Intestinal Microbiome Shows Altered Diversity and Enterobacteriaceae Overgrowth in Carriers of Fluoroquinolone Resistant E. Coli
Fluoroquinolone resistant (FQR) E. coli is the cause of the majority of transrectal ultrasound guided prostate biopsy infections. Our objective is to evaluate the gut microbiome of individuals positive or negative for FQR E. coli to identify bacterial members associated with resistance to FQR colonization, potentially for development of non-antibiotic means to alter gut flora prior to prostate biopsy.
We prospectively collected 116 rectal swab samples at least 2 weeks prior to transrectal prostate biopsy, and performed 16S rRNA amplicon sequencing (MiSeq paired-end) using the V1V2 primer set. Taxonomic assignment was performed using Resphera Insight, and alpha and beta-diversity analysis was performed using QIIME. PERMANOVA was employed to evaluate statistical significance of beta-diversity distances within and between groups of interest. Differential abundance analysis utilized the nonparametric difference test for alpha diversity measures and the negative binomial test for taxonomic count data with P-value correction using the False Discovery Rate (FDR).
Of the clinical cultures we identified 18 isolates (16%, 18/116) that were FQR E. coli positive. Men positive for FQR E. coli maintained relative reduced alpha diversity compared to non-FQR subjects (inverse simpson; P=0.05). The association of microbial community membership with FQR status was found to be significant for Bray-Curtis (P=0.047) and weighted-UniFrac measures (P=0.01). Enterobactericeae relative abundance was significantly over-represented in the FQR subjects (adj. P=0.03), while the bacterial family Aeromonadaceae was absent in the culture group despite low relative abundance in non-FQR subjects (adj. P<0.001). At the species level, Prevotella disiens was significantly enriched in FQR negative subjects (adj. P = 0.012), while Shigella flexneri and Proteus mirabilis were significantly higher in the FQR positive group (adj. P=0.017 and adj. P=0.028, respectively).</p>
Microbiome analysis determined that men colonized with FQR bacteria have less diverse bacterial communities (dysbiosis), higher levels of Enterobacteriaceae and reduced levels of Prevotella disiens. These results may have implications in pre/probiotic intervention studies.
Funding: 5UM1AI104681-05 (PI's Henry F Chambers and Vance G. Fowler, Duke University) Antibiotic Resistant Leadership Group Young Investigator Award