The role of the virome in shaping the gut ecosystem during the first year of life

Project Information

BabyVir

Grant agreement ID: 715772

DOI

10.3030/715772

Project closed

EC signature date 20 February 2017

Start date 1 April 2017

End date 30 June 2023

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 499 881,00

EU contribution

€ 1 499 881,00

Coordinated by

ACADEMISCH ZIEKENHUIS GRONINGEN
Netherlands

Periodic Reporting for period 4 - BabyVir (The role of the virome in shaping the gut ecosystem during the first year of life)

Reporting period: 2021-10-01 to 2023-06-30

Summary of the context and overall objectives of the project

This project is focused on the discovery of the variability and composition of gut virome in babies, in shaping the gut ecosystem during the first year of life, and on the effect of gut virome on health.

Gut microbiome (community of all microorganisms in the gut) is associated with many health conditions and traits. The role of the development of gut microbiome during infancy for long-term health is being studied by several groups. The methods of microbiome studies mainly involve analysis of gut bacteria; however, it has been established that viruses, in particular, bacterial viruses (bacteriophages) form the major component of the gut ecosystem. The studies of viruses are laying behind the bacterial analyses for several reasons: first, viruses have small size therefore they are rather underrepresented in broad microbiome analyses, such as metagenomics sequencing. Therefore, enrichment protocols are necessary to obtain a sufficient quantity of material. Next, the classification and reference databases of viruses are not developed, therefore annotation of virome is challenging. Finally, no well-established bioinformatics pipelines are available for the virome analysis, therefore analysis requires a lot of de-novo developments in the field of bioinformatics.

The objecties of this project was to characterize the gut microbiome and virome composition in a large longitudinal mother-baby cohort from pre-pregnancy till the first year of life, to describe the dynamics of microbiome and virome development, factors that influence abundances and dynamics of gut bacteria and viruses, and to link it with host, environmental factors and diseases.

Identification the contribution of virome to the development of the gut ecosystem and its relation to babies health will add to our understanding of how the early life and inborn factors influence individual health. Identification of bacteriophages that specifically tag particular bacteria and/or are linked to health-related outcomes will pave the path to the development of phage-based prebiotics

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In the cause of the project we developed the methodology for the gut virome analysis, we set up the lab methods for virome enrichment and created the pipeline for the bioinformatic analysis of gut virome. The virome enrichment protocols were extensively tested on adult samples, for which we have a large amount of material. The development of the bioinformatic pipeline for virome analysis is a large achievement since no decent pipeline for data analysis was available in our group before the start of the project.
After optimization, we optimisation, we applied the new protocols first on the pilot studies of ~300 samples, and then on a large dataset of >1000 samples. We also developed the pipeline and performed the analysis of viruses using the metagenomics sequencing data.

We identified large inter-individual differences between virome composition, whereas intra-individual composition remains more stable. The virome in babies has substantially lower diversity compared to adults. We identified the effect of delivery mode and feeding type on the composition of gut virome. We also identified multiple novel associations of delivery factors (such as time of active pushing), diseases (such as gastrointestinal complaints), diseases (i.e. eczema), environmental factors (i.e. pets) to the gut microbiome and virome.

This project led to several publications, as described in the major achievement. Several other papers are in preparation.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The gut metaviromics is a developing field and majority of gut virome enrichments are performed on either small scale or in a cross-sectional design. We have published several pioneering papers on the methods of virome analysis, on the virome dynamics during the first year of life, and on the virome transmission from mothers to babies. For example, we identified cases of vertical transmission of gut viruses from mothers to babies. We also identified that gut viruses at early months of babies are likely come from maternal prophages. The dynamic of lytic vs lysogenic bacteriophages is remarkably different between mothers and babies. Finally, we identified and describe many novel, not yet observed viral sequences. These sequences, as well as corresponding pipelines, are uploaded to the databases and are available for the research community.

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