The human gut microbiota develops soon after birth and can acquire inter-individual variation upon exposure to intrinsic and environmental cues. However, inter-individual variation has not been comprehensively assessed in a multi-ethnic study. We studied a longitudinal birth cohort of 106 infants of three Asian ethnicities (Chinese, Malay, and Indian) that resided in the same geographical location (Singapore). Specific and temporal influences of ethnicity, mode of delivery, breastfeeding status, gestational age, birthweight, gender, and maternal education on the development of the gut microbiota in the first 2 years of life were studied. Mode of delivery, breastfeeding status, and ethnicity were identified as the main factors influencing the compositional development of the gut microbiota. Effects of delivery mode and breastfeeding status lasted until 6M and 3M, respectively, with the primary impact on the diversity and temporal colonization of the genera Bacteroides and Bifidobacterium. The effect of ethnicity was apparent at 3M post-birth, even before the introduction of weaning (complementary) foods, and remained significant after adjusting for delivery mode and breastfeeding status. Ethnic influences remained significant until 12M in the Indian and Chinese infants. The microbiota of Indian infants was characterized by higher abundances of Bifidobacterium and Lactobacillus, while Chinese infants had higher abundances of Bacteroides and Akkermansia. These findings provide a detailed insight into the specific and temporal influences of early life factors and ethnicity in the development of the human gut microbiota. Trial Registration: Clinicaltrials.gov registration no. NCT01174875.
Probiotic Lactobacillus rhamnosus HN001 given in early life has been shown to reduce infant eczema risk, but its effect on gut microbiota development has not been quantitatively and functionally examined. The aim of this study was to investigate the impact of early life probiotic exposure on the composition and functional capacity of infant gut microbiota from birth to 2 years considering the effects of age, delivery mode, antibiotics, pets and eczema. We performed shotgun metagenomic sequencing analysis of 650 infant faecal samples, collected at birth, 3, 12, and 24 months, as part of a randomised, controlled, 3-arm trial assessing the effect of L. rhamnosus HN001, Bifidobacterium animalis subsp. lactis HN019 supplementation on eczema development in 474 infants. There was a 50% reduced eczema risk in the HN001 probiotic group compared to placebo. Both mothers (from 35 weeks gestation until 6 months post-partum if breastfeeding) and infants (from birth to 2 years) received either a placebo or one of two probiotics, L. rhamnosus HN001 (6×109 cfu), or B. animalis subsp. lactis HN019 (9×109 cfu). L. rhamnosus HN001 probiotic supplementation was associated with increased overall glycerol-3 phosphate transport capacity and enrichment of L. rhamnosus. There were no other significant changes in infant gut microbiota composition or diversity. Increased capacity to transport glycerol-3-phosphate was positively correlated with relative abundance of L. rhamnosus. Children who developed eczema had gut microbiota with increased capacity for glycosaminoglycan degradation and flagellum assembly but had no significant differences in microbiota composition or diversity. Early life HN001 probiotic use is associated with both increased L. rhamnosus and increased infant gut microbiota functional capacity to transport glycerol-3 phosphate. The mechanistic relationship of such functional alteration in gut microbiota with reduced eczema risk and long-term health merits further investigation.
The introduction of 'solids' (i.e. complementary foods) to the milk-only diet of early infancy affects the development of the gut microbiota. The aim of this study was to determine whether a 'baby-led' approach to complementary feeding, that encourages early introduction of an adult type diet, results in alterations to gut microbiota composition compared to traditional spoon-feeding. The Baby-Led Introduction to SolidS (BLISS) study randomized 206 infants to BLISS (a modified version of Baby-Led Weaning (BLW): introduction of solids at 6 months of age, followed by self-feeding of family foods) or Control (traditional spoon-feeding of purées) groups. Fecal microbiotas and 3-day weighed diet records were analysed from a subset of 74 infants at 7 and 12 months of age. The composition of the microbiota was determined by sequencing 16S rRNA genes amplified by PCR from bulk DNA extracted from feces. Diet records were used to estimate food and dietary fiber intake. Alpha diversity (number of Operational Taxonomic Units; OTUs) was significantly lower in BLISS infants at 12 months (difference, 95% CI: 31, 3.4 to 58.5; p = 0.028) and, while there were no significant differences between Control and BLISS infants in relative abundances of or at 7 or 12 months of age, OTUs representing the genus were less prevalent in BLISS microbiotas at 12 months. Mediation models demonstrated that 'fruit and vegetables' and 'dietary fiber' intake explained 29% and 25% respectively of the relationship between group (BLISS versus Control) and alpha diversity. The introduction of solid foods (complementary feeding, weaning) to infants leads to more complex compositions of microbial communities (microbiota, microbiome) in the gut. In Baby Led Weaning (BLW), infants are given only finger foods they can pick up and feed themselves - there is no parental spoon-feeding of puréed baby foods - and infants are encouraged to eat family meals. BLW is a new approach to infant feeding that is increasing in popularity in the United States, New Zealand, the United Kingdom and Canada. We used mediation modeling, commonly used in health research but not until now in microbiota studies, to identify particular dietary components that affected the development of the infant gut microbiota.
Background Gut microbiota data obtained by DNA sequencing are complex and compositional because of large numbers of detectable taxa, and because microbiota characteristics are described in relative terms. Nutrition researchers use principal component analysis (PCA) to derive dietary patterns from food data. Although compositional PCA methods are not commonly used to describe patterns from complex microbiota data, this approach would be useful for identifying gut microbiota patterns associated with diet and body composition. Objectives To use compositional PCA to describe the principal components (PCs) of gut microbiota in 5-y-old children and explore associations between microbiota components, diet, and BMI z-score. Methods A fecal sample was provided by 319 children aged 5 y. Their primary caregiver completed a validated 123-item quantitative FFQ. Body composition was determined using DXA, and a BMI z-score was calculated. Compositional PCA identified characterizing taxa and weightings for calculation of gut microbiota PC scores at the genus level, and was examined in relation to diet and body size. Results Three gut microbiota PCs were found. PC1 (negative loadings on uncultured Christensenellaceae and Ruminococcaceae) was related to lower BMI z-scores and longer duration of breastfeeding (per month) (β = −0.14; 95% CI: −0.26, −0.02; and β = 0.02; 95% CI: 0.003, 0.34, respectively). PC2 (positive loadings on Fusicatenibacter and Bifidobacterium; negative loadings on Bacteroides) was associated with a lower intake of nuts, seeds, and legumes (β = −0.05 per gram; 95% CI: −0.09, −0.01). When adjusted for fiber intake, PC2 was also associated with higher BMI z-scores (β = 0.12; 95% CI: 0.01, 0.24). PC3 (positive loadings on Faecalibacterium, Eubacterium, and Roseburia) was associated with higher intakes of fiber (β = 0.02 per gram; 95% CI: 0.003, 0.04) and total nonstarch polysaccharides (β = 0.02 per gram; 95% CI: 0.003, 0.04). Conclusions Our results suggest that specific gut microbiota components determined using compositional PCA are associated with diet and BMI z-score. This trial was registered at clinicaltrials.gov as NCT00892983.
The biological succession that occurs during the first year of life in the gut of infants in Western countries is broadly predictable in terms of the increasing complexity of the composition of microbiotas. Less information is available about microbiotas in Asian countries, where environmental, nutritional, and cultural influences may differentially affect the composition and development of the microbial community. We compared the fecal microbiotas of Indonesian (n = 204) and New Zealand (NZ) (n = 74) infants 6 to 7 months and 12 months of age. Comparisons were made by analysis of 16S rRNA gene sequences and derivation of community diversity metrics, relative abundances of bacterial families, enterotypes, and cooccurrence correlation networks. Abundances of Bifidobacterium longum subsp. infantis and B. longum subsp. longum were determined by quantitative PCR. All observations supported the view that the Indonesian and NZ infant microbiotas developed in complexity over time, but the changes were much greater for NZ infants. B. longum subsp. infantis dominated the microbiotas of Indonesian children, whereas B. longum subsp. longum was dominant in NZ children. Network analysis showed that the niche model (in which trophic adaptation results in preferential colonization) of the assemblage of microbiotas was supported in Indonesian infants, whereas the neutral (stochastic) model was supported by the development of the microbiotas of NZ infants. The results of the study show that the development of the fecal microbiota is not the same for infants in all countries, and they point to the necessity of obtaining a better understanding of the factors that control the colonization of the gut in early life. IMPORTANCE This study addresses the microbiology of a natural ecosystem (the infant bowel) for children in a rural setting in Indonesia and in an urban environment in New Zealand. Analysis of DNA sequences generated from the microbial community (microbiota) in the feces of the infants during the first year of life showed marked differences in the composition and complexity of the bacterial collections. The differences were most likely due to differences in the prevalence and duration of breastfeeding of infants in the two countries. These kinds of studies are essential for developing concepts of microbial ecology related to the influence of nutrition and environment on the development of the gut microbiota and for determining the long-term effects of microbiological events in early life on human health and well-being.
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