Biology subjects

Shulaev, V.

Publications and source records attributed to Shulaev, V..

3 recordsLinked to original sources

bioRxiv2024

Urinary biochemical ecology reveals microbiome-metabolite interactions and metabolic markers of recurrent urinary tract infection

Recurrent urinary tract infections (rUTIs) are a major clinical challenge and their increasing prevalence underscores the need to define host-microbiome interactions underlying susceptibility. How the urinary microbiota engages with the biochemical environment of the urogenital tract is yet to be fully defined. Here, we leverage paired metagenomic and quantitative metabolomic data to establish a microbe-metabolite association network of the female urinary microbiome and define metabolic signatures of rUTI. We observe unique metabolic networks of uropathogens and uroprotective species, highlighting potential metabolite-driven ecological shifts influencing rUTI susceptibility. We find distinct metabolites are associated with urinary microbiome diversity and identify a lipid signature of active rUTI that accurately distinguishes cases from controls. Finally, we identify deoxycholic acid as a prognostic indicator for UTI recurrence. Together these findings provide insight into microbiome-metabolite interactions within the female urinary tract and highlight new biomarkers for the development of new diagnostic tools to improve patient outcomes.

microbiology↗

bioRxiv2023

Urinary Glycosaminoglycans are Associated with Recurrent UTI and Urobiome Ecology in Postmenopausal Women

Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides composed of repeating disaccharide units of uronic acid and amino sugars. The luminal surface of the bladder epithelium is coated with a GAG layer. These urothelial GAGs are thought to provide a protective barrier and serve as a potential interaction site with the urinary microbiome (urobiome). Previous studies have profiled urinary GAG composition in mixed cohorts, but the urinary GAG composition in postmenopausal women remains undefined. To investigate the relationship between GAGs and recurrent UTI (rUTI), we profiled urinary GAGs in a controlled cohort of postmenopausal women. We found that chondroitin sulfate (CS) is the major urinary GAG in postmenopausal women and that urinary CS was elevated in women with active rUTI. We also associated urinary GAGs with urobiome composition and identified bacterial species that significantly associated with urinary GAG concentration. Corynebacterium amycolatum, Porphyromonas somerae, and Staphylococcus pasteuri were positively associated with heparin sulfate or hyaluronic acid and bacterial species associated with vaginal dysbiosis were negatively correlated to urinary CS. Altogether, this work defines changes in urinary GAG composition associated with rUTI and identifies new associations between urinary GAGs and the urobiome that may play a role in rUTI pathobiology.

biochemistry↗

bioRxiv2021

Recurrent urinary tract infection and estrogen shape the taxonomic ecology and functional potential of the postmenopausal urobiome

Community-acquired urinary tract infection (UTI) is among the most common bacterial infections observed in humans. Postmenopausal women are a rapidly growing and underserved demographic group who are severely affected by recurrent UTI (rUTI) with a >50% recurrence rate. In this population, rUTI can persist for years, reducing quality of life and imposing a significant healthcare burden. rUTI is most often treated by antibiotics, but development of antibiotic resistance and allergy limit therapeutic options. The female urinary microbiome (urobiome) has been identified as a key component of the urogenital environment. However, compositional and functional changes in the urobiome underlying rUTI susceptibility in postmenopausal women are not well understood. Here, we used a controlled, cross-sectional cohort of postmenopausal women, to interrogate changes in urobiome structure and function linked to rUTI susceptibility by whole genome metagenomic sequencing (WGMS), advanced urine culture, estrogen metabolite profiling, and antibiotic sensitivity testing. Overall, we detected 276 bacterial, archaeal, and fungal species representing 106 genera. We find a putative commensal population consisting of species known to protect against bacterial vaginosis, such as Lactobacillus crispatus, within the urobiome of postmenopausal women who do not experience UTI. Integration of clinical metadata detected an almost exclusive enrichment of lactobacilli, including L. crispatus and L. vaginalis, in women taking estrogen hormone therapy (EHT). Integrating quantitative metabolite profiling of urinary estrogens with WGMS, we observed robust correlations between urobiome taxa, such as Bifidobacterium breve and L. crispatus, and urinary estrogen conjugate concentrations in women with no history of UTI that were absent in women with rUTI history. We further used functional metagenomic profiling and patient-derived isolate phenotyping to identify microbial metabolic pathways, antimicrobial resistance genes (ARGs), and clinically relevant antimicrobial resistance phenotypes enriched between disease-states. Our data indicate that distinct urobiome metabolic and ARG signatures are associated with current rUTI status and history. Importantly, we observed that rUTI history leaves an imprint of enriched ARGs even in women not currently experiencing UTI. Taken together, our data suggests that rUTI history and estrogen strongly shape the functional and taxonomic composition of the urobiome in postmenopausal women.

microbiology↗