Jia Liu1, Hiromu Miyake2, Haitao Zhu1, Bo Li2, Mashriq Alganabi2, Carol Lee2, Agostino Pierro3. 1. The Hospital for Sick Children, University of Toronto, Toronto, Canada; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China. 2. The Hospital for Sick Children, University of Toronto, Toronto, Canada. 3. The Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: agostino.pierro@sickkids.ca.
Abstract
PURPOSE: Necrotizing Enterocolitis (NEC) is a devastating neonatal disease with a high mortality rate. Fecal Microbiota Transplantation (FMT) has been used to treat a variety of gastrointestinal diseases. We aimed to investigate the role of FMT in NEC. METHODS: NEC was induced by hypoxia, LPS, and hyperosmolar gavage feeding between postnatal days P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). FMT (30 μl/g) was administered by gavage or enema at P6 during NEC induction. Distal ileum was harvested on P9. Disease severity was evaluated by H&E staining. Gene expression of inflammatory markers IL6 and TNFa was measured. Expression of intestinal barrier function was investigated by measuring Claudin-7. Microbiota composition in ileum and colon was analyzed by quantitative PCR. RESULTS: FMT by gavage further increased terminal ileum inflammation and did not improve the histological damage owing to experimental NEC. Conversely, FMT by enema decreased intestinal inflammation and improved histology of the NEC-like injury in the ileum. In addition, compared with NEC alone, FMT by enema increased Claudin-7 expression indicating an improvement in barrier function. These beneficial effects occurred despite no change in microbiota. CONCLUSION: Our results show that FMT by enema may be an effective strategy to reduce NEC progression as it attenuates intestinal inflammation and enhances intestinal barrier function. FMT by enema is a potential novel treatment for NEC. LEVEL OF EVIDENCE: Level IV, Evidence from well-designed case-control or cohort studies.
PURPOSE:Necrotizing Enterocolitis (NEC) is a devastating neonatal disease with a high mortality rate. Fecal Microbiota Transplantation (FMT) has been used to treat a variety of gastrointestinal diseases. We aimed to investigate the role of FMT in NEC. METHODS:NEC was induced by hypoxia, LPS, and hyperosmolar gavage feeding between postnatal days P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). FMT (30 μl/g) was administered by gavage or enema at P6 during NEC induction. Distal ileum was harvested on P9. Disease severity was evaluated by H&E staining. Gene expression of inflammatory markers IL6 and TNFa was measured. Expression of intestinal barrier function was investigated by measuring Claudin-7. Microbiota composition in ileum and colon was analyzed by quantitative PCR. RESULTS: FMT by gavage further increased terminal ileum inflammation and did not improve the histological damage owing to experimental NEC. Conversely, FMT by enema decreased intestinal inflammation and improved histology of the NEC-like injury in the ileum. In addition, compared with NEC alone, FMT by enema increased Claudin-7 expression indicating an improvement in barrier function. These beneficial effects occurred despite no change in microbiota. CONCLUSION: Our results show that FMT by enema may be an effective strategy to reduce NEC progression as it attenuates intestinal inflammation and enhances intestinal barrier function. FMT by enema is a potential novel treatment for NEC. LEVEL OF EVIDENCE: Level IV, Evidence from well-designed case-control or cohort studies.