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There is still much to learn about the human microbiome and its role in fighting disease, but ongoing studies at Lawson Health Research Institute, including a focus on fecal microbial transplants (FMT), are making strides in harnessing this complex system.

FMT is being studied in connection with conditions as varied as non-alcoholic fatty liver disease, rheumatoid arthritis, atherosclerosis, HIV, cancer and multiple sclerosis.

FMT is already in clinical use for the treatment of C. diff (Clostridium difficile), and in addition to showing promise in the treatment of other diseases, it is also being studied as a way to improve response to existing cancer treatments and ease treatment side effects.

Dr. Saman Maleki, a Scientist at Lawson Health Research Institute and the London Regional Cancer Program (LRCP) at London Health Sciences Centre (LHSC), says they’ve just begun to explore the possibilities.

"We are just starting to study FMT as an intervention outside its traditional use in patients with C. difficile infection, and we will be expanding to other areas, particularly in cancer.”

FMT can overhaul a patient’s microbiome, Dr. Maleki explains, and a healthy microbiome is beneficial especially when a treatment is trying to activate the body’s immune system.

Dr. Michael Silverman, Lawson Associate Scientist and Medical Director of St. Joseph’s Health Care London’s Infectious Diseases Care Program, is a pioneer in the field of FMT. He has been performing the procedure since 2003 with C. difficile patients and was one of the first in North America to do so. He sees a wide range of possible applications.

“FMT has enormous potential in being an important adjunctive therapy in many cancers. It may, for example, help cancer patients respond to immunotherapy,” says Dr. Silverman, who is also Chair/Chief of Infectious Disease at St. Joseph’s Health Care London, LHSC and Western University. “The potential to impact autoimmune and metabolic diseases is also quite exciting, but still in early development.”

So how does it work?

After rigorous screening, stool from a healthy donor is collected and then processed in a lab into a liquid or capsule containing the good bacteria, which can then be administered to a patient’s gastrointestinal tract.

The Lawson team is also one of few delivering FMT using specially-prepared oral capsules. Introduced in 2018, they have been a game changer in patient acceptance and ease of administration, according to Research Coordinator Dr. SeemaNair Parvathy, who has been coordinating the program since 2015.

“There is a link between the fitness of the intestinal microbiome and the fitness of the immune system,” says Dr. John Lenehan, Associate Scientist at Lawson and Medical Oncologist at LHSC. “A ‘healthy’ microbiome leads to a more robust immune response when using immunotherapy. FMT from a healthy donor is expected to improve the fitness of the recipient’s intestinal microbiome and promote a better immune response.”

People with chronic disease can often experience what’s called a ‘leaky gut,’ allowing food, bacterial and microbial components to pass through the intestinal wall, negatively impacting the immune system.

“When people get FMTs their intestinal permeability improves – meaning it actually reduces,” says Dr. Jeremy Burton, Lawson Scientist and Research Chair of Human Microbiome and Probiotics at Lawson and St. Joseph’s. “What changes that intestinal permeability? The microbes at the site. They play a role in interacting with the host cells, providing nutrients and vitamins.”

With the immune system so closely tied to the health of the microbiome, it’s not surprising scientists are exploring how strengthening one can have a big impact on the other.

Boosting immunotherapy

Immunotherapy can be used to either stimulate or suppress the immune system to help the body fight disease, and FMT is showing promise in reducing resistance to the treatment.

While immunotherapy has been effective in treating a number of cancers – the number one cause of death in Canada – not all patients respond to the treatment.

But early work presented at a conference by the Lawson team for the Journal for ImmunoTherapy of Cancer has shown that using FMT to modify the microbiome could reduce resistance to immunotherapy. The study involved patients from LHSC with advanced melanoma, a type of skin cancer.

While in the very early stages, the combination of FMT and anti-PD1 immunotherapy has been found to be safe, and it appears that FMT could make tumours more responsive to the immunotherapy treatment.

“Microbiome-based treatment strategies, including FMT, have a high potential in oncology,” says Dr. Maleki. “Our team is also exploring its potential in treating pancreatic cancer.”

The research is so interesting that a recent Nature article listed the Phase I melanoma trial as “seminal” research. The study was also unique in that it used healthy donors, as opposed to donors who had previously responded to immunotherapy treatment.

A separate Lawson study with LHSC patients with metastatic renal cell carcinoma, a type of kidney cancer, published in the Journal of Clinical Oncology, also looked at combining immunotherapy and FMT to ease the adverse effects of the treatment.

The Phase I study, led by Dr. Maleki and Dr. Ricardo Fernandes, Medical Oncologist at LHSC, found adding FMT to doublet immunotherapy was safe, but further study is needed to determine whether it could bring about changes in the microbiome and immune system.

Dr. Lenehan says Lawson researchers are in a position to be leaders in this field in the near future for two reasons.

“One is that other academic researchers have not been able to assemble the expertise, and some who have, do not have the access to healthy donor stool. The second is that some biotechnology companies are interested in FMT, but almost exclusively for C. difficile infections.”

Autoimmune, metabolic and other illnesses

Two other areas that have seen recent advances include FMT for the treatment of non-alcoholic fatty liver disease (NAFLD) and multiple sclerosis.

“The gut microbiome is very important in the metabolism of foods and metabolic products. It can therefore have a major effect on obesity and atherosclerosis,” says Dr. Silverman. “It also is tightly involved in regulating the immune system and therefore moderating the microbiome may potentially impact autoimmune diseases.”

A study published in 2020 by the team in The American Journal of Gastroenterology showed that FMT appears to reduce intestinal permeability in patients with NAFLD.

The number of people with NAFLD is growing rapidly and studies show patients have different microbiota than healthy persons.

The trial included 21 NAFLD patients from LHSC and St. Joseph’s. While the researchers found no changes in percentage of liver fat or insulin resistance, they observed significant reduction in intestinal permeability in those patients who had elevated intestinal permeability at the study’s start (seven patients in total). They also observed changes to the gut microbiome in all patients who received a fecal transplant from a healthy donor.

“Metabolic syndromes including obesity and its complications of NAFLD and atherosclerosis are massive public health problems. Any impact on these would be of huge importance,” Dr. Silverman adds. “Autoimmune diseases also cause major morbidity and mortality. We have a lot of work to do before we can consider FMT as a routine therapy for any of these conditions, but the long-term promise is great.”

Research into the use of FMT for treatment of patients with multiple sclerosis is in the very early stages. But patients with MS show a difference in gut microbiota and higher small intestine permeability, which could contribute to the development of the disease.

A Phase I trial by the Lawson team published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical, found FMT to be safe and tolerable.

While the study was very small, MS patients treated with FMT were found to have beneficial changes to gut microbiota and intestinal permeability, but further study is needed to determine if FMT could be used as a treatment.

Lawson scientists are also currently studying the use of FMT for patients with atherosclerosis, along with ongoing studies on melanoma and lung cancer. Funding for a study on pancreatic cancer has been secured and researchers are in the process of planning trials for a number of other applications.

Dr. Lenehan says, “The microbiome is connected to several diseases and their treatments. Evidence is growing that an individual’s health is related to their microbiome.”

The donor challenge

The challenge of finding fecal donors for FMT and the cost of that process remain an issue for research into this promising treatment, even as more potential applications are discovered.

There is currently no process in place to match donors and recipients – as with organ donation – but there is an extensive screening process for both infectious and non-infectious conditions, one that needs to be repeated if a donor experiences any lifestyle changes.

Dr. Burton says, “We still don't understand the full role of the microbiota. We have to ensure that we're not giving patients a microbiota that might cause them some other issue in the future, so the donors are screened very thoroughly for that.”

Screening also excludes donors with an increased risk of developing the diseases scientists are hoping to treat, such as metabolic syndrome related conditions.

A 2017 article published in Open Forum Infectious Diseases by Drs. Silverman and Burton found the cost of screening high numbers of potential donors could make establishing local programs extremely difficult, so having a central program such as the one in London could help patients in many regions.

In the study, only five of 46 potential donors passed the history, examination, blood, stool and urine tests, and of the five, four later travelled or had illnesses that made donation inadvisable.

The search continues in London for potential donors to help drive this research forward. You can read one donor’s story and learn how you can get involved here. 

More on FMT and the microbiome:

Drugs vs. bugs: Harnessing the microbiome to improve treatments

A golden age in microbiome research

As the research institute of London Health Sciences Centre (LHSC) and St. Joseph’s Health Care London, our teams impact the lives of people in Ontario, Canada and around the globe with groundbreaking studies, world firsts and translational research that enhances care, health and wellbeing. Here are some of Lawson Health Research Institute’s top research highlights of 2022.

Researchers looking to better personalize treatment for PTSD

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A new study by researchers at ICES, Lawson and Western finds that virtual care during the COVID-19 pandemic led to a significant reduction in carbon dioxide emissions and patient travel-related expenses, such as gasoline, parking or public transit costs. Read more.

Novel test that could easily diagnose blast injury created by local scientists

In a world first, researchers at Lawson and Defence Research and Development Canada have developed a breath test that could be used to diagnose repetitive blast injury – a mild traumatic brain injury resulting from pressure changes that occur during explosions. The device will soon go through clinical trials to validate its efficacy. Read more.

Local researchers using artificial intelligence to lead the way in bedside lung imaging

A team at Lawson is testing a new form of artificial intelligence (AI), paired with portable ultrasound machines, to image and identify lung concerns in real time, right at the beside of critically ill patients. Approximately 100 critical care patients at LHSC will be part of this study. Read more.

New tool shows promise in helping people manage traumatic brain injuries one pace at a time

A team at Lawson has developed a new app called MyBrainPacer™ which aims to better assist and treat those living with mild traumatic brain injuries (mTBI), including concussions. mTBI may come with lasting effects that can alter a person’s life.  Although a person with a mTBI may appear fine on the outside, many have to pace their day-to-day activities in order to allow the time needed for the brain to properly heal. Much like point tracking used by dieters to monitor food choices, through MyBrainPacer™ App, users can assign values to tasks like driving, grocery shopping, screen use and exercise so they can plan and pace their daily activity.  Read more.

Study shows a decline in Veterans' mental health throughout the pandemic

When it comes to mental health conditions, Veterans are an at-risk population, often having higher rates of depression and post-traumatic stress disorder (PTSD). When the COVID-19 pandemic hit, scientists at Lawson wanted to understand its effects on this already at-risk population. They found that more than half of Canadian Veterans reported a decline in their mental health. Read more.

Growing evidence that PSMA imaging improves prostate cancer detection

Scientists at Lawson are leading the way in using specialized imaging to detect prostate cancer – the fifth leading cause of cancer death in men around the world. Early evidence indicates that PSMA PET scans have changed how prostate cancer is being treated, but more work is underway to understand the impact of those treatment changes. Read more.

Leveraging virtual reality to manage pain in paediatric patients

A study underway through Lawson and Children’s Hospital at LHSC is using virtual reality (VR) to help paediatric patients during painful and distressing procedures. The study is focusing on paediatric patients who need port access. A port is a little reservoir that sits underneath the skin that allows access to blood or medication with the use of a needle. Ports are most commonly used in paediatric cancer patients. Read more.

Team players: FMT and microbiome research could have widespread impact

There is still much to learn about the human microbiome and its role in fighting disease, but ongoing studies at Lawson, including a focus on fecal microbial transplants (FMT), are making strides in harnessing this complex system. FMT is being studied in connection with conditions as varied as non-alcoholic fatty liver disease, rheumatoid arthritis, atherosclerosis, HIV, cancer and multiple sclerosis. Read more.

London researchers adapt MRI technology to image salt within the kidneys

Scientists at Lawson have adapted PET/MRI technology to accurately image salt within the kidneys of patients with kidney disease. Imaging salt within the kidneys has never been accurately accomplished in patients with kidney disease, but Dr. McIntyre and his team developed new technology and software that was adaptable to a PET/MRI machine at St. Joseph’s. Read more.

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Largest trial ever done in hemodialysis care examines optimal dialysis temperature

Published in the Lancet findings from a large clinical trial through Lawson, ICES Western and Western University suggest that lowering dialysis temperatures does not lead to improved patient outcomes, despite previous studies suggesting otherwise. Read more.

To learn more about Lawson research studies, please visit our News and Media page