February 2019 Issue

Integrative Nutrition: Probiotics for UTIs
By Jamie Santa Cruz
Today's Dietitian
Vol. 21, No. 2, P. 14

A Promising Alternative to Antibiotics Though Evidence Is Still Inconclusive

Urinary tract infections (UTIs) are extremely common in women. Up to 60% of women will develop a UTI at some point in their lives,1 and the risk increases with age and sexual activity.2 Reoccurrence is likely; approximately one-quarter of women who develop a UTI will experience another within a few months to a year, and reoccurrences can continue for years on end.3

The standard treatment for UTIs is antibiotics—typically a short, low-dose course for an uncomplicated infection. For women with recurrent UTIs, continuous antibiotics for a period of several months to a few years often are prescribed as a preventive measure.3 In an age of increasing antibiotic resistance, however, there's a need for safe, effective alternatives to antibiotics.

One potential alternative is probiotics. Although research to date is limited and conflicting, some evidence suggests Lactobacillus species could be an effective prophylactic option for preventing recurrent UTIs.

The Intestinal Microflora Link
In the majority of cases, UTIs are caused by E coli, and the source of the pathogens usually can be traced to the gastrointestinal tract.4 In the development of a typical UTI, uropathogens ascend from the rectum to the vagina, and from there to the urethra, the bladder, and sometimes the kidneys.4 Thus, there's a significant link between the intestinal tract, the microflora of the vagina, and UTIs. (Women are dramatically more susceptible to UTI than men because of their anatomy: The distance between the rectum and the urethra, and between the urethra and the bladder, are shorter in women than in men.)

Healthy vaginal microbiomes without any disease conditions tend to be heavily dominated by Lactobacillus species, especially strains that produce H2O2.4 Several studies have suggested that Lactobacillus crispatus in particular is the single most dominant strain in healthy, premenopausal women.4 Meanwhile, a reduced presence or the complete absence of Lactobacillus species (especially H2O2-producing strains) in the vaginal microbiome is associated with increased risk of various urogenital disease conditions, including vaginal colonization with E coli.4

Because of the link between the vaginal microbiome and UTI risk, probiotics administered for the purpose of combatting UTIs target the vaginal microflora. The theory is that introducing beneficial bacteria to the vagina in the form of probiotics can help stave off vaginal colonization by uropathogens and thereby prevent the spread of those pathogens to the urinary tract.

There are several major mechanisms by which probiotics could inhibit infection, according to Lisa Hanson, PhD, CNM, a professor of nursing at Marquette University in Milwaukee. For one, probiotics acidify the mucosal surface of the vagina.5 Vaginal microbiomes are healthiest when they're acidic, Hanson says, and Lactobacillus strains that produce H2O2 (such as L crispatus) are particularly effective at promoting acidification. Probiotics also prevent the adherence of pathogens to the mucosal surface, and they secrete vitamins and immune-modulating substances that work synergistically with a woman's immune system.5

Trials on Prevention
Although there may be sound reason to suspect benefit from probiotics for prevention of UTI, randomized controlled trials addressing the topic are very limited.

Among the more noteworthy studies is a 2011 double-blinded trial from researchers at the University of Washington in Seattle who tested the effectiveness of probiotics for prevention of recurrent UTIs in a group of premenopausal women.6 Each of the 100 participants received a short course of antibiotics to treat acute UTI, after which they were randomized to receive a 10-week course of either L crispatus (via vaginal suppository) or placebo. The probiotic reduced the risk of recurrent UTIs by almost half compared with placebo (27% of those on placebo had a reoccurrence vs only 15% of those on the probiotic).

In 2012, a group of Dutch researchers conducted another double-blinded trial, this time of 252 postmenopausal women with recurrent UTIs.7 One-half of the participants were randomized to a 12-month course of a probiotic containing Lactobacillus rhamnosus and Lactobacillus reuteri, a combination selected on the grounds that these two species have been proven to be effective in restoring vaginal flora and reducing colonization by uropathogens.8 The other half of the participants received a daily dose of trimethoprim-sulfamethoxazole, an antibiotic. The study was designed as a noninferiority trial, meaning it was testing whether probiotic treatment would produce results comparable to antibiotic treatment or whether the probiotics would prove to be inferior to antibiotics.

The probiotic treatment failed to meet the criteria of noninferiority—in other words, probiotics were in fact inferior to antibiotic treatment. However, both the probiotic and the antibiotic group experienced significantly fewer UTIs during the study period than in the previous year. Those who received the antibiotic had only 2.9 infections during the 12-month study period, and those receiving the probiotic intervention had 3.3 infections, down from a mean of seven infections reported in the year before the study.

Significantly, analysis of a subgroup of participants who experienced complicated (as opposed to uncomplicated) UTIs found that probiotic treatment appeared to be more effective than antibiotics in this specific group. The authors attributed this finding to the fact that participants with complicated infections tended to have high baseline resistance rates to the specific antibiotic used in the study.

A further finding of the Dutch study was that antibiotic use during the study period produced high rates of antibiotic resistance. This is consistent with other studies that have found that even short courses of various antibiotics used to treat UTIs result in substantial rates of resistance.9,10 According to the authors of the Dutch study, the fact that probiotics didn't produce increased antibiotic resistance makes them an acceptable alternative to antibiotics for prevention of UTIs.

Egyptian researchers subsequently conducted a laboratory study to determine whether Lactobacillus species would affect the growth of uropathogenic E coli that had been isolated from the urine of 100 women with recurrent UTIs.10 The researchers tested various species of Lactobacillus that they had determined to be present in the vaginas of healthy women (including Lactobacillus acidophilus, Lactobacillus fermentum, and Lactobacillus delbrueckii) and found that all were effective at inhibiting E coli growth. The weakness of this study is that it was conducted in a lab setting, and the women with recurrent UTIs didn't themselves receive the probiotics (it was only their E coli strains that received Lactobacillus in the lab).

Multiple reviews and meta-analyses have been conducted on probiotics for UTI prevention in the last five years.3,11-16 A Cochrane review published in 2015 found that probiotics didn't demonstrate any significant benefit for UTI over placebo.16 However, this review, as well as all others, acknowledge that the number of studies related to the topic is very limited, that the studies that do exist generally involve small sample sizes, and that the available research has a high risk of bias. Despite these weaknesses and the relatively negative conclusion of the Cochrane review, several other reviews have suggested that probiotics hold promise for preventing UTIs and that additional large, high-quality trials are needed.3,12-15

Applications for RDs
Current research hasn't provided evidence that probiotics can effectively treat an existing UTI, according to Hanson. However, the limited data available suggest that probiotics may help prevent recurrences. Pending further trials, she says, it's reasonable for women to take a probiotic during and after antibiotic treatment for acute UTIs in hopes of preventing a recurrent infection.

The majority of probiotic interventions to prevent UTIs have involved vaginal suppositories to affect the vagina directly. But suppositories are inconvenient, Hanson says, and oral probiotics are known to affect the vaginal microbiome, albeit indirectly.8 (The healthy bacteria in probiotics travel from the intestinal tract to the vagina in the same way pathogens do.) Thus, it's reasonable to opt for an oral supplement. "Both means do affect the vaginal flora," Hanson says. "I don't think the jury is out on which approach is superior."

Because Lactobacillus species are so integral to a healthy vaginal microbiome, and because certain Lactobacillus species are known to have an acidifying effect on the vaginal mucosa, probiotics intended to prevent UTI should contain Lactobacillus.17 However, according to Hanson, it's unclear which specific species are most efficacious. L rhamnosus and L reuteri are the most commonly studied strains,13 but it's difficult to know whether these are the most effective. "We don't really have that answer yet," Hanson says. Her current recommendation: Choose a probiotic that's multispecies, high potency, and refrigerated—and make sure to note the expiration date.

— Jamie Santa Cruz is a freelance writer of health and medical topics based in Parker, Colorado.

1. Al-Badr A, Al-Shaikh G. Recurrent urinary tract infections management in women: a review. Sultan Qaboos Univ Med J. 2013;13(3):359-367.

2. Stapleton A. Prevention of recurrent urinary-tract infections in women. Lancet. 1999;353:7-8.

3. Chisholm AH. Probiotics in preventing recurrent urinary tract infections in women: a literature review. Urol Nurs. 2015;35(1):18-21, 29.

4. Stapleton AE. The vaginal microbiota and urinary tract infection. Microbiol Spectr. 2016;4(6).

5. Akgül T, Karakan T. The role of probiotics in women with recurrent urinary tract infections. Turk J Urol. 2018;44(5):377-383.

6. Stapleton AE, Au-Yeung M, Hooton TM, et al. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis. 2011;52(10):1212-1217.

7. Beerepoot MA, ter Riet G, Nys S, et al. Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women. Arch Intern Med. 2012;172(9):704-712.

8. Reid G, Charbonneau D, Erb J, et al. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol. 2003;35(2):131-134.

9. Murray BE, Rensimer ER, DuPont HL. Emergence of high-level trimethoprim resistance in fecal Escherichia coli during oral administration of trimethoprim or trimethoprim-sulfamethoxazole. N Engl J Med. 1982;306(3):130-135.

10. Kahlmeter G, Menday P. Cross-resistance and associated resistance in 2478 Escherichia coli isolates from the Pan-European ECO.SENS Project surveying the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections. J Antimicrob Chemother. 2003;52(1):128-131.

11. Abdulwahab M, Abdulazim A, Nada MG, Radi NA. A study on the inhibitory effect of vaginal lactobacilli on uropathogenic Escherichia coli. Life Sci J. 2013;10(2):773-778.

12. Hanson L, VandeVusse L, Jermé M, Abad CL, Safdar N. Probiotics for treatment and prevention of urogenital infections in women: a systematic review. J Midwifery Womens Health. 2016;61(3):339-355.

13. Ng QX, Peters C, Venkatanarayanan N, Goh YY, Ho CYX, Yeo WS. Use of Lactobacillus spp. to prevent recurrent urinary tract infections in females. Med Hypotheses. 2018;114:49-54.

14. Grin PM, Kowalewska PM, Alhazzan W, Fox-Robichaud AE. Lactobacillus for preventing recurrent urinary tract infections in women: meta-analysis. Can J Urol. 2013;20(1):6607-6614.

15. Smith AL, Brown J, Wyman JF, Berry A, Newman DK, Stapleton AE. Treatment and prevention of recurrent lower urinary tract infections in women: a rapid review with practice recommendations. J Urol. 2018;200(6):1174-1191.

16. Schwenger EM, Tejani AM, Loewen PS. Probiotics for preventing urinary tract infections in adults and children. Cochrane Database Syst Rev. 2015;(12):CD008772.

17. Akgül T, Karakan T. The role of probiotics in women with recurrent urinary tract infections. Turk J Urol. 2018;44(5):377-383.