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A new study from Lawson Health Research Institute and Western University suggests that fecal transplants could be used as a treatment for non-alcoholic fatty liver disease (NAFLD). The randomized controlled trial published in The American Journal of Gastroenterology found that fecal transplants in patients with NAFLD result in a reduction in how easily pathogens and other unwanted molecules pass through the human gut and into circulation, known as intestinal permeability. The results could have implications for the treatment of numerous conditions including metabolic syndrome and autoimmune diseases. 

“Intestinal permeability plays a role in the development of metabolic syndrome which is a major cause of coronary and cerebrovascular disease. It has also been associated with autoimmune diseases like multiple sclerosis (MS), rheumatoid arthritis, systemic lupus and type 1 diabetes,” explains Dr. Michael Silverman, Associate Scientist at Lawson and Professor at Western’s Schulich School of Medicine & Dentistry.

Many NAFLD patients have increased intestinal permeability which triggers inflammation, increased fat in the liver, insulin resistance and elevated levels of triglycerides in the blood. The human microbiome – the diverse collection of microbes in our body – is thought to play a role. Previous studies have shown differences between the gut microbiome of NAFLD patients compared to healthy individuals. 

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“Our team wondered whether we could change the gut microbiome of NAFLD patients to reduce intestinal permeability,” says Dr. Jeremy Burton, Lawson Scientist and Associate Professor at Schulich Medicine & Dentistry.

The trial included 21 NAFLD patients from London Health Sciences Centre (LHSC) and St. Joseph’s Health Care London. Patients were randomized to receive a fecal transplant using stool from a healthy donor or a placebo (the patient’s own stool). Fecal material was delivered to the small intestine using endoscopy. Patients were followed for six months to assess changes to their gut microbiome, intestinal permeability, percentage of liver fat and insulin resistance. 

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. 

“Our study demonstrates that intestinal permeability can be improved through fecal transplant from a healthy donor,” says Dr. Laura Craven, a recent PhD graduate from Schulich Medicine & Dentistry and first author on the published study. “This suggests that fecal transplant could be used as an early intervention in the treatment of NAFLD to reduce intestinal permeability and prevent inflammation”

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Dr. Laura Craven

“Our findings have implications for other conditions too,” adds Dr. Silverman, who is also Chair/Chief of Infectious Diseases at Western, LHSC and St. Joseph’s. “Changing the gut microbiome could hold promise in preventing and treating metabolic syndrome and autoimmune diseases associated with increased gut permeability.”

The team hopes to next conduct a large multi-centre trial to further investigate FMT as an intervention for NAFLD and as a therapy to reduce intestinal permeability. 

NAFLD is an obesity-related disorder and is the second-leading cause of liver transplant in North America. While reversible if treated early, its progression can lead to liver failure or cancer. Current therapies are not overly effective and the prevalence of NAFLD is increasing. 

Dr. Silverman is a pioneer in the field of fecal transplants, including their use as a treatment for Clostridioides difficile (C. diff). He is involved in multiple studies examining the potential of fecal transplants as treatments or supportive therapies for numerous conditions including multiple sclerosis (MS) and different types of cancer.

“In order to conduct this research, we need stool donors,” notes Dr. Silverman. “By donating your poop, you can help us assess the value of fecal transplants to treat a variety of diseases.”

The team is in need of young, healthy stool donors for fecal transplants. All donors are required to go through a screening process. Those interested in becoming a stool donor can contact Dr. Seema Nair Parvathy, Research Coordinator, Fecal Transplant Program, at 519-646-6100 ext. 61726.

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Drs. Michael Silverman (left) and Jeremy Burton (right)

Researchers at Lawson Health Research Institute are the first in Canada to develop clinical practice guidelines for managing neuropathic pain with patients who have experienced a spinal cord injury (SCI).

Neuropathic pain is complex and chronic, and is the most common complication reported by people following SCI. The research team worked with care providers at Parkwood Institute, part of the St. Joseph’s Health Care London family, and an international panel to address the complex and unique challenges for managing pain during recovery and rehabilitation.

In 2003, Dan Harvey sustained a spinal injury after falling off a trampoline. Using his personal experience, as well as his experiences meeting with newly injured people, Harvey contributed to the development of the new guidelines.

“Neuropathic pain – and pain in general – affects every person with a spinal cord injury very differently. Some people have it, some people don’t. But for those who do have it, it can make rehabilitation and recovery much more difficult,” explains Harvey.

“On top of just learning how to use your body again, you also have to deal with various forms of physical pains, which can make it challenging to mentally adapt to an injury.”

For those with chronic pain, it may be hard to just get out of bed in the morning, feel well enough to leave the house, or even fall asleep. “I have fairly extensive neuropathic pain, so I’m well aware of how difficult it can be to get a full night’s sleep, or show attentiveness at work or at school when it literally feels like your legs are on fire,” says Harvey.

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Dr. Eldon Loh, Lawson Researcher and Physical Medicine and Rehabilitation Specialist at St. Joseph’s, and his team recognized that pain can be an overlooked part of a spinal cord injury and plays a major factor in the success of rehabilitation. It’s difficult for someone in pain to participate fully in their own recovery, and so long-term disability becomes more likely. Pain is difficult to manage and it often takes multiple approaches to find something that works for each person.

“This is a starting point for us to standardize how we approach pain in the clinic. We have identified gaps and offered recommendations to not only manage the pain, but also ensure that our patients can fully benefit from rehabilitation,” says Dr. Loh.

The results of the three-year process led to recommendations for screening and diagnosis, treatment and models of care. Important clinical considerations accompany each recommendation.

“For those in hospital following an injury, it’s about making sure they can be as independent as possible before discharge. Over time, we want to keep pain levels under control so that they are able to live life to the fullest,” adds Dr. Loh.

The research will inform new tools and resources for care providers and patients.

Harvey believes the guidelines will have a tremendous impact for patients whose pain may have been overlooked. “Pain can be created through many different avenues and the effects can snowball after a person is discharged and sent home. If you don’t check all of the boxes, you might be missing a very important item.”

The new guidelines have been published in the international journal Spinal Cord. The Ontario Neurotrauma Foundation and Rick Hansen Institute provided funding for the research study. 

A special thanks to individuals from St. Joseph's who were involved in the project: Steve Orenczuk, Patrick Potter, Keith Sequiera, Lindsey Guilbault, Robert Teasell, Anna Kras-Dupuis, Dalton Wolfe, Alba Casalino and Dwight Moulin.  

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