Maternal obesogenic diet regulates offspring bile acid homeostasis and hepatic lipid metabolism via the gut microbiome in mice

Jan 5, 2022American journal of physiology. Gastrointestinal and liver physiology

Mother's high-fat diet changes offspring's bile acid balance and liver fat processing through gut bacteria in mice

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Abstract

Mice exposed to a maternal high-fat/high-sucrose diet exhibit altered bile acid homeostasis.

Gut microbiomes from HF/HS offspring showed significant differences compared to control offspring, including increased ratios of Firmicutes to Bacteroidetes and higher levels of Verrucomicrobia.
Cecal microbiome transplantation from HF/HS offspring into recipient mice resulted in larger bile acid pools and changes in specific bile acid species.
HF/HS-recipient mice displayed altered gene expression related to bile acid and lipid metabolism, including increased expression of lipogenic genes.
After fructose feeding, HF/HS-recipient mice had larger livers and higher intrahepatic triglyceride levels than control-recipient mice.
These findings suggest a potential causal relationship between maternal diet-induced microbiome changes and hepatic bile acid and lipid metabolism in offspring.

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Mice exposed in gestation to maternal high-fat/high-sucrose (HF/HS) diet develop altered bile acid (BA) homeostasis. We hypothesized that these reflect an altered microbiome and asked if microbiota transplanted from HF/HS offspring change hepatic BA and lipid metabolism to determine the directionality of effect. Female mice were fed HF/HS or chow (CON) for 6 wk and bred with lean males. 16S sequencing was performed to compare taxa in offspring. Cecal microbiome transplantation (CMT) was performed from HF/HS or CON offspring into antibiotic-treated mice fed chow or high fructose. BA, lipid metabolic, and gene expression analyses were performed in recipient mice. Gut microbiomes from HF/HS offspring segregated from CON offspring, with increased Firmicutes to Bacteriodetes ratios and Verrucomicrobial abundance. After CMT was performed, HF/HS-recipient mice had larger BA pools, increased intrahepatic muricholic acid, and decreased deoxycholic acid species. HF/HS-recipient mice exhibited downregulated hepatic, increased hepaticand decreased ilealmRNA expression. HF/HS-recipient mice exhibited decreased cecal butyrate and increased hepatic expression of. HF/HS-recipient mice had larger livers and increased intrahepatic triglyceride versus CON-recipient mice after fructose feeding, with increased hepatic mRNA expression of lipogenic genes includingandCMT from HF/HS offspring increased BA pool and shifted the composition of the intrahepatic BA pool. CMT from HF/HS donor offspring increased fructose-induced liver triglyceride accumulation. These findings support a causal role for vertical transfer of an altered microbiome in hepatic BA and lipid metabolism in HF/HS offspring.We utilized a mouse model of maternal obesogenic diet exposure to evaluate the effect on offspring microbiome and bile acid homeostasis. We identified shifts in the offspring microbiome associated with changes in cecal bile acid levels. Transfer of the microbiome from maternal obesogenic diet-exposed offspring to microbiome-depleted mice altered bile acid homeostasis and increased fructose-induced hepatic steatosis. Mrp2Oatp1b2, Asbt Il6Srebf1, Fabp1, Mogat1, Mogat2. NEW & NOTEWORTHY

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Maternal obesogenic diet regulates offspring bile acid homeostasis and hepatic lipid metabolism via the gut microbiome in mice

Abstract

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