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The contribution of the microbiota to provision of energy and nutrients for intestinal development and the nutritional status of the host are reviewed. Most VLBW infants receive broad-spectrum antibiotics during their early postnatal course possibly resulting in inadequate phase I colonization 13 with an apparent inverse correlation between the of days of antibiotics in the first month postnatally and microbial diversity as well as total bacterial load in stools Early studies suggested that colonization with beneficial bacteria such as Lactobacillus is specifically affected 1933 and that antibiotic usage promotes a bloom of Staphylococcus.

In the term breastfed infant, it has been shown that by 7 d, the beneficial Bifidobacteria and Lactobacillus predominate In formula-fed infants, a more adult-type flora is most prevalent 13323738 along with an abundance of potentially pathogenic bacteria Clostridium difficile and Escherichia coli 536 Most recently, Azad et al. Increased bacterial load supported by the provision of undigested carbohydrates and the resultant microbial synthesis of butyrate is thought to play a role in increased intestinal cell proliferation.

Current guidelines and future strategies for the management of cow’s milk allergy

For example, TLR-2 recognizes peptidoglycan and lipoteichoic acid from Gram-positive bacteria, TLR-4 recognizes lipopolysaccharide, the endotoxin of Gram-negative bacteria, and TLR-5 recognizes flagellin Paradoxically, aling induced by commensal bacteria is required for development of gut epithelial cell protection against inflammatory mediator injury as well as for cell repair The effects of commensal bacteria include enhancement of tight junctions, stimulation of mucin production, and downregulation of cytokine production.

Differences in microbial community composition between normal weight and obese children and adults have been observed Important in reference to the VLBW infant, new data from developing countries suggest that the GIT microbial composition is altered in both marasmus malnutrition due to insufficient energy and kwashiorkor malnutrition due to insufficient protein Interestingly, transplantation of the microbiota of Malawian children with kwashiorkor to gnotobiotic mice fed a rodent diet patterned after the Malawian diet resulted in ificant perturbation of both amino acid and carbohydrate metabolism It has long been recognized that intestinal bacteria are critical in synthesizing a of vitamins, vitamin K being the classic example.

The metagenome refers to the totality of the genomes from the whole community including bacteria, fungi, viruses, and protozoa. Distal organ damage in systemic inflammatory response syndrome has been linked to severe morbidities associated with preterm birth including brain damage periventricular leukomalacia and lung damage chronic lung disease 2. Learn More.

With the advent of molecular technologies, it has become possible to not only study the bacterial species present but also the metabolic differences in the GIT microbiota of infants with and without NEC. Impact of preterm birth on the gastrointestinal microbiota. Our own work in this area suggests that the total amount of the B-vitamin folate synthesized by bacteria in the colon may approach or even exceed dietary intake in both infants and adults and it can be absorbed 53 Other vitamins thought to be synthesized by bacteria include vitamin B12, biotin, thiamine, riboflavin, and pyridoxine.

These metabolites include bile acids facilitate fat absorptioncholine metabolites modulate lipid and glucose homeostasisphenolic, benzoyl, and phenyl derivatives detoxification of xenobioticsindole derivatives protect against stress-induced lesions in the gutlipids, and many more The pathophysiology of these disorders is likely multifactorial involving a combination of intestinal mucosal barrier immaturity, an imbalance in microvascular tone, aberrant microbial colonization and an unbalanced immune response Infectious causes for NEC have been sought for more than 30 years with the implication of several bacteria namely several species of ClostridiumKlebsiella pneumoniaeEscherichia coliand Cronobacter sakazakii and viruses namely Coronavirus, Coxsackie, Rotavirus, Adenovirus, and Torovirus 8.

The VLBW infant is at elevated risk of metabolic syndrome including type II diabetes, hypertension, and obesity in later life. There appear to be ificant differences in the composition of the intestinal microbiota of preterm compared to term infants, with decreased bacterial diversity, increased pathogens potentially related to NEC, and a surprising increase in eukaryotic and viral diversity 3623242526272829 Other limiting factors in studying these data are the heterogeneity or lack of reporting of patient characteristics, diet, mode of delivery, antibiotic course, and sampling frequency and timing some samples only collected after the onset of NEC.

Summary of intestinal microbiota studies from infants with necrotizing enterocolitis NEC. Infants born by cesarean have a different GIT microbiome compared with those born vaginally, and some of these differences are sustained throughout early childhood 314152031 Vaginal birth le to an inoculation of infants with maternal fecal and vaginal bacteria. More than 1, bacterial species have been identified in the adult GIT with the three phyla being prominent: Bacteroides, Actinobacteria, and Firmicutes.

The microbiome, of which the bacterial component alone microbiotais estimated to include 10 times more cells than human cells of the body, blooms immediately after birth and evolves in composition and complexity throughout childhood.

Contrary to studies, this group did not observe differences by mode of delivery in prevalence of Clostridium difficile or the relative abundance of Bifidobacterium or Clostridium.

The online version of this article doi The microbiome describes the totality of the microbes in an environment, including bacteria, protozoa, viruses, fungi, and their genetic elements. Beyond 16S rDNA—based sequencing, metagenomic, metatranscriptomic, metaproteomic, metabolomic, and non—16S rDNA-targeted approaches are increasingly employed to generate functional and quantitative information on microbial communities 8.

Until recently, we believed that the GIT of a healthy-term newborn was sterile; however, meconium is now known to contain microbial rDNA 10suggesting that infants are colonized before birth. Additionally, short-chain fatty acids are believed to influence energy metabolism by binding to and activating G protein-coupled receptors on colonic epithelial and enteroendocrine cells resulting in the release of peptide YY and glucagon-like peptide.

To analyze a metagenome, DNA is extracted and shotgun sequenced to determine functional and biochemical capabilities of the microbial community. The microbiota communicates with host cells via Toll-like receptors TLR which are transmembrane proteins present throughout the GIT that sense microbes by their conserved molecular patterns. Predominant gut organisms from the kingdom bacteria are presented in Figure 1.

The GIT microbiota is crucial in maintaining mucosal integrity, and its breakdown can lead to sepsis, necrotizing enterocolitis NECand systemic inflammatory response syndrome 2. Butyrate is a major energy source for colonocytes, and propionate and acetate are absorbed and enter the portal circulation where they are used by a variety of body tissues, particularly the liver, in energy metabolism, lipogenesis, and gluconeogenesis. Although beyond the scope of this review, the GIT microbiota also contributes a wide variety of other small molecules which have important functions.

Finally, the role of enteral feeding type human milk, formula, and nutrient fortification in mediating these processes is discussed, and guidance is provided for nutritional strategies to promote health in these fragile infants. A metagenomic analysis on stool samples from a set of twins discordant for the diagnosis of NEC demonstrated ificant differences in the genes mapping to carbohydrate metabolism leading to speculation that microbial communities may metabolize milk through different pathways resulting in differing substrates available to the microbiota and thus differential effects on the host Similar perturbations in the GIT microbiota development have been reported for infants with late-onset sepsis A breakdown of the mucosal barrier can result in translocation of inflammatory mediators producing systemic inflammatory response syndrome.

In the past century, investigations of the GIT microbiota were cultured based with the identification of the genus, species, and even strain using a battery of morphological and biochemical tests. Evidence exists for induction of enterocyte protection by LactobacillusBifidobacteriumBacteroides thetaiotaomicronand Streptococcus thermophiles The microbiota may impact not only epithelial cell development but also endothelial cell ontogenesis.

Germ-free rodents have a decrease in transcription of mucin genes and a decreased thickness of the mucus layer along with fewer Goblet cells and less IgA production Germ-free animals have a higher dietary requirement for energy than those with an intact microbiota and when the microbiota of conventionally reared mice are transplanted into to lean germ-free mice, their body weight increases dramatically Many bacterial species in the distal intestine can ferment undigested carbohydrates e.

In an adult human study, exposure to clindamycin for 7 d led to a decline in bacterial diversity that persisted for up to 2 y Given the instability of the newborn GIT microbiota, antibiotics exposure could be expected to induce profound alterations of the microbial community with long-term consequences 2729 Healthy-term newborns appear to be initially colonized by large s of Enterobacter and Streptococcusregardless of feeding type It is proposed that these bacteria are responsible for creating a reduced environment in the GIT which favors establishment of the anaerobes BacteroidesBifidobacteriumand Clostridium by day 4 to 7.

High-throughput sequencing of the 16S ribosomal RNA gene is the most widely employed approach used to characterize a microbial community. The gut microbiome has a profound impact on gastrointestinal tract development, maintenance of mucosal surface integrity, and contributes to the nutritional status of the host and thus plays a pivotal role in health and disease.

This review summarizes the stepwise establishment of the intestinal microbiota, influential environmental factors, and how this may be perturbed in preterm very-low-birth-weight infants. The GIT microbiota best associated with optimal health is unknown; however, an overarching finding in VLBW infants is decreased GIT microbiota diversity and a higher pathogen load 13456.

Oral administration of genetically labeled Enterococcus faecium to pregnant mice led to their presence in the meconium of born pups by cesarean, demonstrating the possibility of prenatal maternal microbial transmission Classification of bacteria documented to colonize the gastrointestinal tract of very-low-birth-weight infants. Preliminary data also suggest that maternal obesity and elective cesarean section may also be associated with microbial diversity and composition in breast milk Human beings are born with a naive immune system that must develop tolerance to its environment and mature to develop an appropriate immunological response to pathogens.

Introduction

A of new molecular-based approaches have been developed over the past decade revolutionizing the study of microbial communities. Advances in molecular technologies have allowed a rapid expansion of knowledge of the human microbiome. The 16S rRNA is part of the small ribosomal unit that is preserved in all organisms and contains highly conserved sequence domains interspersed with hypervariable regions.

Metaproteomics is an attractive alternative but has been limited because of analytical challenges, incomplete reference databases, and highly redundant protein sequences between different microbes. In addition, the crucial role of the gut microbiota in maintaining mucosal integrity is explored along with how its breakdown can lead to sepsis, necrotizing enterocolitis, and systemic inflammatory response syndrome.

Try out PMC Labs and tell us what you think. In term infants, vaginal delivery in a higher GIT bacterial richness of different species and diversity richness and evenness of their distribution 20 While study-to-study differences exist, most recently, Azad et al. Even after cleansing the breast using an iodine solution to minimize bacterial contamination, pyrosequencing of the 16S rRNA gene from milk reveals the microbial community in human milk to be highly diverse and complex 40 Data from human and animal studies suggest that bacteria or their components may actively migrate from the maternal GIT, by way of macrophages or dendritic cells, to the mammary gland and breast milk 2144thereby providing another mechanism for different colonization patterns of human milk-fed compared with formula-fed infants.

It continues through exclusive breastfeeding phase II until weaning phase III in a stepwise manner with the appearance of strict anaerobes such that by 18—24 mo of age, the microbiota resembles the extremely dense and complex microbial colonization of an adult phase IV 712 The infant microbiota is more variable day-to-day in its composition and less stable over time compared with that of the adult 11214 The relative stability of the adult microbiota has been challenged by a recent study demonstrating that a single week of dietary change is sufficient to alter the intestinal microbiota Infant microbial colonization can be ificantly affected by exogenous factors including the mode of delivery, feeding type, antibiotics, and introduction of solid food.

New technologies have enabled the detailed characterization of normal microbial symbionts and dysbiosis—disease associations.

Intestinal angiogenesis is ongoing at the time of acquisition of the microbiome, and a perturbation of angiogenesis may be implicated in intestinal inflammatory conditions such as NEC. In a laboratory model, fibroblasts have been shown to produce proangiogenic factors in response to microbial cell products, and endothelial cells have demonstrated proliferation, migration, tube formation, and vessel sprouting Further evidence for the role of the microbiome on gastrointestinal development comes from experiments with germ-free animals as well as from alteration of the microbiome with antibiotics.

Routine vitamin K prophylaxis of healthy newborns is required to prevent hemorrhagic disease as a result of minimal placental transfer of the vitamin but also due to the low concentrations of vitamin K producing bacteria in the GIT at birth. At present, metatranscriptomics of the GIT microbiome is limited by the inherent instability of RNA and difficulties extracting it from stool.

Metabolomic analyses use mass spectrometry or nuclear magnetic resonance spectrometry to monitor the whole set of small molecules produced by microbes or the host cells within a sample 8. A further step is to identify not only which genes are present in a microbiome but which genes have been expressed into mRNA metatranscriptomics or proteins metaproteomics 8. In addition to sepsis and NEC, systemic inflammatory response syndrome plays a key role in downstream organ inflammation and damage that may result in severe long-term morbidities such as periventricular leukomalacia, chronic lung disease, and retinopathy of prematurity 2.

This may commence with an altered growth during the neonatal period related to suboptimal nutritional intake, illness, and potentially an aberrant microbiota with altered metabolic capacity, resulting in a greater percentage of body fat and considerably less lean mass at term-corrected age 63 Evidence for the role of the microbiota in obesity comes from rodent studies with induction of hepatic lipogenesis and increased lipid storage in adipocytes of germ-free mice after colonization with normal gut microbiota In human twin studies, evidence suggests that physiological phenotype such as adiposity may be better associated with a core microbiome at the gene level rather than at the organismal lineage level with a decrease in bacterial diversity and an alteration in metabolically active genes found in obese patients Dysregulation of the developing immune system has been implicated in a wide array of diseases in childhood and adult life including atopy 67 and food allergy 68inflammatory bowel disease 69and cancer An emerging area of interest is the impact of the gut microbiota on the developing human brain which may be of particular importance for the preterm infant who is at elevated risk for behavioral issues including attention-deficit disorder and autism spectrum disorder.

The human microbiota describes the bacteria colonizing every surface of the body from the skin to the respiratory tract, genitourinary tract, and gastrointestinal tract GIT. The intestinal microbiota constitutes the most abundant microbial community in humans with 10 times more cells and times more genes than human cells. Selective amplification of these hypervariable regions followed by high-throughput sequencing is an efficient way to characterize the microbial community 7.