Necrotizing Enterocolitis and the Preterm Infant Microbiome.

Preterm infants differ significantly from their term infant counterparts regarding bacterial colonization patterns related to maternal microbiota diversity, mode of delivery, feeding type, antibiotic exposure, and the environmental influences related to prolonged hospitalization in the neonatal intensive care unit (NICU). Necrotizing enterocolitis (NEC), a multifactorial intestinal disorder characterized by ischemic bowel disease, disproportionately impacts preterm infants and has a high disease burden. Recent studies in the basic, translational, and clinical scientific literature have advanced knowledge into this complex disease process.

Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring.

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period.

A digital twin of the infant microbiome to predict neurodevelopmental deficits.

Despite the recognized gut-brain axis link, natural variations in microbial profiles between patients hinder definition of normal abundance ranges, confounding the impact of dysbiosis on infant neurodevelopment. We infer a digital twin of the infant microbiome, forecasting ecosystem trajectories from a few initial observations. Using 16 ribosomal RNA profiles from 88 preterm infants (398 fecal samples and 32,942 abundance estimates for 91 microbial classes), the model (Q-net) predicts abundance dynamics with = 0.

Microbiome function and neurodevelopment in Black infants: vitamin B emerges as a key factor.

The early life gut microbiome affects the developing brain, and therefore may serve as a target to support neurodevelopment of children living in stressful and under-resourced environments, such as Black youth living on the South Side of Chicago, for whom we observe racial disparities in health. Microbiome compositions/functions key to multiple neurodevelopmental facets have not been studied in Black children, a vulnerable population due to racial disparities in health; thus, a subsample of Black infants living in urban, low-income neighborhoods whose mothers participated in a prenatal nutrition study were recruited for testing associations between composition and function of the gut microbiome (16S rRNA gene sequencing, shotgun metagenomics, and targeted metabolomics of fecal samples) and neurodevelopment (developmental testing, maternal report of temperament, and observed stress regulation). Two microbiome community types, defined by high or abundance, were discovered in this cohort from 16S rRNA gene sequencing analysis; the -dominant community type was significantly negatively associated with cognition and language scores, specifically in male children.

Microbiota from Preterm Infants Who Develop Necrotizing Enterocolitis Drives the Neurodevelopment Impairment in a Humanized Mouse Model.

Necrotizing enterocolitis (NEC) is the leading basis for gastrointestinal morbidity and poses a significant risk for neurodevelopmental impairment (NDI) in preterm infants. Aberrant bacterial colonization preceding NEC contributes to the pathogenesis of NEC, and we have demonstrated that immature microbiota in preterm infants negatively impacts neurodevelopment and neurological outcomes. In this study, we tested the hypothesis that microbial communities before the onset of NEC drive NDI.

The Impact of Maternal Probiotics on Intestinal Vitamin D Receptor Expression in Early Life.

Vitamin D signaling via the Vitamin D Receptor (VDR) has been shown to protect against intestinal inflammation. Previous studies have also reported the mutual interactions of intestinal VDR and the microbiome, indicating a potential role of probiotics in modulating VDR expression. In preterm infants, although probiotics have been shown to reduce the incidence of necrotizing enterocolitis (NEC), they are not currently recommended by the FDA due to potential risks in this population.

Gut Microbiome-Brain Axis as an Explanation for the Risk of Poor Neurodevelopment Outcome in Preterm Infants with Necrotizing Enterocolitis.

Necrotizing Enterocolitis (NEC) is characterized by an inflammation of intestinal tissue that primarily affects premature infants. It is the most common and devastating gastrointestinal morbidity of prematurity, but beyond intestinal morbidity, this condition has also been associated with an increased risk of neurodevelopmental delays that persist beyond infancy. Prematurity, enteral feeding, bacterial colonization, and prolonged exposure to antibiotics are all risk factors that predispose preterm infants to NEC.

normalizes blood-brain barrier dysfunction and neurodevelopment deficits associated with prenatal exposure to lipopolysaccharide.

Maternal immune activation (MIA) derived from late gestational infection such as seen in chorioamnionitis poses a significantly increased risk for neurodevelopmental deficits in the offspring. Manipulating early microbiota through maternal probiotic supplementation has been shown to be an effective means to improve outcomes; however, the mechanisms remain unclear. In this study, we demonstrated that MIA modeled by exposing pregnant dams to lipopolysaccharide (LPS) induced an underdevelopment of the blood vessels, an increase in permeability and astrogliosis of the blood-brain barrier (BBB) at prewean age.

Neurodevelopmental outcome of infants who develop necrotizing enterocolitis: The gut-brain axis.

Necrotizing enterocolitis (NEC) poses a significant risk for neurodevelopmental impairment in extremely preterm infants. The gut microbiota shapes the development of the gut, immune system, and the brain; and dysbiosis drive neonatal morbidities including NEC. In this chapter, we delineate a gut-brain axis linking gut microbiota to the adverse neurological outcomes in NEC patients.

Early preterm infant microbiome impacts adult learning.

Interventions to mitigate long-term neurodevelopmental deficits such as memory and learning impairment in preterm infants are warranted. Manipulation of the gut microbiome affects host behaviors. In this study we determined whether early maturation of the infant microbiome is associated with neurodevelopment outcomes.

and integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment.

The early life microbiome plays critical roles in host development, shaping long-term outcomes including brain functioning. It is not known which initial infant colonizers elicit optimal neurodevelopment; thus, this study investigated the association between gut microbiome succession from the first week of life and head circumference growth (HCG), the earliest validated marker for neurodevelopment. Fecal samples were collected weekly from a preterm infant cohort during their neonatal intensive care unit stay and subjected to 16S rRNA gene sequencing for evaluating gut microbiome composition, in conjunction with clinical data and head circumference measurements.

The Role of Childhood Asthma in Obesity Development: A Nationwide US Multicohort Study.

Rationale: Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset.

Objectives: To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association.

The microbiome, guard or threat to infant health.

Despite improvements in survival for very low birthweight (VLBW) premature infants, there continues to be significant morbidity for these infants at remarkable cost to the healthcare system. Concurrent development of the preterm infant intestine alongside the gut microbiome in the clinical setting rather than in the protected in utero environment where it would usually occur creates significant vulnerabilities for the infant's immature intestine and immune system, resulting in devastating illness and neurological injury. However, the microbiome also has the capacity to promote healthy development.

The human gut microbiome and health inequities.

Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities.

Childhood Development and the Microbiome-The Intestinal Microbiota in Maintenance of Health and Development of Disease During Childhood Development.

The composition of the intestinal microbiome affects health from the prenatal period throughout childhood, and many diseases have been associated with dysbiosis. The gut microbiome is constantly changing, from birth throughout adulthood, and several variables affect its development and content. Features of the intestinal microbiota can affect development of the brain, immune system, and lungs, as well as body growth.

Effect of Antibiotic Use Within First 48 Hours of Life on the Preterm Infant Microbiome: A Randomized Clinical Trial.

This randomized clinical trial investigates whether withholding the standard 48 hours of intravenous empirical antibiotics immediately after birth in preterm infants protects the developing microbiome and improves clinical outcomes.

The early gut microbiome could protect against severe retinopathy of prematurity.

In this study, 6 infants with type 1 retinopathy of prematurity (ROP) were compared with 4 high-risk preterm neonates without any ROP but similar baseline neonatal comorbidities. The infants with type-1 ROP showed significant enrichment of Enterobacteriaceae at 28 weeks' postmenstrual age. Several metabolic pathways, including several amino acid metabolism pathways, were enriched in gut microbiota of infants without ROP.

Maternal administration of probiotics promotes brain development and protects offspring's brain from postnatal inflammatory insults in C57/BL6J mice.

Neonatal morbidities are associated with long term neurological deficits in life and have also been associated with dysbiosis. We tested whether optimizing the neonate's microbiome through maternal probiotic supplementation can improve offspring's neurodevelopmental outcomes. Maternal LB supplementation, carried out by giving Lactobacillus acidophilus and Bifidobacterium infantis (LB) to pregnant C57/BL6J mice daily from E16 to weaning, significantly suppressed postnatal peripheral proinflammatory insult-induced systemic inflammation and normalized compromised blood-brain barrier permeability and tight junction protein expression in the offspring at pre-weaned age.

Impact of Developmental Age, Necrotizing Enterocolitis Associated Stress, and Oral Therapeutic Intervention on Mucus Barrier Properties.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of incompletely understood pathophysiology predominantly affecting premature infants. While NEC is associated with microbial invasion of intestinal tissues, and mucus modulates interactions between microbes and underlying tissues, variations in mucus barrier properties with NEC-associated risk factors have not been investigated. This study explored differences in mucus composition (total protein, DNA, mucin content, sialic acid, and immunoregulatory proteins), as well as structural and transport properties, assessed by tracking of particles and bacteria (E.

Necrotizing Enterocolitis Pathophysiology: How Microbiome Data Alter Our Understanding.

Necrotizing enterocolitis is a major cause of mortality and morbidity in the preterm infant population. The gut microbiome is of particular interest in research surrounding necrotizing enterocolitis, because variations in the intestinal microbiota seem to correlate with the risk of inflammation and disease. Recent advances in non-culture-based genomic sequencing have also allowed for more intricate analyses of the intestinal microbiome.

Necrotizing Enterocolitis and the Preterm Infant Microbiome.

Bacterial colonization patterns in preterm infants differ from those of their term counterparts due to maternal microbial diversity, delivery mode, feeding methods, antibiotic use, and exposure to commensal microbiota and pathogens in the neonatal intensive care unit (NICU). Early gut microbiome dysbiosis predisposes neonates to necrotizing enterocolitis (NEC), a devastating intestinal disease with high morbidity and mortality. Though mechanisms of NEC pathogenesis are not fully understood, the microbiome is a promising therapy target for prevention and treatment.

Connection between gut microbiome and brain development in preterm infants.

Dysbiosis of the gut microbiome in preterm infants predisposes the neonate to various major morbidities including neonatal necrotizing enterocolitis and sepsis in the neonatal intensive care unit, and adverse neurological outcomes later in life. There are parallel early developmental windows for the gut microbiota and the nervous system during prenatal to postnatal of life. Therefore, preterm infants represent a unique population in which optimization of initial colonization and microbiota development can affect brain development and enhance neurological outcomes.

Lack of Vitamin D Receptor Leads to Hyperfunction of Claudin-2 in Intestinal Inflammatory Responses.

Background: Vitamin D3 and vitamin D receptor (VDR) are involved in the pathogenesis of inflammatory bowel disease (IBD) and bacterial infection. Claudin-2 is a junction protein that mediates paracellular water transport in epithelia. Elevation of Claudin-2 is associated with active IBD.

Using bioreactors to study the effects of drugs on the human microbiota.

The study of complex microbial communities has become a major research focus as mounting evidence suggests the pivotal role microbial communities play in host health and disease. Microbial communities of the gastrointestinal tract, known as the gut microbiota, have been implicated in aiding the host with vitamin biosynthesis, regulation of host energy metabolism, immune system development, and resistance to pathogen invasion. Conversely, disruptions of the gut microbiota have been linked to host morbidity, including the development of inflammatory diseases, metabolic disorders, increased cardiovascular risk, and increased risk of infectious diseases.