Sodium butyrate alleviates pre-eclampsia in pregnant rats by improving the gut microbiota and short-chain fatty acid metabolites production

Aims Pre-eclampsia (PE) affects pregnant patients worldwide, but there is no effective treatment for this condition. We aimed to explore the effect of sodium butyrate (NaB) on PE. Methods and Results In this study, N omega-nitro-L-arginine methyl ester hydrochloride was used to induce PE in pregnant rats. We found that NaB significantly decreased the levels of blood pressure, 24-h protein urine and inflammatory factors (IL-1 beta, IL-6 and TGF-beta), increased the foetal and placental weights and intestinal barrier markers (ZO-1, claudin-5 and occludin) expression. In addition, NaB intervention reduced the levels of soluble fms-like tyrosine kinase 1 and soluble endoglin and increased placental growth factor level. Meanwhile, after NaB treatment, the Treg/Th17 ratio of immune cells in the spleen and small intestine of pregnant rats decreased, while the level of pregnancy-related diamine oxidase increased. Notably, the PE rat treatment with NaB improved gut microbiota compositions, especially for the abundances of Firmicutes and Bacteroides, and significantly increased butyric acid and pentanoic acid levels, which might help to alleviate PE in pregnant rats. Conclusion In the PE rat model, exogenous NaB improved intestinal barrier function and reduced adverse outcomes, which might be associated with the gut microbiota and its production of SCFA metabolites. Significance and Impact of the Study NaB might alleviate the adverse outcomes of PE by regulating gut microbiota and its metabolite SCFA, which revealed that NaB might be a potential regulator of gut microbiota and a therapeutic substance for PE.