Imperial has partnered with biotechnology company EnteroBiotix to investigate the potential of gut bacteria community-based therapies.
The company produces capsules containing diverse microbiota ecosystems obtained from rigorously selected, healthy donors, providing a consistent, safer, and compositionally non-invasive alternative to current methods for transferring microbiota from donors to donors. patients.
Scientists and physicians 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 in the new science. of the microbiome.
The last decade has seen a surge in 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 seeing insects as bad, we accept them as part of a symbiosis, a fundamental part of making us healthy and happy,” says Dr. James McIlroy, WholeBiotix Founder and CEO.
Among the public, this rise is reflected in the popularity of probiotics, along with fermented foods such as kefir and kombucha, which contain large bacterial populations and are believed to be beneficial for gut and general health. In medicine, this interest has been accompanied by growing evidence of the efficacy of IMT, in which processed fecal matter, which is 85% bacteria, is transferred from selected healthy donors to patients with gastrointestinal and other conditions. .
IMT 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 multi-organ failure and death. Although antibiotics are an effective therapy for CDI, there is a risk that the antibiotics will not work or that patients will have a recurrence of the condition once the antibiotics are finished, according to Dr Benjamin Mullishclinician and professor at Imperial’s Department of Metabolism, 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 cycle of antibiotic treatment, then get another infection and treat it again,” explains Dr. Mullish. “What we’ve come to realize is that antibiotics can kill C. difficile, but they also have the ‘collateral damage’ of killing beneficial organisms in the gut that prevent this pathogen from growing and causing infection. If you want to get rid of CDI, it appears to be a more effective strategy to restore 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 medicines that allow IMT to be carried out without an invasive procedure. Their capsules use donations from select donors that are dried using a proprietary process and tested with advanced pathogen detection technology.
“One lesson from patient participation in our studies was that many patients were hesitant to undergo IMT because conventionally they needed invasive ways to deliver it, including stomach tubes or endoscopies,” says Dr. Mullish. “These are often quite sick patients who are already going through a lot of procedures, so we want to do everything we can to prevent more if we can. Enterobiotix is a leading UK company pioneering the capsule-based approach to IMT, so we are very pleased to be working with them.”
One of the first collaborations between Imperial and EnteroBiotix is on a project testing the potential of IMT given to blood cancer patients prior to bone marrow transplant as a means of trying to alter their gut microbiome and try to improve outcomes.
Professor Julian Marchesi at the Department of Metabolism, Digestion and Reproduction, which 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 may be poor, they frequently receive antibiotics due to their high infection rate, and many of them end up colonized with antibiotic-resistant bacteria.
“That last point in particular can be a problem especially when patients need a very demanding treatment, such as a bone marrow transplant – hematologists are sometimes eager to offer this or other treatments because patients are at very high risk of getting a infection that is untreatable.
The phase IIa trial, funded by the Medical Research Council’s Development Path Financing Scheme and supported in kind by EnteroBiotix, will be based on evidence from previous studies at Imperial and elsewhere, which showed that IMT was safe, reduced complications that can occur after bone marrow transplantation, and improved survival.
‘Prehabilitation’ is a new idea for patients undergoing bone marrow transplants, and it’s definitely very new to target the gut microbiome. Professor Julian Marchesi Department of Metabolism, Digestion and Reproduction
“’Prehabilitation’ before significant medical intervention is not new; one example is losing weight and getting fit, which is often recommended before major surgery,” says Professor Marchesi. “But it’s a new idea in the context of patients receiving bone marrow transplants, and definitely very novel to target the gut microbiome as a means of pre-enabling patients. At the moment, we only have correlations, but with this new trial we can start to explore cause and effect.”
This study, the Microbiota Transplant Before to Allogeneic Stem Cell Transplantation (MAST) study, is being conducted by a multidisciplinary team that includes hematologists (Dr Jiri Pavlu Y Dr. Andres Ines), experts in microbiology and infectious diseases (Dr Frances Davies Y Dr Rohma Ghani), together with experts in digestive diseases and microbiomes (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, The Royal Marsden, King’s College London, Leeds Teaching Hospitals and University Hospitals Birmingham.
Advances in Microbiome Research
The partnership between Imperial and EnteroBiotix, in addition to helping explore the safety, tolerability and efficacy of IMT-based medicines for a variety of conditions, is expected to help put microbiome research on a more systematic basis. This trial will exploit another important advantage of capsules, namely that their components are manufactured in a highly standardized way, which is better for patient safety and allows researchers to begin exploring the specific mechanisms of how IMT may have a beneficial impact on patients. immune system and other aspects of your health.
By studying these tools, we can learn about the microbiome and the very specific mechanisms that make microbiome treatments work. Dr James Kinross Department of Surgery and Cancer
Dr. James Kinross, Senior Clinical Professor and Consultant Surgeon in the Department of Surgery and Cancer, says, “At the moment, IMT is a new science and it’s still a very powerful tool. It is a total change of the ecology of the intestine. But donors and patients with very variable gut ecologies and we don’t know precisely which microbes should be introduced into which patients and for what reason, and then when those new microbes are transferred to a patient, how do we maintain them to allow them to grow. .”
“The products that EnteroBiotix is developing are a very interesting experimental tool. By studying whether it works, we can learn 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 it at scale for organizations like the NHS. That is the mission of the company and it aligns with ours.”
The Imperial team is an engine of discovery and EnteroBiotix can help translate that into a commercial product that benefits patients around the world. Dr James McIlroy WholeBiotix
Dr. McIlroy of EnteroBiotix 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: that transferring microorganisms from healthy people to sick people can contribute to better health outcomes. EnteroBiotix is developing a more secure and scalable approach to IMT that is consistent in composition and backed by a strong intellectual property position. Partnering with Imperial allows us to explore different research opportunities and brings us closer to fulfilling our vision of developing products that benefit patients.”
“The first data already generated so far by Imperial is very exciting,” he adds. “It is helping to build a strong case for microbiome improvement. The Imperial team is an engine of discovery and EnteroBiotix can help translate that into a commercial product that benefits patients around the world.”
Photographs: Jo Mieszkowski Photographer