Purified cell wall from the probiotic bacterium Lactobacillus gasseri activates systemic inflammation and, at higher doses, produces lethality in a rat model

INTRODUCTION: One proposed benefit of probiotic therapy is that probiotic bacterial cell-wall binding to intestinal cell pathogen-recognition receptors activates protective innate immunity. However, in critically ill patients, intestinal epithelium disruption by shock or other insults may compromise this compartmentalized response and cause systemic bacteria and cell-wall translocation. The effects of intravascular introduction of probiotic bacterial cell wall are unclear. METHODS: We investigated 24-hour infusions of purified cell wall from Lactobacillus gasseri ATC33323 (L. gasseri), a probiotic bacterium, in Sprague–Dawley rats (n = 49). RESULTS: Increasing cell-wall doses (0 (control), 10, 20, 40, 80, or 160 mg/kg over 24 hours) produced dose-ordered decreases in survival measured after 168 hours (11 survivors/11 total (100%), seven of seven (100%), seven of seven (100%), six of eight (75%), five of eight (63%), and one of nine (11%), respectively, P < 0.0001). The L. gasseri cell wall was equally or more lethal than Staphylococcus aureus cell wall, which was previously studied (100% to 88% survival with the same increasing doses). During challenge, compared with controls, L. gasseri cell wall produced increases in blood IL-1β, IL-10, tumor necrosis factor-α, migratory inhibitory protein-1α, monocyte chemotactic protein-1, and nitric oxide, and decreases in neutrophils, lymphocytes, and platelets that were greater with higher versus lower doses (P ≤ 0.05). Medium-dose cell wall (40 and 80 mg/kg combined) progressively decreased blood pressure and increased heart rate, and all doses increased lactate, hepatic transaminases, and creatinine phosphokinase (P ≤ 0.05). CONCLUSION: Although L. gasseri, like other probiotic bacteria, is considered safe, its cell wall can stimulate the maladaptive inflammatory response associated with pathogenic bacteria. Such effects deserve study, especially regarding critically ill patients.