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Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates inflammatory response and homeostasis of spleen and colon in experimental model of Pseudomonas aeruginosa pneumonia.

Publication ,  Journal Article
Khailova, L; Baird, CH; Rush, AA; Barnes, C; Wischmeyer, PE
Published in: Clin Nutr
December 2017

BACKGROUND & AIMS: Recent clinical trials and in vivo models demonstrate probiotic administration can reduce occurrence and improve outcome of pneumonia and sepsis, both major clinical challenges worldwide. Potential probiotic benefits include maintenance of gut epithelial barrier homeostasis and prevention of downstream organ dysfunction due to systemic inflammation. However, mechanism(s) of probiotic-mediated protection against pneumonia remain poorly understood. This study evaluated potential mechanistic targets in the maintenance of gut barrier homeostasis following Lactobacillus rhamnosus GG (LGG) treatment in a mouse model of pneumonia. METHODS: Studies were performed in 6-8 week old FVB/N mice treated (o.g.) with or without LGG (109 CFU/ml) and intratracheally injected with Pseudomonas aeruginosa or saline. At 4, 12, and 24 h post-bacterial treatment spleen and colonic tissue were collected for analysis. RESULTS: Pneumonia significantly increased intestinal permeability and gut claudin-2. LGG significantly attenuated increased gut permeability and claudin-2 following pneumonia back to sham control levels. As mucin expression is key to gut barrier homeostasis we demonstrate that LGG can enhance goblet cell expression and mucin barrier formation versus control pneumonia animals. Further as Muc2 is a key gut mucin, we show LGG corrected deficient Muc2 expression post-pneumonia. Apoptosis increased in both colon and spleen post-pneumonia, and this increase was significantly attenuated by LGG. Concomitantly, LGG corrected pneumonia-mediated loss of cell proliferation in colon and significantly enhanced cell proliferation in spleen. Finally, LGG significantly reduced pro-inflammatory cytokine gene expression in colon and spleen post-pneumonia. CONCLUSIONS: These data demonstrate LGG can maintain intestinal barrier homeostasis by enhancing gut mucin expression/barrier formation, reducing apoptosis, and improving cell proliferation. This was accompanied by reduced pro-inflammatory cytokine expression in the gut and in a downstream organ (spleen). These may serve as potential mechanistic targets to explain LGG's protection against pneumonia in the clinical and in vivo setting.

Duke Scholars

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Published In

Clin Nutr

DOI

EISSN

1532-1983

Publication Date

December 2017

Volume

36

Issue

6

Start / End Page

1549 / 1557

Location

England

Related Subject Headings

  • Spleen
  • Pseudomonas aeruginosa
  • Probiotics
  • Pneumonia, Pneumococcal
  • Permeability
  • Nutrition & Dietetics
  • Mucin-2
  • Mice
  • Lacticaseibacillus rhamnosus
  • Intestines
 

Citation

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MLA
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Khailova, L., Baird, C. H., Rush, A. A., Barnes, C., & Wischmeyer, P. E. (2017). Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates inflammatory response and homeostasis of spleen and colon in experimental model of Pseudomonas aeruginosa pneumonia. Clin Nutr, 36(6), 1549–1557. https://doi.org/10.1016/j.clnu.2016.09.025
Khailova, Ludmila, Christine H. Baird, Aubri A. Rush, Christopher Barnes, and Paul E. Wischmeyer. “Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates inflammatory response and homeostasis of spleen and colon in experimental model of Pseudomonas aeruginosa pneumonia.Clin Nutr 36, no. 6 (December 2017): 1549–57. https://doi.org/10.1016/j.clnu.2016.09.025.
Journal cover image

Published In

Clin Nutr

DOI

EISSN

1532-1983

Publication Date

December 2017

Volume

36

Issue

6

Start / End Page

1549 / 1557

Location

England

Related Subject Headings

  • Spleen
  • Pseudomonas aeruginosa
  • Probiotics
  • Pneumonia, Pneumococcal
  • Permeability
  • Nutrition & Dietetics
  • Mucin-2
  • Mice
  • Lacticaseibacillus rhamnosus
  • Intestines