MOCIA-WP3: Molecular mechanisms in the gut and the brain affected by lifestyle changes

As people worldwide are living longer, the prevalence of age-related cognitive diseases increases likewise. Alzheimer’s disease (AD) -the most common form of dementia- proves challenging to treat since the irreversible process of neurodegeneration starts decades before the clinical symptoms are manifested. Therefore, strategies to prevent the onset of AD are urgently needed. Emerging evidence suggests that lifestyle (i.e., diet, physical activity, etc) is a modifiable risk factor for AD that might affect cognitive function via the gut-brain (GB) axis, most notably by gut-derived microbial metabolites (GM) and food-related components (FC). However, there is limited understanding of the underlying molecular mechanisms and a myriad of GM and FC with potential brain-related effects remain to be explored. To examine the possible mechanistic links of previously suggested and new GM and FC, via the gut, on neuronal characteristics, we will focus on recapitulating the native GB axis by developing a novel gut-immune-blood-brain barrier-brain (GIBB) in vitro model. Additionally, our research will be connected to the HELI study within the Dutch research consortium MOCIA. The HELI study is a multi-domain lifestyle intervention study in older individuals at risk of cognitive decline, which is expected to result in new leads to GM and FC that will be examined by our GIBB in vitro model, together with GM and FC of interest derived from literature. In conclusion, we envision that by gaining insight into the GM- and FC-derived effects on brain health, we will shed light on the development of novel treatments for AD.