Effects of Prebiotic Phytocompound Administration in Gestational Diabetic Dams and Its Influence on Offspring Cognitive Outcomes

Abstract

Gestational diabetes mellitus (GD)-induced gut dysbiosis in pregnant mothers may increase the risk of cognitive impairment and neurological disorders in both the mother and offspring as they age. Restoring gut balance could improve cognitive outcomes for both. Despite advancements in GD treatment, side effects have increased, and long-term neurocognitive impacts on offspring born to GD mothers remain underexplored. This study uses a GD mouse model, inducing pancreatic dysfunction in 3-month-old pregnant C57BL/6J mice with Streptozotocin. The efficacy and mechanism of the prebiotic phytocompound green leaf extract (Allmania nodiflora) were assessed, with metformin as the standard. GD dams exhibited weight and glucose reduction, pancreatic IL-6 elevation, GLUT3 reduction, astroglia changes in the cerebral cortex, gut barrier impairment, cognitive impairment, and heightened anxiety compared to controls. Bacterial 16s rRNA sequencing revealed dysbiosis, with reduced Erysipelotrichales in GD dams compared to controls. Metformin lowered blood glucose levels but failed to rescue functional and behavioral phenotypes in both GD dams and offspring. Phytocompound treatment improved blood glucose, reduced pancreatic inflammation, improved gut barrier integrity, reversed dysbiosis, and enhanced brain health. It rescued behavioral deficits and improved cognitive outcomes in offspring, suggesting the prebiotic phytocompound may be a more effective therapeutic agent for GD in humans.