Distinct mucosal microbial communities in infants with surgical necrotizing enterocolitis correlate with age and antibiotic exposure

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/23

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

30365522

DOI Digital object identifier for electronic documents.

10.1371/journal.pone.0206366

URI

Authors

Romano-Keeler J, Shilts MH, Tovchigrechko A, Wang C, Brucker RM, Moore DJ, Fonnesbeck C, Meng S, Correa H, Lovvorn HN, Tang YW, Hooper L, Bordenstein SR, Das SR, Weitkamp JH

Journal

PloS one

Year

2018

OBJECTIVE: Necrotizing enterocolitis (NEC) is the most common surgical emergency in preterm infants, and pathogenesis associates with changes in the fecal microbiome. As fecal samples incompletely represent microbial communities in intestinal mucosa, we sought to determine the NEC tissue-specific microbiome and assess its contribution to pathogenesis. DESIGN: We amplified and sequenced the V1-V3 hypervariable region of the bacterial 16S rRNA gene extracted from intestinal tissue and corresponding fecal samples from 12 surgical patients with NEC and 14 surgical patients without NEC. Low quality and non-bacterial sequences were removed, and taxonomic assignment was made with the Ribosomal Database Project. Operational taxonomic units were clustered at 97%. We tested for differences between NEC and non-NEC samples in microbiome alpha- and beta-diversity and differential abundance of specific taxa between NEC and non-NEC samples. Additional analyses were performed to assess the contribution of other demographic and environmental confounding factors on the infant tissue and fecal microbiome. RESULTS: The fecal and tissue microbial communities were different. NEC was associated with a distinct microbiome, which was characterized by low diversity, higher abundances of Staphylococcus and Clostridium_sensu_stricto, and lower abundances of Actinomyces and Corynebacterium. Infant age and vancomycin exposure correlated with shifts in the tissue microbiome. CONCLUSION: The observed low diversity in NEC tissues suggests that NEC is associated with a bacterial bloom and a distinct mucosal bacterial community. The exact bacterial species that constitute the bloom varied by infant and were strongly influenced by age and exposure to vancomycin.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/23

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Mucosa of small intestine Mucosa of organ of small bowel,Mucosa of organ of small intestine,Mucosa of small bowel,Mucous membrane of small bowel,Mucous membrane of small intestine,Organ mucosa of small bowel,Organ mucosa of small intestine,Small bowel mucosa,Small bowel mucosa of organ,Small bowel mucous membrane,Small bowel organ mucosa,Small intestinal mucosa,Small intestine mucosa,Small intestine mucosa of organ,Small intestine mucous membrane,Small intestine organ mucosa,Tunica mucosa (intestinum tenue),Tunica mucosa intestini tenuis,Mucosa of small intestine,mucosa of small intestine

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Necrotizing enterocolitis Enterocolitis, Necrotizing,NEC,necrotizing enterocolitis,necrotizing enterocolitis in fetus or newborn,Necrotizing enterocolitis

Group 0 name Corresponds to the control (unexposed) group for case-control studies: non-NEC

Group 1 name Corresponds to the case (exposed) group for case-control studies: NEC

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: infants who underwent intestinal resection at <180 days of age with NEC

Group 0 sample size Number of subjects in the control (unexposed) group: 14

Group 1 sample size Number of subjects in the case (exposed) group: 10

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V3

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: raw counts

Statistical test: DESeq2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.1

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Chao1 Abundance-based estimator of species richness: decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Richness Number of species: decreased

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/23

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure 5

Description: Comparison of the abundance of tissue bacterial genera between infants with or without necrotizing enterocolitis (NEC)

Abundance in Group 1: increased abundance in NEC

NCBI	Quality Control	Links
Clostridium
Staphylococcus

Revision editor(s): WikiWorks

Signature 2

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Source: Figure 5

Description: Comparison of the abundance of tissue bacterial genera between infants with or without necrotizing enterocolitis (NEC)

Abundance in Group 1: decreased abundance in NEC

NCBI	Quality Control	Links
Arcobacter
Finegoldia
Alicyclobacillus
Actinomyces
Pseudomonas
Chryseobacterium
Comamonas
unclassified Actinomycetales
Chitinophagaceae
unclassified Bacteroidota
Streptococcus
unclassified Bacteria
Corynebacterium

Revision editor(s): Claregrieve1

Experiment 3

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Curated date: 2021/01/10

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Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Lab analysis

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V4

Statistical Analysis

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/23

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure 6

Description: Comparison of the abundance of tissue bacterial genera between infants with or without necrotizing enterocolitis (NEC) after adjusting

Abundance in Group 1: increased abundance in NEC

NCBI	Quality Control	Links
Staphylococcus

Revision editor(s): WikiWorks