Causal effect of gut Streptococcus abundance on maternal genitourinary infection during pregnancy: a two-sample...

Genitourinary infections (GUIs) during pregnancy are a significant clinical concern linked to maternal morbidity. To investigate the potential causal effect of gut Streptococcus abundance on the risk of maternal genitourinary infection during pregnancy using Mendelian randomization (MR), we performed a two-sample MR analysis using publicly available genome-wide association study (GWAS) summary statistics. Genetic instruments for gut Streptococcus abundance were obtained from the MiBioGen consortium (N = 18,340). Outcome data for maternal genitourinary infection (ICD-10 O23.x) were sourced from the FinnGen consortium (N = 111,731). The inverse-variance weighted (IVW) method was used as the primary analysis, supplemented by sensitivity analyses including MR-Egger, weighted median, and MR-PRESSO to assess pleiotropy. We further assessed potential mediation via systemic inflammation (C-reactive protein, interleukin-6) and associations with adverse pregnancy outcomes (APOs). Genetically predicted higher gut Streptococcus abundance was associated with a reduced risk of maternal genitourinary infection (IVW odds ratio [OR] = 0.63, 95% confidence interval [CI]: 0.43-0.93, p = 0.020). Sensitivity analyses supported this protective association, with no evidence of horizontal pleiotropy (MR-Egger intercept p = 0.942) or significant heterogeneity. No causal effects were observed on systemic inflammatory markers (CRP, IL-6, all p > 0.05) or on major APOs, including postpartum haemorrhage and placental abruption. This MR study provides genetic evidence supporting a causal, protective role of gut Streptococcus against the risk of clinically diagnosed genitourinary infection during pregnancy. This effect appears specific and is not mediated through the systemic inflammatory pathways examined, suggesting a localized mechanism within the genitourinary tract.