The human gut microbiota is an incredibly complex, and in some ways enigmatic part of the body. Our microbiome varies widely, based on a plethora of factors including age, geography, ethnicity, and even method of birth delivery. The mutualistic relationship between humans and their gut biota of course plays a role in digestion, but notably is crucial in the immune system.
Our microbiota defends against pathogens by dominating the available nutrients in the gut. Furthermore, those microbes secrete cytokines in order to alert the rest of the immune system to launch an inflammatory response against unwelcome organisms.
Translating Microbiome Therapeutics into the Clinic
Matthew Robinson is the Vice President of Translational Biology at Microbiotica, a company that has been developing a co-therapy for anti PD-1 checkpoint inhibitors for patients with melanoma. Their therapy, says Robinson, takes advantage of the effects of the gut microbiome’s effect on immune response.
There has been an assortment of studies that have investigated an observed association between a patient’s gut microbiome and their response to checkpoint inhibitors. Researchers’ excitement has recently grown stronger now it has been found that this association may be more than just a correlation.
Correlation or Causation?
There has been increasing evidence that transplanting the gut microbiome in mice can increase the probability that the mouse will respond to anti PD-1 therapy. Furthermore, additional studies have shown that a faecal microbiome transplant in humans could increase response to checkpoint inhibitors. This evidence indicates that there could be a causal link between gut microbiome and response to anti PD-1 inhibitors.
However, each of the studies differed in the bacteria that they had found to be associated with the response, so the method of the causal link is as yet unclear. This is what Microbiotica has been working to solve; they take clinical data from patients, analyse their microbiome, and design medicines and biomarkers from those data.
The platform determines a microbiome signature for drug response using bioinformatics and machine learning. So, biomarkers and live bacterial therapeutics are derived from this signature. According to Microbiotica’s co-founder, Trevor Lawley, the starting principle in the field was “when you understand the microbiome, you can develop a consortium of bacteria to treat disease,” says Robinson.
Now, Microbiotica is developing this idea on an industrial scale. They have created a ‘personalised bacterial bank,’ by culturing out individual bacterial species from stool samples to establish a database representing both healthy and diseased patient populations. The bacteria’s genome is sequenced — providing the “blueprint of the human microbiome”. Robinson stated that Microbiotica’s platform can precisely identify over 95% of gut bacteria.
In their melanoma study, Microbiotica was able to determine which patients would respond to immune-checkpoint inhibitors and which would not. Excitingly, they were also able to identify a consortium of nine bacterial species highly associated with response, which has led to the development of their new therapy.
As the industry moves ever closer to clinically proven personalised medicine, Microbiotica’s work in culturing live bacterial therapeutics introduces a new dimension to the field of immuno-oncology. As the frontier of personalised medicine develops more affordable and standardised methods due to new diagnostic and informatic techniques, the future looks bright for novel modalities for difficult indications.
To learn more about similar developments in the field, and to see the breakthroughs in overcoming these challenges, consider joining us at our upcoming Immuno UK: In-Person event. Gain valuable insights into the approaches impacting the immunotherapy field through 40+ outstanding presentations tackling key discussion points in immuno-oncology, immunology, and inflammation.