Altered Gut Microbiome Associated with Overactive Bladder and Daily Urinary Urgency - Beyond the Abstract

Overactive bladder (OAB) is a part of lower urinary tract symptoms (LUTS). One of the most widely accepted theories accounts for the pathophysiology of this condition is irregular activation of sensory pathways and detrusor overactivity, which can result in bladder irritability at low urine volumes (urinary urgency). Specific alterations of the microbiome (dysbiosis) in urine have been reported in association with LUTS. However, the association of LUTS with gut microbiome has not yet been fully understood. We hypothesized that OAB with frequent urinary urgency may be associated with alterations in the gut microbiome. In this study, we explored the relationship between OAB and the gut microbiome among members of a single community in Japan.

This cross-sectional study surveyed 1113 individuals who participated in the Iwaki Health Promotion Project in Japan. OAB was defined as urinary urgency at least once per week and an Overactive Bladder Symptom Score (OABSS) of ≥ 3. OAB with urinary urgency at least once a day was defined as daily urgency. The gut microbiomes were assessed by next-generation sequencing of 16S rRNA genes extracted from fecal samples. The participants were divided into two groups: OAB-daily urgency and non-OAB. Cases were selected for inclusion on the basis of 1:1 propensity score (age, sex, CVD, BMI, hypertension, CKD, and DM) matching; we assigned 58 individuals to each group (23 male and 35 female) for our analysis.

Participants in the OAB-daily urgency group had a higher degree of depressive symptoms than those in the non-OAB group. The diversity between individuals (b diversity; Bray–Curtis distance) in the OAB-daily urgency group was significantly lower than that in the non-OAB group (0.48 vs. 0.53, Fig. 1).

diversity OAB
Similarities between the two groups were evaluated by principal coordinates analysis (PCoA) based on the Bray–Curtis distance. Our data indicate significant differences in the component structure of the microbiome (PERMANOVA, F = 2.08, R2 =0.018, P= 0.023). The relative abundance of genus Bifidobacterium was significantly lower in the OAB-daily urgency group compared to the non-OAB group (Fig. 2).

bifidobacterium OAB

The relative abundances of genus Faecalibacterium were significantly higher in the OAB-daily urgency group compared to the non-OAB group (Fig. 3). 

faecalibacterium OAB

In this study, our results indicated that gut microbiomes from participants with OAB associated with daily urinary urgency may have a lower bacterial diversity and clustered differently from non-OAB controls, which is interpreted as dysbiosis in OAB. Participants with OAB-daily urgency had a depressive tendency in this study. Depressive status has been shown to alter the diversity and structure of the human microbiome. There might be a complex association among the OAB, depression, and gut microbiome.

The relative abundance of genus Bifidobacterium was comparatively lower in the OAB-daily urgency group. Some bacteria of the genus Bifidobacterium may play critical beneficial roles and have been used as probiotics. The relative abundance of genus Bifidobacterium was reduced among patients diagnosed with irritable bowel syndrome (IBS) whose etiology is deeply associated with gut microbiome. Both IBS and OAB are disorders of visceral overactivity and irritability and these conditions are frequently diagnosed concurrently. There might be a complex association among the OAB, IBS, and gut microbiome.

We found that genus Faecalibacterium, another genus that has been associated with improvements in human health, was present in comparative overabundance in the OAB-daily urgency group. Bacteria from this genus are among the major producers of short chain fatty acids (SFCA, e.g., butyric acid), which are beneficial to the gut and general health. Faecalibacterium species are known to be reduced in disorders including IBS, inflammatory bowel disease, and depression. However, other studies have revealed that IBS patients have higher fecal SFCA levels than detected in controls. These findings suggest that excessive SFCA might have a negative impact on human health. In a rat experimental model, the administration of butyric acid resulted in an increase in brain-derived neurotrophic factor (BDNF). Urinary BNDF levels are reported to be higher among OAB patients and may result in enhanced bladder detrusor activity. These findings might explain the result that genus Faecalibacterium, SFCA producing genus, was overrepresented in the OAB-daily urgency group in this study.

Further study is warranted in order to clarify the possibility of a more direct, causal relationship between the gut microbiome and OAB.

Written by: Teppei Okamoto, MD, PhD, and Shingo Hatakeyama, MD, PhD, Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

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