Project No. 2364
STANDARD PROJECT
Primary Supervisor
Prof Jessica Teeling – University of Southampton
Co-Supervisor(s)
Dr Murphy Wan – University of Portsmouth
Prof Jerome Swinny – University of Portsmouth
Summary
Rationale: Gut bacteria are an essential part of the mammalian body.
They help digest our food, control our metabolism and they keep our immune system healthy. Changes in the gut microbiome can greatly influence our behaviour and may even cause depression and age-related cognitive decline [1]. Gut bacteria control brain function through a complex bidirectional communication network between the host and the bacteria, called the gut-brain axis, promoting various signalling pathways that influence brain function. We now know that inflammatory bowel disease or gut infections increase the risk of depression and dementia [2, 3], but the molecular mechanisms leading to brain dysfunction requires further study. One theory is an altered dopamine metabolism. Dopamine is produced by bacteria and the host and has an overall protective role by promoting the relaxation of the gut and dampening the immune system. Upon intestinal inflammation, dopamine levels decrease, which stimulates the immune system to produce inflammatory cytokines [4]. We hypothesize that restoring dopamine function following infections in the gut, may prevent or treat depression and/or dementia.
Approaches to be used: This studentship will use an experimental mouse model of gut inflammation. Behavioural tests will be used to measure brain function and tissue and faecal samples will be collected to characterize levels of inflammation in the gut and brain, and the composition and function of the gut microbiome. We will use metagenomic and transcriptomics technology, and computational modelling to link bacteria and immune markers to brain dysfunction. Dopamine metabolism will be investigated using mass spectrometry, histology and pharmacological intervention studies.
Areas of impact: This studentship will increase our basic understanding of the biological mechanisms underpinning brain dysfunction associated with the gut microbiome. Identifying immune signalling pathways, including those mediated by dopamine, will provide insight into bacteria-host interactions, and contribute to novel strategies to prevent or treat depression and dementia
references
1. Dinan, T.G. and J.F. Cryan, Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. J Physiol, 2017. 595(2): p. 489-503.
2. Zhang, B., et al., Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study. Gut, 2021. 70(1): p. 85-91.
3. Bisgaard, T.H., et al., Depression and anxiety in inflammatory bowel disease: epidemiology, mechanisms and treatment. Nat Rev Gastroenterol Hepatol, 2022.
4. Pacheco, R., F. Contreras, and M. Zouali, The dopaminergic system in autoimmune diseases. Front Immunol, 2014. 5: p. 117.