Childhood lower urinary tract symptoms (LUTS) and urinary tract infections (UTIs) are common clinical concerns with significant implications for lifelong urinary health and quality of life. LUTS are influenced by age and in childhood, they often coexist with nocturnal enuresis (NE) and bladder-bowel-dysfunction (BBD). UTIs, among the most prevalent infections in children, have a multifactorial aetiology that includes anatomical abnormalities, functional bladder disorders and immune responses. While the bidirectional relationship between LUTS and UTIs remains incompletely defined, it is widely accepted that LUTS may predispose children to recurrent infections, while UTIs themselves can exacerbate urinary dysfunction. (1)
Although enhanced urinary and gut microbiome characterization in current literature reveals microbial influences on bladder function and inflammation, the role of microbiome variations in paediatric LUTS and UTIs remains unclear. Identifying microbial biomarkers associated with urinary complaints in children could facilitate early detection, risk stratification and targeted interventions to optimize urinary health outcomes from a lifelong perspective. (2) Therefore, the aim of this systematic review is to summarize evidence regarding alterations in both the gut and urinary microbiome in relation to LUTS and UTIs in the paediatric population.

A systematic review was conducted following PRISMA guidelines. (Figure 1) PubMed, Embase, and CINAHL databases were searched for studies analysing gut and urinary microbiomes in paediatric LUTS and UTI patients. Using software’s Rayyan and Silvi® (Silvi.AI), two reviewers independently screened and reviewed the articles. Data was extracted for LUTS or UTI patients and healthy controls on: method of microbiome analysis, sex distribution, mean age of patients, predominant bacteria phylum, class, order, family, genus and species, alpha diversity and beta-diversities. Quality assessment was performed using QUADOMICS checklist. (3) A total of 9 studies met the inclusion criteria. Study characteristics and patient group distribution are visible in Figure 2.

A total of 619 subjects were identified from the 9 eligible studies (2018-2024), with 274 patients (44,3%) patients part of pathology groups and 345 patients (55,7%) controls. Mean patient age varied significantly across studies ranging from 5 months to 15 years. Both male (38,1%) and female (61,9%) patients were represented. Clinical conditions included were urinary tract infections (UTI), voiding dysfunction (VD), vesicoureteral reflux (VUR) and bladder-bowel dysfunction (BBD). Sample types analysed included stool in 4 studies  and urine in 5 studies. Reduced urine alpha diversity and distinct bacterial compositions were found in UTI and BBD patients (Figure 3), while beta diversity analyses revealed distinct clustering of microbiome compositions between affected and healthy groups. The gut microbiome of UTI patients showed alterations in Actinobacteria and Proteobacteria abundance, while voiding dysfunction (VD) was linked to presence of Fusobacterium nucleatum, Clostridium difficile and Bacteroides clarus without significant VDSS correlation. Sex-based differences were observed, with female microbiota shifting at puberty while male profiles remained stable. Though not a primary outcome, antibiotic use 1–14 days prior to sampling lead to a substantial reduction in species richness and reduced overall microbiome diversity. These differences were near-completely recovered with time.

Paediatric patients with LUTS and UTIs exhibit distinct urinary and gut microbiome alterations, potentially linked to recurrent infections and antibiotic exposure. Sex-based differences in bacterial abundancies emphasize the importance of considering developmental, anatomical and antimicrobial alterations when investigating the paediatric microbiome. The impact of antibiotics on the microbiome underscores the need for careful antimicrobial use in managing urinary conditions.

This review underscores significant microbiome shifts in paediatric LUTS and UTI patients, potentially affecting disease recurrence and treatment response. Understanding sex-specific microbiome changes is crucial. Future research should aim to clarify functional implications of these microbial shifts, explore their potential as predictive biomarkers and evaluate microbiome-targeted interventions for prevention and management of paediatric LUTS and UTI's.

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