To most people, the gut is just a part of your body that helps digest food. But to researchers in BRI’s Gut Immunity Program, the gut is a fascinating world that might hold the answer to one of immunology’s most pressing questions: How does the immune system learn tolerance (what to attack and what to leave alone)?
The program brings together Adam Lacy-Hulbert, PhD, James Lord, MD, PhD, and Oliver Harrison, DPhil, to explore key questions about the gut. Fueled by a game-changing donation, they’re building innovative tools to tackle everything from mysteries of gut biology to improving clinical care.
“The immune system keeps the outside world out. The gut takes the outside world and brings it inside of you,” Dr. Lord says. “Their jobs are opposite, yet they peacefully coexist. That suggests something in the gut is absolutely central to immune tolerance. If we can unravel how that works, it could open up the world of curing autoimmunity.”
Four Reasons to Study the Gut
IMPROVE CLINICAL CARE
This program aims to improve treatments for conditions like celiac Bdisease and inflammatory bowel diseases (IBD) like Crohn’s disease and ulcerative colitis. For example, there are many treatments for IBD — but no way to know which one will work for which person.
“My research aims to take the guesswork out of selecting a treatment by better understanding which therapy will work best for a patient’s unique biology. That will help doctors prescribe the best therapy right away,” says Dr. Lord, a gastroenterologist at Virginia Mason Franciscan Health.
EXAMINE TISSUE SAMPLES
Because most autoimmune diseases affect organs that can’t be biopsied (like the brain or pancreas), most immunologists study the blood. The gut presents a rare opportunity.
“People donate biopsy samples from routine colonoscopies to research,” says Dr. Lacy-Hulbert. “Studying the tissue where disease happens gives us more information than studying the blood. Insights about IBD can help us understand other autoimmune diseases too.”
EXPLORE THE MICROBIOME
The gut microbiome — the three to five pounds of microorganisms living in your gut — is full of clues about immune system disease.
“There’s an emerging idea that gut health is an immune sentinel, that it signals what’s going on in your immune system overall,” Dr. Harrison says. “Take checkpoint inhibitor therapy for cancer. Studies show that people with certain microbiome characteristics respond better to the treatment. And that’s for melanoma, a cancer of the skin, not the gut.”
There’s also growing evidence that the gut might be where your immune system learns to recognize friend versus foe.
“The immune system generally keeps us away from bacteria and viruses, but the gut has massive concentrations of them,” Dr. Lacy-Hulbert says. “We want to learn more about how the immune system learns to tolerate them and how this goes wrong in disease.”
Donor-Funded Tools are Powering Possibility
A generous gift (from a donor who wishes to remain anonymous) enabled BRI to build the Gut Immunity Program. This gift helps solve a catch-22 of research: To ask innovative questions, you need innovative technologies. But traditional funding sources, like the government, don’t typically fund tool acquisition or development.
“Thanks to this donor’s support, we’re creating tools that will help us answer questions that otherwise would take years to answer,” Dr. Harrison says. “Once we have them in our program, we can spin them out across BRI — making an even bigger impact.”
ORGANOID: STUDYING A GUT IN A PETRI DISH
Intestinal organoids are allowing our team to study the factors involved in IBD (like a person’s genetics and how their cells interact with other cells and bacteria).
“Traditional models don’t reflect that level of complexity,” Dr. Lacy-Hulbert says. “Organoids can help us understand why the disease happens and how we might inform better therapies.”
SPATIAL TRANSCRIPTOMICS: EVERY DETAIL OF EVERY CELL
Spatial transcriptomics helps researchers collect vast amounts of information about where cells are located in tissue samples and how they interact.
“It allows us to map every cell in the tissue, the entire genome of each cell and which cells are interacting with each other,” Dr. Harrison says. “That can help us understand what these immune cells see and what might cause them to attack, opening up a world of insight into disease.”
HIGHLY SPECIALIZED TETRAMER: FINDING THE RAREST CELLS
Tetramers allow scientists to find and study a few rare cells among millions. Dr. Lord is using a specialized tetramer to find and study T cells that respond to harmless bacteria.
“We’re examining how these cells are different in people with and without IBD,” Dr. Lord says.
Dr. Lord is on the leading edge of this area of gut immunology and is one of the few scientists who has this tool for human samples.
This was originally published in the Winter 2022 issue of the Powering Possibilities newsletter.
April 5, 2022
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This blog does not provide medical advice, nor is it a substitute
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