Esophageal atresia: a natural experiment of the effects of oral inoculation on the gut microbiome

Pearl Houghteling, MD

Summary

BACKGROUND: Infants with esophageal atresia (EA) may not have anastomosis, or connection, of the upper and lower portions of the esophagus until they are several months old. Even after repair, children with EA experience long term complications such as gastroesophageal reflux and poor growth. GAP: The intestines in children with EA are not exposed to the oropharyngeal microbiota or other components of oral secretions prior to surgery, resulting in an extreme and prolonged disruption to microbial community assembly in the gut. It is anticipated that the delay in oral inoculation of the gut contributes to the persistent comorbidities of esophageal atresia, but there are no data to prove this. HYPOTHESIS: Infants will have delayed colonization of the gut, and fewer of the typical commensal microbes found in healthy children, resulting in abnormal immune development. Giving a patient with EA his or her own saliva via gastrostomy tube will reverse the abnormal gut microbial phenotype. METHODS: Infants with EA and gestational-age matched controls in the neonatal intensive care unit will be evaluated for their microbiome (oral, gastric and stool using 16S rRNA sequencing), metabolomics (blood, urine, stool) and immune profiling (using CyTOF). Infants with EA will be administered their own saliva via G-tube with each feed for one week. RESULTS: Pending IMPACT: An adjunctive therapy for EA using pre-anastomosis gastric inoculation with oral secretions might result directly from this research. In addition, this project may further elucidate the role of the gut microbiota in altered growth and immune development in children.