Development Of Microbiota In Infants Research Articles

Upper airway microbiota development in infants with cystic fibrosis diagnosed by newborn screen

BackgroundChanges in upper airway microbiota may impact early disease manifestations in infants with cystic fibrosis (CF). To investigate early airway microbiota, the microbiota present in the oropharynx of CF infants over the first year of life was assessed along with the relationships between microbiota and growth, antibiotic use and other clinical variables. MethodsOropharyngeal (OP) swabs were collected longitudinally between 1 and 12 months of age from infants diagnosed with CF by newborn screen and enrolled in the Baby Observational and Nutrition Study (BONUS). DNA extraction was performed after enzymatic digestion of OP swabs. Total bacterial load was determined by qPCR and community composition assessed using 16S rRNA gene analysis (V1/V2 region). Changes in diversity with age were evaluated using mixed models with cubic B-splines. Associations between clinical variables and bacterial taxa were determined using a canonical correlation analysis. Results1,052 OP swabs collected from 205 infants with CF were analyzed. Most infants (77%) received at least one course of antibiotics during the study and 131 OP swabs were collected while the infant was prescribed an antibiotic. Alpha diversity increased with age and was only marginally impacted by antibiotic use. Community composition was most highly correlated with age and was only moderately correlated with antibiotic exposure, feeding method and weight z-scores. Relative abundance of Streptococcus decreased while Neisseria and other taxa increased over the first year. ConclusionsAge was more influential on the oropharyngeal microbiota of infants with CF than clinical variables including antibiotics in the first year of life.

Mother-to-infant microbiota transmission and infant microbiota development across multiple body sites

Early-life microbiota seeding and subsequent development is crucial to future health. Cesarean-section (CS) birth, as opposed to vaginal delivery, affects early mother-to-infant transmission of microbes. Here, we assess mother-to-infant microbiota seeding and early-life microbiota development across six maternal and four infant niches over the first 30days of life in 120 mother-infant pairs. Across all infants, we estimate that on average 58.5% of the infant microbiota composition can be attributed to any of the maternal source communities. All maternal source communities seed multiple infant niches. We identify shared and niche-specific host/environmental factors shaping the infant microbiota. In CS-born infants, we report reduced seeding of infant fecal microbiota by maternal fecal microbes, whereas colonization with breastmilk microbiota is increased when compared with vaginally born infants. Therefore, our data suggest auxiliary routes of mother-to-infant microbial seeding, which may compensate for one another, ensuring that essential microbes/microbial functions are transferred irrespective of disrupted transmission routes.

Microbial network signatures of early colonizers in infants with eczema.

In this longitudinal cohort study, our results demonstrated that there are rhythmic changes in gut microbial network signatures in early life, and healthy infants adopt more complex and stable network structure in their gut microbiota than that of the infants with eczema.

Nutrition, Gut Microbiota, and Allergy Development in Infants.

The process of gut microbiota development in infants is currently being challenged by numerous factors associated with the contemporary lifestyle, including diet. A thorough understanding of all aspects of microbiota development will be necessary for engineering strategies that can modulate it in a beneficial direction. The long-term consequences for human development and health of alterations in the succession pattern that forms the gut microbiota are just beginning to be explored and require much further investigation. Nevertheless, it is clear that gut microbiota development in infancy bears strong associations with the risk for allergic disease. A useful understanding of microbial succession in the gut of infants needs to reveal not only changes in taxonomic composition but also the development of functional capacities through time and how these are related to diet and various environmental factors. Metagenomic and metatranscriptomic studies have started to produce insights into the trends of functional repertoire and gene expression change within the first year after birth. This understanding is critical as during this period the most substantial development of the gut microbiota takes place and the relations between gut microbes and host immunity are established. However, further research needs to focus on the impact of diet on these changes and on how diet can be used to counteract the challenges posed by modern lifestyles to microbiota development and reduce the risk of allergic disease.

Exclusively Breastfed Infant Microbiota Develops over Time and Is Associated with Human Milk Oligosaccharide Intakes.

Temporal development of maternal and infant microbiomes during early life impacts short- and long-term infant health. This study aimed to characterize bacterial dynamics within maternal faecal, human milk (HM), infant oral, and infant faecal samples during the exclusive breastfeeding period and to document associations between human milk oligosaccharide (HMO) intakes and infant oral and faecal bacterial profiles. Maternal and infant samples (n = 10) were collected at 2–5, 30, 60, 90 and 120 days postpartum and the full-length 16S ribosomal RNA (rRNA) gene was sequenced. Nineteen HMOs were quantitated using high-performance liquid chromatography. Bacterial profiles were unique to each sample type and changed significantly over time, with a large degree of intra- and inter-individual variation in all sample types. Beta diversity was stable over time within infant faecal, maternal faecal and HM samples, however, the infant oral microbiota at day 2–5 significantly differed from all other time points (all p < 0.02). HMO concentrations and intakes significantly differed over time, and HMO intakes showed differential associations with taxa observed in infant oral and faecal samples. The direct clinical relevance of this, however, is unknown. Regardless, future studies should account for intakes of HMOs when modelling the impact of HM on infant growth, as it may have implications for infant microbiota development.

Targeted Development of Infant Microbiota on Formula Feeding: Modern Options

The review provides the analysis of recent publications covering the biological significance of infant microbiome and showing modern research technologies. Correlations of quantitative and qualitative characteristics of intestinal microbiota with delayed health issues were evaluated. Various concepts of newborn microbiome origin, timing, and stages of bacterial colonization of gastrointestinal tract were considered. Data on the role of delivery method on infant microbiota development is presented (including the significance of contamination with maternal vaginal flora where ontogenetic priority belongs to lactobacilli). It was revealed that Lactobacillus fermentum was the basis microflora providing the conditions for the subsequent successful colonization of the child’s intestines with obligate symbionts. The significance of breastfeeding in adequate microbiota development was confirmed. In case of mandatory formula feeding, it is necessary to enrich infant milk formulas with components that promote the selection of symbiotic microflora such as: long-chain polyunsaturated fatty acids, prebiotics, oligosaccharides, and probiotics of specific action. The innovative formula based on synbiotic/combiotic concept will be able to partially compensate impaired microbiota development in infant on mandatory formula feeding.

Recent advances of intestinal microbiota transmission from mother to infant

The intestinal microbiota of infants plays an important role in early life and affects health throughout lifespan. The mother is closely associated with the infant microbiota, by helping to establish it through her own gut microbiota, intrauterine and birth canal environments, and feeding. In this study, the characteristics, influencing factors, and effects of pregnant women on offspring, the establishment and development of intestinal microbiota in infants, and the significance of mother-to-infant transmission were reviewed, to provide new research impetus on the establishment of intestinal microbiota in infants.

Maternal Diet Shapes the Breast Milk Microbiota Composition and Diversity: Impact of Mode of Delivery and Antibiotic Exposure

ABSTRACTBackgroundBreast milk is a complex biofluid that provides nutrients and bioactive agents, including bacteria, for the development of the infant gut microbiota. However, the impact of maternal diet and other factors, such as mode of delivery and antibiotic exposure, on the breast milk microbiota has yet to be understood.ObjectivesThis study aimed to examine the association between maternal diet and breast milk microbiota and to ascertain the potential role of mode of delivery and antibiotic exposure.MethodsIn a cross-sectional study of the MAMI cohort, breast milk microbiota profiling was assessed in 120 samples from healthy mothers by 16S rRNA gene sequencing. Maternal dietary information was recorded through an FFQ, and clinical characteristics, including mode of delivery, antibiotic exposure, and exclusive breastfeeding, were collected.ResultsMaternal diet was grouped into 2 clusters: Cluster I (high intake of plant protein, fiber, and carbohydrates), and Cluster II (high intake of animal protein and lipids). Breast milk microbiota was shaped by maternal dietary clusters. Staphylococcus and Bifidobacterium were associated with carbohydrate intake whereas the Streptococcus genus was associated with intakes of the n–3 PUFAs [EPA and docosapentaenoic acid (22:5ω-3)]. Mode of delivery and antibiotic exposure influenced breast milk microbiota in a diet cluster–dependent manner. Differences between/among the maternal dietary clusters were found in the milk microbiota of the cesarean-section (C-section)/antibiotic group, whereas no differences were observed in vaginal births. Lower abundances of Lactobacillus, Bacteroides, and Sediminibacterium genera were observed in Cluster II/C-section/antibiotic exposure compared with the other groups.ConclusionsMaternal diet shapes the composition and diversity of breast milk microbiota, with the most important contributions coming from dietary fiber and both plant and animal protein intakes. The relation between the maternal diet and the milk microbiota needs further research because it has a key impact on infant microbiota development and contributes to infant health outcomes in the short and long term.This trial was registered at clinicaltrials.gov as NCT03552939.

Neonatal intensive care unit (NICU) exposures exert a sustained influence on the progression of gut microbiota and metabolome in the first year of life

Emerging evidence has shown a link between the perturbations and development of the gut microbiota in infants with their immediate and long-term health. To better understand the assembly of the gut microbiota in preterm infants, faecal samples were longitudinally collected from the preterm (n = 19) and term (n = 20) infants from birth until month 12. 16S rRNA gene sequencing (n = 141) and metabolomics profiling (n = 141) using nuclear magnetic resonance spectroscopy identified significant differences between groups in various time points. A panel of amino acid metabolites and central metabolism intermediates significantly correlated with the relative abundances of 8 species of bacteria were identified in the preterm group. In contrast, faecal metabolites of term infants had significantly higher levels of metabolites which are commonly found in milk such as fucose and β-hydroxybutyrate. We demonstrated that the early-life factors such as gestational age, birth weight and NICU exposures, exerted a sustained effect to the dynamics of gut microbial composition and metabolism of the neonates up to one year of age. Thus, our findings suggest that intervention at this early time could provide ‘metabolic rescue’ to preterm infants from aberrant initial gut microbial colonisation and succession.

Multi-omics analysis reveals the influence of genetic and environmental risk factors on developing gut microbiota in infants at risk of celiac disease

BackgroundCeliac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals in response to ingesting gluten, a protein found in wheat, rye, and barley. Research shows that genetic predisposition and exposure to gluten are necessary but not sufficient to trigger the development of CD. This suggests that exposure to other environmental stimuli early in life, e.g., cesarean section delivery and exposure to antibiotics or formula feeding, may also play a key role in CD pathogenesis through yet unknown mechanisms. Here, we use multi-omics analysis to investigate how genetic and early environmental risk factors alter the development of the gut microbiota in infants at risk of CD.ResultsToward this end, we selected 31 infants from a large-scale prospective birth cohort study of infants with a first-degree relative with CD. We then performed rigorous multivariate association, cross-sectional, and longitudinal analyses using metagenomic and metabolomic data collected at birth, 3 months and 6 months of age to explore the impact of genetic predisposition and environmental risk factors on the gut microbiota composition, function, and metabolome prior to the introduction of trigger (gluten). These analyses revealed several microbial species, functional pathways, and metabolites that are associated with each genetic and environmental risk factor or that are differentially abundant between environmentally exposed and non-exposed infants or between time points. Among our significant findings, we found that cesarean section delivery is associated with a decreased abundance of Bacteroides vulgatus and Bacteroides dorei and of folate biosynthesis pathway and with an increased abundance of hydroxyphenylacetic acid, alterations that are implicated in immune system dysfunction and inflammatory conditions. Additionally, longitudinal analysis revealed that, in infants not exposed to any environmental risk factor, the abundances of Bacteroides uniformis and of metabolite 3-3-hydroxyphenylproprionic acid increase over time, while those for lipoic acid and methane metabolism pathways decrease, patterns that are linked to beneficial immunomodulatory and anti-inflammatory effects.ConclusionsOverall, our study provides unprecedented insights into major taxonomic and functional shifts in the developing gut microbiota of infants at risk of CD linking genetic and environmental risk factors to detrimental immunomodulatory and inflammatory effects.8YsRcde85W9Y3JefUUhGM4Video

Gut microbiota dysontogeniya in infants as a factor in the development of atopy

The article describes the modern views on the relationship between altered development of gut microbiota in infants and the risk of developing atopic diseases (atopic dermatitis and bronchial asthma). The studies of genetic susceptibility to atopy and the influence of epigenetic mechanisms involved in the regulation of gene expression responsible for the hyperproduction of immunoglobulin E are discussed. The characteristics of the microbiota of infants with already developed atopic diseases and children at risk of atopy are analyzed. In infants who subsequently developed atopy, the composition of gut microbiota at the birth is characterized by a reduced abundance of bifidobacteria and high content of potentially pathogenic microorganisms. The triggering role of active metabolites of altered microbiota on the differentiation of T-regulatory cells has been established. A preventive effect of optimal breastfeeding has been confirmed: meta-analyzes of recent studies indicate a link between the duration of breastfeeding and a decrease in the frequency of bronchial asthma. The microbiota of breast milk contributes to the proper development of the infant’s microbiota, determines its diversity and immunomodulating action. On the basis of the conducted research, methods of targeted correction of the intestinal microbiota in children with risk of atopy can be developed.

Longitudinal development of the airway microbiota in infants with cystic fibrosis

The pathogenesis of airway infection in cystic fibrosis (CF) is poorly understood. We performed a longitudinal study coupling clinical information with frequent sampling of the microbiota to identify changes in the airway microbiota in infancy that could underpin deterioration and potentially be targeted therapeutically. Thirty infants with CF diagnosed on newborn screening (NBS) were followed for up to two years. Two hundred and forty one throat swabs were collected as a surrogate for lower airway microbiota (median 35 days between study visits) in the largest longitudinal study of the CF oropharyngeal microbiota. Quantitative PCR and Illumina sequencing of the 16S rRNA bacterial gene were performed. Data analyses were conducted in QIIME and Phyloseq in R. Streptococcus spp. and Haemophilus spp. were the most common genera (55% and 12.5% of reads respectively) and were inversely related. Only beta (between sample) diversity changed with age (Bray Curtis r2 = 0.15, P = 0.03). Staphylococcus and Pseudomonas were rarely detected. These results suggest that Streptococcus spp. and Haemophilus spp., may play an important role in early CF. Whether they are protective against infection with more typical CF micro-organisms, or pathogenic and thus meriting treatment needs to be determined.

Gut Microbiota and Probiotics in Neonate

The collaboration and symbiotic relationship between microbiota and humans is complex. Development of the gut microbiota in infants is a dynamic process that is dependent on maternal-fetal-neonatal determinants. Vast collaborative enterprises of cooperative, co-dependent, and competitive ecologies are enormously powerful when merged together as one discrete entity or organ. This forgotten and invisible organ has both benefits and harm in health throughout the life cycle and across the next generations for the long term. Rapid advances in microbiology, genomic research and metagenomics analysis have uncovered the microbial contribution in both the hugeness and diversity of the microbial sphere. As a result, simultaneous findings have repercussions for microbial growth and health in the neonatal period and extend into childhood and adulthood. Pioneer microbiota in and on the neonate may find 'windows of opportunity' to promote health and prevent diseases. Oral probiotics is one choice to alter and balance the gut microbiota. However, the heterogeneity of research outcomes cannot be applied routinely in premature infants.

A key genetic factor for fucosyllactose utilization affects infant gut microbiota development.

Recent studies have demonstrated that gut microbiota development influences infants' health and subsequent host physiology. However, the factors shaping the development of the microbiota remain poorly understood, and the mechanisms through which these factors affect gut metabolite profiles have not been extensively investigated. Here we analyse gut microbiota development of 27 infants during the first month of life. We find three distinct clusters that transition towards Bifidobacteriaceae-dominant microbiota. We observe considerable differences in human milk oligosaccharide utilization among infant bifidobacteria. Colonization of fucosyllactose (FL)-utilizing bifidobacteria is associated with altered metabolite profiles and microbiota compositions, which have been previously shown to affect infant health. Genome analysis of infants' bifidobacteria reveals an ABC transporter as a key genetic factor for FL utilization. Thus, the ability of bifidobacteria to utilize FL and the presence of FL in breast milk may affect the development of the gut microbiota in infants, and might ultimately have therapeutic implications.

MICROBIOME REVOLUTION AND NEONATOLOGY

Summary.The community of bacteria, viruses and fungi that colonize the human body, known as the "microbiome" recently began to be seen as an important complex factor of human physiology and pathology. The largest group of microbiome microorganisms is their population in the digestive tract. This population performs important functions – barrier, metabolic, trophic, and immune. The formation and development of the intestinal microbiota in infants is characterized by rapid and significant changes in the number, diversity and composition of bacteria. These processes are affected by medical, environmental and cultural factors, starting from the prenatal effects, gestational age, and types of delivery and feeding to the characteristics of the family environment, diseases and treatment used. Thus, the colonization of the intestine of each child is an individual, making it difficult to practically determine the universal standard of this process and its consequences. Disruption of the formation of intestinal microbiota in genetically susceptible individuals may break the physiological processes of early bacterial "programming" and cause immune disorders of childhood, including necrotizing enterocolitis, atopic disease, inflammatory bowel disease, irritable bowel syndrome etc. Pre- and probiotics may be useful in the prevention and treatment of the diseases modulating the processes of intestinal microbial community formation and regulation of the host’s mucous membranes immune functions. This review discusses recent data about the peculiarities of early bacterial colonization of the intestine, the factors that influence this process and its importance to human health.

Development of the Nasopharyngeal Microbiota in Infants with Cystic Fibrosis.

Cystic fibrosis (CF) is characterized by early structural lung disease caused by pulmonary infections. The nasopharynx of infants is a major ecological reservoir of potential respiratory pathogens. To investigate the development of nasopharyngeal microbiota profiles in infants with CF compared with those of healthy control subjects during the first 6 months of life. We conducted a prospective cohort study, from the time of diagnosis onward, in which we collected questionnaires and 324 nasopharynx samples from 20 infants with CF and 45 age-matched healthy control subjects. Microbiota profiles were characterized by 16S ribosomal RNA-based sequencing. We observed significant differences in microbial community composition (P < 0.0002 by permutational multivariate analysis of variance) and development between groups. In infants with CF, early Staphylococcus aureus and, to a lesser extent, Corynebacterium spp. and Moraxella spp. dominance were followed by a switch to Streptococcus mitis predominance after 3 months of age. In control subjects, Moraxella spp. enrichment occurred throughout the first 6 months of life. In a multivariate analysis, S. aureus, S. mitis, Corynebacterium accolens, and bacilli were significantly more abundant in infants with CF, whereas Moraxella spp., Corynebacterium pseudodiphtericum and Corynebacterium propinquum and Haemophilus influenzae were significantly more abundant in control subjects, after correction for age, antibiotic use, and respiratory symptoms. Antibiotic use was independently associated with increased colonization of gram-negative bacteria such as Burkholderia spp. and members of the Enterobacteriaceae bacteria family and reduced colonization of potential beneficial commensals. From diagnosis onward, we observed distinct patterns of nasopharyngeal microbiota development in infants with CF under 6 months of age compared with control subjects and a marked effect of antibiotic therapy leading toward a gram-negative microbial composition.

On the origin of species: Factors shaping the establishment of infant's gut microbiota.

The human gut microbiota is a complex and dynamic ecosystem, which naturally lives in a symbiotic relationship with the host. Perturbations of the microbial composition (dysbiosis) and reduced diversity may promote disease susceptibility and recurrence. In contrast to the mature intestinal microbiota of healthy adults, which appears relatively stable over time, the infant's microbiome only establishes and matures during the first years of life. In this respect, early childhood seems to represent a crucial age-window in disease prevention, since microbial diversification and maturation of the microbiome primarily occurs during this period of life. A better understanding of ecological processes and pioneer consortia in microbial development is crucial, in order to support the development of a beneficial microbiota. Various deterministic and stochastic aspects seem to shape the microbiome in early life, including maternal, environmental, and host factors. Here, we review the current understanding of the origin of pioneer bacteria and the evolutionary factors that influence the development of the gut microbiota in infants. In addition, future perspectives, including manipulating and promoting the succession of initial bacteria during infancy, will be highlighted.

Metabolic Disease: Obesity, Malnutrition, and Intestinal Microbiota

Obesity is a worldwide epidemic that is accompanied by a dramatic increase in obesity-related disorders; it threatens both industrialized and developing countries. Recent studies have shown that the gut microbial community (microbiota) is an environmental factor of developmental origins of health and diseases (DOHaD) that regulates obesity by increasing energy harvest from the diet and regulating peripheral metabolism. Dysbiosis in neonates and infants is caused by a disrupted environment that influences the initial colonization of microbes in the gut; such disruptions include a C-section delivery, formula feeding, excessive use of antibiotics, or the introduction of inappropriate solid foods containing a high amount of saturated fat. Dysbiosis delays the development of mucosal host defense and immunity, leading to a high risk of obesity, metabolic disease, and immune-mediated disease later in life. Bifidobacteria and Bacteroides , which are found in human milk and are predominant mutualists in healthy microbiota, colonize the gut initially as “pioneer” bacteria; in this way, human milk and its oligosaccharides confer benefits, such as reducing the risks of obesity and metabolic syndrome, to the offspring. As the microbial exposure of neonates is provided mainly from the maternal microbiota, maternal obesity with dysbiosis has an impact on infant microbiota development that can lead to major shifts in the microbiota composition of the child in early life and may cause aberrant immune function and priming for harmful responses to postnatal triggers. Alterations in the gut microbiome have been strongly implicated in childhood malnutrition. This paper reviews the evidence linking gut microbiota, obesity, and malnutrition.

Opportunities to assess factors contributing to the development of the intestinal microbiota in infants living in developing countries.

Recent evidence suggests that establishment of a healthy gut microbiota shortly after birth is important to achieve optimal growth and development of children. Being born into a resource-poor environment presents challenges to the establishment of a healthy gut microbial flora in the newborn. Among these challenges are births that occur at home, traditional pre-lacteal feeding of newborns leading to failure to initiate lactation, poor sanitation and water quality, early environmental exposure to, and infection with, enteric or other pathogens, suboptimal breast feeding duration and intensity, deficiencies in weaning and childhood diets contributing to micro- and macro-nutrient deficiencies, and the frequent use of antibiotics. These factors should be considered in the design and implementation of preventive and therapeutic interventions aimed at improving the health and development of these children.

Neonatal Antibiotic Exposure Alters Compositional Gut Microbiota Development During the First 6 Months of Life

ObjectiveTo investigate the impact of neonatal antibiotic exposure on gut microbiota development in infants born after 36 weeks of gestationMethodsA case‐control study of 6 neonates exposed to brief (&lt;5 days) empirical antibiotics (penicillin G and gentamicin) during the first 72 hours of life, 6 neonates receiving a 7‐day course of the same antibiotics for documented infection and 24 matched healthy non‐exposed neonates. Gut microbiota composition was assessed at 1 and 6 months of age by qPCR, DGGE and 16S rRNA pyrosequencingResultsNeonatal antibiotic exposure resulted in a significant decrease in fecal bifidobacteria at 1 month of age (p=0.015), particularly in B. bifidum (p=0.0061). The bacterial richness of infants exposed to antibiotics was significantly lower compared to non‐exposed infants. The principal coordinates analysis (PCoA) formed separate clusters when compared between antibiotic‐exposed and non‐exposed infants at 6 months of age. In particular, an increased frequency of Firmicutes and a decrease in Bacteroidetes was observed in antibiotic‐exposed infantsConclusionsAberrant gut microbiota colonization is attributable to antibiotic exposure since it was observed also in antibiotic‐exposed neonates in whom infection was later ruled out. Decreased levels of both bifidobacteria and Bacteroidetes in early infancy have previously been linked to increased risk for non‐communicable disease in later life. Means of accurately detecting bacterial infections in neonates are needed to avoid unnecessary exposure to antibiotics during this vulnerable periodResearch supportFunctional Foods Forum, University of Turku