Maternal obesity may promote liver cancer in offspring

Scientists at the University of Geneva (UNIGE) and Geneva University Hospitals (HUG) have been studying the impact of a mother’s obesity on the risk of her offspring developing liver disease and liver cancer. Using an animal model, the team discovered that this risk was indeed much higher in the offspring of mothers suffering from obesity, due to the inheritance of poor intestinal microbiota. Their research has been published in the journal JHEP Reports.

“We wanted to understand whether the children of mothers suffering from obesity were at greater risk of developing liver diseases, and by what biological mechanisms,” said study leader Christian Toso, full professor at the UNIGE Faculty of Medicine and Director of the Division of Digestive Surgery at the HUG. “Indeed, while the risk of liver cancer due to a hepatic virus is decreasing, obesity-related liver diseases are constantly on the rise.”

The scientists studied two groups of female mice: the first group were fed with a diet rich in fat and sugar, while the second were fed normally. All their offspring were fed with a normal diet and were not overweight; the only difference was the maternal obesity of the first group.

“At 20 weeks, which corresponds to adulthood in humans, we could not detect any notable differences,” said Beat Moeckli, a junior staff surgeon and researcher in Toso’s team. “However, at 40 weeks, a senior age in mice, the liver health of the first group began to deteriorate. All the parameters of liver disease — fat deposits, fibrosis and inflammation — were significantly higher in the offspring of mothers suffering from obesity. And these are the main risk factors for liver cancer in humans.”

To confirm whether these mice had a higher risk of developing liver cancer, the team injected two groups of these mice with an oncogenic product just after weaning. The offspring of obese mothers were found to have an 80% risk of developing cancer, compared with 20% for the control group.

“The mother’s obesity thus has an impact long after the birth of its offspring, which seem to inherit a dysfunctional microbiota despite their own living conditions,” Moeckli said. “Obesity alters the composition and diversity of the mother’s microbiota, which is passed on to the next generation and persists throughout life.”

However, by placing mice from both groups in the same cage, the scientists observed a normalisation of the microbiota. As mice are coprophagous (they eat their faeces), they quickly share the same microbiotic strains. Bacterial diversity then increased, favouring the good bacteria. As a result, the healthy microbiota naturally regained the upper hand, and the marker of liver disease dramatically decreased.

“We see a clear effect of the microbiota on the risk of developing liver cancer, indicating its central role in transmitting the risk of disease from mother to child,” Moeckli said.

The researchers acknowledged that their data come from a study on an animal model, in a highly controlled environment. To be applied in a clinical context, they need to be confirmed in humans under real-life conditions; the first stage will consist of an epidemiological study based on large bodies of data obtained from following mothers and their children over several decades.

“However, we already know that it is possible to modify the microbiota, for instance by using probiotics,” the researchers said. “Having highlighted the importance of the microbiome represents a first step towards new therapies.”

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