Discovery, diversity, and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts.

Anastasia Gulyaeva,Arnau Vich Vila,Mihai G Netea,Rinse K Weersma,Cisca Wijmenga,Jingyuan Fu,Niels P Riksen,Daoming Wang,Sanzhima Garmaeva,Alexandra Zhernakova,Alexander Kurilshikov,Renate A.A.A Ruigrok

doi:10.1016/j.celrep.2021.110204

Abstract

The crAss-like phages are a diverse group of related viruses that includes some of the most abundant viruses of the human gut. To explore their diversity and functional role in human population and clinical cohorts, we analyze gut metagenomic data collected from 1,950 individuals from the Netherlands. We identify 1,556 crAss-like phage genomes, including 125 species-level and 32 genus-level clusters absent from the reference databases used. Analysis of their genomic features shows that closely related crAss-like phages can possess strikingly divergent regions responsible for transcription, presumably acquired through recombination. Prediction of crAss-like phage hosts points primarily to bacteria of the phylum Bacteroidetes, consistent with previous reports. Finally, we explore the temporal stability of crAss-like phages over a 4-year period and identify associations between the abundance of crAss-like phages and several human phenotypes, including depletion of crAss-like phages in inflammatory bowel disease patients.

Highlights

Our planet harbors an enormous diversity of viruses
The first representative of these phages, the crAssphage sensu stricto, was discovered in 2014 and is believed to be one of the most abundant viruses in the human gut (Dutilh et al, 2014). This initial discovery was followed by the identification of five groups of crAss-like phages associated with the human gut—alpha/gamma, beta, delta, epsilon, and zeta—as well as diverse crAss-like phages associated with other environments (Guerin et al, 2018; Yutin et al, 2018, 2021)
And identification of crAss-like phage genomes To identify crAss-like phage genomes in our gut metagenomic data, we assembled contigs for 2,291 metagenomic samples from four cohorts: 1,135 LLD, 338 LLD follow-up, 298 300-Obesity cohort (300OB), and 520 inflammatory bowel disease (IBD) samples (Table 1)

Summary

Introduction

Our planet harbors an enormous diversity of viruses. There are millions of distinct species of cellular organisms, and all can likely be infected by viruses. The first representative of these phages, the crAssphage sensu stricto, was discovered in 2014 and is believed to be one of the most abundant viruses in the human gut (Dutilh et al, 2014). This initial discovery was followed by the identification of five groups of crAss-like phages associated with the human gut—alpha/gamma, beta, delta, epsilon, and zeta—as well as diverse crAss-like phages associated with other environments (Guerin et al, 2018; Yutin et al, 2018, 2021)

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