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Exploring how host-fungal dynamics in the human gut drive severe forms of inflammatory bowel disease (IBD) in South Asian patients

Code: BC-DTP_2026_42

Title: Exploring how host-fungal dynamics in the human gut drive severe forms of inflammatory bowel disease (IBD) in South Asian patients

Primary Supervisor: Neil McCarthy

Email: n.e.mccarthy@qmul.ac.uk

Institute: Blizard Institute

Secondary Supervisor: Kieran Bates

Email: k.bates@qmul.ac.uk

Institute: Blizard Institute

Lay Summary:

Human intestine contains many different types of microbe, including various species of Candida fungus. While generally harmless in oval yeast form, changes in local conditions can stimulate Candida to switch to a pathogenic lifestyle, growing toxin-producing filaments that damage the intestinal barrier and resident immune cells. Although fungal injury to gut tissue was recently linked with inflammatory bowel disease (IBD) severity in humans, it remains unknown whether invasive Candidas also promote more aggressive forms of disease commonly observed in South Asian (SA) patients. Indeed, SA people are more frequently colonised with a Candida species called tropicalis, which produces higher potency toxins than the albicans species that dominates in White Europeans (WE). At present, we don’t understand the environmental factors that determine which Candida species dominate the human gut, or favour yeast versus pathogenic lifestyle. We will therefore perform competition experiments using gut biopsy-derived Candidas from healthy individuals and patients with IBD, comparing species and strains from both SA and WE donors. By changing nutrient sources and oxygen levels, we will identify factors that favour different Candida species in SA versus WE intestine, as well as those that promote or limit yeast switching to tissue-invasive behaviour. We will then test which nutrient factors can reduce fungal injury in our established 3D-printed gut tissue model containing immune cells from SA or WE donors. This project will shed important new light on the gut conditions that determine fungal species dominance, extent of mucosal injury, and promote aggressive disease in SA patients with IBD. 

Aims:

  1. Identify metabolic determinants of yeast versus hyphal lifestyle in gut-adapted Candidas.
  2. Determine how host factors influence nutrient requirements of gut-adapted Candida in vitro.
  3. Assess how variable nutrient supply impacts fungal invasion of 3D-printed gut models ‘in vivo’.

References:

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