The study, “Exploring the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) in modulating local and systemic inflammation in experimental models of colitis,” has just been published in the journal Bioelectronic Medicine.

Ulcerative colitis, a type of inflammatory bowel disease, is a chronic immune condition that causes inflammation and ulcers inside the colon. Symptoms can include diarrhea, abdominal cramping, fatigue and weight loss. People with ulcerative colitis can develop life-threatening complications.

To perform the study, scientists from the immunology department in the Max Rady College of Medicine chemically induced a condition that mimics acute ulcerative colitis in mice. As a treatment, they applied gentle electrical pulses to the outer ears of the mice in order to stimulate the vagus nerve.

The researchers used the treatment, called transcutaneous auricular vagus nerve stimulation, to stimulate specific areas of both ears in mice for 10 minutes per day for six days.

“This stimulation activates the brain-gut axis through the vagus nerve, which can control gut inflammation,” said Fatemeh Hesampour, a PhD candidate who led the study as her doctoral research project.

“In both mice and humans, the part of the outer ear where the vagus nerve is most accessible is the cymba conchae, the ‘pocket’ above the ear hole.”

Mice that received the stimulation showed significant symptom improvement. Compared with untreated mice, they experienced less weight loss, reduced intestinal damage and lower inflammatory marker levels. The treatment also increased levels of anti-inflammatory molecules, suggesting that it helps to restore balance in the immune system.

“In the near future, this treatment could offer a safe, drug-free option for patients with ulcerative colitis who have not found success with other treatments, or this treatment could be added to a patient’s therapies,” said Dr. Jean-Eric Ghia, professor of immunology, who supervised the study.  

The researchers were surprised to find that stimulating the vagus nerve via the ears had positive effects even in healthy mice, potentially opening doors for preventive care and improving gut health.

A recent proof-of-concept clinical trial of non-invasive vagus nerve stimulation of the ears in children with inflammatory bowel disease was conducted in the U.S., showing beneficial results. More clinical trials in humans are needed, Ghia said.

The research team is now investigating how the treatment affects specific immune cells in different parts of both diseased and healthy colons in mice.

“This research offers hope for a future where managing ulcerative colitis could be as simple as a daily ear-stimulation session using the same type of earbud that is used for listening to music,” Ghia said.

Most of the 14 funded professors lead labs in the basic science departments of the medical college, such as immunology, physiology and pathophysiology, or biochemistry and medical genetics.

Their five-year discovery grants and one-year discovery launch supplements from NSERC total $545,000.

“Congratulations on obtaining these prestigious grants in support of cutting-edge science,” said Dr. Brian Postl, dean of the Max Rady College of Medicine and the Rady Faculty of Health Sciences. “We are fortunate to have a wealth of experts at UM whose laboratory discoveries have exciting potential to benefit human health.

“These NSERC grants also make it possible for our professors in medicine to train a large number of undergraduate and graduate students in state-of-the-art research techniques.”

Here are the funded studies:

Dr. Heather Armstrong, assistant professor, internal medicine; Canada Research Chair in integrative bioscience; researcher, Children’s Hospital Research Institute of Manitoba (CHRIM)

Discovery Grant: $28,000; Discovery Launch Supplement: $12,500

Armstrong’s team will focus on dietary fibres from agricultural products. They will examine how certain fibres alter microbial communities in the gut that are needed for the fermentation of fibre, and how this influences immune responses in the gut.

Dr. Robert Beattie, assistant professor, biochemistry and medical genetics

Discovery Grant: $37,000; Discovery Launch Supplement: $12,500

Beattie’s project centres on gene function in the normal embryonic development of brain cells in the cerebral cortex. His team will use new genetic technologies to examine molecular regulators of the proliferation of a specific kind of neural stem cell.

Dr. Britt Drögemöller, assistant professor, biochemistry and medical genetics; Canada Research Chair in pharmacogenomics and precision medicine; researcher, CHRIM

Discovery Grant: $37,000; Discovery Launch Supplement: $12,500

Drögemöller’s team will perform genomic analyses to identify novel genes and genetic pathways associated with variability in human hearing. They will also look at sex-specific auditory differences and how genetic pathways for hearing change as people age.

Dr. Jean-Eric Ghia, professor, immunology; researcher, CHRIM

Discovery Grant: $33,000

Ghia will examine the role of a stress protein in the gut microbiota and in smooth muscle contractions of the colon. In mice bred to lack this protein, his team will test whether a fecal microbiota transfer improves colonic muscle contraction.

Dr. Depeng Jiang, associate professor, community health sciences; researcher, CHRIM

Discovery Grant: $18,000

Jiang, a biostatistician, will develop new statistical models for multilevel data research by using a high-efficiency computer lab for statistical computations and simulations. These new models will provide researchers with new ways to understand their data.

Dr. Meaghan Jones, assistant professor, biochemistry and medical genetics; researcher, CHRIM

Discovery Grant: $31,000; Discovery Launch Supplement: $12,500

Jones will investigate how genes help cells to detoxify after exposure to dioxins, which are environmental pollutants. Her team aims to determine whether cells “remember” exposure to dioxins and mount a stronger response upon re-exposure, and whether this differs between embryos and adult mammals.

Dr. Oleg Krokhin, associate professor, internal medicine

Discovery Grant: $24,000

Krokhin, whose field is proteomics (the large-scale study of proteins), seeks to assist labs in separating peptides, which are produced when proteins are broken down. With the goal of advancing peptide separation science, his team will generate innovative tools and techniques.

Dr. Sam Kung, professor, immunology

Discovery Grant: $32,000

Kung’s project focuses on “natural killer” cells, which are important in maintaining immunity to viruses and tumors. His team will examine how a particular protein regulates natural killer cell biology, in part by studying mice that lack this protein.

Dr. Liam O’Neil, assistant professor, internal medicine; researcher, Manitoba Centre for Proteomics and Systems Biology

Discovery Grant: $28,000; Discovery Launch Supplement: $12,500

O’Neil’s study centres on neutrophils, which are blood cells on the front line of the immune system. His team will investigate how neutrophils modify their release of proteins to improve their ability to neutralize invading pathogens.

Dr. Deanna Santer, assistant professor, immunology; GSK Endowed Research Chair in immunobiology of infectious diseases; researcher, CHRIM

Discovery Grant: $28,000; Discovery Launch Supplement: $12,500

Santer’s focus is type III interferons – proteins released by the immune system to fight viruses. Her team will study their signaling and receptor biology, illuminating processes such as what happens immediately after these interferons bind their receptor in individual immune cells.

Dr. Tabrez Siddiqui, associate professor, physiology and pathophysiology; principal investigator, Kleysen Institute for Advanced Medicine

Discovery Grant: $56,000

Siddiqui’s team will explore the role of synapse-organizing proteins in synapse development in the brain. They will investigate, for example, how these proteins govern brain lamination (cell layering) and plasticity, and how they control synapse numbers.

Dr. Galen Wright, assistant professor, pharmacology and therapeutics; Canada Research Chair in neurogenomics; principal investigator, Kleysen Institute for Advanced Medicine

Discovery Grant: $28,000; Discovery Launch Supplement: $12,500

Wright uses genomics to study DNA repair processes in the human brain. His team will use computational analyses and human stem cell-derived neural models to identify important DNA repair genes and explore the mechanisms underlying how they are regulated.

Dr. Jiuyong Xie, professor, physiology and pathophysiology

Discovery Grant: $32,000

Xie aims to understand how genes have evolved to produce diverse RNA and protein products through an innate process called “alternative pre-mRNA splicing.” His team will use state-of-the-art techniques to uncover molecular details, helping to predict how splicing will evolve in the future.

Dr. Frederick Zeiler, associate professor, surgery; Rudy Falk Clinician-Scientist Professor

Discovery Grant: $33,000; Discovery Launch Supplement: $12,500

Zeiler will develop new techniques for continuous rapid assessment of cerebral autoregulation (control of blood flow to the brain by cerebral blood vessels) in healthy humans. This will allow for analysis of variations in brain regions and differences based on age and sex.