Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women

• Published in: Nature microbiology Vol. 7; no. 5; pp. 630 - 639
• Main Authors: Worby, Colin J., Schreiber, Henry L., Straub, Timothy J., van Dijk, Lucas R., Bronson, Ryan A., Olson, Benjamin S., Pinkner, Jerome S., Obernuefemann, Chloe L. P., Muñoz, Vanessa L., Paharik, Alexandra E., Azimzadeh, Philippe N., Walker, Bruce J., Desjardins, Christopher A., Chou, Wen-Chi, Bergeron, Karla, Chapman, Sinéad B., Klim, Aleksandra, Manson, Abigail L., Hannan, Thomas J., Hooton, Thomas M., Kau, Andrew L., Lai, H. Henry, Dodson, Karen W., Hultgren, Scott J., Earl, Ashlee M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2022; Nature Publishing Group
• Subjects: 45/23; 45/91; 631/326/2565/2134; 631/326/41/2530; 692/699/255/1318; Biomedical and Life Sciences; Bladder; Dysbacteriosis; Dysbiosis; Escherichia coli; Escherichia coli Infections - microbiology; Feces; Female; Gastrointestinal Microbiome; Humans; Immune response; Infectious Diseases; Inflammation; Intestinal microflora; Leukocytes, Mononuclear; Life Sciences; Medical Microbiology; Metagenomics; Microbiology; Microbiomes; Microbiota; Parasitology; Peripheral blood mononuclear cells; Risk factors; Transcription; Transcriptomics; Urinary tract; Urinary tract diseases; Urinary tract infections; Urinary Tract Infections - microbiology; Urogenital system; Virology
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/s41564-022-01107-x

Recurrent urinary tract infections (rUTIs) are a major health burden worldwide, with history of infection being a significant risk factor. While the gut is a known reservoir for uropathogenic bacteria, the role of the microbiota in rUTI remains unclear. We conducted a year-long study of women with ( n  = 15) and without ( n  = 16) history of rUTI, from whom we collected urine, blood and monthly faecal samples for metagenomic and transcriptomic interrogation. During the study 24 UTIs were reported, with additional samples collected during and after infection. The gut microbiome of individuals with a history of rUTI was significantly depleted in microbial richness and butyrate-producing bacteria compared with controls, reminiscent of other inflammatory conditions. However, Escherichia coli gut and bladder populations were comparable between cohorts in both relative abundance and phylogroup. Transcriptional analysis of peripheral blood mononuclear cells revealed expression profiles indicative of differential systemic immunity between cohorts. Altogether, these results suggest that rUTI susceptibility is in part mediated through the gut–bladder axis, comprising gut dysbiosis and differential immune response to bacterial bladder colonization, manifesting in symptoms. Multi-omics analyses of faecal, urine and blood samples from women with and without recurrent urinary tract infections reveal that gut dysbiosis and differential immune responses may play a role in risk of infection via the gut–bladder axis.