Multi-Omics Reveal That Gut Microbial Dysbiosis Drives Lipid Metabolic Disturbances and Inflammation in Gestational Hypertension.

BACKGROUND: Gestational hypertension (GH) is a common complication during pregnancy that poses serious health risks to both mother and fetus. Recent studies have underscored the potential roles of gut microbiota, lipid metabolism, and inflammatory response in GH's development and progression. However, the exact mechanisms behind these interactions are still unclear. Understanding how gut microbial composition impacts lipid metabolism and inflammation could offer valuable insights into GH's pathogenesis and may lead to new prevention and treatment methods. METHODS: In this study, we conducted ELISA experiments to detect inflammatory cytokines in the serum of GH patients. Additionally, we performed 16S-rDNA sequencing analysis on the feces of GH patients to investigate the characteristics of their intestinal microbial communities; GH mouse model was constructed to assess the impact of intestinal flora on offspring. Furthermore, we utilized non-targeted lipid metabolomics to analyze lipid metabolic characteristics in the feces and blood of GH patients and established connections between the microbiome and lipidome through correlation analysis. RESULTS: ELISA tests suggested the levels of inflammatory factors in the serum of GH patients increased significantly, including IL-6, IL-8, IL-17, IL-18, and IFN-γ. In comparison to the normal group, the GH group exhibited a marked reduction in microbial richness. LEfSe analysis found 16 distinct bacterial communities between the two groups. Animal models suggested that fecal microbiota transplantation from the GH group's intestinal flora resulted in a significant decrease in the birth weight of the offspring. Furthermore, comparative analysis of fecal and blood metabolic profiles suggested that TG (54:5/FA22:5) may serve as a key metabolite. Correlation analysis demonstrated that f-Oxalobacteraceae exhibited a significant negative correlation with the inflammatory factor IL-17 and TG (54:5/FA22:5) in the blood, while showing a significant positive correlation with g-Oxalobacter and s-formigenes. CONCLUSION: Our results establish a connection between gut microbiota, lipid metabolism, and the inflammatory response in patients with GH. This understanding may enhance our comprehension of the underlying mechanisms associated with GH.