Gestational diabetes augments group B Streptococcus infection by disrupting maternal immunity and the vaginal microbiota

Abstract

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, and altered maternofetal cytokines. Lastly, we observe distinct vaginal microbial taxa associated with GDM status and GBS invasive disease status. Here, we show a model of GBS dissemination in GDM hosts that recapitulates several clinical aspects and identifies multiple host and bacterial drivers of GBS perinatal disease.

Maternal gut microbiota in the health of mothers and offspring: from the perspective of immunology

“…Recently, a study indicated that intrauterine infection by Porphyromonas gingivalis was associated with increased uterine NK cell populations and decreased secretion of IL-18 in rat, accompanied by a reduction of TNF-α + T cells ( 106 ). Another study showed that the depletion of NK cells, mainly uterine NK cells, played a protective role in Group B Streptococcus (GBS) fetal invasion in GDM mice ( 107 ). Crespo et al.…”