Esophageal Atresia: a Natural Experiment of the Effects of Oral Inoculation on the Gut Microbiome

Study Overview
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Brief Summary
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The purpose of this study is to understand changes of the gut microbiome due to esophageal atresia. The intervention will be to give a patient his or her own saliva through their gastrostomy tube (directly into the stomach) to observe if this can normalize microbial colonization of the gut.

Detailed Description
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After being informed about the study and its overall risks, parents will be given the option to enroll their infant. Participants (infants) with esophageal atresia and a gastrostomy tube will be given their own saliva through their gastrostomy tube, directly into the stomach. Samples of saliva and stool will be collected from these infants, and from a comparison group without esophageal atresia, as well as blood and urine to look for changes in immune responses and in metabolism.

Official Title
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Esophageal Atresia: a Natural Experiment of the Effects of Oral Inoculation on the Gut Microbiome

Conditions
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Esophageal Atresia

Intervention / Treatment
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* Other: Patient's own saliva


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonates with Esophageal Atresia (All, no exclusion criteria); maximum age at enrollment is 3 months. Neonates matched for gestational age without EA, also anticipated to require surgery (Infants >=32 weeks), or also premature (<32 weeks) Exclusion Criteria (only for infants without EA): sepsis admission to study hospital after 7 days old expected length of stay <2 weeks

Ages Eligible for Study
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Maximum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Infants with esophageal atresia (EA) and comparison infants without esophageal atresia (but also in the neonatal intensive care unit, NICU) will be recruited. Infants with EA will be given their own saliva for 1 week, with every feed. Infants without EA will receive usual care. All subjects will have samples collected according to the same schedule. Mothers of infants will also be recruited and have samples collected in order to understand the sources of the infant's gut microbiome.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infants with Esophageal Atresia<br>Starting at 3 weeks, infants will be administered 1 mL of their own saliva via gastrostomy tube, with each feed (8x/day) for one week. | Other: Patient's own saliva<br>* Infants with esophageal atresia will be given their own saliva<br>|
| No Intervention: Comparison Infants without Esophageal Atresia<br>Infants do not have EA and thus can swallow their own saliva. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gut Microbial Community Structure | Evaluate community structure and differential abundances of dominant taxa and of key taxa to the newborn (e.g., Bifidobacterium, Bacteroides, Lactobacillus, Staphylococcus and Enterobacteriaceae) | From birth until discharge from the hospital, up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Immune System Profile | Determine immune cell profiles using mass cytometry (CyTOF) | From birth until discharge from the hospital, up to 1 year | 
| Change in Fecal Metabolome Profile | Measure metabolites in the stool using mass spectrometry | From birth until discharge from the hospital, up to 1 year | 
| Change in Blood Metabolome Profile | Measure metabolites in the blood using mass spectrometry | From birth until discharge from the hospital, up to 1 year |