Background: Early introduction of complementary foods has been associated with various immune disorders, oxidative stress, and obesity in childhood. The gut microbiota and the short chain fatty acids (SCFAs) they produce are postulated to be on the causal pathway. The objective of this study was to determine if early complementary feeding (i.e. consumption of solids or non-water/formula liquids at or before 3 months) is prospectively associated with infant gut microbiota composition, diversity and SCFAs at 3 and 12 months of age in the Nurture birth cohort. Results: Mother-infant dyads in the early complementary feeding group (n = 18) had similar baseline characteristics to those in the later feeding group (n = 49). We assessed differential abundance of microbial taxa (measured by 16S rRNA gene sequencing of the V4 region) by timing of complementary feeding using beta-binomial regression models (considering a two-sided FDR corrected p-value of < 0.05 as significant), and we fittted linear regression models to assess the association between early complementary feeding and SCFA concentrations (quantified using gas chromatography). After multivariable adjustment for breastfeeding, delivery method, birth weight, and gestational age, there were 13 differentially abundant microbial amplicon sequence variants (ASVs) by timing of introduction to complementary foods at 3 months and 20 ASVs at 12 months. Infants introduced to complementary foods early (vs. later) had higher concentrations of the SCFA butyric acid (mean difference = 0.65, 95% CI: 0.27, 1.04, p < 0.01) and total SCFAs (mean difference = 38.8, 95% CI: 7.83, 69.7) at 12 months. Bilophila wadsworthia and Lachnospiraceae Roseburia were associated with early (vs. later) complementary feeding and with higher butyric acid concentrations at 3 and 12 months, respectively. Conclusions: Our findings are consistent with the hypothesis that early (vs. later) introduction to complementary foods is associated with altered gut microbiota composition and butyric acid concentrations measured in stool until at least 1 year of age. Further research is needed to determine if these changes mediate future development of metabolic and immune conditions.

Background Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants. Method In this prospective study (Nurture: recruitment 2013–2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months. Results Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend = 0.006) with infants exposed to ≥ 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value < 0.05). Conclusions Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months. Electronic supplementary material The online version of this article (10.1186/s12941-019-0318-9) contains supplementary material, which is available to authorized users.

SummaryBackgroundIntroducing complementary foods other than breastmilk or formula acutely changes the infant gut microbiota composition. However, it is unknown whether the timing of introduction to complementary foods (early vs. late) in infancy is associated with early childhood gut microbiota and BMI, and if these associations depend on breastfeeding duration.ObjectiveOur primary objective was to investigate whether timing of infant complentary feeding with solid foods is associated with early childhood gut microbiota composition and BMI‐z, and whether these associations differ by duration of breastfeeding.MethodsWe used data from a Canadian pre‐birth cohort followed till age 5 years. We examined timing of introduction to solid foods with the gut microbiota, determined by 16S rRNA gene sequencing of stool collected at 5 years of age, and age‐and‐sex specific BMI‐z. We conducted analyses before and after stratifying by breastfeeding duration, and adjusted for delivery mode, gestational age and birth weight.ResultsOf the 392 children in the analysis, 109 (27.8%) had early (≤4 months) solids. The association between early (vs later) solids and BMI‐z at 5 years was modified by breastfeeding status at 4 months (P = .06). Among children breastfed >4 months, early (vs later) solids were associated with differential relative abundance of 6 bacterial taxa, including lower Roseburia, and 0.30 higher BMI‐z (95% CI: 0.05, 0.55) at 5 years. In children breastfed <4 months, early solids were associated with differential relative abundance of 9 taxa, but not with child BMI‐z.ConclusionsEarly (vs. later) introduction to solid foods in infancy is associated with altered gut microbiota composition and BMI in early childhood, however these associations differ by duration of breastfeeding.

Objective Caesarean section (CS) interrupts mother‐to‐newborn microbial transfer at birth. Beyond the neonatal period, the impact of CS on offspring gut microbiota and their short‐chain fatty acids (SCFAs) remains unclear. Here, we examine birth delivery mode (CS versus vaginal delivery) with the infant gut microbiota and faecal SCFAs measured 3 and 12 months after birth. Design Longitudinal study. Setting North Carolina. Population In 2013–15, we enrolled pregnant women and followed up their offspring for 12 months. We asked a subset of participants, enrolled over a 3‐month period, to provide faecal samples at the 3‐ and 12‐month follow‐up visits. Methods and main outcomes We sequenced the 16S rRNA V4 region with Illumina MiSeq and quantified SCFA concentrations using gas chromatography. We examined delivery mode with differential abundance of microbiota amplicon sequence variants (ASVs) using beta‐binomial regression and faecal SCFAs using linear regression. We adjusted models for confounders. Results Of the 70 infants in our sample, 25 (36%) were delivered by CS. Compared with vaginal delivery, CS was associated with differential abundance of 14 infant bacterial ASVs at 3 months and 13 ASVs at 12 months (all FDR P < 0.05). Of note, CS infants had a higher abundance of the potential pathobionts Clostridium neonatale (P = 0.04) and Clostridium perfringens (P = 0.04) and a lower abundance of potentially beneficial Bifidobacterium and Bacteroides spp. (both P < 0.05) at 3 months. Other ASVs were differentially abundant at 12 months. Infants delivered by CS also had higher faecal butyrate concentration at 3 months (P < 0.005) but not at 12 months. Conclusions Caesarean section was associated with increased butyrate excretion, decreased Bifidobacterium and Bacteroides spp., and more colonisation of the infant gut by pathobionts at 3 months of age. CS was also associated with altered gut microbiota composition, but not faecal SCFAs, at 12 months. Tweetable abstract Caesarean section delivery was associated with increased butyrate excretion, decreased Bifidobacterium, and increased colonisation of the infant gut by pathobionts at 3 months of age.