Integrated Host IL-6 Axis, IL6R rs2228145, and Uropathogenic Escherichia coli Virulence Profiling in Obesity and Recurrent Urinary Tract Infection
Zahra Saeed, Hibbat Rickad, Basil AbbasBackground: Obesity-related inflammation and bacterial virulence may contribute to recurrent urinary tract infection (UTI). Examining inflammatory markers, host genetic variation and bacterial characteristics together may help clarify their associations. Objective: The objective of this study is to compare IL-6 and soluble IL-6 receptor (sIL-6R) levels and IL6R rs2228145 genotype distributions among peoples with obesity and normal weight, explore genotype–biomarker associations, and characterize urinary Escherichia coli isolates. Methods: Eighty participants with a reported history of recurrent UTI—40 with obesity and 40 with normal weight—were included in this cross-sectional study. Blood and urine specimens from the same participants were examined by ELISA, DNA-based genotyping, urine culture and bacterial quantitative PCR (qPCR). Two selected uropathogenic E. coli (UPEC) isolates underwent whole-genome sequencing (WGS). Results: Estimated mean ± SD IL-6 levels were higher in participants with obesity than in normal-weight participants (28.04 ± 3.37 versus 18.43 ± 1.41 ng/L; mean difference, 9.61 ng/L; 95% CI, 8.45–10.77). Mean sIL-6R levels were also higher (39.87 ± 9.15 versus 33.69 ± 8.44 ng/mL). Genotype frequencies did not differ significantly between groups. Exploratory BMI-adjusted per C allele fold changes were 1.06 for IL-6 and 1.34 for sIL-6R. Culture data indicated UPEC in 37/80 specimens; among these, qPCR results indicated fimH positivity in 33/37 and papG positivity in 18/37. The two sequenced isolates were assigned to ST127/O6:H31 and ST131/O25:H4. Conclusions: Participants with obesity had higher IL-6 estimates and sIL-6R concentrations, while IL6R genotype frequencies did not differ significantly between groups. Genotype–biomarker associations and the two genomic profiles are exploratory; measurement and record linkage limitations warrant cautious interpretation.