Abstract

The intestinal microbiota is resilient to change, with alterations in community composition and activity occurring as a result of exposure to various environmental factors and insults such as diet, drugs (antibiotics), infection, surgery and lifestyle. Such changes are being increasingly associated with a number of chronic diseases including those affecting organ systems such as the liver, musculoskeletal system and the brain. In particular, there is an increasing appreciation of the role gut microbes play in influencing liver function and central metabolism (the gut-microbiome-liver axis) and brain development and function (the gut-microbiome-brain axis), which may provide future treatments for serious degenerative diseases. Key observations linking the gut microbiome to mental health and chronic age-related neurodegenerative conditions include demonstrating a relationship between diet-related changes in the gut microbiota and altered cognitive flexibility, the ability of key microbial metabolites to influence the physiology of the blood brain barrier, and alterations in neurotransmitter production by gut bacteria. However, the majority of studies to date suffer from being correlative and providing few mechanistic insights. The expertise and track record in commensal microbiology and gut and liver physiology of QIB-based research leaders and in the enteric nervous (ENS) and endocrine (ES) systems provided by our HEI-based partners, provides the skills, expertise and experimental systems required to undertake the mechanistic studies necessary to define the relationship between gut microbes and other organ systems central to human health.
Theme 2 will address how changes in microbiota-host interactions in the gut impact on the functionality of other organ systems including the liver and the brain.
This theme involves a 360-participant longitudinal population based study of age-associated changes in the intestinal microbiome in elderly individuals stratified according to their risk of developing dementia