Obesity constitutes a serious global public health problem that in 2022 will already affect one billion people – one in eight – according to data from the World Health Organization (WHO), and that can also have serious long-term consequences. , since a study carried out by researchers at the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG) has found that maternal obesity increases the risk of liver diseases and liver cancer in offspring.
To study how the mother’s excess weight influenced the development of this type of pathology in her offspring, the researchers used an animal model and discovered that this risk was significantly higher in the children of mothers with obesity, and that one of the main The causes of this were the transmission of an altered intestinal microbiota, which triggers chronic liver disease that manifests in adulthood.
The scientific community already suspected that maternal obesity alters the metabolic balance of the developing baby, even increasing the risk of childhood cancer and colorectal cancer, but the extent to which is unknown. The findings have been published in the journal JHEP Reports and, although they have yet to be confirmed in humans, they represent a warning signal for measures to be taken to help mitigate the negative impact of maternal obesity on children.
“We wanted to understand if children of mothers with obesity had a higher risk of developing liver diseases and through what biological mechanisms,” explains Christian Toso, professor at the UNIGE Faculty of Medicine and director of the Division of Digestive Surgery at HUG. , who led this research. “In fact, while the risk of liver cancer due to a liver virus is decreasing, obesity-related liver diseases are steadily increasing.”
Obesity alters the composition and diversity of the intestinal microbiota
The team investigated two groups of female mice: the first was fed a diet rich in fats and sugars – similar to junk food – and quickly became obese. The second group, the control group, received a normal diet. All their offspring were fed a normal diet and were not overweight. The only difference, therefore, was the maternal obesity of the first group.
“At 20 weeks, which corresponds to adulthood in humans, we could not detect notable differences,” explains Beat Moeckli, junior surgeon and researcher in the team of Professor Toso, the first author of this work. “However, at 40 weeks – an advanced age in mice – the liver health of the first group began to deteriorate. All parameters of liver disease – fat deposits, fibrosis and inflammation – were significantly higher in the offspring of mothers with obesity. And these are the main risk factors for liver cancer in humans.”
To confirm whether these mice had an increased risk of developing liver cancer, the team injected two groups of them with an oncogenic product just after weaning. In fact, the offspring of obese mothers had an 80% risk of developing cancer, compared to 20% in the control group. “The mother’s obesity therefore has an impact long after the birth of her offspring, who appear to inherit a dysfunctional microbiota despite their own living conditions,” says Beat Moeckli. “Obesity alters the composition and diversity of the mother’s microbiota, which is transmitted to the next generation and persists throughout life.”
“We 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”
However, by placing mice from both groups in the same cage, the scientists observed a normalization of the microbiota. Since mice are coprophages (they eat their feces), they quickly share the same microbiotic strains. In this way, bacterial diversity increased, favoring good bacteria. As a result, healthy microbiota naturally prevails and the marker of liver disease decreased dramatically. “We see a clear effect of the microbiota on the risk of developing liver cancer, indicating its central role in transmitting disease risk from mother to child.”
A diet based on junk food encourages the proliferation of harmful bacteria and reduces bacterial diversity in the intestine. This altered microbiota passed on at birth leads to increased inflammation in the liver and, over time, leads to liver fibrosis and steatosis (an excessive presence of fat), which in turn increases the risk of developing liver cancer. Normalizing the microbiota also normalizes the risk of cancer.
These data come from a study with an animal model in a highly controlled environment, so to apply them in a clinical context it is necessary to previously confirm them in humans under real-life conditions. The first stage will consist of an epidemiological study based on large amounts of data obtained from monitoring mothers and their children over several decades. “However, we already know that it is possible to modify the microbiota, for example, through the use of probiotics. Highlighting the importance of the microbiome represents a first step towards new therapies,” the scientists conclude.
