Modifying gut bacteria to treat IBD

By Rob Clancy, staff writer. Reviewed by Associate Professor Samuel Forster

Dr Sam Forster from the Microbiota and Systems Biology Research Group at Hudson Institute
Dr Sam Forster

Hudson Institute’s Dr Samuel Forster has received a highly prestigious fellowship to advance his work using the bacteria of the human microbiome to treat Inflammatory bowel disease (IBD).

IBD is a chronic, painful and disruptive inflammation of the lining of the gut. It affects about 130,000 Australians. Its cause is unknown, and it is incurable. Treatment involves expensive immune suppression that can have life changing side effects.

Dr Samuel Forster will use his $1.25 million CSL Centenary Fellowship to investigate the cause of IBD and open up new avenues for treatment. His team will apply genomics, computational biology, stem cells, and microbiomics, to answer fundamental questions about the immunology of the gut and its microbiome.

Safe and effective IBD treatments

His vision is to design safe and effective treatments for IBD.

Hundreds of species of bacteria form the microbiome in our gut. Sam’s work suggests that some of them influence the gut’s immune system and contribute to the chronic inflammation that is IBD. But which species? Until recently it was impossible to grow and analyse these bacteria as a community.

In 2016, working at the Sanger Institute in the UK, Sam was joint first author on a Nature paper that demonstrated that the vast majority of bacteria within the human microbiome could be cultivated using a single culture medium. In 2018, he returned to Hudson Institute where he applied the technique to grow communities of bacteria and analyse the microbiome of thousands of gut samples from hundreds of children being treated for IBD at the Monash Children’s Hospital, working with paediatric gastroenterologist Dr Edward Giles.

“We have identified bacteria that appear to be blocking the normal, programmed death of cells lining the gut. This may be preventing resolution of inflammatory lesions in IBD,” says Sam.

Now Sam will study the interactions between these bacteria, the gut microbiome they’re part of, and the genetic background of people with IBD.

Testing potential IBD treatments

His team will also grow ‘mini guts-on-a-chip’ that will allow him to test the effect of potential treatments.

“About 20 per cent of patients are diagnosed before the age of 20 and will suffer with this disease their entire adult lives,” says Sam. “Symptoms include cramping, abdominal pain, bloating, gas, diarrhea, and constipation. It’s a nasty disease that can really hit people physically, emotionally, and socially.

“I hope this work will provide the basis for improved diagnosis, better targeting of conventional immunomodulatory therapies and completely new microbiome-based medicines that will all ultimately provide a better quality of life for people with IBD.”

“We know from recent clinical trials of faecal transplantation there’s potential to modify the microbiome to treat IBD,” he continues. “But these treatments only work for about 30 per cent of patients.”

“My vision is to create safe and effective treatments that will improve quality of life for patients. Of the hundreds of bacterial species and thousands of bacterial strains only a handful have been developed for human application and, even then, primarily only as probiotics. We will explore and understand this treasure trove of bacteria to find ways to enable the microbiome of the gut to resist colonisation by harmful bacteria,” he says. “These targeted microbial medicines would be living treatments tailored to suit the genetic predisposition of the patient and the unique characteristics of their microbiome.”

Journal | Nature

Title | Culturing of 'unculturable' human microbiota reveals novel taxa and extensive sporulation

View publication |

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