It is relatively simple to understand how bacteria enter the urinary tract, as the site is open to a microbial environment. In terms of why they are present, the long-standing theory has been that certain species and genera have adapted to the urinary environment and have formed a barrier against disease. The mechanisms include maintenance of epithelial and mucosal integrity, priming of the innate and adaptive immune systems, countering pathogens through excluding them from adhering and growing at the site, helping to control pH, degrading or reducing toxic compounds, and likely through signalling processes helping the overall host’s defences [1, 2]. These constitute a remarkable number of ways in which bacteria are beneficial to urological health, yet the power of these effects has not been propagated to the extent that it could be. Rather, the unfruitful search for vaccines against adhesion to the uroepithelium by pathogens, the narrow-minded design and improper use of broad spectrum antibiotics, the attempt to use compounds to bind and flush out pathogens, and the modest at best effects of cranberry juice [3–7] have not ablated the suffering of hundreds of millions of women worldwide, from urinary tract infection (UTI) nor led to new management options.

If bacteria have deliberately found residence in the urinary tract as part of evolution, one would expect the effects to be symbiotic. For the organisms, a niche with nutrients is an obvious benefit, but what of the host? Given that it has taken sophisticated DNA sequencing to detect a urinary microbiota [8–11], and the organisms are therefore not flourishing in large numbers, presumably they are not very metabolically active. Studies of Mycobacterium tuberculosis have shown that a portion of quiescent bacteria is indeed metabolically active [12], so the same may be true for some members of the urinary microbiota. While purely speculative, the microbiota may be kept quiescent by innate and adaptive host defences, but activity might increase at different times in response to changes in nutrient content, hormones, lowered immune status, or other factors in the urine [13, 14]. These activations might lead to host responses and/or signaling molecules affecting the nervous system [15, 16], resulting in mild symptoms and signs of discomfort. Indeed, such presentations are not uncommon, often verging on being completely asymptomatic.

If bacteria are sparsely distributed around the bladder, in some cases internalized or in small biofilms, could they be helpful to reduce discomfort? It is known that some of the species detected [17], especially Lactobacillus [18] can produce neuroactive compounds including some that can potentially reduce pain. An alteration in the composition of the microbiota, such as an increase in Lactobacillus gasseri and decrease in L. crispatus, might not only induce urgency incontinence [17], but it may trigger other perceptions of discomfort. The necessity for treatment, in most cases with pharmaceutical agents, could in fact make the situation worse through altering the microbiota to a more aberrant one [19, 20]. So, what options remain for managing urinary dysfunction?

The administration of antibiotic therapy is often used not just to treat proven infection, but also to try and prevent recurrences, or in an attempt to reduce symptoms and signs that are otherwise unexplained. These are being questioned primarily because of side effects and antibiotic resistance [21–24], but they may also have consequences for later obesity and its complications [25]. The development and use of broad spectrum antibiotics was somewhat well intentioned, to rapidly provide relief from symptoms of UTI without waiting for culture results. But, on reflection it was poorly conceived. A much better approach would have been to develop agents that specifically and only targeted the offending organism, in the case of UTI mostly E. coli. With few, if any, new antibiotics in the pipeline, and companies reluctant to invest in such research, assuming such agents could even be developed, we are left with needing to carefully assess when to use the current armamentarium and when not to. Options such as relieving pain and using single dose therapy are worthy of consideration [26, 27], albeit with careful follow-up to ensure no precipitation of the infectious process.

The option of administering beneficial bacteria to out-compete pathogenic ones was first considered in the early 1980s [28], but not taken seriously by the medical community until much later. The initial approach was to interrupt the ascension of uropathogens from the vagina and perineum to the urethra and bladder, by instilling lactobacilli with properties that could interfere with pathogen growth and adhesion [29]. Then, direct instillation of lactobacilli into the bladder was attempted but the organisms did not appear to colonize [30, 31]. However, in the late 1980s no DNA sequencing methods were available and the urinary microbiota had not been discovered, so it is possible that this approach had more validity than was realised at the time. Subsequent attempts to colonize the bladder with avirulent E. coli have met with some success [32], although some patients complained of foul odor, and scaling up to widespread use will face many challenges. In neurogenic bladder patients, this could prove to be a useful therapy, and how the E. coli HU2117 strain interacts with the microbiota of responders and non-responders would be worthwhile investigating.

The discovery of uropathogens that persist in and on the uroepithelium, and others that form internalized dense pods, often as a reaction to antibiotics [33, 34], also has consequences for management. Antibiotic therapy disrupts the microbiota composition for months [35, 36], without necessarily eradicating the offending pathogens. The consequences may be temporary eradication of symptoms and signs of infection, but due to pathogen persistence and microbiota disruption, an increased risk of longer term recurrences and complications. This could be particularly problematic for pregnancy where UTI is a preventable cause of maternal and neonatal morbidity and mortality [37], and where antibiotic use might make an initial impact on the UTI, but lead to other later complications.

The ability of lactobacilli to penetrate and disrupt pathogenic biofilms has been shown [38, 39], and may be particularly important if it re-sets the microbiota to homeostasis. In cases where probiotic lactobacilli have been effective at preventing UTI in children with reflux [40] and adult women [41–43], the use of probiotics to prevent infection and possibly recurrence of bladder cancer have merit.

Urinary tract diseases continue to adversely affect quality of life of many people [44]. Until suitable alternative, clinically proven therapies are made available, the only options for urologists remain surgery and pharmaceutical therapy, or possibly use of probiotics. Still, there are critical messages that warrant consideration from the latest research on microorganisms discussed herein: