Inflammatory bowel disease in Australian Aboriginals and Black South Africans

Abstract

Australia has amongst the highest prevalence of inflammatory bowel disease (IBD) in the world. The disease has increased in frequency and effected between 75 302 and 92 571 people by 2018. The number is estimated to reach, close to 100 000 by 2022 (IBD National Action Plan). Indigenous Australians (IA) comprise around 5% of the overall Australian population. The Paediatric and Adolescent, IBD Database, showed that 13% that is 0.57% of 2300 children with IBD, come from families with one or two parents of Aboriginal descent. The low rate of IBD in indigenous people could be due to underreporting of IBD in this population but the significant impacts of IBD upon patients would seem to be unlikely to explain the huge differences. The 2006 point prevalence was 5.2 (per 100 000) for Aboriginal children and 47.9 (per 100 000) for nonAboriginal children. The Northern territories has a population of 244 300 (2015, Australian Bureau of Statistics) a third of whom are indigenous people. IBD is rarely found in IA. The prevalence in the Northern territory is 5/100 000 compared to 186/100 000 in the nonindigenous population. The incidence and characteristics of IBD is similar in the White South African population to that of populations of High Income Countries. The incidence of IBD is significantly lower in the Black population of South Africa while ulcerative colitis (UC) is uncommon and Crohn disease (CD) rare. The coloured (mixed race) populations have a high incidence of aggressive complicated IBD in which CD is more prevalent than UC. The aetiology of IBD is unknown but it is thought to occur in genetically predisposed individuals following an environmental trigger. Iyngkaran’s hypothesis suggests that IA have a distinctive gut microbial profile. He showed that gut microbial profiles of IA are highly abundant in Provotella species and lactic acid producing bacteria. The gut microbiota of IA are also enriched in enzymes that are involved in propionate production, a food source for colonocytes. The gut mucosa of IA would have a higher expression of anti-inflammatory cytokines. It was also shown that there was a trend in increase in the cytokine TSLP (thymic stromal lymphopoetin) 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 of IA and, have a distinctive gut microbial gut profile compared to Caucasian controls and patients with IBD’. Hookworm excretory/secretory products induce Interleukin-4 (IL-4) IL-10 CD4 T cell responses and suppress pathology in a mouse model of colitis. Evidence from human studies and mouse studies shows that infection with parasitic helminths has a suppressive effect on the pathogenesis of some inflammatory diseases. Ferreira et al. demonstrate that some of the suppressive effects of hookworms reside in their excretory/ secretory (ES) products of the hookworm Ancylostoma caninum (AcES) which suppress intestinal pathology, in a model of chemically induced colitis. This suppression was associated with potent induction of a type 2 cytokine response characterised by coexpression of IL-4 and IL-10by CD4 T cells, down regulation by proinflammatory cytokine expression in the draining lymph nodes and the colon, and recruitment of alternatively activated (M2) macrophages and eosinophils to the site of ES administration. Identification of specific parasite-derived molecules responsible for reducing pathology during chemically induced colitis could lead to the development of novel therapeutics for the treatment of human IBD. Protein digestion and heat denaturation of AcES resulted in impaired induction of CD4 IL-4 IL10 cell responses and diminished ability to suppress colitis, indicating that protein component(s) are responsible for some of the immunosuppressive effects of AcES. In Soweto, Mitchell et al. demonstrated a difference in the T cell response to Helicobacter pylori in symptomatic subjects as compared with symptomatic subjects from Australia and Germany. Soweto subjects were shown to mount a T2-dominant H. pylori-specific immune response while subjects from Australia and Germany mounted a T1-dominant response. This study indicated for the first time, that the host immune response to H. pylori infection in the Sowetan population differed to that in developed countries. While the effect of concurrent helminthic infection on the immune response to H. pylori in Sowetan subjects was not directly investigated, determination of total serum immunoglobulin E (IgE) responses showed that 70% of symptomatic children and 58% of symptomatic adults to