title: Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates inflammatory response and homeostasis of spleen and colon in experimental model of Pseudomonas aeruginosa pneumonia.
abstract: 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.
  
  
  
  Studies were performed in 6-8 week old FVB/N mice treated (o.g.) with or without LGG (109CFU/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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Khailova
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Baird
authors.affiliation: Valparaiso University, Valparaiso, IN, 46383, USA.
authors.forename: Aubri A
authors.initials: AA
authors.lastname: Rush
authors.affiliation: Valparaiso University, Valparaiso, IN, 46383, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Barnes
authors.affiliation: Department of Anesthesiology, Duke University School of Medicine, Durham, NC, 27710, USA. Electronic address: Paul.Wischmeyer@Duke.edu.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Wischmeyer
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D062446:Claudin-2 / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000382:microbiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D000069196:Gastrointestinal Microbiome; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D052201:Lacticaseibacillus rhamnosus; D051379:Mice; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism; D010539:Permeability; D011018:Pneumonia, Pneumococcal / Q000628:therapy*; D019936:Probiotics / Q000008:administration & dosage; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D013154:Spleen / Q000378:metabolism / Q000382:microbiology*
chemical_list: D062446:Claudin-2; D016207:Cytokines; C524626:Muc2 protein, mouse; D055262:Mucin-2
keywords: Apoptosis; Gut barrier; Mouse; Mucin; Probiotics