The endogenous bacteria alter gut epithelial apoptosis and decrease mortality following pseudomonas aeruginosa pneumonia

Amy C. Fox, Kevin W. McConnell, Benyam P. Yoseph, Elise Breed, Zhe Liang, Andrew T. Clark, David O'Donnell, Brendan Zee-Cheng, Enjae Jung, Jessica A. Dominguez, W. Michael Dunne, Eileen M. Burd, Craig M. Coopersmith

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The endogenous bacteria have been hypothesized to play a significant role in the pathophysiology of critical illness, although their role in sepsis is poorly understood. The purpose of this study was to determine how commensal bacteria alter the host response to sepsis. Conventional and germ-free (GF) C57Bl/6 mice were subjected to Pseudomonas aeruginosa pneumonia. All GF mice died within 2 days, whereas 44% of conventional mice survived for 7 days (P = 0.001). Diluting the dose of bacteria 10-fold in GF mice led to similar survival in GF and conventional mice. When animals with similar mortality were assayed for intestinal integrity, GF mice had lower levels of intestinal epithelial apoptosis but similar levels of proliferation and intestinal permeability. Germ-free mice had significantly lower levels of tumor necrosis factor and interleukin 1β in bronchoalveolar lavage fluid compared with conventional mice without changes in systemic cytokine production. Under conventional conditions, sepsis unmasks lymphocyte control of intestinal epithelial apoptosis, because sepsis induces a greater increase in gut apoptosis in Rag-1-/- mice than in wild-type mice. However, in a separate set of experiments, gut apoptosis was similar between septic GF Rag-1-/- mice and septic GF wild-type mice. These data demonstrate that the endogenous bacteria play a protective role in mediating mortality from pneumonia-induced sepsis, potentially mediated through altered intestinal apoptosis and the local proinflammatory response. In addition, sepsis-induced lymphocyte-dependent increases in gut epithelial apoptosis appear to be mediated by the endogenous bacteria.

Original languageEnglish (US)
Pages (from-to)508-514
Number of pages7
JournalShock
Volume38
Issue number5
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

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Keywords

  • apoptosis
  • commensal microflora
  • endogenous bacteria
  • germ-free
  • gut
  • intestine
  • pneumonia
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Fox, A. C., McConnell, K. W., Yoseph, B. P., Breed, E., Liang, Z., Clark, A. T., ... Coopersmith, C. M. (2012). The endogenous bacteria alter gut epithelial apoptosis and decrease mortality following pseudomonas aeruginosa pneumonia. Shock, 38(5), 508-514. https://doi.org/10.1097/SHK.0b013e31826e47e8