Thesis defense Anouk Tengeler (Donders series 464)

21 December 2020 

Promotors: prof. dr. A. Kiliaan, prof. dr. B. Franke, prof. dr. L. Kozicz
Co-promotor: dr. M. Wiesmann

Mind the microbes. The impact of microbiota and diet on brain structure and function in mouse models

The gut micro-organisms (gut microbiota) are important for gut health and the brain. For example, disturbances in the gut microbiota are linked to neuropsychiatric conditions such as attention deficit hyperactivity disorder (ADHD). However, how changes in the intestinal microbiota affect brain structure and function is poorly understood.

In this thesis, we studied the impact of the gut microbiota on the mouse brain. We found that mice that received microbiota from individuals with ADHD showed reduced gray and white matter structural integrity in several brain regions.

The gut microbiota produces short chain fatty acids (SCFA) such as propionic acid. Using neuroimaging, we found that propionic acid reverted high-fat diet-induced effects in functional connectivity and microstructural gray and white matter integrity to healthy control levels.

The gut microbiota and SCFA can also affect the function of mitochondria. Dysfunctional mitochondria are associated with several neurodevelopmental disorders and psychiatric diseases, including ADHD and autism spectrum disorder (ASD). We targeted the mitochondria with the antibiotic chloramphenicol that is known to affect mitochondrial function. We found that chloramphenicol reduced mitochondrial activity in the brain and increased compulsive-like behavior possibly via the gut microbiota.

The findings described in this thesis may contribute to a better understanding of the impact of the gut microbiota on the brain.