The intestinal virome in children with cystic fibrosis differs from healthy controls

Intestinal bacterial dysbiosis is evident in children with cystic fibrosis (CF) and intestinal viruses may be contributory, given their influence on bacterial species diversity and biochemical cycles. We performed a prospective, case-control study on children with CF and age and gender matched healt...

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Published inPloS one Vol. 15; no. 5; p. e0233557
Main Authors Coffey, Michael J, Low, Ivan, Stelzer-Braid, Sacha, Wemheuer, Bernd, Garg, Millie, Thomas, Torsten, Jaffe, Adam, Rawlinson, William D, Ooi, Chee Y
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Published United States Public Library of Science 22.05.2020
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Abstract Intestinal bacterial dysbiosis is evident in children with cystic fibrosis (CF) and intestinal viruses may be contributory, given their influence on bacterial species diversity and biochemical cycles. We performed a prospective, case-control study on children with CF and age and gender matched healthy controls (HC), to investigate the composition and function of intestinal viral communities. Stool samples were enriched for viral DNA and RNA by viral extraction, random amplification and purification before sequencing (Illumina MiSeq). Taxonomic assignment of viruses was performed using Vipie. Functional annotation was performed using Virsorter. Inflammation was measured by calprotectin and M2-pyruvate kinase (M2-PK). Eight CF and eight HC subjects were included (50% male, mean age 6.9 ± 3.0 and 6.4 ± 5.3 years, respectively, p = 0.8). All CF subjects were pancreatic insufficient. Regarding the intestinal virome, no difference in Shannon index between CF and HC was identified. Taxonomy-based beta-diversity (presence-absence Bray-Curtis dissimilarity) was significantly different between CF and HC (R2 = 0.12, p = 0.001). Myoviridae, Faecalibacterium phage FP Taranis and unclassified Gokushovirinae were significantly decreased in CF compared with HC (q<0.05). In children with CF (compared to HC), the relative abundance of genes annotated to (i) a peptidoglycan-binding domain of the peptidoglycan hydrolases (COG3409) was significantly increased (q<0.05) and (ii) capsid protein (F protein) (PF02305.16) was significantly decreased (q<0.05). Picornavirales, Picornaviridae, and Enterovirus were found to positively correlate with weight and BMI (r = 0.84, q = 0.01). Single-stranded DNA viruses negatively correlated with M2-PK (r = -0.86, q = 0.048). Children with CF have an altered intestinal virome compared to well-matched HC, with both taxonomic and predicted functional changes. Further exploration of Faecalibacterium phages, Gokushovirinae and phage lysins are warranted. Intestinal viruses and their functions may have important clinical implications for intestinal inflammation and growth in children with CF, potentially providing novel therapeutic targets.
AbstractList Intestinal bacterial dysbiosis is evident in children with cystic fibrosis (CF) and intestinal viruses may be contributory, given their influence on bacterial species diversity and biochemical cycles. We performed a prospective, case-control study on children with CF and age and gender matched healthy controls (HC), to investigate the composition and function of intestinal viral communities. Stool samples were enriched for viral DNA and RNA by viral extraction, random amplification and purification before sequencing (Illumina MiSeq). Taxonomic assignment of viruses was performed using Vipie. Functional annotation was performed using Virsorter. Inflammation was measured by calprotectin and M2-pyruvate kinase (M2-PK). Eight CF and eight HC subjects were included (50% male, mean age 6.9 ± 3.0 and 6.4 ± 5.3 years, respectively, p = 0.8). All CF subjects were pancreatic insufficient. Regarding the intestinal virome, no difference in Shannon index between CF and HC was identified. Taxonomy-based beta-diversity (presence-absence Bray-Curtis dissimilarity) was significantly different between CF and HC (R.sup.2 = 0.12, p = 0.001). Myoviridae, Faecalibacterium phage FP Taranis and unclassified Gokushovirinae were significantly decreased in CF compared with HC (q<0.05). In children with CF (compared to HC), the relative abundance of genes annotated to (i) a peptidoglycan-binding domain of the peptidoglycan hydrolases (COG3409) was significantly increased (q<0.05) and (ii) capsid protein (F protein) (PF02305.16) was significantly decreased (q<0.05). Picornavirales, Picornaviridae, and Enterovirus were found to positively correlate with weight and BMI (r = 0.84, q = 0.01). Single-stranded DNA viruses negatively correlated with M2-PK (r = -0.86, q = 0.048). Children with CF have an altered intestinal virome compared to well-matched HC, with both taxonomic and predicted functional changes. Further exploration of Faecalibacterium phages, Gokushovirinae and phage lysins are warranted. Intestinal viruses and their functions may have important clinical implications for intestinal inflammation and growth in children with CF, potentially providing novel therapeutic targets.
Intestinal bacterial dysbiosis is evident in children with cystic fibrosis (CF) and intestinal viruses may be contributory, given their influence on bacterial species diversity and biochemical cycles. We performed a prospective, case-control study on children with CF and age and gender matched healthy controls (HC), to investigate the composition and function of intestinal viral communities. Stool samples were enriched for viral DNA and RNA by viral extraction, random amplification and purification before sequencing (Illumina MiSeq). Taxonomic assignment of viruses was performed using Vipie. Functional annotation was performed using Virsorter. Inflammation was measured by calprotectin and M2-pyruvate kinase (M2-PK). Eight CF and eight HC subjects were included (50% male, mean age 6.9 ± 3.0 and 6.4 ± 5.3 years, respectively, p = 0.8). All CF subjects were pancreatic insufficient. Regarding the intestinal virome, no difference in Shannon index between CF and HC was identified. Taxonomy-based beta-diversity (presence-absence Bray-Curtis dissimilarity) was significantly different between CF and HC (R2 = 0.12, p = 0.001). Myoviridae, Faecalibacterium phage FP Taranis and unclassified Gokushovirinae were significantly decreased in CF compared with HC (q<0.05). In children with CF (compared to HC), the relative abundance of genes annotated to (i) a peptidoglycan-binding domain of the peptidoglycan hydrolases (COG3409) was significantly increased (q<0.05) and (ii) capsid protein (F protein) (PF02305.16) was significantly decreased (q<0.05). Picornavirales, Picornaviridae, and Enterovirus were found to positively correlate with weight and BMI (r = 0.84, q = 0.01). Single-stranded DNA viruses negatively correlated with M2-PK (r = -0.86, q = 0.048). Children with CF have an altered intestinal virome compared to well-matched HC, with both taxonomic and predicted functional changes. Further exploration of Faecalibacterium phages, Gokushovirinae and phage lysins are warranted. Intestinal viruses and their functions may have important clinical implications for intestinal inflammation and growth in children with CF, potentially providing novel therapeutic targets.
Intestinal bacterial dysbiosis is evident in children with cystic fibrosis (CF) and intestinal viruses may be contributory, given their influence on bacterial species diversity and biochemical cycles. We performed a prospective, case-control study on children with CF and age and gender matched healthy controls (HC), to investigate the composition and function of intestinal viral communities. Stool samples were enriched for viral DNA and RNA by viral extraction, random amplification and purification before sequencing (Illumina MiSeq). Taxonomic assignment of viruses was performed using Vipie. Functional annotation was performed using Virsorter. Inflammation was measured by calprotectin and M2-pyruvate kinase (M2-PK). Eight CF and eight HC subjects were included (50% male, mean age 6.9 ± 3.0 and 6.4 ± 5.3 years, respectively, p = 0.8). All CF subjects were pancreatic insufficient. Regarding the intestinal virome, no difference in Shannon index between CF and HC was identified. Taxonomy-based beta-diversity (presence-absence Bray-Curtis dissimilarity) was significantly different between CF and HC (R 2 = 0.12, p = 0.001). Myoviridae , Faecalibacterium phage FP Taranis and unclassified Gokushovirinae were significantly decreased in CF compared with HC (q<0.05). In children with CF (compared to HC), the relative abundance of genes annotated to (i) a peptidoglycan-binding domain of the peptidoglycan hydrolases (COG3409) was significantly increased (q<0.05) and (ii) capsid protein (F protein) (PF02305.16) was significantly decreased (q<0.05). Picornavirales , Picornaviridae , and Enterovirus were found to positively correlate with weight and BMI (r = 0.84, q = 0.01). Single-stranded DNA viruses negatively correlated with M2-PK (r = -0.86, q = 0.048). Children with CF have an altered intestinal virome compared to well-matched HC, with both taxonomic and predicted functional changes. Further exploration of Faecalibacterium phages, Gokushovirinae and phage lysins are warranted. Intestinal viruses and their functions may have important clinical implications for intestinal inflammation and growth in children with CF, potentially providing novel therapeutic targets.
Audience Academic
Author Coffey, Michael J
Thomas, Torsten
Low, Ivan
Rawlinson, William D
Jaffe, Adam
Stelzer-Braid, Sacha
Wemheuer, Bernd
Ooi, Chee Y
Garg, Millie
AuthorAffiliation 8 Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney, New South Wales, Australia
1 School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
Hospital Universitario Ramon y Cajal, SPAIN
2 School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia
4 School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
7 Molecular and Integrative Cystic Fibrosis (miCF) Research Centre, Sydney, New South Wales, Australia
3 Virology Research Laboratory, Prince of Wales Hospital, Sydney, New South Wales, Australia
5 School of Biological, Earth and Environmental Sciences, Centre for Marine Science and Innovation, University of New South Wales, Sydney New South Wales, Australia
6 Department of Respiratory, Sydney Children's Hospital Randwick, Sydney, New South Wales, Australia
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/32442222$$D View this record in MEDLINE/PubMed
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2020 Coffey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2020 Coffey et al 2020 Coffey et al
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– notice: 2020 Coffey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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PublicationDate 2020-05-22
PublicationDateYYYYMMDD 2020-05-22
PublicationDate_xml – month: 05
  year: 2020
  text: 2020-05-22
  day: 22
PublicationDecade 2020
PublicationPlace United States
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PublicationTitle PloS one
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Snippet Intestinal bacterial dysbiosis is evident in children with cystic fibrosis (CF) and intestinal viruses may be contributory, given their influence on bacterial...
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SubjectTerms Age
Annotations
Antibiotics
Biochemical cycles
Biochemistry
Biodiversity
Biology and Life Sciences
Capsid protein
Children
Children & youth
Childrens health
Complications and side effects
Computer and Information Sciences
Cystic fibrosis
Deoxyribonucleic acid
Development and progression
Digestive system
DNA
DNA sequencing
DNA viruses
Dysbacteriosis
Dysbiosis
Ecology and Environmental Sciences
Enteroviruses
Environmental science
Enzymes
F protein
Faecalibacterium
Fibrosis
Genes
Health aspects
Hospitals
Hydrolases
Inflammation
Intestine
Laboratories
Lysins
Medicine and Health Sciences
Microbiota
Microbiota (Symbiotic organisms)
Mutation
Novels
Nutrition research
Pancreas
Pediatric research
People and Places
Peptidoglycans
Phages
Physiological aspects
Proteins
Pyruvate kinase
Pyruvic acid
Relative abundance
Ribonucleic acid
Risk factors
RNA
Single-stranded DNA
Species diversity
Taxonomy
Therapeutic applications
Viral proteins
Virology
Viruses
Womens health
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Title The intestinal virome in children with cystic fibrosis differs from healthy controls
URI https://www.ncbi.nlm.nih.gov/pubmed/32442222
https://www.proquest.com/docview/2405840609
https://pubmed.ncbi.nlm.nih.gov/PMC7244107
https://doaj.org/article/1b4788400dab4b23be75642ad0d102a2
http://dx.doi.org/10.1371/journal.pone.0233557
Volume 15
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