Gut microbes in health and disease
The overarching objective of our research is to understand how a healthy gut is established and maintained throughout life. We want to understand how this healthy state is altered in diseases of the gastrointestinal tract (e.g. IBD), as well as diseases elsewhere in the body (e.g. ME/CFS) including other organ systems such as the brain, where we are exploring the gut-brain axis and dementia.
We are carrying out fundamental studies to better understand the microbiome by identifying pathways used for crosstalk between microbes and the host, the transport of bacterial products to host cells via vesicles. We aim to use this system to develop and deploy bacteria-generated microvesicles for mucosal drug delivery. We are also, in collaboration with Alastair Watson at the University of East Anglia (UEA), studying interactions between the microbiota and mucosal immune cells to understand how a healthy microbiome is established that can still mount a defence against food-borne pathogens.
We work collaboratively with academics and clinicians, both locally on the Norwich Research Park and more widely, to try to understand the causes of complex diseases linked to changes in intestinal homeostasis. We aim to unpick the complicated interactions between the microbiome, the cells lining the gut, the immune system and host genome, to understand where these have altered in disease, and suggest new therapies based on these observations.
We are currently studying IBD with colleagues at UEA to establish the role autophagy plays in intestinal epithelial cell homeostasis and, with Tamas Korcmaros, to understand the role of the microbiome and host genome in IBD diagnosis and prognosis, with a view to developing personalised therapies.
In collaboration with colleagues at Imperial College London, we’re investigating the nature of immune cell (auto)reactivity to members of the intestinal microbiota in IBD patients and in those with ME. Further ME research is characterising the intestinal virome and the role it plays in microbial dysbiosis as a possible cause of this debilitating condition.
We have a strong interest in understanding how the microbiota affects organ systems beyond the gut, including the brain, and we are working with the University of Hull to develop technologies to investigate the gut-brain axis and to understand how the intestinal microbiota influences cells of the central nervous system. We are also, in collaboration with UEA, studying the link between the ageing microbiome and declining mental health and the development of dementia.
The group has expertise in cellular and molecular commensal microbiology particularly working with Bacteroides species. This includes imaging of bacteria-host cell interactions and the uptake and fate of bacterial products on host (epithelial, immune, endocrine, neuronal) cell signaling and physiology.
We also use genomics, metabolomics and other nucleic acid and metabolite-based ‘omics techniques, and associated bioinformatics, in analysing the structure and function of the microbiome. We use a number of model systems including in vitro bacterial, viral and mammalian (animal and human) cell and organ (co-)culture systems and in vivo model systems (gnotobiotics).
The group also carries out human studies in the community and in primary and secondary care relating to obesity, ME/CFS, and dementia.
Click to download poster: The Nature and Outcome of Microbe-host Interactions in the Mammalian GI-tract