Probiotic-fermented milk alleviates hypertension in preeclampsia rats and is associated with increases in branched fatty acid esters of hydroxy fatty acids.

Branched fatty acid esters of hydroxy fatty acids (FAHFAs), a newly-discovered class of endogenous lipids closely associated with obesity, cardiovascular disease, and aging, are potential drug candidates or targets for the prevention and treatment of related conditions. The antihypertensive potential of probiotic-fermented milk has been recognized, but its relevance to preeclampsia (PE) is unclear. It was hypothesized that probiotic-fermented milk could reduce blood pressure in PE rats and influence the contents of FAHFAs, with FAHFAs potentially playing a critical role in this process. To test this hypothesis, the PE rat model was constructed using L-NAME (125 mg/kg), and probiotic-fermented milk (20 mg/kg) was administered for a total of 21 d. Metagenomic sequencing and LC-MS/MS based metabolomics were used. Probiotic-fermented milk substantially attenuated hypertension in PE rats, with an efficacy comparable to that of labetalol (4 mg/kg). Probiotic-fermented milk significantly increased the contents of specific FAHFAs (e.g., 18:0/20:2, 16:0/18:2) in the gut and serum (P < .05) and FAHFAs was negatively correlated with blood pressure (P < .05). Probiotic-fermented milk regulated the composition of gut microbiota (increasing Lactiplantibacillus and Staphylococcus and decreasing Methanobrevibacter and Limosilactobacillus), and down-regulated purine, glyoxylate/dicarboxylate, and amino metabolism, and the one-carbon pool produced by folate. These metabolic shifts were strongly correlated with the gut microbiota and FAHFAs. These results indicate that probiotic-fermented milk alleviates hypertension in PE rats, potentially mediated by FAHFAs. This study provides foundational evidence for the antihypertensive mechanism of probiotic-fermented milk in preeclampsia and supports the development of novel strategies for its prevention and treatment.