Recurrent urinary tract infection and estrogen shape the taxonomic ecology and function of the postmenopausal urogenital microbiome

Neugent, Michael L.; Kumar, Ashwani; Hulyalkar, Neha V.; Lutz, Kevin C.; Nguyen, Vivian; Fuentes, Jorge L.; Zhang, Cong; Nguyen, Amber; Sharon, Belle M.; Kuprasertkul, Amy; Arute, Amanda P.; Ebrahimzadeh, Tahmineh; Natesan, Nitya; Xing, Chao; Shulaev, Vladimir; Li, Qiwei; Palmer, Kelli L.; Nisco, Nicole J. De

doi:10.1016/j.xcrm.2022.100753

Cited by 33 publications

(51 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To exclude the possibility of low-quality mapped reads from other species, the source of these E. coli reads was further confirmed by mapping each read manually to the NCBI-NT database (Methods). This observation is consistent with the increasing recognition that a culture-independent approach may provide additional information that can complement standard urine culture in the pathogen genomes in UTI and other infectious diseases [57][58][59] .…”

Section: Selective Enrichment Of E Coli Genomes From Urine Samplessupporting

confidence: 86%

mEnrich-seq: Methylation-guided enrichment sequencing of bacterial taxa of interest from microbiome

Cao

Kong

Fan

et al. 2022

Preprint

View full text Add to dashboard Cite

Metagenomics has enabled the comprehensive study of microbiomes. However, many applications would benefit from a method that can sequence specific bacterial taxa of interest (pathogens, beneficial microbes, or low-abundance taxa), but not the vast background of other taxa in a microbiome sample. To address this need, we developed mEnrich-seq, a method that can enrich taxa of interest from metagenomic DNA before sequencing. The core idea is to exploit the self vs. non-self genome differentiation provided by natural bacterial DNA methylation and rationally choose methylation-sensitive restriction enzymes (REs), individually or in combination, to deplete host DNA and most background microbial DNA while enriching bacterial taxa of interest. This core idea is integrated with library preparation procedures in a way that only non-digested DNA libraries are sequenced. We performed in-depth evaluations of mEnrich-seq and demonstrated its use in several applications to enrich (up to 117-fold) genomic DNA of pathogenic or beneficial bacteria from human urine and fecal samples, including several species that are hard to culture or of low abundance. We also assessed the broad applicability of mEnrich-seq and found that 3130 (68.03%) of the 4601 strains with mapped methylomes to date can be targeted by at least one commercially available RE, representing 54.78% of the species examined in this analysis. mEnrich-seq provides microbiome researchers with a versatile and cost-effective approach for selective sequencing of diverse taxa of interest directly from the microbiome.

show abstract

Section: Selective Enrichment Of E Coli Genomes From Urine Samplessupporting

confidence: 86%

mEnrich-seq: Methylation-guided enrichment sequencing of bacterial taxa of interest from microbiome

Cao

Kong

Fan

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…34 We previously showed with this cohort that EHT strongly shapes the taxonomic profile of the postmenopausal urobiome, enriching for protective species, such as Lactobacillus crispatus . 29 Interestingly, previous reports also suggest that EHT thickens the luminal GAG layer of the urothelium and regulates the GAG sulfotransferase enzyme HS6ST1. 22, 35 Given these observations, we hypothesized that EHT may augment urinary GAGs derived from the urothelium.…”

Section: Resultsmentioning

confidence: 98%

“…To model the pathobiology of rUTI, we previously curated a controlled cross-sectional cohort of postmenopausal women. 29 Briefly, postmenopausal women (aged 51-88) were recruited into one of three cohort groups depending on history of rUTI and current UTI status. Group 1 (No UTI History, n =25) served as a healthy comparator and consisted of postmenopausal women with no lifetime history of symptomatic UTI.…”

Section: Resultsmentioning

confidence: 99%

“…Because rUTI disproportionally affects postmenopausal women, we sought to quantitatively measure urinary GAG composition in a controlled, cross-sectional cohort of postmenopausal women designed to capture the cyclic nature of rUTI using a targeted UHPLC MS/MS-based disaccharide analysis. 8, 29 We observed that CS was the most abundant urinary GAG in postmenopausal women and that the creatinine-normalized urinary CS concentration was higher in women who were experiencing an active rUTI compared to those not experiencing UTI. We further found evidence that a history of rUTI and estrogen hormone therapy use are associated with altered sulfonation patterns in urinary GAGs.…”

Section: Introductionmentioning

confidence: 82%

“…Using whole genome metagenomic sequencing on the same cohort of women, we recently described changes in both the taxonomic composition and functional potential of the urobiome associated with rUTI. 29 We used this previously described metagenomic dataset to identify urobiome bacterial species associated with urinary GAG concentration. We found that the abundance of taxa associated with urogenital dysbiosis, such as Atopobium vaginae and Peptoniphilus , negatively correlated with urinary CS concentration.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Neugent

Hulyalkar

Kumar

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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, andStaphylococcus pasteuriwere 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.

show abstract

“Urinary tract infection: Conventional testing to developing Technologies”

Ramaiah,

Suresh,

Nesakumar

et al. 2025

Clinica Chimica Acta

View full text Add to dashboard Cite

Recurrent urinary tract infection and estrogen shape the taxonomic ecology and function of the postmenopausal urogenital microbiome

Cited by 33 publications

References 102 publications

mEnrich-seq: Methylation-guided enrichment sequencing of bacterial taxa of interest from microbiome

mEnrich-seq: Methylation-guided enrichment sequencing of bacterial taxa of interest from microbiome

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

“Urinary tract infection: Conventional testing to developing Technologies”

Contact Info

Product

Resources

About