title: Homeostasis alteration within small intestinal mucosa after acute enteral refeeding in total parenteral nutrition mouse model.
abstract: Feeding strategies to care for patients who transition from enteral nutrient deprivation while on total parenteral nutrition (TPN) to enteral feedings generally proceed to full enteral nutrition once the gastrointestinal tract recovers; however, an increasing body of literature suggests that a subgroup of patients may actually develop an increased incidence of adverse events, including death. To examine this further, we studied the effects of acute refeeding in a mouse model of TPN. Interestingly, refeeding led to some beneficial effects, including prevention in the decline in intestinal epithelial cell (IEC) proliferation. However, refeeding led to a significant increase in mucosal expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), as well as an upregulation in Toll-like receptor 4 (TLR-4). Refeeding also failed to prevent TPN-associated increases in IEC apoptosis, loss of epithelial barrier function, and failure of the leucine-rich repeat-containing G protein-coupled receptor 5-positive stem cell expression. Transitioning from TPN to enteral feedings led to a partial restoration of the small bowel microbial population. In conclusion, while acute refeeding led to some restoration of normal gastrointestinal physiology, enteral refeeding led to a significant increase in mucosal inflammatory markers and may suggest alternative strategies to enteral refeeding should be considered.
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, the University of Michigan Medical School and the C. S. Mott Children's Hospital, Ann Arbor, Michigan;
authors.forename: Yongjia
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, the University of Michigan Medical School and the C. S. Mott Children's Hospital, Ann Arbor, Michigan; General Surgery, Department of Surgery, the University of Michigan Medical School, Ann Arbor, Michigan;
authors.forename: Meredith
authors.initials: M
authors.lastname: Barrett
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, the University of Michigan Medical School and the C. S. Mott Children's Hospital, Ann Arbor, Michigan; University of Michigan, Ann Arbor, Michigan; and.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, the University of Michigan Medical School and the C. S. Mott Children's Hospital, Ann Arbor, Michigan; University of Michigan, Ann Arbor, Michigan; and.
authors.forename: Hong Keun
authors.initials: HK
authors.lastname: Yoon
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, the University of Michigan Medical School and the C. S. Mott Children's Hospital, Ann Arbor, Michigan; Department of Pediatric Surgery, Juntendo Hospital, Juntendo University, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ochi
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, the University of Michigan Medical School and the C. S. Mott Children's Hospital, Ann Arbor, Michigan; dttlbm@umich.edu.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004750:Enteral Nutrition / Q000009:adverse effects*; D000069196:Gastrointestinal Microbiome; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics; D013234:Stem Cells; D062725:Tight Junction Proteins / Q000096:biosynthesis / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D062725:Tight Junction Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: enteral nutrition; intestinal epithelial cell proliferation; tumor necrosis factor-α