Leading the way in Inflammatory Bowel Disease


First published in the DAA Gastro IG Newsletter:
  April 2020

Dietitians would be very familiar with the prevalence of Inflammatory Bowel Disease (IBD) in Australia. IBD is a chronic disease that is characterised by episodic inflammation of the gut.

Australia has one of the highest incidences of IBD worldwide, affecting 1 in every 250 Australians[1] (equating to over 80,000 people), with 14 new cases diagnosed every day.

IBD is incurable and associated with significant comorbidities. There is a critical need for safe and effective therapeutics to improve patient quality of life, maintain remission over long periods, reduce surgery and curtail the individual and public health costs.

Inspired by the emerging evidence of the role the microbiome plays in IBD, a leading Australian company that analyses gut microbiome has launched an IBD Research and Development (R&D) program in 2019 to tackle IBD by mining the gut microbiome for novel biotherapeutics.

Heading up the team is Dr Páraic Ó Cuív – Lead, Live Biotherapeutics – and Associate Professor Lutz Krause – Head of Data-Mining and Artificial Intelligence.The company’s world-leading DNA sequencing platform affords them a great opportunity to contribute to diagnostics and therapeutics for IBD sufferers. Establishing the R&D program allowed the company to capitalise on the advanced technologies in use and their rapidly growing genomic database.

Microbiome expert, Professor Gene Tyson leads microbiome research at the Queensland University of Technology. He said that the gut microbiome holds significant promise for the identification of novel therapeutics to treat inflammatory bowel disease.

 


“Using advanced DNA sequencing approach, we are able to discover novel species which we believe may play protective or causative roles in IBD,” he said.


 

Thus far, the team has identified 20 bacterial species commonly found in healthy individuals but rarely detected in Crohn’s and/or Ulcerative Colitis. They are now performing pre-clinical studies to translate these discoveries into effective therapeutics.

Associate Professor Krause said that identifying microbes with therapeutic potential among the companies extensive database of 6000+ gut microbiomes required big data approaches and they were performing proof of concept studies with the aim of translating the discovered leads for IBD treatment into the clinic.

“Our cohort of more than 6,000 customer samples is an invaluable resource for studying host microbe interactions and for identifying gut bacteria involved in disease.

Using artificial intelligence, we mine this data to rationally identify candidate therapeutics in a data driven approach,” A. Prof Krause explained.

When asked how alterations noted in the gut microbiome of those with IBD contribute to inflammation or symptoms, Krause said that the team do see an altered gut microbiome when individuals are having a flare up with their IBD in comparison to those in remission from active IBD.

“However, increased abundance of pro-inflammatory bacteria like Ruminococcus gnavus and reduced abundance of bacteria with anti-inflammatory properties like Faecalibacterium prausnitzii in are seen in active IBD.”

Once key bacteria are identified the next step is to isolate and investigate them which is where Dr Paraic Ó Cuív, an expert in gut microbiology, comes in. To date, his team have cultured several of these gut bacteria, including isolates that were previously uncultured and others widely considered to be resistant to laboratory cultivation.

“We have demonstrated that some of these species have the ability to suppress key inflammatory pathways that underly the development of IBD,” he said. “We are now developing these bacteria into novel therapeutics under the premise that reintroduction of these bacteria into IBD patients will alleviate active disease, increase disease free remission periods and prevent progression of disease to more severe states.”

How will the duo see diet playing a role in developing therapeutics? They do concur that one of the common ways to alter the gut microbiome is through diet, and some dietary-based interventions have been recognised to assist IBD sufferers.

“It has been recognised for many years that dietary-based interventions for Crohn’s disease, Exclusive Enteral Nutrition (EEN), are comparable to corticosteroids in terms of remission rates but are superior in reversing the nutritional defects associated with chronic inflammation and inducing mucosal healing. In particular, mucosal healing is prognostic of long-term health outcomes,” Dr. Ó Cuív explained.

“However, long term compliance with EEN based diets is poor and there is no similar treatment for ulcerative colitis.”

As part of their gut microbiome analysis products, data is collected from customers via a Food Frequency Questionnaire (FFQ). Customers who opt-in to have their de-identified data used for research will provide invaluable information which will be used to investigate how food shapes the gut microbiome and how the gut microbiome can be modulated to a healthier state via dietary interventions.

The FFQ was developed by their Lead Accredited Practising Dietitian, Dr Paula Smith-Brown, who pioneered the world’s first microbiome-focused FFQ. Ultimately, dietary suggestions would be able to come from discoveries made in the IBD program and feedback into the Insight kit for clients and help to improve their dietary recommendations.

The ultimate goal is to improve the quality of life and health outcomes of IBD patients via the development of effective and well tolerated gut-microbiome derived therapeutics, and to develop precision medicine tools to personalise patient treatment. 


“The best outcome we could hope for is that therapeutics developed by this research will assist IBD patients to maintain disease-free remission over long periods with little toxicity or side effects,” Dr. Ó Cuív said.


To learn more about the IBD program, visit www.microba.com/media.

 

[1] PricewaterhouseCoopers Australia, (2013).
Improving Inflammatory Bowel Disease Care Across Australia,
March 2013, Australia.