Shohei Akagawa

Introduction: Urobiome dysbiosis has been implicated in the pathogenesis of overactive bladder (OAB). In this study, the efficacy of a cranberry supplement for OAB symptoms was investigated, and concurrent urobiome alterations were evaluated in young women. Methods: This double-blind, randomized, placebo-controlled trial enrolled 26 women (median age, 23 years) with OAB (Overactive Bladder Symptom Score [OABSS] ≥ 3), who received either a cranberry supplement (36 mg proanthocyanidins per day) or placebo for 4 weeks. Clinical efficacy was assessed using the OABSS reduction rate, and urobiome composition was evaluated by 16S rRNA gene sequencing. Results: Twenty-five participants were included in the analysis. At 4 weeks, the OABSS reduction rate was greater in the cranberry group than in the placebo group (median, 66.7% vs. 40.0%; p = 0.039). At baseline, the urobiome was dominated by Lactobacillus (median relative abundance, 64.2%). After cranberry supplementation, the relative abundance of Lactobacillus decreased within the cranberry group (median change, −4.39%; p = 0.027; q = 0.096). No compositional changes were observed in the placebo group. Conclusions: Cranberry supplementation was associated with greater improvement in OAB symptoms than was observed with placebo in young women, while a decrease in Lactobacillus relative abundance was observed within the cranberry group. Given the small sample size of this exploratory pilot trial and the limited species-level resolution of 16S rRNA sequencing, these concurrent findings should be regarded as hypothesis-generating and warrant further investigation. Clinical trial registration: https://www.umin.ac.jp/ctr/ , identifier UMIN000057544.

Urinary indoxyl sulfate (IS), a gut microbiota-derived uremic toxin, is associated with the adult gut microbiota and is elevated in children with autism spectrum disorder. However, its age-related trajectory and association with microbiota in healthy children remain uncharacterized. Therefore, we aimed to elucidate age-related changes in urinary IS in healthy children and to investigate the potential utility of urinary IS as a surrogate marker for their gut microbiota. We measured urinary IS/creatinine (Cr) ratios and analyzed the fecal gut microbiota composition (16S rRNA gene sequencing) in 102 healthy Japanese children aged 5 months to 12 years. Associations were assessed using Spearman’s correlation. An empirical age-adjustment model (inverse proportional) was developed to derive an age-adjusted IS/Cr ratio (actual/predicted), thereby removing the strong age dependence before re-evaluating correlations with gut microbiota. The unadjusted IS/Cr ratio showed a strong negative correlation with age (rs=–0.47, p<0.001) and declined markedly during early childhood, stabilizing at approximately 5 years. Weak correlations with microbiota metrics were observed before adjustment; however, the age-adjusted IS/Cr ratio showed no correlation with age (rs=–0.03, p=0.768). Notably, age adjustment revealed significant positive correlations between the IS/Cr ratio and the phylum Bacteroidota (rs=0.26, p=0.008) and strengthened the correlation with the genus Bacteroides (rs=0.31, p=0.002), associations that were not apparent before adjustment. Correcting for this age-dependent variation is crucial, after which the IS/Cr ratio can serve as a potential non-invasive surrogate marker reflecting the abundance of Bacteroidota, particularly the genus Bacteroides, in the pediatric gut microbiota

Purpose: Cranberry juice is widely consumed to improve urinary health; however, its effects on the urinary microbiome (urobiome) of healthy individuals are unclear. We aimed to investigate the effect of continuous consumption of cranberry juice on the urobiome of healthy adults. Methods: This randomized, double-blind, placebo-controlled crossover trial included 40 healthy adults (21 women and 19 men) who completed the study. Participants consumed 80 mL of either cranberry juice or a placebo daily for 4 weeks, followed by a 4-week washout period and crossover to the alternate intervention. The urobiome was analyzed by 16S rRNA gene sequencing. Results: At baseline, the urobiome composition differed significantly between men and women (PERMANOVA, P = .015). Overall, alpha and beta diversities did not change significantly after either intervention. In women, cranberry juice consumption was associated with decreased relative abundance of the genus Lactobacillus (median: 28.4%-18.4%; P = .025); however, this change was not significant following correction for multiple comparisons (q = 0.25). No significant compositional changes were observed in men after the intervention. Conclusion: In this exploratory study, continuous cranberry juice consumption showed a potential to modulate the urobiome in a sex-specific manner. The observed trend toward decreased Lactobacillus abundance in women provides a basis for future, larger studies for validation and assessment of its clinical relevance for female urinary health.

Purpose: To determine the characteristics of the urobiome in boys with nocturnal enuresis. Materials and Methods: We enrolled 25 boys aged 5 to 12 years with untreated nocturnal enuresis (nocturnal enuresis group; median age, 7.4 years) and 17 boys aged 5 to 12 years without nocturnal enuresis (healthy control group; median age, 9.3 years). Among the 25 children with nocturnal enuresis, 15 had monosymptomatic nocturnal enuresis, and 10 had non-monosymptomatic nocturnal enuresis. First morning mid-stream urine samples were collected for deoxyribonucleic acid extraction and 16S ribosomal ribonucleic acid gene sequencing. The diversity and bacterial abundance of the urobiome were compared between the groups and between the monosymptomatic and non-monosymptomatic nocturnal enuresis groups. Results: Regarding alpha diversity, Shannon and Simpson indices were significantly lower in the nocturnal enuresis group. Beta diversity differed significantly on the permutational multivariate analysis of variance test. The relative abundance of Ezakiella was significantly greater in the nocturnal enuresis group than the healthy control group; however, in the nocturnal enuresis group, the relative abundance of Peptoniphilus was significantly lower, and predictive functional analyses revealed a greater proportion of bacteria involved in the synthesis of aromatic amino acids. Comparison of the monosymptomatic and non-monosymptomatic groups revealed no significant differences in diversity indices or relative abundance of bacterial taxa at the phylum or genus levels. Conclusions: The urobiome differed between the nocturnal enuresis and healthy control groups, with the nocturnal enuresis group exhibiting dysbiosis characterized by decreased microbial diversity, increased abundance of Ezakiella, and decreased abundance of Peptoniphilus.