Substances released from probioticLactobacillus rhamnosusGR-1 potentiate NF-κB activity inEscherichia coli-stimulated urinary bladder cells

Abstract

Lactobacillus rhamnosus GR-1 is a probiotic bacterium used to maintain urogenital health. The putative mechanism for its probiotic effect is by modulating the host immunity. Urinary tract infections (UTI) are often caused by uropathogenic Escherichia coli that frequently evade or suppress immune responses in the bladder and can target pathways, including nuclear factor-kappaB (NF-κB). We evaluated the role of L. rhamnosus GR-1 on NF-κB activation in E. coli-stimulated bladder cells. Viable L. rhamnosus GR-1 was found to potentiate NF-κB activity in E. coli-stimulated T24 bladder cells, whereas heat-killed lactobacilli demonstrated a marginal increase in NF-κB activity. Surface components released by trypsin- or LiCl treatment, or the resultant heat-killed shaved lactobacilli, had no effect on NF-κB activity. Isolation of released products from L. rhamnosus GR-1 demonstrated that the induction of NF-κB activity was owing to released product(s) with a relatively large native size. Several putative immunomodulatory proteins were identified, namely GroEL, elongation factor Tu and NLP/P60. GroEL and elongation factor Tu have previously been shown to elicit immune responses from human cells. Isolating and using immune-augmenting substances produced by lactobacilli is a novel strategy for the prevention or treatment of UTI caused by immune-evading E. coli.

UroPathogenic Escherichia coli (UPEC) Infections: Virulence Factors, Bladder Responses, Antibiotic, and Non-antibiotic Antimicrobial Strategies

“…For instance, Lactobacilli prophylaxis did not decrease the rate of UTI recurrence in several open randomized trials with women who had a UTI caused by UPEC (Kontiokari et al, 2001 ; Beerepoot et al, 2013 ; Schwenger et al, 2015 ). On the other hand, Lactobacilli were shown to actively stimulate the immune system by up- and down-regulation of NF-κB activity (Karlsson et al, 2012 ), and to colonize and protect the vagina (Reid, 2000 ), thus suggesting some sort of indirect-cooperative function.…”

Efficient and Cost-Effective Alternative Treatment for Recurrent Urinary Tract Infections and Interstitial Cystitis in Women: A Two-Case Report

“…Hence, oral probiotics preparations are used to help repopulate the normal flora in the GI tract. Probiotics are thought to aid the GI tract or vagina to resist invasion and adhesion of uropathogens, regulate intestinal flora, decrease constipation at the right doses, enhance the immune system, and increase the population of Lactobacillus that modulate local pH [ 24 ]. A Dutch double-blind trial has shown that a preparation containing Lactobacillus rhamnosus decreased antibiotic resistance as compared to trimethoprim-sulfamethoxazole [ 25 ].…”

Probiotics for Prophylaxis and Treatment of Urinary Tract Infections in Children

“…Nuclear factor-κB is a transcription factor that regulates immunological genes. This method has been shown to enhance the clearance of uropathogens and used for prevention and treatment of UTI, which may also be valuable if live bacteria are not preferred to be used (11).…”