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

• Published in: PloS 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.05.2020; Public Library of Science (PLoS)
• Subjects: 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; Australia; United Kingdom > UK; New South Wales Australia; Wales
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0233557

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.