title: Intestinal epithelial cell apoptosis and loss of barrier function in the setting of altered microbiota with enteral nutrient deprivation.
abstract: Total parenteral nutrition (TPN), a commonly used treatment for patients who cannot receive enteral nutrition, is associated with significant septic complications due in part to a loss of epithelial barrier function (EBF). While the underlying mechanisms of TPN-related epithelial changes are poorly understood, a mouse model of TPN-dependence has helped identify several contributing factors. Enteral deprivation leads to a shift in intestinal microbiota to predominantly Gram-negative Proteobacteria. This is associated with an increase in expression of proinflammatory cytokines within the mucosa, including interferon-γ and tumor necrosis factor-α. A concomitant loss of epithelial growth factors leads to a decrease in epithelial cell proliferation and increased apoptosis. The resulting loss of epithelial tight junction proteins contributes to EBF dysfunction. These mechanisms identify potential strategies of protecting against TPN-related complications, such as modification of luminal bacteria, blockade of proinflammatory cytokines, or growth factor replacement.
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan Health System Ann Arbor, MI, USA.
authors.forename: Farokh R
authors.initials: FR
authors.lastname: Demehri
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan Health System Ann Arbor, MI, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Barrett
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan Health System Ann Arbor, MI, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Ralls
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan Health System Ann Arbor, MI, USA.
authors.forename: Eiichi A
authors.initials: EA
authors.lastname: Miyasaka
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan Health System Ann Arbor, MI, USA.
authors.forename: Yongjia
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan Health System Ann Arbor, MI, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
mesh_terms: D000818:Animals; D017209:Apoptosis; D058448:Biota; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology*; D051379:Mice; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D062725:Tight Junction Proteins / Q000378:metabolism
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D062725:Tight Junction Proteins
keywords: epithelial barrier function; epithelial call proliferation; epithelial cell apoptosis; microbiome; parenteral nutrition; small intestine