Professor Bettina Platt - University of Aberdeen School of Medicine, Medical Sciences & Nutrition - firstname.lastname@example.org
Professor Gernot Riedel - University of Aberdeen School of Medicine, Medical Sciences & Nutrition - email@example.com
Rationale: A link between gut and brain health has recently attracted significant attention, and led to the gut-brain-axis hypothesis of a range of disorders. However, human and animal data suggest that there is considerable heterogeneity of the gut microbiome, both in healthy controls, but even more so in ageing and under conditions of compromised diets. This heterogeneity needs to be studied and understood, and healthy vs dysbiotic gut microbiome profiles better defined to advance our systems understanding of healthy ageing per se, but specifically probing for connections with brain function and malfunction.
Aims and Hypothesis:
The principal aim of this project is to identify robust biomarkers of gut health in mice and rats, that are also indicative of brain function. We predict alterations of the gut microbiome with age and dietary alterations will correlate with physiological hallmarks, such as inflammation and blood-brain barrier leakiness. Skewing the composition of the gut microbiome with chronic antibiotic treatment may exacerbate age-relevant changes of both gut and brain. The impact of other factors such as sex, activity, environmental enrichment, food intake, sleep and microbiome treatments will also be assessed.
We seek to address this by a systematic analysis of i) two different mouse lines (C57 and NMRI) as well as Sprague Dawley rats; ii) monitor ageing by studying different age groups (4, 8, 12 and 24 months) to observe associations between changes in brain and gut microbial profiles; iii) exploration of treatment options in terms of antibiotics (acute and chronic, to create microbiome dysbiosis), dietary deficiencies (e.g. low fibre, high fat or carbohydrates)and targeted microbiome interventions.
Proposed endpoints include analysis of general physiological parameters over time (body weight and temperature, food & water intake, motor activity & sleep, at the IMS, Aberdeen University), gut and microbiome analyses (at 4DPharma, metabolomics, faeces and gut tissue samples) based on 16S microbiome sequencing and inflammatory profiling (qPCR, histology, flow cytometry), as well as CNS phenotypes (Aberdeen University: inflammation, BBB integrity, synaptic markers), using protein analyses, immunohistochemistry and microscopy as well as single-cell RNAseq. Data analysis will be supported by bioinformatic specialists at 4DPharma and AU.
A comparison between strains and species and confounding factors such as age, sex and diet, as well as correlative assessments of brain and gut profiling, will lead to a better understanding of associations between health-relevant factors and biomarkers, and identify key parameters for future research.