Intestinal dysbiosis and necrotizing enterocolitis: assessment for causality using Bradford Hill criteria

Fundora, Jennifer; Guha, Pallabi; Shores, Darla R.; Pammi, Mohan; Maheshwari, Akhil

doi:10.1038/s41390-019-0482-9

Cited by 42 publications

(41 citation statements)

References 117 publications

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“…The initial development of intestinal microbiome is important in establishing both intestinal and systemic immunity. Immediate consequences of infant gut microbiome dysbiosis can include growth impairment [ 8 , 9 ] and an increased risk of sepsis and necrotizing enterocolitis (NEC), especially in preterm newborns [ 10 , 11 , 12 ]. The associated long-term health consequences include allergies, metabolic syndrome, diabetes and inflammatory bowel diseases [ 3 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Maternal Diet and Milk Lipid Composition on the Infant Gut and Maternal Milk Microbiomes

et al. 2020

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Inter-subject variability in human milk microbiome is well known; however, its origins and possible relationship to the mother’s diet are still debated. We investigated associations between maternal nutrition, milk fatty acids composition and microbiomes in mother–infant dyads. Breast milk and infant fecal samples were collected across three time points (one week, one month and three months postpartum) from 22 mother–infant pairs. Food frequency questionnaires for the months of pregnancy and three months postpartum were collected. Milk fatty acids were analyzed by GC–MS and the microbiome in breast milk and infant feces was determined by 16S rRNA sequencing. Statistical interactions were computed using Spearman’s method and corrected for multiple comparisons. We found significant negative correlation between Streptococcus relative abundance in maternal milk and intake of unsaturated fatty acids and folic acid at one month postpartum. At three months postpartum, vitamin B-12 consumption was significantly associated with a single operational taxonomic unit belonging to Streptococcus. Comparison between milk microbiome and lipid composition showed, one-month postpartum, significant negative correlation between Streptococcus relative abundance and the abundance of oleic acid. Additional correlations were detected between Staphylococcus hominis and two medium-chain saturated fatty acids. Our results reinforce the hypothesis that maternal nutrition may affect milk microbiome.

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Section: Introductionmentioning

confidence: 99%

Effect of Maternal Diet and Milk Lipid Composition on the Infant Gut and Maternal Milk Microbiomes

et al. 2020

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“…The pathophysiology of NEC is multifactorial and has not as of yet been fully clarified. Prematurity, formula feeding, and intestinal dysbiosis are the main risk factors, while the genetic predisposition as well as certain prenatal and postnatal factors increase the risk of NEC ( Table 1) (12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

Section: Pathophysiology and Current Diagnosis Of Necrotizing Enterocmentioning

confidence: 99%

Emerging Biomarkers for Prediction and Early Diagnosis of Necrotizing Enterocolitis in the Era of Metabolomics and Proteomics

et al. 2020

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Necrotizing Enterocolitis (NEC) is a catastrophic disease affecting predominantly premature infants and is characterized by high mortality and serious long-term consequences. Traditionally, diagnosis of NEC is based on clinical and radiological findings, which, however, are non-specific for NEC, thus confusing differential diagnosis of other conditions such as neonatal sepsis and spontaneous intestinal perforation. In addition, by the time clinical and radiological findings become apparent, NEC has already progressed to an advanced stage. During the last three decades, a lot of research has focused on the discovery of biomarkers, which could accurately predict and make an early diagnosis of NEC. Biomarkers used thus far in clinical practice include acute phase proteins, inflammation mediators, and molecules involved in the immune response. However, none has been proven accurate enough to predict and make an early diagnosis of NEC or discriminate clinical from surgical NEC or other non-NEC gastrointestinal diseases. Complexity of mechanisms involved in NEC pathogenesis, which remains largely poorly elucidated, could partly explain the unsatisfactory diagnostic performance of the existing NEC biomarkers. More recently applied technics can provide important insight into the pathophysiological mechanisms underlying NEC but can also aid the detection of potentially predictive, early diagnostic, and prognostic biomarkers. Progress in omics technology has allowed for the simultaneous measurement of a large number of proteins, metabolic products, lipids, and genes, using serum/plasma, urine, feces, tissues, and other biological specimens. This review is an update of current data on emerging NEC biomarkers detected using proteomics and metabolomics, further discussing limitations and future perspectives in prediction and early diagnosis of NEC.

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“…The increase in proteobacteria, along with increased enterocyte Toll like receptor 4 activity in neonates with NEC, suggests a hyperinflammatory response to a dysbiotic microbiome [59,60]. A recent paper by Fundora et al aimed at assessing the causality for intestinal dysbiosis leading to NEC: Although causality was supported by biological plausibility of an aetiological role of Gram-negative bacteria and temporal evidence of enteric dysbiosis preceding NEC, consistency among studies was low, and the effect appeared to be non-specific [61].…”

Section: Human Milk Microbiome and Its Influence On Infant Gut Colonimentioning

confidence: 99%

Human Milk’s Hidden Gift: Implications of the Milk Microbiome for Preterm Infants’ Health

et al. 2019

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Breastfeeding is considered the gold standard for infants’ nutrition, as mother’s own milk (MOM) provides nutritional and bioactive factors functional to optimal development. Early life microbiome is one of the main contributors to short and long-term infant health status, with the gut microbiota (GM) being the most studied ecosystem. Some human milk (HM) bioactive factors, such as HM prebiotic carbohydrates that select for beneficial bacteria, and the specific human milk microbiota (HMM) are emerging as early mediators in the relationship between the development of GM in early life and clinical outcomes. The beneficial role of HM becomes even more crucial for preterm infants, who are exposed to significant risks of severe infection in early life as well as to adverse short and long-term outcomes. When MOM is unavailable or insufficient, donor human milk (DHM) constitutes the optimal nutritional choice. However, little is known about the specific effect of DHM on preterm GM and its potential functional implication on HMM. The purpose of this narrative review is to summarize recent findings on HMM origin and composition and discuss the role of HMM on infant health and development, with a specific focus on preterm infants.

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Intestinal dysbiosis and necrotizing enterocolitis: assessment for causality using Bradford Hill criteria

Cited by 42 publications

References 117 publications

Effect of Maternal Diet and Milk Lipid Composition on the Infant Gut and Maternal Milk Microbiomes

Effect of Maternal Diet and Milk Lipid Composition on the Infant Gut and Maternal Milk Microbiomes

Emerging Biomarkers for Prediction and Early Diagnosis of Necrotizing Enterocolitis in the Era of Metabolomics and Proteomics

Human Milk’s Hidden Gift: Implications of the Milk Microbiome for Preterm Infants’ Health

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