Medicine (RMH) - Theses
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ItemIndigenous Australians have a distinctive gut microbial profile compared to Caucasian controls and patients with inflammatory bowel disease( 2015)The aetiology of inflammatory bowel disease (IBD) is yet unknown but it is thought to occur in a genetically predisposed individual following an environmental trigger. The incidence of IBD has risen rapidly in industrialised nations but remains low in developing countries. In Canada, the incidence of IBD is high in their urban population but extremely low in their Indigenous populations. This has led to the “hygiene hypothesis”, which postulates that a reduced exposure to antigens due to urbanisation may lead to an increase in immune mediated diseases such as IBD. Many studies have shown that patients with active IBD have changes in gut microbiota or “dysbiosis”. My first hypothesis was that IBD is rare in Indigenous Australians (IA). I confirmed this by setting up an IBD database at the Royal Darwin Hospital in the Northern Territory (NT) and by interrogating the hospital records from 2007-2014. The NT has a large Indigenous population with a third of its population being Indigenous. The IBD database revealed that the prevalence of IBD in Indigenous Australians in the NT is 5/100,000 compared to 186/100,000 in the non- Indigenous population. My second hypothesis was that IA have a distinct gut microbial profile that may account for their low incidence of IBD. I utilised 16S amplicon based techniques to study gut microbial profiles in IA, Caucasian controls and IBD patients. Whilst it is difficult to prove causality, I demonstrated that gut microbial profiles of IA are highly abundant in Prevotella sp and lactic acid producing bacteria, and are different from Caucasian controls and IBD patients. The gut microbiota of IA are also enriched in enzymes that are involved in propionate production, a food source for colonocytes. My third hypothesis was that the gut mucosa of IA would have a higher expression of anti-inflammatory cytokines. I showed, through quantitative real-time PCR, that there was a trend in increased expression of Thymic Stromal Lymphopoeitin (TSLP) in IA. TSLP is a cytokine that is involved in preventing helminthic infections and has been shown in mouse models to confer some protection to IBD. Patients with IBD showed a typical pro-inflammatory cytokine expression pattern. My results demonstrate that IA, who have a low incidence of IBD, have a distinctive gut microbial profile and a trend in increase of the cytokine TSLP. This may be directly related to their traditional lifestyle. Testing their gut microbial profiles in mouse models of colitis may reveal if their gut microbiota are truly protective against IBD.