Linking Inflammatory Bowel Disease to the Hygiene Hypothesis.

Professor Simon M. Cutting, Dept. Biological Sciences, Royal Holloway University of London, Egham, Surrey, TW20 0EX.

Mr Philip Bearn MS FRCS, Dept of Colorectal Surgery, Ashford and St Peter’s NHS Foundation Trust, Guildford St, Chertsey Surrey KT16 0PZ. Honorary Senior Lecturer, Dept. Biological Sciences, Royal Holloway University of London, Egham, Surrey, TW20 0EX

Inflammatory bowel disease (IBD) broadly covers two inflammatory disorders of the GI-tract, ulcerative colitis and Crohn’s disease. Both cause diarrhoea, abdominal pain and weight loss. In severe cases surgical intervention may be required and in some the disease can be life-threatening. Diet and stress can aggravate the disease but the underlying causes are poorly understood. Immune malfunction is a likely cause and IBD is more common in families with a history of the disease.

What is known is that those at greatest risk of developing IBD are aged >30 years old, have a family history of IBD and are those who live in industrialised countries. Intriguingly rates of IBD have risen dramatically in the last 30 years posing a potentially significant financial burden on public health (Lancet Gastroenterol Hepatol. 2020; 5:17-30).

We are interested in understanding whether the Western lifestyle contributes to the rising rates of IBD? The Hygiene Hypothesis has been shown to play a role in the rise in allergic disorders over the last 50 years (Scudellari, PNAS, 2017, 114:1433-1436; Stiemsma et al, Immunotargets and Therapy, 2015, 4:143-157). In work being concluded in the Cutting lab we have shown that reduced exposure to environmental bacteria contributes to increased susceptibility to C. difficile infection witnessed in the USA and UK. We wonder then whether a sedentary lifestyle and poor diet coupled and a hyper-sanitised environment may also comprise a risk factor for IBD.

In this project you will first establish an animal (murine) model of IBD. Three models of IBD are known (Kiesler et al,, and working with skilled staff in the Cutting lab you will establish and validate the model. This will involve analysis of clinical signs, pathology as well as immunological assessment (e.g., FACS analysis of cytokines). Next, you will work on a large collection of environmental bacteria in the Cutting lab and rapidly screen these for potential in vitro activity to markers linked to IBD. Finally, you will evaluate bacteria or bacterial compounds for efficacy against IBD in your animal models.

During the 3 years, the successful candidate will have a contract of employment at ASPH NHS Foundation Trust with on call and clinical commitments at appropriate level. In addition endoscopy training can be provided around laboratory hours.