Official Title
Phages Dynamics and Influences During Human Gut Microbiome Establishment
Brief Title
Phages Dynamics and Influences During Human Gut Microbiome Establishment
Protocol ID
NCT03296631
Lead Sponsor
Institut Pasteur
Brief Summary
Microbial communities are key components of human environment. Consequently, human gut
microbiome have been extensively studied providing a better understanding of the
relations between bacterial populations and host physiology. However, a typical analysis
tends to elude the complexity of the mixes in term of species, strains, as well as
extra-chromosomal DNA molecules such as and phages. MetaKids project aims at bringing, at
an unprecedented resolution, a new view of those populations and the internal
relationships during human gut establishment, a crucial step with long-term impacts on
host health. This project relies on the ability of Meta3C, a newly technique developed in
the lab, to identify the bacterial host genomes of the different phages the investigators
will detect thanks to the physical collision these molecules experience. Given the role
that human gut phages may play in shaping the development of host microbiomes, their
potential for application is of great interest.
Detailed Description
Over the last decade, the role of microorganisms residing in human intestines has been
intensively studied. The intestinal microbiome includes bacteria, viruses, fungi and
archaea. The importance of microbiome to human health is highlighted by the observation
that dysbiotic shifts in these microbial communities have been associated with numerous
human diseases, including obesity, inflammatory bowel disorders, autoimmune disease or
gastrointestinal cancer. It is also clearly established that some of these microorganisms
interact with the immune system and contribute to its development. The intestinal
microbiome is established soon after birth, and its composition changes over the next
several years toward a stereotypical 'adult-like' bacterial community structure.
Epidemiological studies have demonstrated the importance of this period for a long-term
health. It also has been shown that this process can be influenced by multiple
interacting factors such as nutrition, antibiotic use and others environmental factors.
Much less is known on the viral part of human microbiome. Most of them are phages
(phageome) that are known to modulate microbial population through predation or transfer
of genetic information between bacteria, and are likely to have important effects on
intestinal microbiome establishment and, consequently, human physiology. MetaKids project
aims at understanding how the gut phageome develops during the early human life and how
it influences the composition of the bacterial microbiome. The investigators will carry a
longitudinal study of 15-20 infants from 3-9 months till age 24-30 months. By combining
latest metagenomic methods, will be investigated: 1) the composition, evolution and
dynamic of the phageome and bacterial microbiome over this critical period; 2) the
interactions between phages and bacteria and their relationships; and 3) the impact of
environmental factors, like vaccinations or antibiotics treatment on the phages
populations. The project is based on the combination of innovative recent metagenomic
techniques developed in the lab. DNA is an ubiquitous and stable molecule that can be
used as a marker of "compartmentalization" at cellular and population levels, providing
important information regarding the genomic structure of a mix of species. Therefore, by
combining approaches like purification of virales particles and 3C related methods, the
investigators propose to characterize infant gut microbiome establishment and decipher
the relationships between the different genomic entities present during this period. This
project will bring crucial data on the role of phages during early life of human
intestinal tract. Intervention to modify/control intestinal population is a dynamic field
and MetaKids project will bring new perspectives for this research area.
Study Period
-
Enrollment Count
19 participants
Eligibility Criteria
Inclusion Criteria:
1. Child attending at least 4 days a week one of the two municipal municipal nursery
(crèches) in the town of Orsay (91, France);
2. Aged less than 9 months at the time of entry to the crèche (August-October 2017);
3. Parent (s) / legal representative not opposed to the child's participation in the
research;
Exclusion Criteria:
- Toilet training;
- Prematurity;
- Participation in clinical research requiring the use of a drug.
Filters
Human Gut Microbiome Development
TERMINATED
CHILD