Study could help investigate role of gut virome in health and disease

A new study has added many previously uncharacterized viral genomes and genes to the ever-growing global pool of human intestinal viromes. The study, published in mSystems, an open access journal of the American Society for Microbiology, will prove useful in studying the role of the intestinal virome in human health and disease.

The human intestinal virome is still largely under-explored and many new viruses are yet to be discovered, some of which could have important influences on processes impacting human health and disease. “

Jelle Matthijnssens, Ph.D., principal investigator of the study, professor in the Department of Microbiology, Immunology and Transplantation, Rega Institute, Division of Clinical and Epidemiological Virology, Viral Metagenomics Laboratory, KU Leuven, Louvain, Belgium

The human intestine contains a complex ecosystem of microorganisms, the bacteria of which have been extensively studied. Dr Matthijnssens said studies of viruses in the gut were lagging behind. The objective of the MicrobLiver project is to understand the interaction between the host and the gut microbiome in humans and the role of the gut-liver axis in the early stages of alcoholic and non-alcoholic fatty liver disease. “As part of the MicrobLiver project, we sought to generate a catalog of viral genomes, which could be used in subsequent studies on several cohorts of people with early stages of alcoholic and non-alcoholic fatty liver disease,” said Dr Matthijnssens .

In the new study, the researchers used 254 fecal samples from 204 Danish subjects to generate the Danish Catalog of Enteric Viromas (DEVoC). The pediatric cohort included 50 children and adolescents (6-18 years) with a body mass index (BMI) greater than 90e percentile, with 50 healthy controls matched by age and sex. The adult cohort (34-76 years) included 52 patients with alcohol-related liver disease and 52 healthy controls of the same age, by sex, BMI and age.

The researchers used the NetoVIR (Novel Enrichment Technique Of Viromes) protocol to purify all viral particles from stool samples and sequenced their genomes using deep sequencing technologies. (NetoVir enables researchers to achieve a fast, reproducible, high throughput sample preparation protocol for next-generation sequencing intestinal viromic studies.)

In addition, they used an advanced bioinformatics tool to identify nearly 13,000 (partial) viral genomes, many of which were new and not present in public databases.

Although intestinal viromes are known to be very specific to each individual, the researchers identified 39 genomes that were present in at least 10 healthy subjects. These 39 genomes were then compared to datasets of public viromes from around the world showing several prevalence patterns related to age, geography and disease. In particular, 2 genomes have shown a remarkably high prevalence in the world. The first was a crAss-like phage (20.6% prevalence), belonging to the AlphacrAssvirinae subfamily, while the second was a temperate phage infecting Bacteroides dorei (prevalence 14.4%), called LoVEphage. The researchers then sifted through public databases and were able to recover 18 additional LoVEphage-type circular genomes (67.9 to 72.4 kb).

“Our results further underscore that the human intestinal virome is still under-studied and that many new viruses are yet to be discovered. In particular, the identification of new phages shared by people around the world merits further study. depth, “said Dr Matthijnssens. . “Then the catalog will be used to further study the differences in the virome of various cohorts of patients with early stages of alcoholic and non-alcoholic fatty liver disease. We hope that these studies will provide us with some background information about the role of the virome. may have in the development of alcoholic and non-alcoholic fatty liver disease.In addition, we will examine the virome to identify biomarkers of disease progression or prediction of treatment success.


Journal reference:

Espen, LV, et al. (2021) A highly widespread phage previously not described and identified in a Danish catalog of enteric viromes. mSystems.

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