Lactobacillus plantarum IOB602 and Its Postbiotics Attenuate Hypertension-Induced Damage by Modulating the RAS, PI3K/AKT/eNOS Pathways, and Gut Microbiota

Hypertension is a common cardiovascular disorder, and current pharmacological treatments are often associated with significant side effects, highlighting the need for safer alternatives. Probiotics and their postbiotics have emerged as promising candidates due to their favorable safety profiles. This study evaluated the potential of Lactobacillus plantarum IOB602 and its 602P postbiotic to attenuate hypertension-induced damage. We first assessed their ACE inhibitory activity in vitro. Subsequently, we investigated their protective effects against organ damage and the underlying mechanisms in L-NAME-induced hypertensive rats using biochemical assays, real-time qPCR, histopathological analysis, and 16S rRNA sequencing. In vitro results showed that IOB602 exhibited strong tolerance to simulated gastric acid and bile salts, indicating good gastrointestinal survivability. Both the culture supernatant and the postbiotic displayed significant ACE inhibitory activity, with the postbiotic achieving an inhibition rate of 82.21%. In vivo, treatment with IOB602 or 602P significantly reduced plasma angiotensin II levels, upregulated the PI3K-Akt-eNOS pathway, restored nitric oxide bioavailability, and attenuated oxidative stress and inflammatory responses in hypertensive rats. Histological analysis revealed that both interventions alleviated pathological damage in the thoracic aorta, heart, and kidneys. Furthermore, IOB602 and its postbiotic reshaped the gut microbiota composition by decreasing harmful genera such as Ruminococcus and enriching beneficial taxa including Akkermansia and Christensenellaceae. In conclusion, L. plantarum IOB602 and its 602P postbiotic show potential for development as functional foods or pharmaceutical adjuvants for the treatment of hypertension-induced organ damage.: