Maternal obesity increases the risk for hepatocellular carcinoma in offspring through the transmission of an altered gut microbiome

Objective: The obesity pandemic leads to a rising number of obese women of reproductive age. Emerging evidence suggests that maternal obesity has a negative impact on the long-term health of offspring. Additionally, obesity is an independent risk factor for malignancies, particularly hepatocellular carcinoma (HCC). The aim of our study is to investigate the impact of maternal obesity on the risk for HCC in the offspring and identify potential mechanisms of transmission.
Methods: Female mice were fed either a high fat (HFD) or a normal diet (ND) before mating. Offspring received ND throughout life. In the offspring, we studied the gut microbiome, liver histology, inflammatory patterns, and tumor load in a diethylnitrosamine-induced HCC mouse model. To normalize the gut microbiome, we co-housed offspring of HFD and ND mothers after weaning. The composition of the gut microbiota was assessed through 16S rRNA sequencing.