The gut microbiome and inflammaging

Dementia and early onset neurological disease has overtaken respiratory infectious disease as a leading cause of death in the UK and is a priority for UK and international government health departments. A distinctive feature of ageing is immune senescence and the functional decline of the immune system, which is associated with low grade chronic inflammation (inflammaging) that together compromises host defences and the ability to mount effective responses to persistent infections in the elderly. The gut is the largest immune organ in the body and age-related changes in the makeup and function of resident gut microbes (the microbiota) have been linked with immune senescence and increased susceptibility to infection. However, it is not known if microbial dysbiosis and age-associated alterations in the intestinal microbiota are a cause of immune senescence.
The project aims to address this question by investigating in a primate model of human ageing how age-related changes in the intestinal microbiota contribute to immune senescence and chronic inflammaging in old age, by evaluating microbiome targeted interventions to redress immune senescence.
(1) Determining how the intestinal microbiome changes with age in young, ageing and elderly animals using whole genome metagenomic sequencing and immune profiling and function studies to develop a comprehensive picture of the dynamics of the microbiome and immune function during healthy ageing.
(2) Evaluating microbiota-targeted therapy including microbiota replacement to slow or halt the progression of immune senescence.