INTERSECTION BETWEEN CHRONIC AND INFECTIOUS DISEASE IN TROPICAL AUSTRALIA
Indigenous communities in northern Australia represent a relatively unique public health problem, where incidence of type 2 diabetes mellitus (T2DM) and infectious diseases approaches epidemic-type levels, hence more research is needed to identify the potential biological and lifestyle factors contributing to these epidemics.
A major project led by Professor Robyn McDermott, Dr Paul Giacomin, Dr Matt Field and Professor Alex Loukas has investigated associations between parasitic helminth infections and the prevalence of metabolic diseases such as T2DM and Metabolic Syndrome (MetS) in people living in remote Aboriginal communities of Northern Australia. Emerging evidence from the literature suggests that dysregulated metabolism may be a contributor to increased susceptibility to infections.
The research group’s hypothesis is based on recent published findings about an Indigenous community in the Kimberley, in north Western Australia, where the presence of worm infections may protect against metabolic diseases by influencing the nature of immune responses. The group also hypothesised that the development of metabolic disorders is associated with alterations in the balance of good and bad bacteria in the intestine (the microbiota). The project involves parallel experimental animal model studies to define the protective role of worms and the microbiota in more detail and potentially identify the worm-derived molecules that might have an immune or metabolic regulatory effect.
The human study has incorporated the annual young people’s health check in the Yarrabah community south of Cairns. As part of the study the research group collected demographic and medical history data, as well as biological material for use in exploratory studies. This includes serum and blood (for inflammatory and metabolic markers, as well as for detecting co-infections with bacteria, viruses or parasites), faeces and nasopharyngeal swabs (for microbiota analysis). The study involved 132 individuals from the community, and the serum, blood and demographic data have been received and entered into a database for statistical analysis. Tissue processing and gene sequencing for the microbiota analyses are in progress in collaboration with expert researchers from the South Australian Health and Medical Research Institute (SAHMRI).
The primary outcome of this research is to define whether the presence of specific immune pathways, or bacterial species, is associated with protection against metabolic disease, or conversely, whether some immune parameters or bacteria are associated with a higher instance of metabolic diseases. While the data is still being analysed, the research group is undertaking a second young person’s health check on Thursday and Mer Islands in the Torres Strait with a similar cohort, to see if the association between worms, bacteria and metabolic disease are conserved across distinct communities. The data derived from these ambitious studies will provide a unique and powerful resource for understanding the potential contributors for metabolic disease in northern Australian Aboriginal and Torres Strait Islander communities.
In parallel with these human studies, PhD student Zainab Agha has established an animal (murine) model of T2DM in the laboratory at AITHM Cairns. The project involves testing different species of parasitic worm to determine if infection can influence the progression of T2DM, and assess whether protection against diabetes involves a specific immune or microbiota pathway. Ms Agha has shown that two distinct species of worm, a hookworm like parasite and a whipworm-like parasite, both appear to reduce the severity of T2DM. These findings are consistent with previously published research and provides further evidence of the protective effects of worms, and the immune responses they elicit, in metabolic disease.
In addition to the live worm infection experiments, Ms Agha has also used the animal model to determine if specific molecules released by the worms have a similar protective effect. This novel research could potentially result in the identification of a therapeutic medication for metabolic disease, which would be far more acceptable and marketable than being infected with live worms. AITHM researchers have already conducted a preliminary experiment with a hookworm derived protein, and the data is currently being analysed. The research laboratory at AITHM Cairns is a world leader in identifying worm secretion molecules for inflammatory diseases, hence the team will have first access to a broadening portfolio of candidate molecules to test in this system.