Expanding known viral diversity in the healthy infant gut

Abstract

The gut microbiome is shaped through infancy and impacts the maturation of the immune system, thus protecting against chronic disease later in life. Phages, or viruses that infect bacteria, modulate bacterial growth by lysis and lysogeny, with the latter being especially prominent in the infant gut. Viral metagenomes (viromes) are difficult to analyse because they span uncharted viral diversity, lacking marker genes and standardized detection methods. Here we systematically resolved the viral diversity in faecal viromes from 647 1-year-olds belonging to Copenhagen Prospective Studies on Asthma in Childhood 2010, an unselected Danish cohort of healthy mother–child pairs. By assembly and curation we uncovered 10,000 viral species from 248 virus family-level clades (VFCs). Most (232 VFCs) were previously unknown, belonging to the Caudoviricetes viral class. Hosts were determined for 79% of phage using clustered regularly interspaced short palindromic repeat spacers within bacterial metagenomes from the same children. Typical Bacteroides-infecting crAssphages were outnumbered by undescribed phage families infecting Clostridiales and Bifidobacterium. Phage lifestyles were conserved at the viral family level, with 33 virulent and 118 temperate phage families. Virulent phages were more abundant, while temperate ones were more prevalent and diverse. Together, the viral families found in this study expand existing phage taxonomy and provide a resource aiding future infant gut virome research.

The influence of early life exposures on the infant gut virome

“…A total of 645 stool samples from 1-year old infants in the COPSAC2010 cohort 32 were obtained and analyzed 9 . Virions were isolated, concentrated and their genome was sequenced using a shotgun metagenome strategy 9,33 .…”

“…A total of 645 stool samples from 1-year old infants in the COPSAC2010 cohort 32 were obtained and analyzed 9 . Virions were isolated, concentrated and their genome was sequenced using a shotgun metagenome strategy 9,33 . Following assembly, a total of 16,118 species-level clustered viral representative contigs (here termed viral Operational Taxonomic Units -vOTUs) were obtained.…”

“…To date, GM research has generally focused on understanding the importance of the bacterial GM component, but recent findings indicate that the vast and diverse population of viruses found in the gut (collectively called the "virome") also play a prominent role in gut microbial ecology [6][7][8][9] . Amidst these biological entities, bacterial viruses, also termed bacteriophages (phages), are the most diverse and abundant particles of the GM [9][10][11] and they represent a major reservoir of genetic diversity influencing not only GM composition, but also the GM metabolic potential 12,13 .…”

“…To date, GM research has generally focused on understanding the importance of the bacterial GM component, but recent findings indicate that the vast and diverse population of viruses found in the gut (collectively called the "virome") also play a prominent role in gut microbial ecology [6][7][8][9] . Amidst these biological entities, bacterial viruses, also termed bacteriophages (phages), are the most diverse and abundant particles of the GM [9][10][11] and they represent a major reservoir of genetic diversity influencing not only GM composition, but also the GM metabolic potential 12,13 . Disease-specific alterations in the gut virome have been reported in several chronic conditions 14 such as inflammatory bowel disease 15 , colorectal cancer 16 , necrotizing enterocolitis in preterm infants 17 , severe acute malnutrition 18 , type-1 diabetes 19,20 and other autoimmune diseases such as rheumatoid arthritis 21 .…”

“…In a recent detailed investigation of the infant gut virome, we showed a massive diversity of hitherto undescribed phages 9 . In this cross-sectional study of the gut virome of 645 infants at one year of age enrolled in the COPSAC2010 cohort 32 more than ten thousand viral species distributed over 248 viral families and 17 viral order-level clades were detected.…”