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

Periodic Reporting for period 3 - BabyVir (The role of the virome in shaping the gut ecosystem during the first year of life)

Reporting period: 2020-04-01 to 2021-09-30

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. It is established that delivery mode and feeding pattern during infancy have an effect on gut microbiome composition, and potentially can mediate individuals health later in life. 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.

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
In the past 30 months 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 performed the pilot studies of gut virome composition and stability in adults and babies, two papers describing these results are in preparation. 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.
Currently, we are extending this analysis to a large group of mothers and babies in the longitudinal design. We also collect extensive environmental factors from all participants, that include diet, medication, lifestyle, socio-economical factors and genetics. We will investigate the effect of these factors on microbiome composition on a large scale. We will also link the virome development to health parameters in babies, such as growth, gastrointestinal health, allergies and others.
By the end of the project we expect to run the virome analysis in the full longitudinal collection of Lifelines-NEXT samples, and link the virome composition with gut microbial community, with environmental and maternal factors, and with babies health outcomes.