Lactobacillus rhamnosus GG Improves Outcome in Experimental Pseudomonas aeruginosa Pneumonia

Abstract

Introduction Recent clinical trials show Lactobacillus rhamnosus GG (LGG) administration in critical illness has the potential to reduce nosocomial infections and improve clinical outcome. However, the mechanism(s) of LGG-mediated benefit following illness and injury remain elusive. Objective The aim of this study was to determine the effect of LGG treatment on survival and lung injury in a mouse model of Pseudomonas aeruginosa–induced pneumonia. As increased T regulatory (Treg) cell numbers have been shown to improve outcome in experimental pneumonia, we examined the potential role of Treg cells in probiotic-mediated benefit. Methods FVB/N mice were subjected to intratracheal injection of either P. aeruginosa or saline and received LGG or vehicle immediately before procedure. T regulatory cell responses in the lung were evaluated by polymerase chain reaction, Western blotting, and flow cytometry. Results Mice treated with LGG had significantly improved 7-day survival (P < 0.01) compared with saline-treated control pneumonia mice (55% LGG vs. 14% control). The survival advantage was associated with reduced bacterial counts in bronchoalveolar lavage and with decreased markers of the systemic inflammatory response and improved lung pathology in the probiotic group. Probiotic treatment influenced immune response in the lungs of mice with pneumonia as demonstrated by increased levels of Treg cell marker Foxp3. Conclusions These data demonstrate that early administration of LGG improves outcome following P. aeruginosa–induced pneumonia. An effect of LGG on Treg cells may play a role in this protection.

Dynamics of Gut Microbiota in Autoimmune Lupus

“…Lactobacillus rhamnosus GG, for example, suppresses proinflammatory responses by increasing interleukin-10 and regulatory T (Treg) cells (61,62). Several other members of Lactobacillaceae, including L. acidophilus and L. reuteri, were also found to induce anti-inflammatory Treg cells (63,64).…”

“…Lactobacillus spp. can also suppress proinflammatory responses by increasing the number of inducible Treg cells (61,62). Thus, it is likely that RA and Lactobacillaceae that RA can enrich in the gut of lupus-prone mice (Fig.…”

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

“…Specifically mice were orally gavaged with 200 µl of either LGG (1×10 9 colony forming unit (CFU)/ml)) or sterile water (vehicle) immediately prior to procedure. Pneumonia was initiated via direct intratracheal instillation of P. aeruginosa as previously described (21). All mice were then treated with antibiotics (gentamicin 0.2mg/ml, subcutaneously) following surgery to mimic the clinical setting.…”

“…Total RNA was isolated from colon and spleen tissue (snap frozen in liquid N 2 , collected at 12h) as described (21). RNA concentrations were quantified at 260 nm, and the purity and integrity were determined using a NanoDrop.…”

“…Interestingly, recent meta-analysis data indicates that the clinical benefit of probiotics on pneumonia may be most significant in prevention of pneumonia from P. aeruginosa (11). In support of this, our laboratory has also recently shown that Lactobacillus rhamnosus GG (LGG) (a commonly used clinical probiotic) can reduce mortality and bacteremia from experimental P. aeruginosa pneumonia (21). However, as stated, the mechanisms of probiotic-mediated protection against pneumonia, and sepsis in general, are poorly understood.…”