Project description:There are limited data on meconium and faecal bacterial profiles from African infants and their mothers. We characterized faecal bacterial communities of infants and mothers participating in a South African birth cohort. Stool and meconium specimens were collected from 90 mothers and 107 infants at birth, and from a subset of 72 and 36 infants at 4-12 and 20-28 weeks of age, respectively. HIV-unexposed infants were primarily exclusively breastfed at 4-12 (49%, 26/53) and 20-28 weeks (62%, 16/26). In contrast, HIV-exposed infants were primarily exclusively formula fed at 4-12 (53%; 10/19) and 20-28 weeks (70%, 7/10). Analysis (of the bacterial 16S rRNA gene sequences of the V4 hypervariable region) of the 90 mother-infant pairs showed that meconium bacterial profiles [dominated by Proteobacteria (89%)] were distinct from those of maternal faeces [dominated by Firmicutes (66%) and Actinobacteria (15%)]. Actinobacteria predominated at 4-12 (65%) and 20-28 (50%) weeks. HIV-exposed infants had significantly higher faecal bacterial diversities at both 4-12 (p?=?0.026) and 20-28 weeks (p?=?0.002). HIV-exposed infants had lower proportions of Bifidobacterium (p?=?0.010) at 4-12 weeks. Maternal faecal bacterial profiles were influenced by HIV status, feeding practices and mode of delivery. Further longitudinal studies are required to better understand how these variables influence infant and maternal faecal bacterial composition.
Project description:Establishing a diverse gut microbiota after birth is being increasingly recognised as important for preventing illnesses later in life. It is well established that bacterial diversity rapidly increases post-partum; however, few studies have examined the infant gut virome/phageome during this developmental period. We performed a metagenomic analysis of 20 infant faecal viromes at one year of age to determine whether spontaneous vaginal delivery (SVD) or caesarean section (CS) influenced viral composition. We find that birth mode results in distinctly different viral communities, with SVD infants having greater viral and bacteriophage diversity. We demonstrate that CrAssphage is acquired early in life, both in this cohort and two others, although no difference in birth mode is detected. A previous study has shown that bacterial OTU's (operational taxonomic units) identified in the same infants could not discriminate between birth mode at 12 months of age. Therefore, our results indicate that vertical transmission of viral communities from mother to child may play a role in shaping the early life microbiome, and that birth mode should be considered when studying the early life gut virome.
Project description:BACKGROUND:HIV-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa especially with the increasing coverage of more effective prevention of mother-to-child transmission (PMTCT) antiretroviral therapy regimens. This study describes the characteristics of South African HEU infants, investigates factors impacting birth weight and assesses their growth within the first 28 weeks of life. METHODS:This is a retrospective cohort based on routine clinical data from two South African PMTCT programmes. Data were collected between 2007 and 2013. Linear regression assessed factors affecting birth weight-for-age z-scores (WAZ) while growth (longitudinal WAZ) was assessed using mixed effects models. RESULTS:We assessed the growth of 2621 HEU infants (median birth WAZ was -0.65 (IQR -1.46; 0.0) and 51% were male). The feeding modalities practised were as follows: 0.5% exclusive breastfeeding, 7.9% breastfeeding with unknown exclusivity, 0.08% mixed breastfeeding and 89.2% formula feeding. Mothers with CD4 <200 cells/?l delivered infants with a lower birth WAZ (adjusted ß -0.253 [95% CI -0.043; -0.072], p = 0.006) compared to mothers with aCD4 ?500 cells/?l. Similarly, mothers who did not receive antiretroviral drugs delivered infants with a lower birth WAZ (adjusted ß -0.39 [95% CI -0.67; -0.11], p = 0.007) compared to mothers who received antenatal antiretrovirals. Infants with a birth weight <2 500g (ß 0.070 [95% CI 0.061; 0.078], p <0.0001) experienced faster growth within the first 28 weeks of life compared to infants with a birth weight ?2 500g. Infants with any breastfeeding exposure experienced slower longitudinal growth compared to formula fed infants (adjusted ß -0.012 [95% CI 0.021; -0.003], p = 0.011). CONCLUSION:Less severe maternal disease and the use of antiretrovirals positively impacts birth weight in this cohort of South African HEU infants. Formula feeding was common with breastfed infants experiencing marginally slower longitudinal growth.
Project description:The early years of life are important for immune development and influence health in adulthood. Although it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or 'virome'), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome were more similar between co-twins than between unrelated infants. From birth to 2 years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator-low prey dynamic, consistent with the Lotka-Volterra prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophages with age.
Project description:While the association between early life determinants and the development of the gut microbiome composition in infancy has been widely investigated, a potential persistent influence of early life determinants on the gut microbial community after its stabilization at later childhood remains largely unknown. Therefore, we aimed to identify the association between several early life determinants and the gut microbiome composition in six-year-old children from the LISA birth cohort. A total number of 166 fecal samples were analyzed using 16S rRNA gene-based barcoding to assess bacterial diversity pattern. The bacterial profiles were investigated for their association with maternal smoking during pregnancy, mode of delivery, breastfeeding, antibiotic treatment between one and two years of age, gender and socioeconomic status (SES). While alpha and beta diversity of the infants' gut microbiome remained unaffected, amplicon sequence variants (ASVs) annotated to Firmicutes and Actinobacteria responded to early life determinants, mostly to feeding practice and antibiotics use. ASVs associated to Bacteriodetes remained unaffected. Our findings indicate that early life determinants could have a long-term sustainable effect on the gut microflora of six-year-old children, however, associations with early life determinates are weaker than reported for infants.
Project description:OBJECTIVE:To evaluate the potential impact of intrapartum antibiotics, and their specific classes, on the infant gut microbiota in the first year of life. DESIGN:Prospective study of infants in the New Hampshire Birth Cohort Study (NHBCS). SETTINGS:Rural New Hampshire, USA. POPULATION OR SAMPLE:Two hundred and sixty-six full-term infants from the NHBCS. METHODS:Intrapartum antibiotic use during labour and delivery was abstracted from medical records. Faecal samples collected at 6 weeks and 1 year of age were characterised by 16S rRNA sequencing, and metagenomics analysis in a subset of samples. EXPOSURES:Maternal exposure to antibiotics during labour and delivery. MAIN OUTCOME MEASURE:Taxonomic and functional profiles of faecal samples. RESULTS:Infant exposure to intrapartum antibiotics, particularly to two or more antibiotic classes, was independently associated with lower microbial diversity scores as well as a unique bacterial community at 6 weeks (GUnifrac, P = 0.02). At 1 year, infants in the penicillin-only group had significantly lower ? diversity scores than infants not exposed to intrapartum antibiotics. Within the first year of life, intrapartum exposure to penicillins was related to a significantly lower increase in several taxa including Bacteroides, use of cephalosporins was associated with a significantly lower rise over time in Bifidobacterium and infants in the multi-class group experienced a significantly higher increase in Veillonella dispar. CONCLUSIONS:Our findings suggest that intrapartum antibiotics alter the developmental trajectory of the infant gut microbiome, and specific antibiotic types may impact community composition, diversity and keystone immune training taxa. TWEETABLE ABSTRACT:Class of intrapartum antibiotics administered during delivery relates to maturation of infant gut microbiota.
Project description:SCOPE:Understanding biological functions of different free human milk oligosaccharides (HMOs) in shaping gastrointestinal tract microbiota during infancy is of great interest. We examined a link between HMOs in maternal milk and infant faecal microbiota composition and investigated the role of microbiota in degrading HMOs within the GI tract of healthy, breastfed, one-month old infants. METHODS AND RESULTS:Maternal breast milk and corresponding infant faeces originated from the KOALA Birth Cohort. HMOs were quantified in milk and infant faecal samples using PGC-UPLC-MS and HPAEC-PAD. Faecal microbiota composition was characterised using Illumina HiSeq amplicon 16S rRNA sequencing. The composition associated with gender, mode of delivery, and milk HMOs: Lacto-N-fucopentaose I and 2'-Fucosyllactose. Overall, Bifidobacterium, Bacteroides, Escherichia-Shigella and Parabacteroides were predominating genera. We detected three different patterns in the infant faecal microbiota structure. Gastrointestinal degradation of HMOs was strongly associated with faecal microbiota composition, and there was a link between utilisation of specific HMOs and abundance of various phylotypes (OTUs). CONCLUSIONS:HMOs in maternal milk are among important factors shaping GI tract microbiota composition in one-month old breastfed infants. Infant's ability to metabolise different HMOs strongly correlate with faecal microbiota composition, and with phylotypes within genera Bifidobacterium, Bacteroides and Lactobacillus. This article is protected by copyright. All rights reserved.
Project description:PURPOSE:HELMi (Health and Early Life Microbiota) is a longitudinal, prospective general population birth cohort, set up to identify environmental, lifestyle and genetic factors that modify the intestinal microbiota development in the first years of life and their relation to child health and well-being. PARTICIPANTS:The HELMi cohort consists of 1055 healthy term infants born in 2016-2018 mainly at the capital region of Finland and their parents. The intestinal microbiota development of the infants is characterised based on nine, strategically selected, faecal samples and connected to extensive online questionnaire-collected metadata at weekly to monthly intervals focusing on the diet, other exposures and family's lifestyle as well as the health and growth of the child. Motor and cognitive developmental screening takes place at 18 months. Infant's DNA sample, mother's breast milk sample and both parent's spot faecal samples have been collected. FINDINGS TO DATE:The mean age of the mothers was 32.8 (SD 4.1) and fathers/coparents 34.8 (5.3) years at the time of enrolment. Seventeen percentage (n=180) of the infants were born by caesarean section. Just under half (49%) were firstborns; 50.7% were males. At 3 months of age, 86% of the babies were exclusively breastfed and 2% exclusively formula-fed. FUTURE PLANS:The current follow-up from pregnancy to first 24 months will be completed in March 2020, totalling to over 10?000 biological samples and over 50?000 questionnaire entries. The results are expected to identify environmental and host factors that affect early gut microbiota development and health, and hence give indications of how to prevent or reverse microbiota perturbations in infancy. This prospective cohort will be followed up further to identify how the early microbiota relates to later health outcomes, especially weight gain, infections and allergic and other chronic diseases. TRIAL REGISTRATION NUMBER:NCT03996304; Pre-results.
Project description:Rectal swabs are potentially a valuable method for monitoring the gut microbiome in research and clinical settings, where it is important to adhere to strict timing, or where acute sampling is needed. It is currently unknown whether rectal swabs give comparable results to faecal samples regarding microbiota community composition in neonates and infants. To study how well the two sampling methods correlate in infants, we compared the 16S-rRNA-based sequencing results of 131 paired rectal swabs and faecal samples collected from 116 infants at two timepoints in early life. The paired samples were highly comparable regarding both diversity and overall community composition, and strongly correlated on taxonomical level. We observed no significant nor relevant contribution of sampling method to the variation in overall gut microbiota community composition in a multivariable model. Our study provides evidence supporting the use of rectal swabs as a reliable proxy for faecal samples in infant gut microbiota research.
Project description:Establishment of low birth weight (LBW) infant gut microbiota may have lifelong implications for the health of individuals. However, no longitudinal cohort studies have been conducted to characterize the gut microbial profiles of LBW infants and their influencing factors. Our objective was to understand how the gut bacterial community structure of LBW and normal birth weight (NBW) infants varies across the first 3 months of life and assess the influencing factors. In this observational cohort study, gut bacterial composition was identified with sequencing of the 16S rRNA gene in fecal samples of 69 LBW infants and 65 NBW controls at 0 day, 3 days, 2 weeks, 6 weeks, and 3 months (defined as stages 1-5) after birth. Alpha-diversity of both groups displayed a decreasing trend followed by slight variations. There were significant differences on the Shannon index of the two groups at stages 1 to 3 (P = 0.041, P = 0.032, and P = 0.014, respectively). The microbiota community structure of LBW infants were significantly different from NBW infants throughout the 3 months (all P < 0.05) but not at stage 2 (P = 0.054). There was a significant increase in abundance in Firmicutes while a decrease in Proteobacteria, and at genus level the abundance of Enterococcus, Klebsiella, and Streptococcus increased while it decreased for Haemophilus in LBW group. Birth weight was the main factor explaining the observed variation at all stages, except at stage 2. Delivery mode (4.78%) and antibiotic usage (3.50%) contributed to explain the observed variation at stage 3, and pregestational BMI (4.61%) partially explained the observed variation at stage 4. In conclusion, gut microbial communities differed in NBW and LBW infants from birth to 3 months of life, and were affected by birth weight, delivery mode, antibiotic treatment, and pregestational BMI.