Distinct urinary microbiome signatures are associated with urinary tract infection risk in patients with liver cirrhosis: A pilot study

Study information

Needs review

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

40886797

DOI Digital object identifier for electronic documents.

https://doi.org/10.1016/j.ijid.2025.108031

URI Uniform resource identifier for web resources.

Authors

Woltsche J., Pacher-Deutsch C., Fürst S., Gulden L., Schwarzl J., Feldbacher N., Nepel M., Rebol L., Hasl N., Rieper V., Stadlbauer V., Horvath A.

Journal

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

Year

2025

Keywords:

Cirrhosis, Urinary microbiome, Urinary tract infection

OBJECTIVES: Individuals with liver cirrhosis are at increased risk of developing urinary tract infections (UTIs); however, the role of the urinary microbiome (UMB) in this susceptibility remains poorly understood. This pilot study aimed to characterize the UMB in patients with liver cirrhosis with and without UTIs using 16S rRNA gene sequencing. METHODS: Urine samples from 39 patients were analyzed: 17 who developed at least one UTI (dUTI) within 3 years and 22 who remained UTI-free (no_UTI). Microbial profiles were assessed via 16S rRNA gene sequencing and analyzed using QIIME 2, analysis of composition of microbiomes, and linear discriminant analysis effect size. RESULTS: Significant differences in beta diversity were observed between the dUTI and no_UTI groups (Bray-Curtis ADONIS: R2 = 0.044, P = 0.023; Jaccard ADONIS: R2 = 0.039, P = 0.028). The no_UTI group exhibited higher relative abundances of Bacteroidetes, Prevotella, and Corynebacteriaceae-microbes typically associated with a healthy urinary environment. In contrast, Streptococcus was enriched in the dUTI group. CONCLUSIONS: Patients with liver cirrhosis who did not develop UTIs demonstrated distinct UMB patterns that may confer protection. These findings suggest that elements of the UMB, such as Prevotella and Corynebacterium, may play a protective role and represent potential targets for preventive strategies.

Experiment 1

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Curated date: 2025/10/16

Curator: Busiwa Liuma

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Subjects

Location of subjects: Austria

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Urine Urine,urine

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Urinary tract infection INFECTION, URINARY TRACT,TRACT, INFECTION OF URINARY,urinary tract infection,urinary tract infection (disease),Urinary tract infection

Group 0 name Corresponds to the control (unexposed) group for case-control studies: No Urinary Tract Infection group

Group 1 name Corresponds to the case (exposed) group for case-control studies: Diagnosed Urinary Tract Infection group

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: These were patients with liver cirrhosis who developed at least one urinary tract infection (UTI) within a 3-year follow-up period after urine sample collection. The group included 17 participants, mostly male (71%), who had more advanced liver disease compared to the UTI-free group.

Group 0 sample size Number of subjects in the control (unexposed) group: 22

Group 1 sample size Number of subjects in the case (exposed) group: 17

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 month

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V2

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2.0

Matched on Factors on which subjects have been matched on in a case-control study: age, sex

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: antibiotic exposure, Confounders controlled for: "hospitalization" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.hospitalization, Confounders controlled for: "catheterization" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.catheterization

Alpha Diversity

Pielou Quantifies how equal the community is numerically: unchanged

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: unchanged

Richness Number of species: unchanged

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample: unchanged

Signature 1

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Source: Fig. 3C, Fig. S-5D-E,Table S-3 (Supplementary materials)

Description: 1. Fig.3C This figure shows taxa with increased abundance in urine samples of patients diagnosed with urinary tract infection compared to those without Urinary tract infection. The analysis was performed using LEfSe (relative abundance transformation).

2. Fig. S-5D-E (Supplementary Material) The figures reflect relative abundances of selected genera of the diagnosed urinary tract group compared to the non-urinary Tract Infection group. The plots depict mean relative abundance and standard deviation. Urinary microbiome composition of patients with liver cirrhosis in females in comparison to males.

3. Table S-3 (Supplementary material). The table shows the comparison of phylum-level urinary microbiome profiles between cirrhotic patients who developed urinary tract infection and those who did not develop urinary tract infection. Firmicutes and Actinobacteria were relatively more abundant in the group that developed urinary tract infection.

Abundance in Group 1: increased abundance in Diagnosed Urinary Tract Infection group

NCBI	Quality Control	Links
Lactobacillus
Streptococcus
ActinobacteriaActinobacteria
FirmicutesFirmicutes
ProteobacteriaProteobacteria

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Signature 2

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Source: Fig. 3A, Fig. S-FD-E, Table S-3,Table S-2 (Supplementary material)

Description: 1. Fig. 3A.This figure shows taxa with decreased abundance in urine samples of patients diagnosed with urinary tract infection compared to those without Urinary tract infection. The analysis was performed using ANCOM (log-transformed abundance).

2. Fig. S-FD-E (Supplementary materials)- The figures reflect relative abundances of selected microbial taxa of the diagnosed Urinary tract infection group compared to the non-urinary tract Infection group. The plots depict mean relative abundance and standard deviation. Urinary microbiome composition of patients with liver cirrhosis in females in comparison to males.

3. Table S-3(Supplementary materials)- The table shows a comparison of phylum-level urinary microbiome profiles between cirrhotic patients who developed urinary tract infection and those who did not develop urinary tract infection. Bacteroidetes and Epsilonbacteraeota were decreased in the group that developed urinary tract infections.

4. Table S-2. The table shows a linear regression model testing associations between clinical covariates and urinary microbiome alpha diversity. In terms of liver status, Phylogenetic diversity (PD) significantly decreased in patients with decompensated cirrhosis (p = 0.038).

Abundance in Group 1: decreased abundance in Diagnosed Urinary Tract Infection group

NCBI	Quality Control	Links
Corynebacterium
Dialister
Prevotella
Enterococcus
Veillonella
Anaerococcus
BacteroidetesBacteroidetes
EpsilonbacteraeotaEpsilonbacteraeota
phylogenetic diversityphylogenetic diversity

Revision editor(s): Busiwa Liuma

Experiment 2

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: No UrinaryTract Infection group

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: These patients had liver cirrhosis and developed at least one urinary tract infection (UTI) within three years after their urine samples were collected. The group comprised 17 participants, 71% of whom were men and had more advanced liver disease than those who remained UTI-free.

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: log transformation

Statistical test: ANCOM

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: antibiotic exposure, Confounders controlled for: "hospitalization" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.hospitalization, Confounders controlled for: "cathetization" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.cathetization