Project R-16425

Microbiota-gut-brain axis signaling in neurodevelopmental disorders: what the brain needs from the gut? (Research)

The pathophysiological mechanisms underlying gastrointestinal dysfunction, and how these relate to behavioural changes in patients with neurodevelopmental disorders (NDDs), are incompletely understood. In a rodent model for NDDs, we found that abnormal gut function and behaviour are associated with alterations in intestinal microbiota, and that fecal microbiota transfer (FMT) has the potential to rescue cognitive impairment. The studies here, performed in controlled laboratory settings, will investigate how NDD modelling affects enteric nervous system structure and function, aiming to elucidate the reasons for gut symptom generation in NDD patients. In addition, we will investigate the impact of FMT on brain function and behaviour. This will allow us to gain precise mechanistic insight into the cellular and molecular effects of FMT on the brain and on its output. Collectively, our experiments will enhance understanding of both the peripheral and central pathophysiology implicated in psychiatric disorders, and as such, will help to design novel therapeutic strategies for NDD patients. Moreover, our microbiome analyses and FMT interventions promise to uncover microbiota signalling routes that can be targeted with pre- and/or probiotic approaches, improving the lives of millions of humans suffering from NDDs such as schizophrenia, major depression and autism spectrum disorder.

23 October 2025 - 22 April 2027