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

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.

SUBMITTER: Coffey MJ

PROVIDER: S-EPMC7244107 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Coffey Michael J MJ Low Ivan I Stelzer-Braid Sacha S Wemheuer Bernd B Garg Millie M Thomas Torsten T Jaffe Adam A Rawlinson William D WD Ooi Chee Y CY

PloS one 20200522 5

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 purificat ...[more]

PMID: 32442222

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Project description:Background:Culture-independent next generation sequencing has identified diverse microbial communities within the cystic fibrosis (CF) airway. The study objective was to test for differences in the upper airway microbiome of children with CF and healthy controls and age-related differences in children with CF. Methods:Oropharyngeal swabs and clinical data were obtained from 25 children with CF and 50 healthy controls aged ?6 years. Bacterial DNA was amplified and sequenced for the V4 region of 16S rRNA marker-gene. Alpha diversity was measured using operational taxonomic units (OTUs), Shannon diversity, and the inverse Simpson's index. Beta diversity was measured using Morisita-Horn and Bray-Curtis and Jaccard distances. General linear models were used for comparison of alpha diversity measures between groups to account for differences in demographics and exposures. Mixed effects general linear models were used for longitudinal comparisons 1) between children with CF of different ages and 2) between children with CF receiving CF transmembrane conductance regulator (CFTR) modulators, children with CF not receiving CFTR modulators, and healthy controls to adjust for repeated measures per subject. Results:Children with CF were more likely to have received antibiotics in the prior year than healthy controls (92% vs 24%, p < 0.001). Controlling age, race, ethnicity, length of breastfeeding, and having siblings, children with CF had a lower richness than healthy controls: OTUs 62.1 vs 83, p = 0.022; and trended toward lower diversity: Shannon 2.09 vs 2.35, p = 0.057; inverse Simpson 5.7 vs 6.92, p = 0.118. Staphylococcus, three Rothia OTUs, and two Streptococcus OTUs were more abundant in CF children versus healthy controls (all p < 0.05). Bray-Curtis and Jaccard distances, which reflect overall microbial community composition, were also significantly different (both p = 0.001). In longitudinally collected samples from children with CF, Morisita-Horn trended toward more similarity in those aged 0-2 years compared to those aged 3-6 years (p = 0.070). In children >2 years of age, there was a significant trend in increasing alpha diversity measures between children with CF not receiving CFTR modulators, children with CF receiving CFTR modulators, and healthy controls: OTUs 63.7 vs 74.7 vs 97.6, p < 0.001; Shannon 2.11 vs 2.34 vs 2.56, p < 0.001; inverse Simpson 5.78 vs 7.23 vs 7.96, p < 0.001. Conclusions:Children with CF have lower bacterial diversity and different composition of organisms compared with healthy controls. This appears to start in early childhood, is possibly related to the use of antibiotics, and may be partially corrected with the use of CFTR modulators.

Project description:BackgroundThe Cystic Fibrosis Questionnaire (CFQ) is widely used in research as an instrument to measure quality of life in patients with cystic fibrosis (CF). In routine patient care however, measuring quality of life is still not implemented in guidelines. One of the reasons might be the lack of consensus on how to interpret CFQ scores of an individual patient, because appropriate reference data are lacking. The question which scores reflect normal functioning and which scores reflect clinically relevant problems is still unanswered. Moreover, there is no knowledge about how healthy children and adolescents report on their quality of life (on the CFQ). With regard to quality of life the effect of normal development should be taken into account, especially in childhood and adolescence. Therefore, it is important to gain more knowledge about how healthy children and adolescents report on their quality of life and if there are any difference in a healthy populations based on age or gender. Without these data we cannot adequately interpret the CFQ as a tool in clinical care to provide patient-tailored care. Therefore this study collected data of the CFQ in healthy children and adolescents with the aim to refer health status of CF youngsters to that of healthy peers.MethodsThe CFQ was completed by 478 healthy Dutch children and adolescents (aged 6-20) in a cross-sectional study.ResultsThe majority of healthy children (over 65%) did not reach maximum scores on most domains of the CFQ. Median CFQ-scores of healthy children and adolescents ranged from 67 to 100 (on a scale of 0-100) on the different CFQ-domains. Significant differences in quality of life exist among healthy children and adolescents, and these depend on age and gender.ConclusionsReference data of quality of life scores from a healthy population are essential for adequate interpretation of quality of life in young patients with CF. Clinicians should be aware that the perception of health-related quality of life is not as disease-specific as one might think and also relies on factors such as age, normal maturation and gender.

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

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

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