The researchers published their findings in the International Journal of Molecular Sciences.

"Globally, the incidence and mortality rates of pancreatic cancer continue to rise, with a five-year survival rate of less than 10%," said co-author Narandalai Danshiitsoodol, associate professor in Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences. "Pancreatic cancer is highly invasive and prone to metastasis, showing significant resistance to existing treatments, such as surgery, radiotherapy and chemotherapy. As such, there is an urgent need to identify new and effective anticancer compounds, particularly those derived from medicinal plants."

Prior studies by other researchers indicated that stevia leaf extract demonstrated potential as an anticancer drug, but isolating and applying the specific bioactive components that protect against cancer cells has remained challenging, Danshiitsoodol said. However, fermenting with bacteria can structurally change the extract and produce bioactive metabolites, which are compounds that can impact living organisms.

"To enhance the pharmacological efficacy of natural plant extracts, microbial biotransformation has emerged as an effective strategy," said corresponding author Masanori Sugiyama, professor in the Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences. Sugiyama's lab has isolated and evaluated the health benefits of more than 1,300 lactic acid bacteria (LAB) strains from fruits, vegetables, flowers and medicinal plants. "In this study, we aimed to compare LAB-fermented and non-fermented extracts to identify key compounds that enhance bioactivity, ultimately contributing to the efficacy of herbal medicine in cancer prevention and therapy."

Specifically, the team fermented stevia leaf extract with plant-derived Lactobacillus plantarum SN13T strain (FSLE) and compared its effects on pancreatic cancer (PANC-1) cells in the lab, alongside non-cancerous human embryonic kidney cells HEK-293, to the effects of non-fermented stevia extract. The cells utilized in these experiments were acquired from established commercial cell lines.

"Our findings indicate that FSLE demonstrates significantly greater cytotoxicity than the non-fermented extract at equivalent concentrations, suggesting that the fermentation process enhances the bioactivity of the extract," Sugiyama said. "Notably, FSLE exhibited lower toxicity toward the HEK-293 cells, with minimal inhibition observed even at the highest concentration tested."

Additional analyses identified chlorogenic acid methyl ester (CAME) as the active anti-cancer compound. When fermented, the concentration of chlorogenic acid in the extract dropped six-fold, indicating a microbial transformation, according to Danshiitsoodol.

"This microbial transformation was likely due to specific enzymes in the bacteria strain used," Danshiitsoodol said. "Our data demonstrate that CAME exhibits stronger toxicity to cells and pro-apoptotic effects -- which encourage cell death -- on PANC-1 cells compared to chlorogenic acid alone."

Next, the researchers said they plan to study the effects in a mouse model to better understand the effectiveness of various dosages across a whole-body system.

"The present study has substantially enhanced our understanding of the mechanism of action of the Lactobacillus plantarum SN13T strain in the fermentation of herbal extracts, while also offering a valuable research perspective on the potential application of probiotics as natural anti-tumor agents," Danshiitsoodol said.

Other contributors include Rentao Zhang and Masafumi Noda, Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University; and Sayaka Yonezawa and Keishi Kanno, Department of General Internal Medicine, Hiroshima University Hospital.

By drawing on genetic data from over five million people, an international team of researchers has created a genetic test called a polygenic risk score (PGS) that predicts adulthood obesity already in early childhood. This finding could help to identify children and adolescents at higher genetic risk of developing obesity, who could benefit from targeted preventative strategies, such as lifestyle interventions, at a younger age.

"What makes the score so powerful is its ability to predict, before the age of five, whether a child is likely to develop obesity in adulthood, well before other risk factors start to shape their weight later in childhood. Intervening at this point can have a huge impact," says Assistant Professor Roelof Smit from the NNF Center for Basic Metabolic Research (CBMR) at the University of Copenhagen and lead author of the research published in Nature Medicine.

The study arises from the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, an international collaboration of human genetics researchers dedicated to studying the genetic architecture of anthropometric traits such as human height and body mass index. The research involved a collaboration with the consumer genetics and research company 23andMe, inc., and the contributions of more than 600 scientists from 500 institutions, globally.

Twice as effective at predicting obesity as the next best test

The subtle variations in our genomes can greatly impact our health. Thousands of genetic variants have been identified that increase our risk of obesity, for example, variants that act in the brain and influence our appetite. A PGS is like a calculator that combines the effects of the different risk variants that a person carries and provides an overall score.

To create their PGS, the scientists drew on the genetic data of more than five million people - the largest and most diverse genetic dataset ever. They then tested their new PGS for obesity on datasets of the physical and genetic characteristics of more than 500,000 people. They found that their new PGS was twice as effective as the previous best test at predicting a person's risk of developing obesity.

"This new polygenic score is a dramatic improvement in predictive power and a leap forward in the genetic prediction of obesity risk, which brings us much closer to clinically useful genetic testing," says Professor Ruth Loos from CBMR at the University of Copenhagen.

Genetics is not destiny

The scientists also investigated the relationship between a person's genetic risk of obesity and the impact of lifestyle weight loss interventions, such as diet and exercise. They discovered that people with a higher genetic risk of obesity were more responsive to interventions but also regained weight more quickly when the interventions ended.

However, the new PGS has its limitations. Despite drawing on the genomes of a broader, more globally representative population, it was far better at predicting obesity in people with European-like ancestry than in people with African ancestry.