Maternal Fecal Microbiota Transplantation Mitigates Hypertension in Offspring Exposed to a High-Fructose Diet

Excessive maternal fructose intake contributes to the developmental programming of hypertension in offspring, partly via gut microbiota dysbiosis and oxidative stress. Fecal microbiota transplantation (FMT) may restore microbial balance and modulate short-chain fatty acid (SCFA) production. We investigated whether maternal FMT from healthy donors could prevent hypertension in offspring exposed to a high-fructose (HF) diet. Pregnant Sprague Dawley rats (n = 12) were fed normal chow (ND) or a 60% HF diet from mating to delivery. Cross-FMT was performed: HF dams received FMT from ND donors, and ND dams received FMT from HF donors. Male offspring (n = 8/group) were assigned to ND, HF, ND + HF-FMT, or HF + ND-FMT groups. Offspring of HF dams developed higher systolic blood pressure (+13 mmHg vs. ND, p < 0.05). Maternal FMT from ND donors reduced this elevation by ~8 mmHg (p < 0.05). Protective effects were accompanied by higher plasma butyrate, increased expression of SCFA receptors (GPR41, GPR43), reduced renal oxidative stress markers (8-OHdG), and distinct gut microbiota profiles. Maternal FMT generated four enterotypes in offspring, each associated with differential blood pressure outcomes. These findings suggest that maternal microbiota-targeted interventions, such as FMT, can mitigate hypertension of developmental origin by restoring gut microbial and metabolic homeostasis.