Recently, the world has seen a surge in GLP-1RA medication for weight loss. Due to its relative high costs and side effects, it is important to better understand its mechanisms and relevant target groups. However, due to a lack of neuroimaging studies directly examining the effects of GLP-1RAs on different dimensions of uncontrolled eating in obesity, the specificity of this gut-brain axis in modulating non-homeostatic eating remains unclear. The first objective of the project therefore is to investigate the role of the gut-brain axis in uncontrolled eating, employing GLP-1signaling.
The second objective focuses on the influence of prebiotic fibers, such as inulin, which enhance satiety signaling via microbial short-chain fatty acid (SCFA) production. SCFA levels are typically reduced in ADHD. The influence of SCFAs on broader neurocognitive processes remains unclear. As prebiotics may provide a lifestyle-based strategy to prevent long-term pharmacological treatment, understanding their impact is particularly relevant as well.
Aarts: “Obesity rates are estimated to be 70% increased in ADHD, and differences in behavioural and emotional regulation play an important role in these higher rates. By using controlled pharmacological and nutritional interventions we can make more causal claims about the gut-brain axis in such higher-order regulatory processes involved in overeating.”
Societal impact and long-term potential
These insights will advance understanding of gut–brain interactions in higher cognition and help guide personalised prevention and treatment strategies for obesity. The project is highly relevant for people experiencing ADHD, or both, as well. In the Netherlands, around 3.2% of adults have ADHD, a group with elevated risks of obesity, insulin resistance, and type 2 diabetes. By identifying neurocognitive or metabolic differences between individuals with ADHD and BMI‑matched controls, the research may raise awareness of the metabolic challenges this group faces and help reduce stigma by showing that overeating can stem from neurobiological factors. Aarts: “Despite the known metabolic challenges in ADHD, no GLP-1 receptor agonist or prebiotic fiber studies have been performed in ADHD.”
In the longer term, the findings could guide future studies on chronic GLP‑1RA treatment in people with ADHD and obesity, helping determine whether the costs (and side-effects) of such medications are worthwhile for this group. While prebiotics alone are unlikely to induce major weight loss, they may support lifestyle interventions and could eventually serve as a preventive strategy or a lower‑risk alternative to long‑term medication. The work may also inspire targeted prebiotic studies in other groups with impulsive overeating or conditions linked to reduced SCFA levels, such as major depressive disorder, Parkinson’s disease, and Alzheimer’s disease.
