title: Parenteral nutrition decreases paneth cell function and intestinal bactericidal activity while increasing susceptibility to bacterial enteroinvasion.
abstract: BACKGROUND
  Parenteral nutrition (PN) increases the risk of infection in patients with contraindication to enteral feeding. Paneth cells produce and secrete antimicrobial products that protect the mucosa from pathogens. Their loss is associated with increased host-pathogen interactions, mucosal inflammation, and altered microbiome composition.
  
  
  OBJECTIVE
  We hypothesized that PN reduces Paneth cell product expression, and these changes would reduce bactericidal properties of tissue secretions following cholinergic stimulation, increase mucosal enteroinvasion, and shift the intestinal microbiome.
  
  
  METHODS
  Experiment 1: Male ICR mice were randomized to Chow (n = 8) or PN (n = 8). Ileum tissue was collected for Paneth cell antimicrobial expression using RT-PCR, stimulated with a cholinergic agonist degranulate Paneth cells bactericidal activity, or used to assess bacterial enteroinvasion in EVISC. Experiment 2: Mice were randomized to Chow (n = 11) or PN (n = 8) and ileum washing was collected for 16s pyrosequencing analysis.
  
  
  RESULTS
  Compared to Chow, PN decreased tissue expression of REGIII-g (p < 0.002), lysozyme (p < 0.002), and cryptdin-4 (p < 0.03). At the phylum level, PN decreased total Firmicutes but increased total Bacteroidetes, and Proteobacteria. Functionally, secretions from PN tissue was less bactericidal (p < 0.03) and demonstrated increased susceptibility to enteroinvasion by E coli (p < 0.02).
  
  
  CONCLUSIONS
  PN without enteral nutrition impairs innate mucosal immune function. Tissue expression of Paneth cell antimicrobial proteins decreases associated with compositional shifts to the microbiome, decreased bactericidal activity of mucosal secretions and greater susceptibility of to enteroinvasion by E coli. These changes may explain in-part the increased risk of infection in parenterally fed patients.
authors.affiliation: Surgical Service of the William S. Middleton Veteran Memorial Hospital, Madison WI, USA.|Department of Surgery, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Heneghan
authors.affiliation: Surgical Service of the William S. Middleton Veteran Memorial Hospital, Madison WI, USA.|Department of Surgery, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Pierre
authors.affiliation: Department of Food Science, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Tandee
authors.affiliation: Reed Research Group, Department of Animal Sciences, University of Wisconsin -Madison, Madison, WI 53706.
authors.forename: Dhanansayan
authors.initials: D
authors.lastname: Shanmuganayagam
authors.affiliation: Department of Surgery, University of Wisconsin-Madison, Madison, WI, USA.|Department of Surgery, Nanjing University, Jinling hospital, Nanjing, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Reed Research Group, Department of Animal Sciences, University of Wisconsin -Madison, Madison, WI 53706.
authors.forename: Jess D
authors.initials: JD
authors.lastname: Reed
authors.affiliation: Department of Food Science, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Steele
authors.affiliation: Surgical Service of the William S. Middleton Veteran Memorial Hospital, Madison WI, USA.|Department of Surgery, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kudsk
mesh_terms: D000818:Animals; D001419:Bacteria / Q000254:growth & development*; D004198:Disease Susceptibility; D004926:Escherichia coli / Q000254:growth & development; D007082:Ileum / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D018928:Immunity, Mucosal; D008297:Male; D008813:Mice, Inbred ICR; D064307:Microbiota; D009113:Muramidase / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D019879:Paneth Cells / Q000378:metabolism*; D010288:Parenteral Nutrition / Q000009:adverse effects*; D011506:Proteins / Q000378:metabolism; D023084:alpha-Defensins / Q000378:metabolism
chemical_list: D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490255:Reg3g protein, mouse; D023084:alpha-Defensins; C401847:cryptdin 4, mouse; D009113:Muramidase
keywords: Paneth cells; innate immunity, cryptdins, microbiome; parenteral nutrition; small intestine
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