MCI-BIOME: Relationship between socioeconomic status and the gut microbiome as a risk of dementia

by A. Leist, P. Wilmes and R. Krüger

Dementia is one of the greatest scientific, medical and socioeconomic challenges of our times, as it affects more than 46 million people worldwide, with incidence numbers projected to double within the next 20 years.

There is no medical treatment to prevent, halt or reverse the progression of neurodegeneration underlying dementia. Educational gradients in the onset and progression of dementia on top of the contribution of innate cognitive abilities suggest a role of socioeconomic factors in the development of this syndrome. At the same time, recent evidence for dysregulation of the gut microbiome in patients with dementia indicates that the microbiome may play a role in modulating brain function linked to neurodegeneration and suggests the presence of a diet-microbiome-gut-brain axis. Interestingly, socioeconomic factors can also influence food choices, which in turn may impact the microbiome composition. However, the underlying mechanisms of how the microbiome might contribute to neurodegeneration remain unclear, and little is known on how the composition of the gut microbiome is modulated by environmental and socioeconomic factors. The proposed Audacity project, MCI-BIOME, aims to further our knowledge of the relationship between socioeconomic factors, diet, and changes in the gut microbiome in relation to Mild Cognitive Impairment (MCI). MCI is considered a prodromal stage of dementia and represents a transition state between normal cognitive ageing and dementia. We focus on MCI as, at this stage, identification of individuals at highest risk to progress towards dementia for potential preventive interventions would be most relevant. The project relies on a unique interdisciplinary team composed of clinical experts in neurodegeneration, specialists in socioeconomic research, and specialists in high-resolution microbiome characterisation (integrated multi-omics) and big data analytics. Samples and data to be collected include stool samples of 60 MCI patients of the Programme Démence Prévention (pdp) and 60 healthy controls (in terms of cognition) as well as relevant information on demographic, socioeconomic, and diet-related variables. The main objectives of the project are

1. to develop a novel interdisciplinary framework at the interface between social sciences, neurology and microbial ecology to open new research horizons and to strengthen the University's excellent research profile,
2. to develop a multivariate microbiome biomarker model for MCI based on integrated multi-omic data by comparing MCI patients to a group of healthy controls,
3. to explore how microbiome characteristics differ between sub-groups defined by socioeconomic factors including education and diet,
4. to build a research infrastructure that will be vital for acquiring high-level follow-up funding for future projects including the analysis of progression of MCI in relation to microbiome shifts and the validation of the microbiome biomarker model in the large Luxembourg-based cohort of the National Centre for Excellence in Research on Parkinson Disease (NCER-PD) including individuals with and without MCI and dementia.