Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly

Mukhopadhyay, Sagori; Lee, Jung-Jin; Hartman, Erica; Woodford, Emily C.; Dhudasia, Miren B.; Mattei, Lisa M.; Daniel, Scott G.; Wade, Kelly C.; Underwood, Mark A.; Bittinger, Kyle

doi:10.1080/19490976.2022.2154091

Cited by 9 publications

(2 citation statements)

References 54 publications

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“…Moreover, increased neonatal clinical risk in the at-risk subgroup is consistent with previous findings, showing that perinatal medical complications following VPT birth may lead to increased behavioral and developmental problems [ 15 , 16 , 63 ]. The resilient and at-risk subgroups, however, did not differ in any of the neonatal brain measures investigated, suggesting that there may be additional non-measured variables underlying different childhood outcomes that need further investigation, such as alterations in pro-inflammatory immunomarkers [ 64 , 65 ] and/or microbiome assembly [ 66 , 67 ], which are reportedly associated with increased behavioral difficulties.…”

Section: Discussionmentioning

confidence: 99%

Parsing brain-behavior heterogeneity in very preterm born children using integrated similarity networks

et al. 2023

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Very preterm birth (VPT; ≤32 weeks’ gestation) is associated with altered brain development and cognitive and behavioral difficulties across the lifespan. However, heterogeneity in outcomes among individuals born VPT makes it challenging to identify those most vulnerable to neurodevelopmental sequelae. Here, we aimed to stratify VPT children into distinct behavioral subgroups and explore between-subgroup differences in neonatal brain structure and function. 198 VPT children (98 females) previously enrolled in the Evaluation of Preterm Imaging Study (EudraCT 2009-011602-42) underwent Magnetic Resonance Imaging at term-equivalent age and neuropsychological assessments at 4–7 years. Using an integrative clustering approach, we combined neonatal socio-demographic, clinical factors and childhood socio-emotional and executive function outcomes, to identify distinct subgroups of children based on their similarity profiles in a multidimensional space. We characterized resultant subgroups using domain-specific outcomes (temperament, psychopathology, IQ and cognitively stimulating home environment) and explored between-subgroup differences in neonatal brain volumes (voxel-wise Tensor-Based-Morphometry), functional connectivity (voxel-wise degree centrality) and structural connectivity (Tract-Based-Spatial-Statistics). Results showed two- and three-cluster data-driven solutions. The two-cluster solution comprised a ‘resilient’ subgroup (lower psychopathology and higher IQ, executive function and socio-emotional scores) and an ‘at-risk’ subgroup (poorer behavioral and cognitive outcomes). No neuroimaging differences between the resilient and at-risk subgroups were found. The three-cluster solution showed an additional third ‘intermediate’ subgroup, displaying behavioral and cognitive outcomes intermediate between the resilient and at-risk subgroups. The resilient subgroup had the most cognitively stimulating home environment and the at-risk subgroup showed the highest neonatal clinical risk, while the intermediate subgroup showed the lowest clinical, but the highest socio-demographic risk. Compared to the intermediate subgroup, the resilient subgroup displayed larger neonatal insular and orbitofrontal volumes and stronger orbitofrontal functional connectivity, while the at-risk group showed widespread white matter microstructural alterations. These findings suggest that risk stratification following VPT birth is feasible and could be used translationally to guide personalized interventions aimed at promoting children’s resilience.

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Section: Discussionmentioning

confidence: 99%

Parsing brain-behavior heterogeneity in very preterm born children using integrated similarity networks

et al. 2023

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“…The gut microbiome has extensive interactions with the host immune system and has been associated with risk or severity of both enteric infections and infections at other body sites (e.g., bloodstream infection, LRTI). These infections are particularly frequent among populations with frequent exposure to broad-spectrum antibiotics, immature or disrupted gut barrier function, or impaired immunity [8, 21,22]. Schwartz et al [22] reported that premature infants who developed a bloodstream infection often had gut colonization by this strain weeks prior to infection.…”

Section: The Gut Microbiome and Childhood Infectionsmentioning

confidence: 99%

Host microbiome-pathogen interactions in pediatric infections

Hurst

Heston

Kelly

2023

Current Opinion in Infectious Diseases

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Purpose of review In this review, we discuss recent research that has furthered our understanding of microbiome development during childhood, the role of the microbiome in infections during this life stage, and emerging opportunities for microbiome-based therapies for infection prevention or treatment in children. Recent findings The microbiome is highly dynamic during childhood and shaped by a variety of host and environmental factors. In turn, the microbiome influences risk and severity of a broad range of infections during childhood, with recent studies highlighting potential roles in respiratory, gastrointestinal, and systemic infections. The microbiome exerts this influence through both direct interactions with potential pathogens and indirectly through modulation of host immune responses. The elucidation of some of these mechanisms by recent studies and the development of effective microbiome-based therapies for adults with recurrent Clostridioides difficile infection highlight the enormous promise that targeting the microbiome has for reducing the burden of infectious diseases during childhood. Summary The microbiome has emerged as a key modifier of infection susceptibility and severity among children. Further research is needed to define the roles of microbes other than bacteria and to elucidate the mechanisms underlying microbiome-host and microbiome-pathogen interactions of importance to infectious diseases in children.

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Gram-Negative Colonization and Bacterial Translocation Drive Neonatal Sepsis in the Indian Setting

Iqbal,

Barche,

Shenoy

et al. 2024

J Epidemiol Glob Health

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Background The gut microbiota, comprising billions of microorganisms, plays a pivotal role in health and disease. This study aims to investigate the effect of sepsis on gut microbiome of neonates admitted to the Neonatal Intensive Care Unit. Methods A prospective cohort study was carried out in the NICU of tertiary care hospital in Karnataka, India, from January 2021 to September 2023. Preterm neonates with birth weight < 1500 g and gestational age < 37 weeks were recruited, excluding those with congenital gastrointestinal anomalies, necrotizing enterocolitis, or blood culture-negative infections. The study population was divided into three groups: healthy neonates (Group A), neonates with drug-sensitive GNB sepsis (Group B), and neonates with pan drug-resistant GNB sepsis (Group C). Stool samples were collected aseptically, snapped in liquid nitrogen, and stored at -80⁰C for extraction of DNA and microbiome analysis. Results The gut microbiota of healthy neonates (Group A) was dominated by Proteobacteria (24.04%), Actinobacteria (27.13%), Firmicutes (12.74%), and Bacteroidetes (3%). Predominant genera included Bifidobacterium (55.17%), Enterobacter (12.55%), Enterococcus (50.69%), Streptococcus (7.92%), and Bacteroides (3.58%).Groups B and C, the microbiota exhibited higher Proteobacteria abundance (57.16% and 66.58%, respectively) and reduced diversity of beneficial bacteria. Notably, the presence of sepsis was associated with an increase in pathogenic bacteria and a decrease in beneficial commensal bacteria. Conclusion Neonates with sepsis exhibited significant gut microbiome dysbiosis, characterized by increased Proteobacteria and reduced beneficial bacteria diversity. These findings highlight the potential of microbiome profiling as a diagnostic tool and underscore the importance of gut microbiota modulation in managing neonatal sepsis.

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Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly

Cited by 9 publications

References 54 publications

Parsing brain-behavior heterogeneity in very preterm born children using integrated similarity networks

Parsing brain-behavior heterogeneity in very preterm born children using integrated similarity networks

Host microbiome-pathogen interactions in pediatric infections

Gram-Negative Colonization and Bacterial Translocation Drive Neonatal Sepsis in the Indian Setting

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