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

Background and 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 (109CFU/ml) and intratracheally injected with Pseudomonas aeruginosa or saline. At 4, 12, and 24h 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.

The Cross-Talk Between Gut Microbiota and Lungs in Common Lung Diseases

“…The administration of Lactobacillus rhamnosus GG via oral improved gut permeability and modulated inflammatory response and homeostasis of spleen and colon in FVB/N mice with Pseudomonas aeruginosa pneumonia. The mechanism underlying its protection is enhancing gut mucin expression, improving cell proliferation and reducing the pro-inflammatory cytokine expression (Khailova et al, 2017). A Lactobacillus reuteri probiotic preparation was demonstrated to improve gastrointestinal health and decrease the calprotectin levels due to the reduction of gamma-proteobacterial populations by a double blind prospective study of cystic fibrosis patients (del Campo et al, 2014).…”

Lactobacillus paracasei feeding improves the control of secondary experimental meningococcal infection in flu-infected mice

“…Mice treated with L. rhamnosus GG showed significantly better seven-day survival than saline-treated control mice in another experimental model of Pseudomonas aeruginosa -induced pneumonia [ 28 ]. This model also reveal the gut-lung axis and suggests that probiotic ( L. rhamnosus GG) consumption may help to maintain the homeostasis of mucosal barriers [ 29 ]. Indeed, the gut microbiota has been reported to improve the outcome of experimental pneumococcal pneumonia in mice, as suggested by increased bacterial dissemination, inflammation, organ damage, and mortality in microbiota-depleted mice [ 30 ].…”

Towards Individualized Use of Probiotics and Prebiotics for Metabolic Syndrome and Associated Diseases Treatment: Does Pathophysiology-Based Approach Work and Can Anticipated Evidence Be Completed?

“…The spleen and intestine are two major immune organs involved in the innate immune response to infection [199]. Spleen structure and size might be supposed as promising imaging biomarker for immunity-and stress-related conditions.…”