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Perinatal High-Salt Diet Induces Gut Microbiota Dysbiosis, Bile Acid Homeostasis Disbalance, and NAFLD in Weanling Mice Offspring.

ABSTRACT: A perinatal high-salt (HS) diet was reported to elevate plasma triglycerides. This study aimed to investigate the hypothesis that a perinatal HS diet predisposed offspring to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of abnormal lipid metabolism, and the possible mechanism. Female C57BL/6 mice were fed a control diet (0.5% NaCl) or HS diet (4% NaCl) during pregnancy and lactation and their offspring were sacrificed at weaning. The perinatal HS diet induced greater variation in fecal microbial beta-diversity (β-diversity) and increased bacteria abundance of Proteobacteria and Bacteroides. The gut microbiota dysbiosis promoted bile acid homeostasis disbalance, characterized by the accumulation of lithocholic acid (LCA) and deoxycholic acid (DCA) in feces. These alterations disturbed gut barrier by increasing the expression of tight junction protein (Tjp) and occludin (Ocln), and increased systemic lipopolysaccharide (LPS) levels and hepatic inflammatory cytokine secretion (TNF-α and IL-6) in the liver. The perinatal HS diet also inhibited hepatic expression of hepatic FXR signaling (CYP7A1 and FXR), thus triggering increased hepatic expression of pro-inflammatory cytokines (TNF-α and IL-6) and hepatic lipid metabolism-associated genes (SREBP-1c, FAS, ACC), leading to unique characteristics of NAFLD. In conclusion, a perinatal HS diet induced NAFLD in weanling mice offspring; the possible mechanism was related to increased bacteria abundance of Proteobacteria and Bacteroides, increased levels of LCA and DCA in feces, and increased expressions of hepatic FXR signaling.

SUBMITTER: Guo Q

PROVIDER: S-EPMC8308454 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Perinatal High-Salt Diet Induces Gut Microbiota Dysbiosis, Bile Acid Homeostasis Disbalance, and NAFLD in Weanling Mice Offspring.

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