Abstract
The origin of most bacterial infections in the urinary tract is often presumed to be the gut. Herein, we investigate the relationship between the gut microbiota and future development of bacteriuria and urinary tract infection (UTI). We perform gut microbial profiling using 16S rRNA gene deep sequencing on 510 fecal specimens from 168 kidney transplant recipients and metagenomic sequencing on a subset of fecal specimens and urine supernatant specimens. We report that a 1% relative gut abundance of Escherichia is an independent risk factor for Escherichia bacteriuria and UTI and a 1% relative gut abundance of Enterococcus is an independent risk factor for Enterococcus bacteriuria. Strain analysis establishes a close strain level alignment between species found in the gut and in the urine in the same subjects. Our results support a gut microbiota–UTI axis, suggesting that modulating the gut microbiota may be a potential novel strategy to prevent UTIs.
Highlights
The origin of most bacterial infections in the urinary tract is often presumed to be the gut
Conventional urine cultures were performed at every routine clinic visit, allowing for a comprehensive evaluation of bacteriuria in these subjects. 16S rRNA gene deep sequencing of the V4–V5 hypervariable region was performed on the 510 fecal specimens and the mean average ± standard deviation (SD) high quality classified reads were 18,179 ± 11,033
To assess the relatedness of strains in the gut and in the urine, we evaluated 17 fecal specimens that were paired to 17 urine specimens in which urine cultures were positive for Escherichia coli (n = 14), Enterococcus faecalis (n = 2), and Enterococcus faecium (n = 2) and in which relative gut abundance of Escherichia or Enterococcus was above two percent by 16S rRNA gene sequencing
Summary
The origin of most bacterial infections in the urinary tract is often presumed to be the gut. In a pilot study of 26 kidney transplant recipients in which we performed serial gut microbiota profiling, we reported an association between gut Enterococcus abundance and Enterococcus UTIs10. In another recent case-control study of children with UTIs and without UTIs, the relative gut abundance of Escherichia coli was significantly higher in children with UTIs than children without UTIs11. We report that gut abundance of uropathogens is associated with future development of bacteriuria and UTI and that strain analysis establishes a close strain level alignment between species found in the gut and in the urine in the same subjects with bacteriuria
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