Does birth mode modify associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome?
ABSTRACT: BACKGROUND:Mother-to-newborn transmission of obesity-associated microbiota may be modified by birth mode (vaginal vs. Cesarean delivery). Prospective data to test this hypothesis are still sparse. OBJECTIVE:To examine prospective associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome by birth-mode strata. SUBJECTS/METHODS:In 335 mother-infant pairs in the New Hampshire Birth Cohort, we ascertained data from questionnaires and medical records, and generated microbiome data from 6-week-old infants' stool using Illumina 16s rRNA gene sequencing (V4-V5 region). Analyses were stratified by birth mode and conducted before and after adjusting for potential confounders, which included maternal age, education, parity, and Mediterranean diet score. RESULTS:Among 335 mothers, 56% had normal pre-pregnancy BMI (??30). Among the 312 mothers with weight gain data, 10% had inadequate weight gain, 30% adequate (referent), and 60% excess. Birth mode modified associations of pre-pregnancy BMI with several genera, including the most abundant genus, Bacteroides (P for interaction?=?0.05). In the vaginal-delivery group, maternal overweight or obesity was associated with higher infant gut microbiome diversity and higher relative abundance of 15 operational taxonomic units (OTUs), including overrepresentation of Bacteroides fragilis, Escherichia coli, Veillonella dispar, and OTUs in the genera Staphylococcus and Enterococcus. In the Cesarean-delivered group, there were no significant associations of pre-pregnancy BMI with infant microbiome (alpha) diversity or OTUs. Gestational weight gain was not associated with differential relative abundance of infant gut microbial OTUs or with measures of microbial diversity in infants delivered vaginally or by Cesarean section. CONCLUSIONS:Among vaginally-delivered infants, maternal overweight and obesity was associated with altered infant gut microbiome composition and higher diversity. These associations were not observed in Cesarean-delivered infants, whose microbiome development differs from vaginally-delivered infants. Our study provides additional evidence of birth-mode dependent associations of maternal body weight status with the infant gut microbiota. The role of these associations in mediating the intergenerational cycle of obesity warrants further examination.
Project description:The short and long-term impact of birth mode on the developing gut microbiome in neonates has potential implications for the health of infants. In term infants, the microbiome immediately following birth across multiple body sites corresponds to birth mode, with increased Bacteroides in vaginally delivered infants. We aimed to determine the impact of birth mode of the preterm gut microbiome over the first 100 days of life and following neonatal intensive care unit (NICU) discharge. In total, 867 stool samples from 46 preterm infants (21 cesarean and 25 vaginal), median gestational age 27 weeks, were sequenced (V4 region 16S rRNA gene, Illumina MiSeq). Of these, 776 samples passed quality filtering and were included in the analysis. The overall longitudinal alpha-diversity and within infant beta-diversity was comparable between cesarean and vaginally delivered infants. Vaginally delivered infants kept significantly more OTUs from 2 months of life and following NICU discharge, but OTUs lost, gained, and regained were not different based on birth mode. Furthermore, the temporal progression of dominant genera was comparable between birth modes and no significant difference was found for any genera following adjustment for covariates. Lastly, preterm gut community types (PGCTs) showed some moderate differences in very early life, but progressed toward a comparable pattern by week 5. No PGCT was significantly associated with cesarean or vaginal birth. Unlike term infants, birth mode was not significantly associated with changes in microbial diversity, composition, specific taxa, or overall microbial development in preterm infants. This may result from the dominating effects of NICU exposures including the universal use of antibiotics immediately following birth and/or the lack of Bacteroides colonizing preterm infants.
Project description:BACKGROUND:The gut microbiome has an important role in infant health and immune development and may be affected by early-life exposures. Maternal diet may influence the infant gut microbiome through vertical transfer of maternal microbes to infants during vaginal delivery and breastfeeding. We aimed to examine the association of maternal diet during pregnancy with the infant gut microbiome 6 weeks post-delivery in mother-infant dyads enrolled in the New Hampshire Birth Cohort Study. Infant stool samples were collected from 145 infants, and maternal prenatal diet was assessed using a food frequency questionnaire. We used targeted sequencing of the 16S rRNA V4-V5 hypervariable region to characterize infant gut microbiota. To account for differences in baseline and trajectories of infant gut microbial profiles, we stratified analyses by delivery mode. RESULTS:We identified three infant gut microbiome clusters, characterized by increased abundance of Bifidobacterium, Streptococcus and Clostridium, and Bacteroides, respectively, overall and in the vaginally delivered infant stratum. In the analyses stratified to infants born vaginally and adjusted for other potential confounders, maternal fruit intake was associated with infant gut microbial community structure (PERMANOVA, p?<?0.05). In multinomial logistic regression analyses, increased fruit intake was associated with an increased odds of belonging to the high Streptococcus/Clostridium group among infants born vaginally (OR (95% CI)?=?2.73 (1.36, 5.46)). In infants delivered by Cesarean section, we identified three clusters that differed slightly from vaginally delivered infants, which were characterized by a high abundance of Bifidobacterium, high Clostridium and low Streptococcus and Ruminococcus genera, and high abundance of the family Enterobacteriaceae. Maternal dairy intake was associated with an increased odds of infants belonging to the high Clostridium cluster in infants born by Cesarean section (OR (95% CI)?=?2.36 (1.05, 5.30)). Linear models suggested additional associations between maternal diet and infant intestinal microbes in both delivery mode strata. CONCLUSIONS:Our data indicate that maternal diet influences the infant gut microbiome and that these effects differ by delivery mode.
Project description: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.
Project description:Importance:Maternal overweight, which often results in cesarean delivery, is a strong risk factor for child overweight. Little is known about the joint contribution of birth mode and microbiota in the infant gut to the association between maternal prepregnancy overweight and child overweight. Objective:To investigate the association of birth mode with microbiota in the infant gut, and whether this mediates the association between maternal and child overweight. Design, Setting, and Participants:An observational study was conducted of 935 full-term infants born between January 1, 2009, and December 31, 2012, in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Maternal prepregnancy body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared using height and weight data taken from medical records or maternal report. Infant gut microbiota were profiled with 16S ribosomal RNA sequencing in fecal samples collected at a mean (SD) age of 3.7 (1.0) months. At ages 1 and 3 years, BMI z scores adjusted for age and sex were generated according to World Health Organization criteria. Statistical analysis was conducted from January 29 to June 15, 2017. Exposures:Mothers of normal weight (BMI, 18.5-24.9) and overweight or obese (BMI, ≥25.0) mothers. Main Outcome and Measures:Risk of overweight and obesity (>97th percentile BMI z scores) among children at ages 1 and 3 years. Results:Of the 935 mother-infant pairs in the study (mean [SD] age, 32.5 [4.5] years) 382 (40.9%) were overweight, 69 of 926 infants (7.5%) were overweight at age 1 year, and 90 of 866 infants (10.4%) were overweight at age 3 years. Compared with being born vaginally to a mother of normal weight, infants born vaginally to overweight or obese mothers were 3 times more likely to become overweight at age 1 year (adjusted odds ratio [OR], 3.33; 95% CI, 1.49-7.41), while cesarean-delivered infants of overweight mothers had a 5-fold risk of overweight at age 1 year (adjusted OR, 5.02; 95% CI, 2.04-12.38). Similar risks were also observed at age 3 years. Multiple mediator path modeling revealed that birth mode and infant gut microbiota (Firmicutes species richness, especially of the Lachnospiraceae family) sequentially mediated the association between maternal prepregnancy overweight and childhood overweight at ages 1 and 3 years. Bacterial genera belonging to the Lachnospiraceae family were more abundant in infants of overweight mothers; however, the participating genera of Lachnospiraceae differed between infants delivered vaginally and those delivered via cesarean birth. Conclusions and Relevance:This study found evidence of a novel sequential mediator pathway involving birth mode and Firmicutes species richness (especially higher abundance of Lachnospiraceae) for the intergenerational transmission of overweight.
Project description:Exposure of newborns to the maternal vaginal microbiota is interrupted with cesarean birthing. Babies delivered by cesarean section (C-section) acquire a microbiota that differs from that of vaginally delivered infants, and C-section delivery has been associated with increased risk for immune and metabolic disorders. Here we conducted a pilot study in which infants delivered by C-section were exposed to maternal vaginal fluids at birth. Similarly to vaginally delivered babies, the gut, oral and skin bacterial communities of these newborns during the first 30 d of life was enriched in vaginal bacteria--which were underrepresented in unexposed C-section-delivered infants--and the microbiome similarity to those of vaginally delivered infants was greater in oral and skin samples than in anal samples. Although the long-term health consequences of restoring the microbiota of C-section-delivered infants remain unclear, our results demonstrate that vaginal microbes can be partially restored at birth in C-section-delivered babies.
Project description:Previous studies have revealed significant differences in microbiome compositions between infants delivered via cesarean section (C-section) and natural vaginal birth. However, the importance of the delivery mode in the first days of life remains unclear. Importantly, this stage is minimally affected by infant feeding. Here, we used a metagenomic sequencing technique to characterize the meconium microbiome from the feces of a Chinese cohort of vaginally and C-section-delivered infants, including in vitro fertilization (IVF) newborns, during the first 24?h after birth. Meconium microbiome diversity was higher in vaginally delivered infants than that in C-section-delivered infants. Propionibacterium species were most abundant in the vaginally delivered infants, whereas the C-section group had high levels of Bacillus licheniformis. The two IVF newborns delivered by C-section harbored microbial communities similar to the vaginal microbiome in terms of taxonomic composition. Metabolic functions of the C-section group suffered more from the influence of the dominant group (B. licheniformis), whereas the vaginal group was more homogeneous, with a metabolism dominated by multi-microbes. Moreover, different modes of delivery affected the antibiotic resistance gene (ARG) prevalence. These findings provide novel information for the development of strategies to guide a healthy mode of delivery and promote the formation of healthy microbiota.
Project description:Established during infancy, our complex gut microbial community is shaped by medical interventions and societal preferences, such as cesarean section, formula feeding, and antibiotic use. We undertook this study to apply the significance analysis of microarrays (SAM) method to quantify changes in gut microbial composition during later infancy following the most common birth and postnatal exposures affecting infant gut microbial composition. Gut microbiota of 166 full-term infants in the Canadian Healthy Infant Longitudinal Development birth cohort were profiled using 16S high-throughput gene sequencing. Infants were placed into groups according to mutually exclusive combinations of birth mode (vaginal/cesarean birth), breastfeeding status (yes/no), and antibiotic use (yes/no) by 3?months of age. Based on repeated permutations of data and adjustment for the false discovery rate, the SAM statistic identified statistically significant changes in gut microbial abundance between 3?months and 1?year of age within each infant group. We observed well-known patterns of microbial phyla succession in later infancy (declining Proteobacteria; increasing Firmicutes and Bacteroidetes) following vaginal birth, breastfeeding, and no antibiotic exposure. Genus Lactobacillus, Roseburia, and Faecalibacterium species appeared in the top 10 increases to microbial abundance in these infants. Deviations from this pattern were evident among infants with other perinatal co-exposures; notably, the largest number of microbial species with unchanged abundance was seen in gut microbiota following early cessation of breastfeeding in infants. With and without antibiotic exposure, the absence of a breast milk diet by 3?months of age following vaginal birth yielded a higher proportion of unchanged abundance of Bacteroidaceae and Enterobacteriaceae in later infancy, and a higher ratio of unchanged Enterobacteriaceae to Alcaligenaceae microbiota. Gut microbiota of infants born vaginally and exclusively formula fed became less enriched with family Veillonellaceae and Clostridiaceae, showed unchanging levels of Ruminococcaceae, and exhibited a greater decline in the Rikenellaceae/Bacteroidaceae ratio compared to their breastfed, vaginally delivered counterparts. These changes were also evident in cesarean-delivered infants to a lesser extent. The clinical relevance of these trajectories of microbial change is that they culminate in taxon-specific abundances in the gut microbiota of later infancy, which we and others have observed to be associated with food sensitization.
Project description:The intergenerational association of obesity may be driven by mother-to-newborn transmission of microbiota at birth. Yet cesarean delivery circumvents newborn acquisition of vaginal microbiota, and has been associated with greater childhood adiposity. Here we examined the independent and joint associations of maternal pre-pregnancy body mass index (BMI; kg?m-2) and delivery mode with childhood overweight or obesity.We prospectively followed 1441 racially and ethnically diverse mother-child dyads in the Boston Birth Cohort until age 5 years (range: 2.0-8.0 years). We used logistic regression to examine the independent and joint associations of delivery mode (cesarean and vaginal delivery) and pre-pregnancy BMI with childhood overweight or obesity (age-sex-specific BMI ?85th percentile).Of 1441 mothers, 961 delivered vaginally and 480 by cesarean. Compared with vaginally delivered children, cesarean delivered children had 1.4 (95% confidence interval (CI) 1.1-1.8) times greater odds of becoming overweight or obese in childhood, after adjustment for maternal age at delivery, race/ethnicity, education, air pollution exposure, pre-pregnancy BMI, pregnancy weight gain and birth weight. Compared with children born vaginally to normal weight mothers, after multivariable adjustment, odds of childhood overweight or obesity were highest in children born by cesarean delivery to obese mothers (odds ratio (OR): 2.8; 95% CI: 1.9-4.1), followed by children born by cesarean delivery to overweight mothers (OR: 2.2; 95% CI: 1.5-3.2), then children born vaginally to obese mothers (OR: 1.8; 95% CI: 1.3-2.6) and finally children born vaginally to overweight mothers (OR: 1.7; 95% CI: 1.2-2.3).In our racially and ethnically diverse cohort, cesarean delivery and pre-pregnancy overweight and obesity were associated with childhood overweight or obesity. Needed now are prospective studies that integrate measures of the maternal and infant microbiome, and other potentially explanatory covariates, to elucidate the mechanisms driving this association and to explore whether exposure to vaginal microbiota in cesarean delivered newborns may be an innovative strategy to combat the intergenerational cycle of obesity.
Project description:The maternal vaginal microbiome is an important source for infant gut microbiome development. However, infants delivered by Cesarean section (CS) do not contact the maternal vaginal microbiome and this delivery method may perturb the early establishment and development of the gut microbiome. The aim of this study was to investigate the early gut microbiota of Korean newborns receiving the same postpartum care services for two weeks after birth by delivery mode using fecal samples collected at days 3, 7, and 14. Early gut microbiota development patterns were examined using 16S rRNA gene-based sequencing from 132 infants either born vaginally (VD, n = 64) or via Cesarean section (CS, n = 68). VD-born neonates showed increased alpha diversity in infant fecal samples collated at days 7 and 14 compared to those from day 3, while those of CS infants did not differ (p < 0.015). Bacterial structures of infants from both groups separated at day 7 (p < 0.001) and day 14 (p < 0.01). The bacterial structure of VD infants gradually changed over time (day 3 vs. day 7, p < 0.012; day 3 vs. day 14, p < 0.001). Day 14 samples of CS infants differed from day 3 and 7 samples (day 3 vs. day 14, p < 0.001). VD infant relative abundance of Bifidobacterium (days 7, 14), Bacteroides (days 7, 14), and Lachnospiraceae (day 7) significantly increased compared to CS infants, with a lower abundance of Enterobacteriaceae (found in all periods of the CS group) (LDA > 3.0). Relative abundances of Bifidobacterium, Lactobacillus, and Staphylococcus were significantly increased in both VD and CS groups at day 14 (LDA > 3.0). Predicted functional analysis showed that VD infants had overrepresented starch/sucrose, amino acid and nucleotide metabolism in gut microbiota with depleted lipopolysaccharide biosynthesis until day 14 compared to CS infants. This study confirmed that delivery mode is the major determinant of neonatal intestinal microbiome establishment and provides a profile of microbiota perturbations in CS infants. Our findings provide preliminary insight for establishing recovery methods to supply the specific microbes missing in CS infants.
Project description:BACKGROUND:Potentially driven by the lack of mother-to-infant transmission of microbiota at birth, cesarean delivery has been associated with higher risk of offspring obesity. Yet, no studies have examined when delivery-mode differences in adiposity begin to emerge. In this study, we examine differences in infant weight and adiposity trajectories from birth to 12 months by delivery mode. METHODS:From 2013 to 2015, we recruited pregnant women into the Nurture Study and followed up their 666 infants. We ascertained maternal delivery method and infant birth weight from medical records. We measured weight, length, and skinfold thicknesses (subscapular, triceps, abdominal) when infants were 3, 6, 9, and 12 months of age. The main outcome, infant weight-for-length z score, was derived based on the WHO Child Growth Standards. We used linear regression models to assess the difference at each time point and used linear mixed models to examine the growth rate for infant weight and adiposity trajectories. We controlled for maternal age, race, marital status, education level, household income, smoking status, maternal pre-pregnancy body mass index, and infant birth weight. RESULTS:Of the 563 infants in our final sample, 179 (31.8%) were cesarean delivered. From birth to 12 months, the rate of increase in weight-for-length z score was 0.02/month (p?=?0.03) greater for cesarean-delivered than vaginally-delivered infants. As a result of more rapid growth, cesarean-delivered infants had higher weight-for-length z score (0.26, 95% CI: 0.05, 0.47) and sum of subscapular and triceps (SS?+?TR) skinfold thickness (0.95?mm, 95% CI: 0.30, 1.60)-an indicator for overall adiposity-at 12 months, compared to vaginally-delivered infants. CONCLUSIONS:Compared to vaginal delivery, cesarean delivery was associated with greater offspring rate of weight gain over the first year and differences in adiposity that appear as early as 3 months of age. Monitoring cesarean-delivered infants closely for excess weight gain may help guide primordial prevention of obesity later in life.