Parenteral nutrition decreases paneth cell function and intestinal bactericidal activity while increasing susceptibility to bacterial enteroinvasion

Aaron F. Heneghan, Joseph Pierre, Kanokwan Tandee, Dhanansayan Shanmuganayagam, Xinying Wang, Jess D. Reed, James L. Steele, Kenneth A. Kudsk

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Introduction: 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. Hypothesis: 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. Method: 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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)817-824
Number of pages8
JournalJournal of Parenteral and Enteral Nutrition
Volume38
Issue number7
DOIs
StatePublished - Sep 19 2014
Externally publishedYes

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Paneth Cells
Parenteral Nutrition
Microbiota
Enteral Nutrition
Ileum
Bacteroidetes
Escherichia coli
Host-Pathogen Interactions
Cholinergic Agonists
Proteobacteria
Inbred ICR Mouse
Total Parenteral Nutrition
Muramidase
Infection
Cholinergic Agents
Mucous Membrane
Inflammation
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Parenteral nutrition decreases paneth cell function and intestinal bactericidal activity while increasing susceptibility to bacterial enteroinvasion. / Heneghan, Aaron F.; Pierre, Joseph; Tandee, Kanokwan; Shanmuganayagam, Dhanansayan; Wang, Xinying; Reed, Jess D.; Steele, James L.; Kudsk, Kenneth A.

In: Journal of Parenteral and Enteral Nutrition, Vol. 38, No. 7, 19.09.2014, p. 817-824.

Research output: Contribution to journalArticle

Heneghan, Aaron F. ; Pierre, Joseph ; Tandee, Kanokwan ; Shanmuganayagam, Dhanansayan ; Wang, Xinying ; Reed, Jess D. ; Steele, James L. ; Kudsk, Kenneth A. / Parenteral nutrition decreases paneth cell function and intestinal bactericidal activity while increasing susceptibility to bacterial enteroinvasion. In: Journal of Parenteral and Enteral Nutrition. 2014 ; Vol. 38, No. 7. pp. 817-824.
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abstract = "Introduction: 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. Hypothesis: 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. Method: 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). Conclusion: 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.",
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T1 - Parenteral nutrition decreases paneth cell function and intestinal bactericidal activity while increasing susceptibility to bacterial enteroinvasion

AU - Heneghan, Aaron F.

AU - Pierre, Joseph

AU - Tandee, Kanokwan

AU - Shanmuganayagam, Dhanansayan

AU - Wang, Xinying

AU - Reed, Jess D.

AU - Steele, James L.

AU - Kudsk, Kenneth A.

PY - 2014/9/19

Y1 - 2014/9/19

N2 - Introduction: 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. Hypothesis: 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. Method: 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). Conclusion: 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.

AB - Introduction: 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. Hypothesis: 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. Method: 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). Conclusion: 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.

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