Clinical trial NCT03296631: Phages Dynamics and Influences During Human Gut Microbiome Establishment
Official title: Phages Dynamics and Influences During Human Gut Microbiome Establishment
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Human Gut Microbiome Development
Keywords: microbiome
gut
infant gut
phages
phages-bacteria interactions
microbiome development
Lead sponsor: Institut Pasteur
Sponsor class: INDUSTRY
Collaborators: name: City of Orsay
First posted: 2017-09-28
Enrollment: 19
Sex: ALL
Minimum age (years): 10
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children being in age to attend in a nursery day care structure of the town of Orsay (France) and aged less than 9 months.

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.

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.

Primary outcomes:
measure: Characterization of phages and bacteria genomes during infant gut development.
timeFrame: 3 years
measure: Characterization of phages and bacteria abundance and variations during infant gut development
timeFrame: 3 years
measure: Characterization of phages-bacteria interactions
timeFrame: 3 years
Secondary outcomes:
measure: Characterization of phages and bacteria variations in response to environmental perturbations during infant gut development
timeFrame: 2 to 3 weeks
Other outcomes:
Locations:
city: Orsay
country: France
facility: Crèche du Parc
state: Essonne
city: Orsay
country: France
facility: Crèche La Farandole
state: Essonne
Study officials:
affiliation: Institut Pasteur / CNRS
name: Martial Marbouty
role: STUDY_DIRECTOR
References: