High Glucose Promotes Inflammation and Weakens Placental Defenses against E. coli and S. agalactiae Infection: Protective Role of Insulin and Metformin Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What Was Studied?
This study explored the effects of hyperglycemia on inflammation and the innate defense mechanisms of the placenta against Escherichia coli (E. coli) and Streptococcus agalactiae (S. agalactiae). It also evaluated the roles of insulin and metformin in mitigating these effects. Placental explants were cultured in hyperglycemic environments and challenged with these bacteria to assess inflammatory cytokine secretion, beta defensin production, bacterial counts, and tissue invasiveness.
Who Was Studied?
The research used placental explants from 35 normoevolutive, term pregnancies (37.2–40 weeks). The placental tissues were exposed to varying glucose concentrations, insulin, and metformin in vitro. Pathogenic strains of E. coli and S. agalactiae were used to test bacterial growth and invasion under hyperglycemic and treated conditions.
What Were the Most Important Findings?
Hyperglycemia significantly increased placental secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) while reducing beta defensin (HBD1-4) production, weakening innate immunity. These changes promoted greater bacterial counts and invasiveness, especially for E. coli, which exhibited a strong tropism for capillaries. The study found that insulin reduced bacterial invasiveness by fortifying the placental barrier, but did not affect bacterial counts. Metformin, on the other hand, significantly reduced bacterial counts of both E. coli and S. agalactiae in addition to mitigating bacterial invasiveness. Despite these protective effects, neither treatment restored beta defensin synthesis. Furthermore, hyperglycemia combined with bacterial infection induced “cytokine tolerization,” resulting in a pathogen-specific reduction in pro-inflammatory cytokine secretion, which potentially increases vulnerability to infections.
What Are the Greatest Implications of This Study?
Hyperglycemia impairs placental immunity in GDM by weakening defenses against infections through reduced beta defensin synthesis and cytokine tolerization. While insulin limits bacterial invasion, metformin provides additional benefits by actively reducing bacterial counts of E. coli and S. agalactiae. These findings emphasize the need for optimizing therapeutic strategies to enhance placental defenses in GDM, particularly leveraging metformin’s antimicrobial properties.
Streptococcus agalactiae (GBS)
Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a Gram-positive, facultative anaerobe commonly found as a commensal organism in the gastrointestinal and urogenital tracts of humans. While asymptomatic colonization is frequent, GBS is also a major pathogen, particularly in neonates, pregnant women, and immunocompromised individuals.