Prolonged antibiotic use induces intestinal injury in mice that is repaired after removing antibiotic pressure: implications for empiric antibiotic therapy.
Metabolic profiling of urine and fecal extracts, histological investigation of intestinal ilea, and fecal metagenomics analyses were used to investigate effects of prolonged antibiotic use in mice. The study provides insight into the effects of extended empiric antibiotic therapy in humans. Mice were administered a broad-spectrum antibiotic for four consecutive days followed by oral gavage withClostridium butyricum, an opportunistic gram-positive pathogenic bacteria commonly isolated in fecal and blood cultures of necrotizing enterocolitis patients. Metagenomics data indicated loss of bacterial diversity after 4 days on antibiotics that was restored after removing antibiotic pressure. Histological analyses indicated damage to ileal villi after antibiotic treatment that underwent repair after lifting antibiotic pressure. Metabolic profiling confirmed intestinal injury in antibiotic-treated mice indicated by increased urinary trans-4-hydroxy-l-proline, a breakdown product of collagen present in connective tissue of ileal villi that may serve as a biomarker for antibiotic-induced injury in at risk populations.
Department of Chemistry & Biochemistry, Miami University, 701 East High Street, Oxford, OH 45056, USA.
Lindsey E
LE
Romick-Rosendale
Perinatal Institute, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 7009, Cincinnati, OH 45218, USA.
Anne
A
Legomarcino
Department of Chemistry & Biochemistry, Miami University, 701 East High Street, Oxford, OH 45056, USA.
Neil B
NB
Patel
Perinatal Institute, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 7009, Cincinnati, OH 45218, USA.
Ardythe L
AL
Morrow
Department of Chemistry & Biochemistry, Miami University, 701 East High Street, Oxford, OH 45056, USA.
Michael A
MA
Kennedy
Antibiotic; Metabolomics; Mouse model; NMR; Necrotizing enterocolitis; PCA