmental factors that may influence long-term health. The aim of this study was to determine the single and combined impacts of the delivery mode, feeding pattern and postnatal antibiotic exposure on the initial establishment of infant gut microbiome at 6 weeks postpartum. A cross-sectional study was conducted at a single center in China. Fecal samples were collected from 120 infants at 6 weeks postpartum. The V3-V4 regions of 16S rRNA gene were analyzed by Illumina sequencing, and clinical information was obtained from medical records and questionnaire survey. Compared with vaginally delivered infants, the gut microbial community structure of cesarean delivered infants were significantly different (P = 0.044), in parallel with the decreased relative abundance of Bifidobacterium (P = 0.028), which contrasts with the normal gut microbial establishment. Using the vaginally delivered and exclusively breastfed (VB) infants as a reference, the comparative analysis of cesarean delivered and exclusively breastfed (CB) infants with cesarean delivered and mixed-fed (CM) infants showed that both within- and between-group UniFrac distance were significantly smaller in CB infants (P < 0.001, P < 0.001). LEfSe analysis showed that the relative abundances of Enterococcus, Veillonella, and Faecalibacterium were significantly different between CB and CM infants, whereas the relative abundances of those genera in VB infants were close to those of CB infants, and distinct from those of CM infants. Additionally, no significant difference of microbial composition, alpha diversity, or community structure was observed between postnatal antibiotics exposed infants and unexposed infants. In summary, delivery mode had a significant impact on the infant gut microbial community structure and composition, and the gut microbiota was disturbed in infants delivered by cesarean section. However, our study showed that this disturbance of gut microbiota in cesarean delivered infants was partially restored by exclusive breastfeeding in comparison with mixed feeding. No distinct impact of postnatal antibiotic exposure on infant gut microbiome was found at 6 weeks of age.

Keywords: breastfeeding; delivery mode; early life; gut microbiome; infant; postnatal antibiotic exposure.

Figures

FIGURE 1
FIGURE 1
The impact of delivery mode on infant gut microbiota. (A) Comparison of alpha diversity between vaginally delivered and cesarean delivered infants. (B) Principal coordinates analysis (PCoA) based on weighted UniFrac distances is shown along the first two principal coordinate (PC) axes with Adonis p-value. Percentages are the percent variation explained by each PC axis. Individual samples are represented by green triangles (vaginally delivered) and red points (cesarean delivered). (C) Enriched taxa of different level from vaginally delivered infants with a positive linear discriminant analysis (LDA) score are shown in green; cesarean delivered infants with negative LDA score are shown in red (cut off value ≥3).
FIGURE 2
FIGURE 2
The impact of feeding pattern on the infant gut microbiota. (A) Comparison of alpha diversity between exclusively breastfed and mixed-fed infants. (B) Principal coordinates analysis (PCoA) based on weighted UniFrac distances is shown along the first two principal coordinate (PC) axes with Adonis p-value. Percentages are the percent variation explained by each PC axis. Individual samples are represented by yellow points (exclusively breastfed) and blue triangles (mixed-fed). (C) Enriched taxa of different level from mixed-fed infants with a positive linear discriminant analysis (LDA) score are shown in blue (cut off value >3).
FIGURE 3
FIGURE 3
Exclusive breastfeeding significantly restores the gut microbiota of cesarean delivered infants. (A) Principal coordinates analysis (PCoA) based on unweighted UniFrac distances is shown along the first two principal coordinate (PC) axes with Adonis p-value. Percentages are the percent variation explained by each PC axis. Individual samples are represented by yellow points (CB) and green triangles (CM). Comparison of the within-groups (B) and between-groups (C) unweighted UniFrac distances of CB and CM infants. Shorter distance indicated greater similarity between microbial community composition. Significant difference was determined by Mann-Whitney U-test (∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001). (D) Enriched taxa of different level from CB infants with a positive linear discriminant analysis (LDA) score are shown in yellow; CM infants with negative LDA score are shown in green (cut off value ≥3). (E) Comparison of relative abundance of Enterococcus, Veillonella, and Faecalibacterium among VB, CB, and CM infants. VB, vaginally delivered and exclusive breastfed; CB, cesarean delivered and exclusive breastfed; CM, cesarean delivered and mixed-fed.
FIGURE 4
FIGURE 4
The impact of postnatal antibiotic exposure on the infant gut microbiota. (A) Comparison of relative abundance of the top 15 genera between antibiotic exposed and unexposed infants. Significant difference was determined by Mann-Whitney U-test (∗∗p < 0.01). (B) Comparison of alpha diversity between antibiotic exposed (orange) and unexposed (dark gray) infants. (C) Principal coordinates analysis (PCoA) based on weighted UniFrac distances is shown along the first two principal coordinate (PC) axes with Adonis p-value. Percentages are the percent variation explained by each PC axis. Individual samples are represented by orange points (antibiotic exposed) and dark gray triangles (antibiotic unexposed).

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