Intestinal microbiome as a risk factor for urinary tract infections in children

Abstract

As urinary tract infection (UTI) pathogens originate from the gut, we hypothesized that the gut environment reflected by intestinal microbiome influences the risk of UTI. Our prospective case-control study compared the intestinal microbiomes of 37 children with a febrile UTI with those of 69 healthy children. We sequenced the regions of the bacterial 16S rRNA gene and used the LefSe algorithm to calculate the size of the linear discriminant analysis (LDA) effect. We measured fecal lactoferrin and iron concentrations and quantitative PCR for Escherichia coli. At the phylum level, there were no significant differences. At the genus level, Enterobacter was more abundant in UTI patients with an LDA score > 3 (log 10), while Peptostreptococcaceae were more abundant in healthy subjects with an LDA score > 3 (log 10). In total, 20 OTUs with significantly different abundances were observed. Previous use of antimicrobials did not associate with intestinal microbiome. The relative abundance of E. coli was 1.9% in UTI patients and 0.5% in controls (95% CI of the difference-0.8 to 3.6%). The mean concentration of E.coli in quantitative PCR was 0.14 ng/μl in the patients and 0.08 ng/μl in the controls (95% CI of the difference-0.04 to 0.16). Fecal iron and lactoferrin concentrations were similar between the groups. At the family and genus level, we noted several differences in the intestinal microbiome between children with UTI and healthy children, which may imply that the gut environment is linked with the risk of UTI in children.

Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection

“…Literature investigating the role of uropathogenic genes like FimH in increasing the propensity for gut E. coli strains to cause UTI is also relatively limited 24 . Recent studies have found increased gut abundance of Escherichia or Enterococcus in patients with UTI compared to patients without UTIs 10,11 , but they did not evaluate temporal dynamics of the gut microbiota. Our study expands upon this idea by demonstrating that increased fecal abundance of Escherichia and Enterococcus is associated with an increased risk of developing future bacteriuria with the respective organism.…”

“…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 UTIs 10 . 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 UTIs 11 . Both of these studies assessed whether the gut microbiota is associated with UTIs at the time of UTI, but not whether the gut microbiota is a risk factor for development of bacteriuria and UTI.…”

Impact of intrapartum and postnatal antibiotics on the gut microbiome and emergence of antimicrobial resistance in infants

“…The F519 primer contained an Ion Torrent pyrosequencing adapter sequence A (Lifescience Technologies, USA), a 9-bp unique barcode sequence, and one nucleotide linker, while the R926 primer contained an Ion Torrent adapter trP1 sequence. We have earlier used similar methodology for NGS and bioinformatics of fecal samples obtained in infancy 40 .…”

Deciphering the Urinary Microbiota Repertoire by Culturomics Reveals Mostly Anaerobic Bacteria From the Gut

“…As a matter of fact, gut microbiota contributing to the diversity of prokaryotes inhabiting the urinary tract was suggested by a recent study highlighting the reduction in the recurrence of UTIs following fecal microbiota transplantation (FMT) (Staley et al, 2017;Tariq et al, 2017). It has also been recently suggested that the composition of the intestinal microbiota could impact the occurrence of UTI in children (Paalanne et al, 2018). These data suggest that UTI are in fact the consequences of ecosystem disruptions and that uropathogens could be acquired from the environment, particularly from animals (Jakobsen et al, 2010;Giufre et al, 2012;Maluta et al, 2014;Mellata et al, 2018).…”