What is the microbiome?
Put simply, the gut’s microbiome refers to the vast and complicated community of microbes that coexist in our digestive tract, in greater numbers and more diverse than anywhere else on the human body.
The gut microbiome serves many uses: as a barrier to harmful bacteria and viruses, as an immune system booster and to metabolise certain otherwise indigestible carbohydrates in food. In recent studies, however, it has also been linked to a whole host of diseases and conditions, from cancer to obesity and asthma to autism. So how can this newly acquired knowledge help us better understand our own gut flora and assist in improving patient health?
A “healthy” gut
Studies have shown that patients with conditions such as Irritable Bowel Syndrome (IBS), types 1 and 2 diabetes, coeliac disease and eczema also have a less diverse gut microbiome than healthy patients. This would suggest that a more diverse gut microbiome is more robust, better able to fight off certain pathogens and is therefore “healthier”.
Many things can affect the gut microbiome including diet, disease, medicines and environmental factors such as pollution and pesticides in food. So how are companies and researchers tackling this complex issue?
Microbial transplants to fight infection
Microbes from healthy individuals are being used to treat patients with chronic bacterial infections using faecal microbial transplants (FMT). In 2012, a study was conducted by the University of Amsterdam where patients with recurring Clostridium difficile infections were treated with either a faecal transfusion from healthy donors or with the standard two week course of the antibiotic Vancomycin. The cure rate among the faecal transfusion recipients was so high (94% versus 27% of the patients taking the antibiotic), the trial was stopped early because it was viewed as unethical to the “control” group. They were then given the faecal transplant and also cured.
Since then, faecal transplants have become the standard treatment for recurring Clostridium difficile where a course of antibiotics has failed, and evidence has been mounting that this method of treatment may be effective for other conditions such as IBS, Crohn’s disease or ulcerative colitis. In fact, a study published in the Lancet in 2017 showed that FMT led to complete remission in ~ 25% of the ulcerative colitis patients.
A gut feeling?
Realising that patients with depression had a less diverse gut microbiome, scientists at the APC Microbiome centre transferred microbiome samples from depressed patients to healthy rats and were surprised to discover the rats would then display depressive symptoms themselves. The same happened when gut bacteria from Parkinson’s disease sufferers were transplanted into rats bred to be genetically predisposed to the disease; the rats’ symptoms became more severe.
This new research has opened up some exciting new possibilities and has seen the microbiome as a target for potential therapies for neurological conditions. There is even talk of “psychobiotics” potentially being prescribed in the future; essentially a probiotic that could alleviate depression, anxiety and other stress disorders. For now, though, more research is needed.
Microbes as medicines
4D Pharma is developing microbial strains, so-called live biotherapeutics, derived from the human gut microbiome as treatments for diseases like asthma, cancer, colitis, cardiovascular disease and neurodegeneration. Microbiotica utilises its microbiome platform to analyse patient samples from clinical trials to identify microbiome biomarker signatures of drug response, novel drug targets and live bacterial therapeutic products. Having spun out of the Wellcome Trust Sanger Institute less than 2 years ago, the company has already inked a deal with Genentech to investigate new biomarkers and medicines for inflammatory bowel disease.
Predicting drug behaviour
Gut bacteria don’t just help break down our food, they metabolise our medicines too. Intract Pharma analyses how drugs behave and are broken down in the intestine. The company has produced a series of coatings which allow oral medication to be reliably and effectively delivered to the large and small intestine. This not only improves drug efficacy but also paves the way for targeted oral medication where previously this was not possible.
Eagle Genomics is using its bioinformatics and analytics platform to collate the raft of microbiome data from clinical studies and develop new biomarkers. It has already helped GlaxoSmithKline to catalogue its clinical and molecular datasets to identify biomarkers for acute pancreatitis.
Rising recruitment needs
We have seen an increasing demand for microbiologists, biomarker scientists, bioprocessing scientists and engineers, preclinical and clinical research associates and study managers, as well as bioinformaticians in microbiome research over the last few years.
Although this field is still in its relatively early stages, the impact of the microbiome on disease and the potential use of microbes as medicine will cause us to listen to, and learn from, our gut.