TY - JOUR
T1 - Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis
T2 - A systematic review and meta-analysis
AU - Pammi, Mohan
AU - Cope, Julia
AU - Tarr, Phillip I.
AU - Warner, Barbara B.
AU - Morrow, Ardythe L.
AU - Mai, Volker
AU - Gregory, Katherine E.
AU - Simon Kroll, J.
AU - McMurtry, Valerie
AU - Ferris, Michael J.
AU - Engstrand, Lars
AU - Lilja, Helene Engstrand
AU - Hollister, Emily B.
AU - Versalovic, James
AU - Neu, Josef
N1 - Funding Information:
Drs Tarr and Warner are funded by the NIH (NIAID; UH3AI083265) and the NIDDK-supported Digestive Diseases Research Core Center (P30DK052574) and the Washington University Institute of Clinical and Translational Sciences (UL1RR024992). Katherine Gregory is funded by the K23 NR011320-01 and Pilot/ Feasibility Grant from Harvard Catalyst CTSA Grant UL1 RR 025758–01. AM is funded by the NIH grant NICHD R01 HD059140. Work in the Kroll laboratory was supported by funding from the Winnicott Foundation and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial Healthcare NHS Trust and Imperial College London.
Funding Information:
26. Viswanathan M, Berkman ND, Dryden DM, Hartling L. Assessing Risk of Bias and Confounding in Observational Studies of Interventions or Exposures: Further Development of the RTI Item Bank. Methods Research Report. (Prepared by RTI–UNC Evidence-based Practice Center under Contract No. 290-2007-10056-I). AHRQ Publication No. 13-EHC106-EF. Rockville: Agency for Healthcare Research and Quality; 2013. www.effectivehealthcare.ahrq.gov/ reports/final.cfm. Accessed 27 June 2015.
Publisher Copyright:
© The Author(s) 2017.
PY - 2017
Y1 - 2017
N2 - Background: Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the microbiome in NEC and preterm infants lack power and have reported inconsistent results. Methods and results: Our objectives were to perform a systematic review and meta-analyses of stool microbiome profiles in preterm infants to discern and describe microbial dysbiosis prior to the onset of NEC and to explore heterogeneity among studies. We searched MEDLINE, PubMed, CINAHL, and conference abstracts from the proceedings of Pediatric Academic Societies and reference lists of relevant identified articles in April 2016. Studies comparing the intestinal microbiome in preterm infants who developed NEC to those of controls, using cultureindependent molecular techniques and reported a and β-diversity metrics, and microbial profiles were included. In addition, 16S ribosomal ribonucleic acid (rRNA) sequence data with clinical meta-data were requested from the authors of included studies or searched in public data repositories. We reprocessed the 16S rRNA sequence data through a uniform analysis pipeline, which were then synthesized by meta-analysis. We included 14 studies in this review, and data from eight studies were available for quantitative synthesis (106 NEC cases, 278 controls, 2944 samples). The age of NEC onset was at a mean ± SD of 30.1 ± 2.4 weeks post-conception (n = 61). Fecal microbiome from preterm infants with NEC had increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes prior to NEC onset. Alpha- or beta-diversity indices in preterm infants with NEC were not consistently different from controls, but we found differences in taxonomic profiles related to antibiotic exposure, formula feeding, and mode of delivery. Exploring heterogeneity revealed differences in microbial profiles by study and the target region of the 16S rRNA gene (V1-V3 or V3-V5). Conclusions: Microbial dysbiosis preceding NEC in preterm infants is characterized by increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes. Microbiome optimization may provide a novel strategy for preventing NEC.
AB - Background: Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the microbiome in NEC and preterm infants lack power and have reported inconsistent results. Methods and results: Our objectives were to perform a systematic review and meta-analyses of stool microbiome profiles in preterm infants to discern and describe microbial dysbiosis prior to the onset of NEC and to explore heterogeneity among studies. We searched MEDLINE, PubMed, CINAHL, and conference abstracts from the proceedings of Pediatric Academic Societies and reference lists of relevant identified articles in April 2016. Studies comparing the intestinal microbiome in preterm infants who developed NEC to those of controls, using cultureindependent molecular techniques and reported a and β-diversity metrics, and microbial profiles were included. In addition, 16S ribosomal ribonucleic acid (rRNA) sequence data with clinical meta-data were requested from the authors of included studies or searched in public data repositories. We reprocessed the 16S rRNA sequence data through a uniform analysis pipeline, which were then synthesized by meta-analysis. We included 14 studies in this review, and data from eight studies were available for quantitative synthesis (106 NEC cases, 278 controls, 2944 samples). The age of NEC onset was at a mean ± SD of 30.1 ± 2.4 weeks post-conception (n = 61). Fecal microbiome from preterm infants with NEC had increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes prior to NEC onset. Alpha- or beta-diversity indices in preterm infants with NEC were not consistently different from controls, but we found differences in taxonomic profiles related to antibiotic exposure, formula feeding, and mode of delivery. Exploring heterogeneity revealed differences in microbial profiles by study and the target region of the 16S rRNA gene (V1-V3 or V3-V5). Conclusions: Microbial dysbiosis preceding NEC in preterm infants is characterized by increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes. Microbiome optimization may provide a novel strategy for preventing NEC.
KW - 16S rRNA sequencing
KW - Intestinal
KW - Microbiome
KW - NEC
KW - Neonate
KW - Preterm
UR - http://www.scopus.com/inward/record.url?scp=85015945763&partnerID=8YFLogxK
U2 - 10.1186/s40168-017-0248-8
DO - 10.1186/s40168-017-0248-8
M3 - Article
C2 - 28274256
AN - SCOPUS:85015945763
VL - 5
JO - Microbiome
JF - Microbiome
IS - 1
M1 - 31
ER -