University of Toronto researchers are calling for more study of obesity, gut bacteria and metabolic conditions that arise in childhood and adolescence, with an eye to curbing the global rise of type 2 diabetes.
The team says a better understanding of how genetic and environmental factors that lead to obesity also alter the make-up and function of the gut microbiota — the community of microbes living in the gut — will yield better interventions for children most at risk for youth-onset diabetes.
"Metabolic diseases in childhood, including type 2 diabetes, are modifiable and in some cases preventable — so it's really important to understand the best ways to identify children who are at greater risk for metabolic dysfunction. Once we know that, we can tailor earlier and more personalized interventions," says Quin Xie, a research fellow in the lab of Jayne Danska, professor at U of T's Temerty Faculty of Medicine and senior scientist at The Hospital for Sick Children .
The research team — which includes Jill Hamilton, a professor of paediatrics and a researcher at U of T's Joannah & Brian Lawson Centre for Child Nutrition, who is also a pediatric endocrinologist and senior associate scientist at SickKids — published their call in a recent review paper in Cell Reports Medicine.
Over half a billion people live with diabetes globally, and rates of youth-onset diabetes have risen sharply since 2000. Obesity is a key driver of diabetes, and child obesity rates are up about 250 per cent over the last three decades. The rise in childhood obesity is particularly large in low- and middle-income countries.
"We know that obesity is associated with changes in the gut microbiota, and drugs to treat metabolic disease interact with and are affected by the gut microbiota," says Xie. "As we learn more about how the gut microbiota is involved in metabolism and obesity, we can account for differences in the microbiota when designing prevention and treatment strategies and better predict who will benefit from certain therapies."
For example, Xie and her colleagues, including Danska and Hamilton, showed in another study that children with obesity who had a higher biomass of gut bacteria also had a more diverse and healthier microbiome profile — and fewer bacteria associated with inflammation. The study, published last year in the journal Diabetes , found that lower biomass in the gut microbiota increases the risk of metabolic dysregulation in children, particularly boys, before type 2 diabetes develops.
"In our adolescent cohort, lower gut bacterial biomass tracked with signals of inflammation and insulin resistance, which suggests that integrating microbiome‑informed measures with routine clinical data could help us identify higher‑risk youth earlier and personalize interventions," says Hamilton. "As this science advances, I expect we'll increasingly tailor therapies — whether dietary, pharmacologic or microbiome‑targeted — based on factors that could include a child's microbial profile."
The authors also note that gut microbiota is established within the first few years of life, and that early environmental changes can steer microbiota toward a more resilient community to reduce metabolic risk. Xie says that reading about research on these environmental factors increased her awareness of the social dimension of health in diabetes development.
"Environmental risks for diabetes are clearly connected to social determinants of health," says Xie. "Some of these factors are structural and outside an individual's control, but others, such as physical activity and diet, are modifiable."
Xie first became interested in the gut microbiota during her undergraduate studies in pathobiology, statistics and math at U of T. She later pursued a PhD on gut bacteria, the immune system and diabetes under the supervision of Danska.
"Quin displays deep critical thinking, remarkable independence, and highly skilled team-working abilities. She is an outstanding intellect and engaged colleague within our lab and with our collaborators at SickKids and other institutions," Danska says. "She is an emerging leader in her field, among the very top students that I have mentored during my academic career."
In the next few months, Xie will start a Novo-Nordisk fellowship at Oxford University in the U.K., with a focus on the effects of obesity on the brain. The fellowship will enable her to pursue her interest in weight loss medications that act on the brain to reduce appetite. She will use large datasets to look for genetic variants associated with changes in the brain and increased metabolic risk in people with obesity.
Xie says her time at U of T has prepared her well to undertake the next stage of her research career. "All my scientific training has been at U of T, and I've grown a lot during my PhD thanks to my supervisor and colleagues," she says. "I feel really lucky to have trained in the Danska lab, and in a broader research environment with strong links to clinical care."
