Maternal Obesity Can Promote Liver Cancer

Obesity, a condition that could reach 50% of the population in some industrialized countries by 2030, is a major public health problem. It not only affects the health of those affected, but can also have serious consequences for their offspring. Scientists from the University of Geneva (UNIGE) and Geneva University Hospitals (HUG) led by Christian Toso, Full Professor at the UNIGE Faculty of Medicine and Director of the Division of Digestive Surgery at HUG, who led this study, have investigated the impact of maternal obesity on the risk of developing liver disease and liver cancer.

Using an animal model, the team discovered that this risk is actually much higher in the offspring of obese mothers. One of the main causes was the transmission of a disturbed gut microbiota from the mother, leading to chronic liver disease, the effects of which only became apparent in adulthood. These findings, which have yet to be confirmed in humans, are a warning signal and a call to action to limit the harmful effects of obesity on children. This research was published in the journal JHEP Reports.

Maternal Obesity and Liver Disease in Offspring

Science suggests that maternal obesity disrupts the metabolic balance of the unborn child and even increases the risk of childhood cancer and colorectal cancer. But to what extent? The researchers wanted to find out whether the children of obese mothers have a higher risk of developing liver disease and through which biological mechanisms. While the risk of developing liver cancer decreases due to a liver virus, obesity-related liver diseases are steadily increasing.

The scientists studied two groups of female mice: the first was fed a diet high in fat and sugar – similar to junk food – and quickly became obese. The second – the control group – was fed a normal diet. All their offspring were fed a normal diet and were not overweight. So the only difference was maternal obesity in the first group. At 20 weeks of age, which corresponds to adulthood in humans, the researchers were unable to detect any significant differences. However, at the age of 40 weeks, which is an advanced age in mice, the health of the liver in the first group began to deteriorate. All parameters of liver disease – fat deposits, fibrosis and inflammation – were significantly higher in the offspring of mothers who suffered from obesity. And these are the main risk factors for liver cancer in humans.

Altered Microbiota Transmitted at Birth can Increase the Risk of Developing Liver Cancer

To test whether these mice had a higher risk of developing liver cancer, the team injected two groups of these mice with an oncogenic product shortly after weaning. And indeed, the offspring of obese mothers had an 80% risk of developing cancer, compared to 20% in the control group. The mother’s obesity therefore continues to affect the offspring long after birth, who appear to inherit a dysfunctional microbiota despite their own living conditions. Obesity alters the composition and diversity of the maternal microbiota, which is passed on to the next generation and persists throughout life.

However, when the scientists placed mice from both groups in the same cage, they observed a normalization of the microbiota. Since mice are coprophagous (they eat their feces), they quickly share the same microbiotic strains. As a result, bacterial diversity increased, favoring the good bacteria. As a result, the healthy microbiota naturally regained the upper hand and the marker for liver disease decreased dramatically. The researchers see a clear effect of the microbiota on the risk of developing liver cancer, indicating its central role in the transmission of disease risk from mother to child.

The junk food diet promotes the proliferation of bad bacteria and reduces bacterial diversity. This altered microbiota transmitted at birth then leads to increased inflammation in the liver and, over time, fibrosis and steatosis (excessive fat deposition), which in turn increase the risk of developing liver cancer. Normalizing the microbiota also normalizes the risk of cancer.

What This Means for Humans

This data comes from a study on an animal model in a very controlled environment. In order to be able to apply them in a clinical context, they need to be confirmed in humans under real conditions. The first step will be an epidemiological study based on extensive data obtained from observing mothers and their children over several decades. However, it is already known that it is possible to modify the microbiota, for example through the use of probiotics. According to the researchers, highlighting the importance of the microbiome is a first step towards new therapies.