PrimiBiota: Influence of Intestinal Microbiota Implantation in Preterm Infants on Microbiota and Immune Orientation at 3 Years
Study Details
Study Description
Brief Summary
The main objective of this research is to study the links between changes in the intestinal microbiota (in terms of diversity) during the first 6 weeks of life for preterm infants and the presence / absence of a TH1 immune status at 36 months of age.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
The secondary objectives are to study the links between changes of the intestinal microbiota premature infants in terms of:
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changing diversity of the microbiota in the first 6 weeks of life;
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changes in the bacterial community (UniFrac study) during the first 6 weeks of life;
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diversity of the microbiota up to 6 weeks;
-AND-
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diversity of the microbiota at 1, 2 & 3 years;
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bacterial communities (UniFrac study) at 1, 2 & 3 years;
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lymphocyte subpopulation profiles at 3 years;
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serum immunoglobulin A, G, M, E levels at 3 years;
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history of infectious episodes, allergic and inflammatory episodes during the first 3 years of life.
The links between certain variables known in the literature and neonatal microbiota will be confirmed / studied in our population:
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mode of delivery;
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length (and type) of antibiotic therapy in the neonatal period;
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duration of breastfeeding.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| The study population The study population corresponds to infants born at less than 33 weeks of gestation. |
Outcome Measures
Primary Outcome Measures
- The presence/absence of a Th1 type immune orientation [36 months]
Immune orientation will be determined according to the following ratio determined by lymphocyte stimulation tests: INF-gamma/(INF-gamma+IL+4). The latter ratio varies between 0 and 0.5 with IL-4 > INF-gamma (TH2 orientation) and between 0.5 and 1 when INF-gamma > IL-4 (TH1 orientation).
Secondary Outcome Measures
- Blood lymphocyte subset determination [36 months]
Subsets are determined according to the presence/absence of the following differentiation clusters: CD3, CD4, CD8, CD19, CD25, CD56, CD127, FOXP3.
Other Outcome Measures
- Serum Immunoglobulin A level [36 months]
- Serum Immunoglobulin G level [36 months]
- Serum Immunoglobulin M level [36 months]
- Serum Immunoglobulin E level [36 months]
- The number of days in good health and no medications [36 months]
- Richness of fecal microbiota (number of operational taxonomic units observed) [Day 0 (first meconium)]
- Richness of fecal microbiota (number of operational taxonomic units observed) [Week 1]
- Richness of fecal microbiota (number of operational taxonomic units observed) [Week 2]
- Richness of fecal microbiota (number of operational taxonomic units observed) [Week 3]
- Richness of fecal microbiota (number of operational taxonomic units observed) [Week 4]
- Richness of fecal microbiota (number of operational taxonomic units observed) [Week 5]
- Richness of fecal microbiota (number of operational taxonomic units observed) [Week 6]
- Richness of fecal microbiota (number of operational taxonomic units observed) [12 months]
- Richness of fecal microbiota (number of operational taxonomic units observed) [24 months]
- Richness of fecal microbiota (number of operational taxonomic units observed) [36 months]
- Diversity of fecal microbiota (Shannon's index) [Day 0 (first meconium)]
- Diversity of fecal microbiota (Shannon's index) [Week 1]
- Diversity of fecal microbiota (Shannon's index) [Week 2]
- Diversity of fecal microbiota (Shannon's index) [Week 3]
- Diversity of fecal microbiota (Shannon's index) [Week 4]
- Diversity of fecal microbiota (Shannon's index) [Week 5]
- Diversity of fecal microbiota (Shannon's index) [Week 6]
- Diversity of fecal microbiota (Shannon's index) [12 months]
- Diversity of fecal microbiota (Shannon's index) [24 months]
- Diversity of fecal microbiota (Shannon's index) [36 months]
- Functional richness of fecal microbiota (number of functional groups observed) [Day 0 (first meconium)]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional richness of fecal microbiota (number of functional groups observed) [Week 1]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional richness of fecal microbiota (number of functional groups observed) [Week 2]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional richness of fecal microbiota (number of functional groups observed) [Week 3]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional richness of fecal microbiota (number of functional groups observed) [Week 4]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional richness of fecal microbiota (number of functional groups observed) [Week 5]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional richness of fecal microbiota (number of functional groups observed) [Week 6]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional richness of fecal microbiota (number of functional groups observed) [12 months]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional richness of fecal microbiota (number of functional groups observed) [24 months]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional richness of fecal microbiota (number of functional groups observed) [36 months]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional diversity of fecal microbiota (Shannon's index) [Day 0 (first meconium)]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional diversity of fecal microbiota (Shannon's index) [Week 1]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional diversity of fecal microbiota (Shannon's index) [Week 2]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional diversity of fecal microbiota (Shannon's index) [Week 3]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional diversity of fecal microbiota (Shannon's index) [Week 4]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional diversity of fecal microbiota (Shannon's index) [Week 5]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional diversity of fecal microbiota (Shannon's index) [Week 6]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional diversity of fecal microbiota (Shannon's index) [12 months]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional diversity of fecal microbiota (Shannon's index) [24 months]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- Functional diversity of fecal microbiota (Shannon's index) [36 months]
Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.
- The relative abundance of primary fecal microbiota families [Day 0 (first meconium)]
- The relative abundance of primary fecal microbiota families [Week 1]
- The relative abundance of primary fecal microbiota families [Week 2]
- The relative abundance of primary fecal microbiota families [Week 3]
- The relative abundance of primary fecal microbiota families [Week 4]
- The relative abundance of primary fecal microbiota families [Week 5]
- The relative abundance of primary fecal microbiota families [Week 6]
- The relative abundance of primary fecal microbiota families [12 months]
- The relative abundance of primary fecal microbiota families [24 months]
- The relative abundance of primary fecal microbiota families [36 months]
- Fecal microbiota unifrac ordination score [Day 0 (first meconium)]
- Fecal microbiota unifrac ordination score [Week 1]
- Fecal microbiota unifrac ordination score [Week 2]
- Fecal microbiota unifrac ordination score [Week 3]
- Fecal microbiota unifrac ordination score [Week 4]
- Fecal microbiota unifrac ordination score [Week 5]
- Fecal microbiota unifrac ordination score [Week 6]
- Fecal microbiota unifrac ordination score [12 months]
- Fecal microbiota unifrac ordination score [24 months]
- Fecal microbiota unifrac ordination score [36 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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The parents of the patient (or legal guardian if any) have been informed about the implementation of the study, its objectives, its constraints, and patient rights
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The parents of the patient (or legal guardian if any) must have given their free and informed consent and signed the consent form
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The patient must be affiliated with or beneficiary of a health insurance plan
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Premature infants born at less than 33 weeks of gestation
Exclusion Criteria:
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The patient is participating in another interventional study (Excepted " Recherche du Portage de Clostridium butyricum et de Toxines de Clostridium chez les Prématurés Hospitalisés en Néonatologie afin de prédire la survenue d'Entérocolites Nécrosantes", RCB 2016-A00-529-42 ; " BetaDose Dose reduction of antenatal betamethasone given to prevent the neonatal complications associated with very preterm birth ", RCB 2016-001486-90.
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It is not possible to correctly inform the parent (or legal guardian, if applicable)
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A serious deformity or digestive malformation was diagnosed at birth
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During the hospital stay in the neonatology department, the patient had a digestive disease requiring surgery (except necrotizing enterocolitis)
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A transfer to another hospital is foreseen/predictable (eg, due to geographical distance)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHRU de Montpellier - Hôpital Arnaud de Villeneuve | Montpellier | France | 34295 | |
| 2 | CHRU de Nîmes - Hôpital Universitaire Carémeau | Nîmes Cedex 09 | France | 30029 | |
| 3 | Réseau GRANDIR EN LANGUEDOC-ROUSILLON | Saint Gely Du Fesc | France | 34980 |
Sponsors and Collaborators
- Centre Hospitalier Universitaire de Nīmes
Investigators
- Study Director: Anne Filleron, MD, PhD, Centre Hospitalier Universitaire de Nîmes
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PHRC-I/2015/AF-01