Good gut bacteria helps immune system resist Covid-19, says Microbiotica

Microbiotica is collaborating with Cancer Research UK (CRUK) and Cambridge University Hospitals NHS Foundation Trust (CUH) to develop microbiome co-therapeutics and biomarkers for cancer patients receiving immune checkpoint inhibitor therapy.

The partnership is based on clinical studies conducted by CUH that evaluate immune checkpoint inhibitor drug response in cancer patients, combined with Microbiotica’s unrivalled microbiome profiling and analysis capability.

Of two clinical studies involved one, MELRESIST, a three-year class-leading melanoma study, is already completed, while MITRE, a major landmark study in melanoma, lung and renal cancer involving 1,800 patients, is set to start this month.

“MELRESIST was initiated by Dr Trevor Lawley, our co-founder and CSO,” says Mike Romanos, CEO of Microbiotica, “and Dr Pippa Corrie, consultant in medical oncology at CUH. They’re also leading MITRE going forward.

“The samples will be collected and the clinical work led by Addenbrooke’s, though there will be many other hospitals involved. Cancer Research UK is funding that side of the project, within the overall collaboration.

“The samples will be sent to us and we will then do the microbiome profiling including mass culturing of patient gut bacteria, microbiome sequencing and machine learning analysis. The MITRE study is starting about now and will last several years, but we expect to have early data late next year. There are three

cancers involved – melanoma, lung cancer and renal cancer.”

The collaboration will result in an evaluation of immune checkpoint inhibitor drug response in cancer patients. The checkpoints weaken the immune system response to cancer. When the checkpoints are blocked, T cells kill cancer cells more efficiently.

Checkpoint inhibitors have transformed the management of cancer, due to the range of cancers they can be used for, and their high levels of efficacy, including complete remission in some cases.

However, response rates are low, typically between 10 and 40 per cent of patients. There is a major unmet need for co-therapies to extend the number of responders and for biomarkers to stratify patients for treatment.

Several studies have shown that the gut microbiome plays a critical and causative role in determining which patients respond to these medicines. However, they have thus far failed to identify a consistent gut bacterial signature associated with treatment response or resistance. Dr Romanos is convinced that is about to change.

“The gut is the biggest immune organ in the body,” he says. “It contains trillions of bacteria that have evolved with us and control our entire immune system, either by affecting immune cells in the gut, or through molecules that travel from the bacteria around the body. This affects not just cancer, but also infections: for example, there is evidence that the gut microbiome affects Covid-19 severity.”

Never did the term “you are what you eat” seem more relevant – but there is more, because having a healthy microbiome provides all sorts of benefits for all sorts of conditions.

“The gut microbiome controls brain conditions such as Parkinson’s and depression, obesity and diabetes, infection and autoimmune diseases,” says Dr Romanos. “We can do the same analysis for all these to identify the gut bacteria involved to use as medicines or biomarkers.”

“The gut-brain-microbiome axis is very topical. Parkinson’s is believed to start in the gut with abnormally folded protein that is transported to the brain via the vagus nerve. Certain gut bacteria are associated with depression and they can produce human neurotransmitters.” says Dr Romanos. “Currently there are clinical trials ongoing on the use of faecal transplants from healthy donors for symptoms of autism.”

Microbiotica’s platform comprises the world’s leading reference genome database and culture collection of gut bacteria, and an unrivalled capability to culture and characterise the samples from patients at scale.

This is complemented by a suite of bioinformatic and machine learning tools that enable the identification of previously undetectable gut bacterial signatures linked to patient phenotype. The company also has capabilities to develop and take such products to the clinic.

Tony Hickson, chief business officer, Cancer Research UK, said: “Cancer Research UK is always looking at the most promising new science to advance the treatment of patients, and we believe that the microbiome represents a very exciting new area that could play a major role in cancer therapy.

“We believe this partnership is very well placed to do the quality of science required to identify the specific link between the gut microbiome and checkpoint inhibitors in multiple cancers. We look forward to working with the excellent teams in Microbiotica and Cambridge University Hospitals to progress new microbiome medicines and biomarkers toward the clinic.”

Dr Romanos concluded: “Checkpoint inhibitors have already impacted the lives of many cancer patients for the better but fewer than half of patients respond.

“There is strong evidence that response rates can be increased through manipulation of the microbiome and Microbiotica’s platform has already been able to identify consistent bacterial signatures predictive of drug response in melanoma for the first time.

“Following our major collaboration with Genentech/Roche in inflammatory bowel disease, we are delighted that Cancer Research UK and CUH have also recognized Microbiotica’s leadership in the microbiome and have chosen to partner with us in this landmark cancer microbiome study.”

The collaboration with CUH and CRUK will further reveal the possibilities for the gut microbiome and cancer immunotherapy – and that will underpin a new generation of treatments for a wide variety of disorders.

Microbiotica continues some lab work at its Wellcome Genome Campus site. It also has two units at Chesterford Research Park, with 60 units due to open on the Park later this year.