Bacterial species in the gut microbiome of Inflammatory Bowel Disease (IBD) sufferers is enabling researchers in Brisbane, Australia, to develop new diagnostics and therapeutics for the condition...
A small laboratory in the Translational Research Institute (TRI) housed within Brisbane’s Princess Alexandra Hospital’s Campus, may hold the key to future gut microbiome-derived therapeutics for IBD sufferers.
Australia has one of the highest incidences of IBD worldwide, affecting 1 in every 250 Australians (equating to over 80,000 people), with 14 new cases diagnosed every day. IBD is incurable and associated with significant comorbidities. Currently, there remains an unmet clinical need for safe and effective therapeutics to improve patient quality of life, maintain remission for longer periods, reduce surgery rates and curtail individual and public health costs.
IBD is a chronic disease characterised by episodic inflammation of the gut, meaning that the bacteria living inside the gut microbiome could play a significant role in research and clinical interventions in the future. Inspired by the emerging evidence of the role the microbiome plays in IBD, Brisbane-based Microba, launched an IBD Research and Development (R&D) program in 2019 to tackle IBD by mining the gut microbiome for novel biotherapeutics.
The team is led by Dr Páraic Ó Cuív – Lead, Live Biotherapeutics and Associate Professor Lutz Krause – Head of Data-Mining and Artificial Intelligence. They head the Ventures team, which utilises the company’s world-leading DNA MAP™ (Metagenomic Analysis Platform) sequencing platform to develop diagnostics and therapeutics for IBD sufferers. Microba are also building an extensive genomic database which is used by the Ventures team to identify common species found in the gut microbiome of those diagnosed with IBD.
To date, the team have identified over 20 bacterial species commonly found in healthy individuals but rarely detected in Crohn’s and Ulcerative Colitis. The aim will be to translate these discoveries into effective therapeutics. According to Krause, big data approaches are being used to identify the microbes with therapeutic potential among Microba’s more than 6,000 sample database of gut microbiome samples.
“We are currently performing proof of concept studies with the aim of translating the discovered leads for IBD treatment into clinic,” he explains. “Our database is rapidly growing from customers who opt-in to de-identified use of their data, and this information is invaluable. It allows us to study host-microbe interactions and identify gut bacteria involved in diseases such as IBD. We use artificial intelligence to mine this data and rationally identify candidate therapeutics in a data-driven approach.”
There are obvious differences, Krause says, between the gut microbiomes of those with IBD and those without. “In active IBD samples, we see increased abundance of pro-inflammatory bacteria such as Ruminococcus gnavus and reduced abundance of anti-inflammatory bacteria like Faecalibacterium prausnitzii.”
After this data is mined and species are identified as being at increased or decreased levels in IBD patients, research moves across to the laboratory. This is where expert in gut microbiology, Dr Páraic Ó Cuív steps in to isolate and investigate these species. His team have already cultured several of these important gut bacteria, including isolates that were previously uncultured and others widely considered to be resistant to laboratory cultivation.
Ó Cuív’s team are demonstrating that some of the species have the ability to suppress key inflammatory pathways that underly IBD. “Now that we have more information and have begun isolating and investigating key species in IBD, we are progressing towards pre-clinical studies and aiming to develop these bacteria into novel therapeutics,” he says. “We do this under the premise that re-introduction of these bacteria into IBD patients will alleviate active disease, increase disease free remission periods and prevent progression of disease to more severe states.”
The duo say that the ultimate goal of the IBD program is to improve the quality of life and the health outcomes of IBD patients. Through the development of effective and well-tolerated gut microbiome-derived therapeutics and precision medicine tools, the aim is to personalise patient treatment.
What’s next for the Ventures team? Ó Cuív and Krause explain that their work will continue toward diagnostics and therapeutics, no simple task. This will include work from the Ventures team, as well as across the business. The Ventures team also runs the microbiome profile data through advanced machine learning algorithms to determine if there is a strong enough signal that could be developed into a diagnostic. Form there, a clinical cohort of medically diagnosed individuals will be used to validate and further refine the diagnostic tool.
According to Ó Cuív, “the aim of this project is that we see our therapeutics assisting IBD patients in maintaining disease-free remission over long periods with little toxicity or side effects.”
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