The microbiome has been hailed as the “new frontier” in medicine. In this week’s Holy Grail, Professor Emad El-Omar, director of the new Microbiome Research Centre based at St George’s Hospital and University of NSW in Sydney, predicts where the next decade will take us in translational research.
When did research into the gut microbiome kick off?
The research dates back many decades but was hindered by our inability to culture most bugs in the lab. Genetic sequencing since the early 2000s has enabled us to identify and study these bacteria, and since then we have moved forward in leaps and bounds.
What do we know so far?
There is now good evidence to show gut dysbiosis causes inflammation in the body, leading to what we call a “leaky gut” where bacteria and their products translocate to other parts of the body. This can lead to a range of conditions like bowel cancer, inflammatory bowel disease, obesity, allergic conditions, asthma and mental health problems.
Where is translational research up to?
For certain conditions we have moved almost to therapeutic interventions where we try to manipulate the microbiome to restore it back to health. If you understand what has changed, you can reverse it back. This is done through three methods: ingesting probiotics (to date there are very few adequately powered clinical trials), ingesting pre-biotics (there are clinical trials showing pre-biotics can manipulate the microbiome) and faecal microbiota transplantation (FMT) which has been proven to clear Clostridium difficile infection.
To date this is the only condition FMT has been shown to work on. Obesity or inflammatory bowel disease are much more complex diseases, where the imbalance of microbiota differs between individuals. So who is to say that a healthy person is the ideal donor for your disease? That’s not been established yet and that’s why the clinical trials to date have been very mixed. Some show no benefit, some show benefit and some show some ill benefit.
What about diagnostics and treatments currently available?
There are labs overseas that will analyse samples and report on the balance between so-called healthy and nasty bugs, then give you dietary advice like ‘you’re eating too many, or too little, apples!’ But the advice hasn’t been tested or validated in clinical trials. They’re using suggestions from peer-reviewed studies to generalise for an entire population. Now that is wrong because your diet in Korea might be completely different to your diet in North America.
Any therapy needs to be personalised and individualised and in my humble opinion that is achievable; this is not sci-fi, but will probably take five to 10 years before it becomes part of our clinical armamentarium.
Most of the probiotics on the market in Australia have not been clinically trialled, so they may or may not work, but they have not been proven.
Where is your research heading in the future?
I can see patients with conditions like obesity, Crohn’s disease or depression submitting a sample, we then define what strains of bacteria are missing in their microbiome, culture those strains in the lab and create a personalised capsule. We then study the effects in a clinical trial.
Are you describing creating the perfect formula for a healthy human microbiome?
That is the holy grail. That is what the research is aiming to define ‘what is the ideal human microbiome?’
What treatments do you see emerging in the future?
Within five to 10 years patients will be able to come to a hospital-based centre and see a specialist who will take a sample, consider the make up of microbes in relation to the patient’s diet and any medicines they are taking, then make a reasoned judgement as to what microbes are missing and order a (TGA-approved) formula that would try to restore balance in the microbiome for the particular condition you suffer from.
I don’t want to just treat conditions, I want to prevent conditions. If we understand the signature that defines obesity in childhood or adverse maternal outcomes these are situations where we can intervene before things go wrong.
My hope is that we will get every discipline in medicine interested. I want the cardiologists, the psychiatrists and every other type of specialist to be aware of the potential of the microbiome in terms of therapeutics. My vision for the future is that every specialist will have the microbiome knowledge that is relevant to the diseases they deal with, and how to manipulate it.
How close are we to being able to create these formulas?
We roughly know what the ratios of good and bad should be, we roughly know what the superstars of the bugs are. But the precision is yet to come.
What are the first projects at the Microbiome Research Centre?
We have a great study on pregnancy, big programs on GI cancer and inflammatory bowel disease, studies on dementia and thrombosis and SLE. These are a mix of clinical and basic studies.
Professor El-Omar graduated in Medicine from Glasgow University, Scotland, and trained as a gastroenterologist. He worked as a Visiting Scholar/Scientist at Vanderbilt
University, TN, and National Cancer Institute, MD, USA, and was Professor of Gastroenterology at Aberdeen University, Scotland, for 16 years before taking up the
Chair of Medicine at St George & Sutherland Clinical School, University of New South Wales, Sydney, Australia. He is the Editor-in-Chief of the journal Gut. His research
interests include the gut microbiome, inflammation driven GI cancer and IBD. He is the Director of the Microbiome Research Centre at St George Hospital, Sydney.