The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis

Wandro, Stephen; Osborne, Stephanie; Enriquez, Claudia; Bixby, Christine; Arrieta, Antonio; Whiteson, Katrine

doi:10.1128/msphere.00104-18

Cited by 123 publications

(121 citation statements)

References 53 publications

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“…Importantly, the observed reduced enteral nutrition volume in NEC-1 is not a protective factor during NEC but rather it may lengthen hospitalization and infections risk [17]. NEC-1 children showed a high general variance for gut microbiota and fecal metabolome which is in line with a personalized microbiota and fecal metabolome profiles of preterm infant [18]. Both this datum and the delayed intestinal colonization of preterm infants [19,20] may explain the lack of NEC-1-specific microbial group in the first decade of life.…”

Section: Discussionmentioning

confidence: 68%

Evolution of Gut Microbiome and Metabolome during Stage 1 Necrotizing Enterocolitis: a Case-Control Study

Bréhin

Dubois

Dicky

et al. 2020

Preprint

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Background : Necrotizing enterocolitis (NEC) is a devastating condition of the preterm new-born due to multiple factors, including gut microbiota dysbiosis. Since NEC development is poorly understood due to main focus on late stages 2 and 3, we studied the gut microbiota and metabolome evolution of NEC at a very early onset. Results NEC-1 gut microbiota had a higher abundance of Streptococcus (second decade of life) and Staphylococcus (third decade of life) species. NEC-1 children showed a microbiome evolution in the third decade of life being the most divergent and associated to a different metabolomic signature than in healthy children. NEC-1 microbiome had increased glycosaminoglycan degradation and lysosome activity by the first decade of life and was more sensitive to factors such as childbirth, low birth weight and gestational age, than healthy microbiome. NEC-1 fecal metabolome was more divergent by the second month of life. Conclusions: The modifications of gut microbiota and microbiome during NEC-1 development appear more distinguishable by the third decade of life, when compared to healthy children. These data identify a precise window of time (i.e. third decade of life) and provide microbial targets to fight/blunt the progression of NEC by stage 1.

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Section: Discussionmentioning

confidence: 68%

Evolution of Gut Microbiome and Metabolome during Stage 1 Necrotizing Enterocolitis: a Case-Control Study

Bréhin

Dubois

Dicky

et al. 2020

Preprint

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“…Breastfeeding is known to protect against NEC (61,62): the reason is that breastfeeding facilitates colonization by a balanced commensal flora which contrasts bacterial overgrowth; instead formula feeding is associated with harmful gut bacterial proliferation (63). Preterm infants early come into contact with different environmental microbic species and are also precociously exposed to antibiotic therapies which have shown to reduce the diversity of infant microbiota; moreover, perturbations in the composition of infant microbiota may let pathogenic microbes prevail over commensal species (64).…”

Section: The Preterm Gut Microbiota and Necmentioning

confidence: 99%

Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes

et al. 2019

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In recent years, an aberrant gastrointestinal colonization has been found to be associated with an higher risk for postnatal sepsis, necrotizing enterocolitis (NEC) and growth impairment in preterm infants. As a consequence, the reasons of intestinal dysbiosis in this population of newborns have increasingly become an object of interest. The presence of a link between the gut and lung microbiome's development (gut-lung axis) is emerging, and more data show as a gut-brain cross talking mediated by an inflammatory milieu, may affect the immunity system and influence neonatal outcomes. A revision of the studies which examined gut and lung microbiota in preterm infants and a qualitative analysis of data about characteristic patterns and related outcomes in terms of risk of growing impairment, Necrotizing Enterocolitis (NEC), Bronchopulmonary Dysplasia (BPD), and sepsis have been performed. Microbiota take part in the establishment of the gut barrier and many data suggest its immune-modulator role. Furthermore, the development of the gut and lung microbiome (gut-lung axis) appear to be connected and able to lead to abnormal inflammatory responses which have a key role in the pathogenesis of BPD. Dysbiosis and the gut predominance of facultative anaerobes appear to be crucial to the pathogenesis and subsequently to the prevention of such diseases.

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“…to cover possible early onset infection from birth) and treatment) these infants receive in the first days and weeks post birth. The microbiota in preterm infants is enriched for bacteria such as Enterobacteriaceae , Enterococcus and Staphylococcus [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors

Chen

Brook

Soe

et al. 2019

Preprint

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Klebsiella spp. are frequently enriched in the gut microbiota of preterm neonates, and overgrowth is associated with necrotizing enterocolitis, nosocomial infections and late-onset sepsis. Little is known about the genomic and phenotypic characteristics of preterm-associated Klebsiella as previous studies have focussed on recovery of antimicrobial-resistant isolates or culture-independent molecular analyses. Faecal samples from a UK cohort of healthy and sick preterm neonates (n=109) were screened on MacConkey agar to isolate lactose-positive Enterobacteriaceae. Whole-genome sequences were generated for isolates. Approximately one-tenth of faecal samples harboured Klebsiella spp. (Klebsiella pneumoniae, 7.3 %; Klebsiella quasipneumoniae, 0.9 %; Klebsiella grimontii, 2.8 %; Klebsiella michiganensis, 1.8 %). Isolates recovered from NEC- and sepsis-affected infants and those showing no signs of clinical infection (i.e. ‘healthy’) encoded multiple β-lactamases, which may prove problematic when defining treatment regimens for NEC or sepsis, and suggest ‘healthy’ preterm infants contribute to the resistome. No difference was observed between isolates recovered from ‘healthy’ and sick infants with respect to in vitro siderophore production (all encoded enterobactin in their genomes). All K. pneumoniae, K. quasipneumoniae, K. grimontii and K. michiganensis faecal isolates tested were able to reside and persist in macrophages, indicating their immune evasion abilities. Using a curated dataset of Klebsiella oxytoca, K. grimontii and K. michiganensis whole-genome sequences, metapangenome analyses of published metagenomic data confirmed our findings regarding the presence of K. michiganensis in the preterm gut, and highlight the importance of refined analyses with curated sequence databases when studying closely related species present in metagenomic data.

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The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis

Cited by 123 publications

References 53 publications

Evolution of Gut Microbiome and Metabolome during Stage 1 Necrotizing Enterocolitis: a Case-Control Study

Evolution of Gut Microbiome and Metabolome during Stage 1 Necrotizing Enterocolitis: a Case-Control Study

Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes

Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors

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