Imperial is partnering with biotech company EnteroBiotix to research the potential of therapies based on the gut bacterial community.
The company produces capsules that contain diverse ecosystems of microbiota obtained from healthy and rigorously selected donors, which offer a consistent, safer and non-invasive alternative to current methods of transferring microbiota from donors to patients.
Scientists and clinicians at Imperial and other collaborating centers will use the company’s products to test the ability of gut microbiota transplantation (IMT) to improve patient outcomes in conditions such as blood cancers and antibiotic-resistant infections, and to accelerate systematic research into new microbiota science.
The past decade has seen a resurgence of interest in the gut microbiome – the community of trillions of bacteria, fungi and other microorganisms that live in the digestive tract – and its importance to human health. “Instead of viewing bugs as bad, we view them as part of a symbiosis – a fundamental element in making us happy and healthy,” says Dr. James McIlroy, Founder and CEO of EnteroBiotix.
Among the public, this surge is reflected in the popularity of probiotics, as well as fermented foods such as kefir and kombucha, which contain large bacterial populations and are believed to benefit gut and overall health. In medicine, this interest has been accompanied by growing evidence of the effectiveness of IMT, in which treated feces – which are 85% bacteria – are transferred from selected healthy donors to patients with gastrointestinal problems. -intestinal and other conditions.
ITM and infection
One condition for which IMT has been shown to be safe and effective is recurrent C. difficile infection (rCDI), a bacterial infection of the gastrointestinal tract that can sometimes lead to multiple organ failure and death. Even though antibiotics are an effective therapy for CDI, there is a risk that the antibiotics will not work or that patients will have a new recurrence of the disease after the antibiotics are finished, according to Dr. Benjamin Mullish, clinician and lecturer at the Imperial Metabolism Department. , Digestion and Reproduction.
If you want to get rid of C. difficile infection, a more effective strategy is to restore the composition and function of your gut microbiome to what it was before you got sick. Dr Benjamin Mullish Department of Metabolism, Digestion and Reproduction
“Patients go into a treatment cycle using antibiotics, then get another infection and treat it again,” says Dr Mullish. “What we’ve realized is that antibiotics can kill C. difficile, but they also have the ‘collateral damage’ of killing the beneficial organisms in the gut that are preventing this pathogen from growing and causing an infection. If you want to get rid of CDI, it appears to be a more effective strategy for restoring the composition and function of your gut microbiome to what it was before you got sick.
EnteroBiotix is a UK company pioneering a new class of orally administered drugs that allow IMT to take place without an invasive procedure. Its capsules use donations from selected donors that are dried using a proprietary process and tested using advanced pathogen screening technology.
“A lesson learned from patient engagement in our studies was that many patients were reluctant to have IMT due to the conventional need for invasive means of administering it, including tubes in their stomachs or endoscopies,” explains Dr Mullish. “These are often quite sick patients who are already undergoing many procedures, so we want to do everything we can to avoid more if we can. Enterobiotix is a leading UK company pioneering the capsule-based approach to IMT, so we are very happy to work with them.
One of the first collaborations between Imperial and EnteroBiotix involves a project testing the potential of IMT given to blood cancer patients prior to bone marrow transplantation as a means of trying to alter their gut microbiome and try to improve the results.
Professor Julian Marchesi from the Department of Metabolism, Digestion and Reproduction, who is leading the research, explains: “Patients with blood cancers are a group whose gut microbiome is particularly under attack. They often receive strong chemotherapy, which has side effects of mouth ulcers and intestinal inflammation. Their nutrition can be poor, they frequently receive antibiotics due to their high rate of infections, and many end up colonized with antibiotic-resistant bacteria.
“This last point in particular can be particularly problematic when patients need very demanding treatment, such as a bone marrow transplant – hematologists are sometimes anxious about offering this treatment or other treatments because patients are at such a high risk of contracting an incurable infection.”
The Phase IIa trial, funded by the Medical Research Council’s Developmental Pathway Funding Scheme and supported in-kind by EnteroBiotix, will build on evidence from previous studies at Imperial and elsewhere that have shown IMT to be safe, reduced complications that may occur after bone marrow transplantation and improved survival.
“Pre-habilitation” is a new idea for patients having bone marrow transplants, and it’s certainly very new to target the gut microbiome. Professor Julian Marchesi Department of Metabolism, Digestion and Reproduction
“‘Pre-habilitation’ before a major medical procedure is nothing new – one example is getting leaner and fitter, which is often recommended before major surgery,” says Professor Marchesi. “But it’s a new idea in the context of patients undergoing bone marrow transplantation, and certainly a very new one to target the gut microbiome as a way to pre-empower patients. At the moment we only have correlations, but with this new trial we can begin to explore cause and effect. »
This study – the Microbiota Transplant Before Allogeneic Stem Cell Transplantation (MAST) study – is being conducted by a multidisciplinary team that includes hematologists (Dr Jiri Pavlu and Dr Andrew Innes), microbiology and infectious disease experts (Dr Frances Davies and Dr Rohma Ghani), as well as experts in digestive diseases and the microbiome (Dr Benjamin Mullish and Professor Julian Marchesi).
The study will be conducted at six of the UK’s leading blood cancer centers and includes, along with Imperial, UCLH, Royal Marsden, King’s College London, University Hospitals Leeds and Birmingham University Hospitals.
Advancing microbiome research
The partnership between Imperial and EnteroBiotix, in addition to helping explore the safety, tolerability and efficacy of IMT-based drugs for a range of conditions, is expected to help place microbiome research on a stronger footing. systematic. This trial will exploit another important advantage of the capsules, which is that their components are manufactured in a very standardized way, which is both better for patient safety and allows researchers to begin to explore the specific mechanisms of the beneficial impact. of IMT on patients. immune system and other aspects of their health.
By studying these tools, we can learn more about the microbiome and the very specific mechanisms that make microbiome treatments work. Dr. James Kinross Department of Surgery and Cancerology
Dr. James Kinross, Clinical Lecturer and Consultant Surgeon in the Department of Surgery and Cancer, says: “At the moment, IMT is a new science and remains a very rudimentary tool. It is a radical change in the ecology of the intestine. But donors and patients with widely varying gut ecologies and we don’t know precisely which insects need to enter which patients and for what reason – and then, when these new insects are transferred to a patient, how we support them to allow them to develop oneself .”
“The products developed by EnteroBiotix are a very interesting experimental tool. By studying whether it works, we can learn more about the microbiome and the very specific mechanisms that make microbiome treatments work. We could produce drugs or take advantage of biomarkers. Then we can refine it so we can deliver at scale for organizations like the NHS. This is the mission of the company and it joins ours.
The Imperial team is a driver of discovery and EnteroBiotix can help translate that into a commercial product that benefits patients around the world. Dr James McIlroy EnteroBiotix
EnteroBiotix’s Dr. McIlroy says, “When we founded EnteroBiotix there were 13 clinical trials listed on clinicaltrials.gov investigating IMT, now there are hundreds. Most of the studies published so far show the same thing: the transfer of microorganisms from healthy people to sick people can help improve health outcomes. EnteroBiotix is developing a safer and more scalable approach to IMT that is compositionally consistent and supported by a strong intellectual property position. Our partnership with Imperial allows us to explore different research opportunities and brings us closer to achieving our vision of developing products that benefit patients. »
“The first data already generated so far by Imperial is very interesting,” he adds. “It helps build a strong case for improving the microbiome. The Imperial team is a driver of discovery and EnteroBiotix can help translate that into a commercial product that benefits patients around the world.
Photographs: Jo Mieszkowski Photographer