Novel directions in the management of recurrent urinary tract infections

Genetic similarity established by sequencing between the strains isolated from the urine and faeces of patients gives additional value to the future management of gut microbiota. Gut and vagina serve as a reservoir for bacteria to re-invade urinary bladder. Research indicates that prophylactic supplementation with either vaginal probiotics or in combination with oral probiotics demonstrates effectiveness in preventing recurrent symptomatic UTI episodes (1). 

Diet behaviour for gut microbiota modification is also significant - vegetable protein consumption is associated with an increase in Bifidobacterium spp. and Lactobacillus spp. presence in the gut. The commensals of gut microbiota can be considered as one of the key factors in E. coli virulence suppression. 

The vaginal microbiota of reproductive-age women normally dominated Lactobacillus and the main dominant Lactobacteria is L. crispatus. Communities dominated by L. crispatus are thought to offer the most protective benefits. 

In vitro studies have demonstrated that acidic conditions in the vagina can inhibit the growth of less beneficial bacterial species including Gardnerella, E. coli, bacterial vaginosis associated bacteria (BVAB). 

To decrease the rate of rUTI we need vaginal normocenosis dominated by L. crispatus. This can be achieved by special probiotics (oral or vaginal or combination of both). Bacterial movement between the vagina and bladder microbiota is not only limited to ascending uropathogenic species, such as E. coli or BVAB, but also includes health-associated commensal bacteria, like a L. crispatus. 

It was recently shown that L. crispatus in vitro markedly reduced the intracellular uropathogenic Escherichia coli (UPEC) load in a study of the bladder microflora of 31 female patients with rUTIs and eight healthy female controls (2). It was found that whereas the majority (∼90%) of bladder microflora in healthy women were Lactobacillus spp., the bladder microflora of patients with rUTIs was much more heterogeneous (Fig. 1). In the patient group, a sharp reduction in the abundance of Lactobacillus spp. was observed, accounting for less than 20% of the bacterial load (Fig. 2). This finding raised the notion that the presence of Lactobacilli protects bladder colonisation by E. coli and other pathogens. 

After reaching the bladder, UPECs adhere and invade the superficial bladder epithelial cells (BECs), initially multiplying in vesicles and later within the cytosol, forming intracellular bacterial communities that sustain recurrent bladder infections. L. crispatus modulated the host’s innate bladder immunity via type I interferon (IFN-α or IFN-β) responses, which promote the maturation of phagolysosomes containing intracellular UPEC in BECs (2). Lysosomal cathepsin D, a protease previously implicated in binding to and degrading various bacteria within lysosomes, mediated UPEC killing, including those residing in BECs.  

Our review highlights a novel mechanism by which endogenous microflora, such as Lactobacillus, can protect against rUTIs. In this way, probiotics present a promising therapeutic perspective. 

1. Effectiveness of Prophylactic Oral and/or Vaginal Probiotic Supplementation in the Prevention of Recurrent Urinary Tract Infections: A Randomized, Double-Blind, Placebo-Controlled Trial
2. Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response