Necrotizing enterocolitis is preceded by increased gut bacterial replication, Klebsiella , and fimbriae-encoding bacteria

Olm, Matthew R.; Bhattacharya, Nicholas; Crits-Christoph, Alexander; Firek, Brian A.; Baker, Robyn; Song, Yun S.; Morowitz, Michael J.; Banfield, Jillian F.

doi:10.1126/sciadv.aax5727

Necrotizing enterocolitis is preceded by increased gut bacterial replication, Klebsiella , and fimbriae-encoding bacteria

Journal Article · Tue Dec 10 23:00:00 EST 2019 · Science Advances

DOI:https://doi.org/10.1126/sciadv.aax5727· OSTI ID:1591850

^[1]; Bhattacharya, Nicholas ^[1]; Crits-Christoph, Alexander ^[1]; Firek, Brian A. ^[2]; ^[3]; ^[4]; Morowitz, Michael J. ^[2]; ^[5]

Univ. of California, Berkeley, CA (United States)
Univ. of Pittsburgh School of Medicine, PA (United States)
Univ. of Pittsburgh Medical Center Magee Womens Hospital, PA (United States)
Univ. of California, Berkeley, CA (United States); Chan Zuckerberg Biohub, San Francisco, CA (United States)
Chan Zuckerberg Biohub, San Francisco, CA (United States); Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Necrotizing enterocolitis (NEC) is a devastating intestinal disease that occurs primarily in premature infants. We performed genome-resolved metagenomic analysis of 1163 fecal samples from premature infants to identify microbial features predictive of NEC. Features considered include genes, bacterial strain types, eukaryotes, bacteriophages, plasmids, and growth rates. A machine learning classifier found that samples collected before NEC diagnosis harbored significantly more Klebsiella, bacteria encoding fimbriae, and bacteria encoding secondary metabolite gene clusters related to quorum sensing and bacteriocin production. Notably, replication rates of all bacteria, especially Enterobacteriaceae, were significantly higher 2 days before NEC diagnosis. The findings uncover biomarkers that could lead to early detection of NEC and targets for microbiome-based therapeutics.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); Alfred P. Sloan Foundation; National Science Foundation (NSF)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1591850

Journal Information:: Science Advances, Journal Name: Science Advances Journal Issue: 12 Vol. 5; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

References (75)

Mechanism of pathogen-specific TLR4 activation in the mucosa: Fimbriae, recognition receptors and adaptor protein selection Fischer, Hans; Yamamoto, Masahiro; Akira, Shizuo European Journal of Immunology, Vol. 36, Issue 2 https://doi.org/10.1002/eji.200535149	journal	February 2006
Necrotizing enterocolitis of the neonate with Clostridium perfringens: diagnosis, clinical course, and role of alpha toxin Dittmar, Elke; Beyer, Peter; Fischer, Doris European Journal of Pediatrics, Vol. 167, Issue 8 https://doi.org/10.1007/s00431-007-0614-9	journal	October 2007
The role of quorum sensing in Escherichia coli (ETEC) virulence factors Sturbelle, Régis Tuchtenhagen; Avila, Luciana Farias da Costa de; Roos, Talita Bandeira Veterinary Microbiology, Vol. 180, Issue 3-4 https://doi.org/10.1016/j.vetmic.2015.08.015	journal	November 2015
Origins and virulence mechanisms of uropathogenic Escherichia coli Wiles, Travis J.; Kulesus, Richard R.; Mulvey, Matthew A. Experimental and Molecular Pathology, Vol. 85, Issue 1 https://doi.org/10.1016/j.yexmp.2008.03.007	journal	August 2008
Evidence for persistent and shared bacterial strains against a background of largely unique gut colonization in hospitalized premature infants Raveh-Sadka, Tali; Firek, Brian; Sharon, Itai The ISME Journal, Vol. 10, Issue 12 https://doi.org/10.1038/ismej.2016.83	journal	June 2016
dRep: a tool for fast and accurate genomic comparisons that enables improved genome recovery from metagenomes through de-replication Olm, Matthew R.; Brown, Christopher T.; Brooks, Brandon The ISME Journal, Vol. 11, Issue 12 https://doi.org/10.1038/ismej.2017.126	journal	July 2017
Measurement of bacterial replication rates in microbial communities Brown, Christopher T.; Olm, Matthew R.; Thomas, Brian C. Nature Biotechnology, Vol. 34, Issue 12 https://doi.org/10.1038/nbt.3704	journal	November 2016
MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets Steinegger, Martin; Söding, Johannes Nature Biotechnology, Vol. 35, Issue 11 https://doi.org/10.1038/nbt.3988	journal	October 2017
Fast gapped-read alignment with Bowtie 2 Langmead, Ben; Salzberg, Steven L. Nature Methods, Vol. 9, Issue 4 https://doi.org/10.1038/nmeth.1923	journal	March 2012
Fast and sensitive protein alignment using DIAMOND Buchfink, Benjamin; Xie, Chao; Huson, Daniel H. Nature Methods, Vol. 12, Issue 1 https://doi.org/10.1038/nmeth.3176	journal	November 2014
Strain-resolved analysis of hospital rooms and infants reveals overlap between the human and room microbiome Brooks, Brandon; Olm, Matthew R.; Firek, Brian A. Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-02018-w	journal	November 2017
Developmentally regulated I B expression in intestinal epithelium and susceptibility to flagellin-induced inflammation Claud, E. C.; Lu, L.; Anton, P. M. Proceedings of the National Academy of Sciences, Vol. 101, Issue 19 https://doi.org/10.1073/pnas.0401710101	journal	April 2004
Strain-resolved community genomic analysis of gut microbial colonization in a premature infant Morowitz, M. J.; Denef, V. J.; Costello, E. K. Proceedings of the National Academy of Sciences, Vol. 108, Issue 3 https://doi.org/10.1073/pnas.1010992108	journal	December 2010
Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation Letunic, I.; Bork, P. Bioinformatics, Vol. 23, Issue 1 https://doi.org/10.1093/bioinformatics/btl529	journal	October 2006
Search and clustering orders of magnitude faster than BLAST Edgar, Robert C. Bioinformatics, Vol. 26, Issue 19, p. 2460-2461 https://doi.org/10.1093/bioinformatics/btq461	journal	August 2010
IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth Peng, Y.; Leung, H. C. M.; Yiu, S. M. Bioinformatics, Vol. 28, Issue 11 https://doi.org/10.1093/bioinformatics/bts174	journal	April 2012
MaxBin 2.0: an automated binning algorithm to recover genomes from multiple metagenomic datasets Wu, Yu-Wei; Simmons, Blake A.; Singer, Steven W. Bioinformatics, Vol. 32, Issue 4 https://doi.org/10.1093/bioinformatics/btv638	journal	October 2015
FastTree: Computing Large Minimum Evolution Trees with Profiles instead of a Distance Matrix Price, M. N.; Dehal, P. S.; Arkin, A. P. Molecular Biology and Evolution, Vol. 26, Issue 7 https://doi.org/10.1093/molbev/msp077	journal	April 2009
MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability Katoh, K.; Standley, D. M. Molecular Biology and Evolution, Vol. 30, Issue 4 https://doi.org/10.1093/molbev/mst010	journal	January 2013
VFDB: a reference database for bacterial virulence factors Chen, L. Nucleic Acids Research, Vol. 33, Issue Database issue https://doi.org/10.1093/nar/gki008	journal	December 2004
antiSMASH 3.0—a comprehensive resource for the genome mining of biosynthetic gene clusters Weber, Tilmann; Blin, Kai; Duddela, Srikanth Nucleic Acids Research, Vol. 43, Issue W1 https://doi.org/10.1093/nar/gkv437	journal	May 2015
The Pfam protein families database in 2019 El-Gebali, Sara; Mistry, Jaina; Bateman, Alex Nucleic Acids Research, Vol. 47, Issue D1 https://doi.org/10.1093/nar/gky995	journal	October 2018
Bacterial Quorum Sensing: Its Role in Virulence and Possibilities for Its Control Rutherford, S. T.; Bassler, B. L. Cold Spring Harbor Perspectives in Medicine, Vol. 2, Issue 11 https://doi.org/10.1101/cshperspect.a012427	journal	November 2012
Gamma-Butyrolactone Regulatory System of Streptomyces chattanoogensis Links Nutrient Utilization, Metabolism, and Development Du, Yi-Ling; Shen, Xue-Ling; Yu, Pin Applied and Environmental Microbiology, Vol. 77, Issue 23 https://doi.org/10.1128/aem.05898-11	journal	September 2011
Isolation of a Variant of Subtilosin A with Hemolytic Activity Huang, T.; Geng, H.; Miyyapuram, V. R. Journal of Bacteriology, Vol. 191, Issue 18 https://doi.org/10.1128/jb.00541-09	journal	July 2009
Complete Sequencing and Diversity Analysis of the Enterotoxin-Encoding Plasmids in Clostridium perfringens Type A Non-Food-Borne Human Gastrointestinal Disease Isolates Miyamoto, K.; Fisher, D. J.; Li, J. Journal of Bacteriology, Vol. 188, Issue 4 https://doi.org/10.1128/jb.188.4.1585-1598.2006	journal	February 2006
Evolution of the Chaperone/Usher Assembly Pathway: Fimbrial Classification Goes Greek Nuccio, S. -P.; Baumler, A. J. Microbiology and Molecular Biology Reviews, Vol. 71, Issue 4 https://doi.org/10.1128/mmbr.00014-07	journal	December 2007
Prodigal: prokaryotic gene recognition and translation initiation site identification Hyatt, Doug; Chen, Gwo-Liang; LoCascio, Philip F. BMC Bioinformatics, Vol. 11, Issue 1 https://doi.org/10.1186/1471-2105-11-119	journal	March 2010
BIGSdb: Scalable analysis of bacterial genome variation at the population level Jolley, Keith A.; Maiden, Martin CJ BMC Bioinformatics, Vol. 11, Issue 1 https://doi.org/10.1186/1471-2105-11-595	journal	December 2010
A performance study of the impact of recombination on species tree analysis Wang, Zhiwei; Liu, Kevin J. BMC Genomics, Vol. 17, Issue S10 https://doi.org/10.1186/s12864-016-3104-5	journal	November 2016
Genome-resolved metagenomics of eukaryotic populations during early colonization of premature infants and in hospital rooms Olm, Matthew R.; West, Patrick T.; Brooks, Brandon Microbiome, Vol. 7, Issue 1 https://doi.org/10.1186/s40168-019-0638-1	journal	February 2019
Early Intestinal Bacterial Colonization and Necrotizing Enterocolitis in Premature Infants: The Putative Role of Clostridium de la Cochetière, Marie-France; Piloquet, Hugues; des Robert, Clotilde Pediatric Research, Vol. 56, Issue 3 https://doi.org/10.1203/01.pdr.0000134251.45878.d5	journal	September 2004
Profile Hidden Markov Models for the Detection of Viruses within Metagenomic Sequence Data Skewes-Cox, Peter; Sharpton, Thomas J.; Pollard, Katherine S. PLoS ONE, Vol. 9, Issue 8 https://doi.org/10.1371/journal.pone.0105067	journal	August 2014
Factors Influencing the Composition of the Intestinal Microbiota in Early Infancy Penders, J.; Thijs, C.; Vink, C. PEDIATRICS, Vol. 118, Issue 2 https://doi.org/10.1542/peds.2005-2824	journal	August 2006
Redefining the Role of Intestinal Microbes in the Pathogenesis of Necrotizing Enterocolitis Morowitz, M. J.; Poroyko, V.; Caplan, M. PEDIATRICS, Vol. 125, Issue 4 https://doi.org/10.1542/peds.2009-3149	journal	March 2010
A Critical Role for TLR4 in the Pathogenesis of Necrotizing Enterocolitis by Modulating Intestinal Injury and Repair Leaphart, Cynthia L.; Cavallo, Jaime; Gribar, Steven C. The Journal of Immunology, Vol. 179, Issue 7 https://doi.org/10.4049/jimmunol.179.7.4808	journal	September 2007
Gut bacteria are rarely shared by co-hospitalized premature infants, regardless of necrotizing enterocolitis development Raveh-Sadka, Tali; Thomas, Brian C.; Singh, Andrea eLife, Vol. 4 https://doi.org/10.7554/elife.05477	journal	March 2015
VirSorter: mining viral signal from microbial genomic data Roux, Simon; Enault, Francois; Hurwitz, Bonnie L. PeerJ, Vol. 3 https://doi.org/10.7717/peerj.985	journal	January 2015
Diversity and composition of the North Sikkim hot spring mycobiome using a culture-independent method Das, Sayak; Roy, Goshaidas; Najar, Ishfaq Nabi Folia Microbiologica, Vol. 66, Issue 3 https://doi.org/10.1007/s12223-021-00859-z	journal	March 2021
Pathology of neonatal necrotizing enterocolitis: A ten-year experience Ballance, William A.; Dahms, Beverly B.; Shenker, Nancy The Journal of Pediatrics, Vol. 117, Issue 1 https://doi.org/10.1016/S0022-3476(05)81124-2	journal	July 1990
Pathogenesis of Neonatal Necrotising Enterocolitis Lawrence, Gregor; Bates, John; Gaul, Anne The Lancet, Vol. 319, Issue 8264 https://doi.org/10.1016/S0140-6736(82)90383-X	journal	January 1982
Metagenomic Sequencing with Strain-Level Resolution Implicates Uropathogenic E. coli in Necrotizing Enterocolitis and Mortality in Preterm Infants Ward, Doyle V.; Scholz, Matthias; Zolfo, Moreno Cell Reports, Vol. 14, Issue 12 https://doi.org/10.1016/j.celrep.2016.03.015	journal	March 2016
Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium Zhang, Sicai; Lebreton, Francois; Mansfield, Michael J. Cell Host & Microbe, Vol. 23, Issue 2 https://doi.org/10.1016/j.chom.2017.12.018	journal	February 2018
Pathogenesis of Neonatal Necrotising Enterocolitis Gray, E. S.; Lloyd, D. J.; Horne, C. H. W. The Lancet, Vol. 319, Issue 8269 https://doi.org/10.1016/s0140-6736(82)91654-3	journal	February 1982
Binning metagenomic contigs by coverage and composition Alneberg, Johannes; Bjarnason, Brynjar Smári; de Bruijn, Ino Nature Methods, Vol. 11, Issue 11 https://doi.org/10.1038/nmeth.3103	journal	September 2014
Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins Carim, Sean; Azadeh, Ashley L.; Kazakov, Alexey E. The ISME Journal, Vol. 15, Issue 8 https://doi.org/10.1038/s41396-021-00921-1	journal	March 2021
Recovery of genomes from metagenomes via a dereplication, aggregation and scoring strategy Sieber, Christian M. K.; Probst, Alexander J.; Sharrar, Allison Nature Microbiology, Vol. 3, Issue 7 https://doi.org/10.1038/s41564-018-0171-1	journal	May 2018
Metagenomic engineering of the mammalian gut microbiome in situ Ronda, Carlotta; Chen, Sway P.; Cabral, Vitor Nature Methods, Vol. 16, Issue 2 https://doi.org/10.1038/s41592-018-0301-y	journal	January 2019
Environmental dissemination of pathogenic Listeria monocytogenes in flowing surface waters in Switzerland Raschle, Susanne; Stephan, Roger; Stevens, Marc J. A. Scientific Reports, Vol. 11, Issue 1 https://doi.org/10.1038/s41598-021-88514-y	journal	April 2021
Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature Arnison, Paul G.; Bibb, Mervyn J.; Bierbaum, Gabriele Nat. Prod. Rep., Vol. 30, Issue 1 https://doi.org/10.1039/C2NP20085F	journal	January 2013
Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature Arnison, Paul G.; Bibb, Mervyn J.; Bierbaum, Gabriele Nat. Prod. Rep., Vol. 30, Issue 1 https://doi.org/10.1039/c2np20085f	journal	January 2013
Necrotizing Enterocolitis Neu, Josef; Walker, W. Allan New England Journal of Medicine, Vol. 364, Issue 3 https://doi.org/10.1056/NEJMra1005408	journal	January 2011
Necrotizing Enterocolitis Kim, Wontae; Seo, Jeong-Meen New England Journal of Medicine, Vol. 383, Issue 25 https://doi.org/10.1056/nejmicm2020782	journal	December 2020
IQ-TREE: A Fast and Effective Stochastic Algorithm for Estimating Maximum-Likelihood Phylogenies Nguyen, Lam-Tung; Schmidt, Heiko A.; von Haeseler, Arndt Molecular Biology and Evolution, Vol. 32, Issue 1 https://doi.org/10.1093/molbev/msu300	journal	November 2014
The histone deacetylase inhibitor trichostatin A alters the pattern of DNA replication origin activity in human cells Kemp, M. G. Nucleic Acids Research, Vol. 33, Issue 1 https://doi.org/10.1093/nar/gki177	journal	January 2005
The histone deacetylase inhibitor trichostatin A alters the pattern of DNA replication origin activity in human cells Kemp, M. G. Nucleic Acids Research, Vol. 33, Issue 2 https://doi.org/10.1093/nar/gki229	journal	January 2005
Functional interactions of archaea, bacteria and viruses in a hypersaline endolithic community: Halite metagenome Crits-Christoph, Alexander; Gelsinger, Diego R.; Ma, Bing Environmental Microbiology, Vol. 18, Issue 6 https://doi.org/10.1111/1462-2920.13259	journal	March 2016
Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples Korem, T.; Zeevi, D.; Suez, J. Science, Vol. 349, Issue 6252 https://doi.org/10.1126/science.aac4812	journal	July 2015
Antibiotics, birth mode, and diet shape microbiome maturation during early life Bokulich, Nicholas A.; Chung, Jennifer; Battaglia, Thomas Science Translational Medicine, Vol. 8, Issue 343 https://doi.org/10.1126/scitranslmed.aad7121	journal	June 2016
Gamma-Butyrolactone Regulatory System of Streptomyces chattanoogensis Links Nutrient Utilization, Metabolism, and Development Du, Yi-Ling; Shen, Xue-Ling; Yu, Pin Applied and Environmental Microbiology, Vol. 77, Issue 23 https://doi.org/10.1128/AEM.05898-11	journal	September 2011
Isolation of a Variant of Subtilosin A with Hemolytic Activity Huang, T.; Geng, H.; Miyyapuram, V. R. Journal of Bacteriology, Vol. 191, Issue 18 https://doi.org/10.1128/JB.00541-09	journal	July 2009
Complete Sequencing and Diversity Analysis of the Enterotoxin-Encoding Plasmids in Clostridium perfringens Type A Non-Food-Borne Human Gastrointestinal Disease Isolates Miyamoto, K.; Fisher, D. J.; Li, J. Journal of Bacteriology, Vol. 188, Issue 4 https://doi.org/10.1128/JB.188.4.1585-1598.2006	journal	February 2006
Evolution of the Chaperone/Usher Assembly Pathway: Fimbrial Classification Goes Greek Nuccio, S. -P.; Baumler, A. J. Microbiology and Molecular Biology Reviews, Vol. 71, Issue 4 https://doi.org/10.1128/MMBR.00014-07	journal	December 2007
Machine Learning Leveraging Genomes from Metagenomes Identifies Influential Antibiotic Resistance Genes in the Infant Gut Microbiome Rahman, Sumayah F.; Olm, Matthew R.; Morowitz, Michael J. mSystems, Vol. 3, Issue 1 https://doi.org/10.1128/mSystems.00123-17	journal	January 2018
Necrotizing Enterocolitis Henry, Marion C. W.; Moss, R. Lawrence Annual Review of Medicine, Vol. 60, Issue 1 https://doi.org/10.1146/annurev.med.60.050207.092824	journal	February 2009
Necrotizing Enterocolitis – 150 Years of Fruitless Search for the Cause Obladen, Michael Neonatology, Vol. 96, Issue 4 https://doi.org/10.1159/000215590	journal	January 2009
Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants Morrow, Ardythe L.; Lagomarcino, Anne J.; Schibler, Kurt R. Microbiome, Vol. 1, Issue 1 https://doi.org/10.1186/2049-2618-1-13	journal	April 2013
ViromeScan: a new tool for metagenomic viral community profiling Rampelli, Simone; Soverini, Matteo; Turroni, Silvia BMC Genomics, Vol. 17, Issue 1 https://doi.org/10.1186/s12864-016-2446-3	journal	March 2016
Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis Pammi, Mohan; Cope, Julia; Tarr, Phillip I. Microbiome, Vol. 5, Issue 1 https://doi.org/10.1186/s40168-017-0248-8	journal	March 2017
VirFinder: a novel k-mer based tool for identifying viral sequences from assembled metagenomic data Ren, Jie; Ahlgren, Nathan A.; Lu, Yang Young Microbiome, Vol. 5, Issue 1 https://doi.org/10.1186/s40168-017-0283-5	journal	July 2017
Polinton-like viruses are abundant in aquatic ecosystems Bellas, Christopher M.; Sommaruga, Ruben Microbiome, Vol. 9, Issue 1 https://doi.org/10.1186/s40168-020-00956-0	journal	January 2021
Early Intestinal Bacterial Colonization and Necrotizing Enterocolitis in Premature Infants: The Putative Role of Clostridium de la Cochetière, Marie-France; Piloquet, Hugues; des Robert, Clotilde Pediatric Research, Vol. 56, Issue 3 https://doi.org/10.1203/01.PDR.0000134251.45878.D5	journal	September 2004
New Insights Into the Pathogenesis and Treatment of Necrotizing Enterocolitis: Toll-Like Receptors and Beyond Afrazi, Amin; Sodhi, Chhinder P.; Richardson, Ward Pediatric Research, Vol. 69, Issue 3 https://doi.org/10.1203/PDR.0b013e3182093280	journal	March 2011
The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis Jilling, Tamas; Simon, Dyan; Lu, Jing The Journal of Immunology, Vol. 177, Issue 5 https://doi.org/10.4049/jimmunol.177.5.3273	journal	August 2006
Gut bacteria are rarely shared by co-hospitalized premature infants, regardless of necrotizing enterocolitis development Raveh-Sadka, Tali; Thomas, Brian C.; Singh, Andrea eLife, Vol. 4 https://doi.org/10.7554/eLife.05477	journal	March 2015

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Additional file 1 of Probiotics mixture reinforces barrier function to ameliorate necrotizing enterocolitis by regulating PXR-JNK pathway Zhao, Xiuhao; Zhou, Jin; Liang, Wenhua figshare https://doi.org/10.6084/m9.figshare.13632855	image	January 2021
Additional file 2 of Probiotics mixture reinforces barrier function to ameliorate necrotizing enterocolitis by regulating PXR-JNK pathway Zhao, Xiuhao; Zhou, Jin; Liang, Wenhua figshare https://doi.org/10.6084/m9.figshare.13632858.v1	image	January 2021

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