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Circulating beta chemokine and MMP 9 as markers of oxidative injury in extremely low birth weight infants.

ABSTRACT: Matrix metalloproteinases (MMPs) and chemokines seem to be induced by hyperoxia in preclinical studies. We hypothesized that O2 exposure immediately after birth is associated with altered blood spot MMP 9 and beta chemokine concentrations. The following analytes were measured on blood spots on d 1 and 3 of life, using luminex technology in 1059 infants (birth weights <1000 g) in the NICHD Neonatal Research Network: MMP 9, monocyte chemoattractant protein 1 (MCP 1), macrophage inflammatory proteins (1alpha and beta), and regulated upon activation, normal t cell expressed and secreted (RANTES). Infants administered O2 continually from 6 to 24 h of life (n = 729), when compared with those with <6 h exposure (n = 330), had significantly lower mean birth weight and higher rate of respiratory distress syndrome (p < 0.002). On d 3, MCP 1 was higher and RANTES lower among infants with early prolonged O2 exposure. After adjusting for covariates, prolonged early O2 exposure retained a statistically significant association with higher MCP 1 on d 3 (p = 0.003). The consistent association between O2 exposure and MCP 1 among extremely preterm infants suggests that further investigation of its role in oxidative injury is warranted.

SUBMITTER: Natarajan G

PROVIDER: S-EPMC2831535 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Circulating beta chemokine and MMP 9 as markers of oxidative injury in extremely low birth weight infants.

Natarajan Girija G Shankaran Seetha S McDonald Scott A SA DAS Abhik A Stoll Barbara J BJ Higgins Rosemary D RD Thorsen Poul P Skogstrand Kristin K Hougaard David M DM Carlo Waldemar A WA

Pediatric research 20100101 1

Matrix metalloproteinases (MMPs) and chemokines seem to be induced by hyperoxia in preclinical studies. We hypothesized that O2 exposure immediately after birth is associated with altered blood spot MMP 9 and beta chemokine concentrations. The following analytes were measured on blood spots on d 1 and 3 of life, using luminex technology in 1059 infants (birth weights <1000 g) in the NICHD Neonatal Research Network: MMP 9, monocyte chemoattractant protein 1 (MCP 1), macrophage inflammatory protei ...[more]

PMID: 19755933

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Project description:Infants born prematurely, particularly extremely low birth weight infants (ELBW) have altered gut microbial communities. Factors such as maternal health, gut immaturity, delivery mode, and antibiotic treatments are associated with microbiota disturbances, and are linked to an increased risk of certain diseases such as necrotising enterocolitis. Therefore, there is a requirement to optimally characterise microbial profiles in this at-risk cohort, via standardisation of methods, particularly for studying the influence of microbiota therapies (e.g. probiotic supplementation) on community profiles and health outcomes. Profiling of faecal samples using the 16S rRNA gene is a cost-efficient method for large-scale clinical studies to gain insights into the gut microbiota and additionally allows characterisation of cohorts were sample quantities are compromised (e.g. ELBW infants). However, DNA extraction method, and the 16S rRNA region targeted can significantly change bacterial community profiles obtained, and so confound comparisons between studies. Thus, we sought to optimise a 16S rRNA profiling protocol to allow standardisation for studying ELBW infant faecal samples, with or without probiotic supplementation.Using ELBW faecal samples, we compared three different DNA extraction methods, and subsequently PCR amplified and sequenced three hypervariable regions of the 16S rRNA gene (V1 + V2 + V3), (V4 + V5) and (V6 + V7 + V8), and compared two bioinformatics approaches to analyse results (OTU and paired end). Paired shotgun metagenomics was used as a 'gold-standard'.Results indicated a longer bead-beating step was required for optimal bacterial DNA extraction and that sequencing regions (V1 + V2 + V3) and (V6 + V7 + V8) provided the most representative taxonomic profiles, which was confirmed via shotgun analysis. Samples sequenced using the (V4 + V5) region were found to be underrepresented in specific taxa including Bifidobacterium, and had altered diversity profiles. Both bioinformatics 16S rRNA pipelines used in this study (OTU and paired end) presented similar taxonomic profiles at genus level.We determined that DNA extraction from ELBW faecal samples, particularly those infants receiving probiotic supplementation, should include a prolonged beat-beating step. Furthermore, use of the 16S rRNA (V1 + V2 + V3) and (V6 + V7 + V8) regions provides reliable representation of ELBW microbiota profiles, while inclusion of the (V4 + V5) region may not be appropriate for studies where Bifidobacterium constitutes a resident microbiota member.

Dataset Information

Circulating beta chemokine and MMP 9 as markers of oxidative injury in extremely low birth weight infants.

Publications

Circulating beta chemokine and MMP 9 as markers of oxidative injury in extremely low birth weight infants.

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