How inflammation imprints on the gut and affects its everyday functions
By Bethany Mauger
WW hen Miss Frizzle's class climbed aboard the Magic School Bus and explored the digestive system, they cruised down the esophagus and splashed through the stomach.
They dove into the small intestine and tunneled down to the large intestine. But what you didn't see is a system of neurons hard at work behind the scenes.
Brian Gilbransen, MSU Research Foundation Professor of Physiology.
Millions of neurons in your gut form the enteric nervous system, also known as the second brain. Every time you reach for a snack or sit down to dinner, this system springs into action. That's what allows your gut — everything from the mouth on down — to digest food without communicating with your brain.
"That's one of the coolest things about this system," Michigan State University Professor Brian Gulbransen said. "You can take the gut and put it in a dish, and it still performs all the motor functions all by itself."
Gulbransen's lab is dedicated to understanding how the enteric nervous system responds to inflammation and how those memories impact the gut's everyday functions. This understanding could be the key to new treatments that would drastically improve quality of life for millions.
Setting the temperature for the gut
Inflammatory bowel diseases have a major impact on quality of life for those who suffer from them. Irritable bowel syndrome is one of the most common diseases, affecting an estimated 10% of people worldwide.
"It's a massive problem," Gulbransen said. "It's hard to function when you're living with gut pain. It's not necessarily lethal, but the daily toll it takes on people is huge."
Whether studying Hawaiian coral or the inner workings of the human gut, the through line of Associate Professor Rob Quinn's work is the microbiome.
Gulbransen studies a cell called glia. These cells work as partners with neurons, surrounding them and regulating their environment. Glia cells control everything from nutrient supply and waste removal to chemical signals. If a neuron is an office, then glia cells are the office managers. They set the mood for their workers and determine whether an office feels positive and productive — or stressful and chaotic.
People with normal, healthy guts can suddenly experience inflammation from a stomach bug or food poisoning. Sometimes, that inflammation changes the nervous system and how it controls the gut. When that happens, a one-time problem can turn into chronic, long-term battles with constipation, diarrhea or visceral pain.
Gulbransen's hypothesis is glia cells remember an inflammation event. Even after a person heals from an illness, the glia can release compounds that promote an inflammatory environment to the neurons. The neurons, in turn, become more easily excitable.
Gulbransen's goal is that this research will lead to a treatment that reprograms glia cells and erases their response to past inflammation. Understanding how the glia cells work could lead to new therapies that harness their power and change the enteric nervous system's activity.
"The idea is, what if we could find a way to make the glia forget experiencing inflammation?" Gulbransen said. "If you could make a glia cell forget and reset these cells back to their normal state, maybe you could reset the gut to more normal function."
Gut Check: Inside the Microbiome
By Connor Yeck
OO n any given day in Rob Quinn's laboratory, you'll find tanks of Hawaiian coral haloed with fluorescent fish and graduate students parsing mountains of data in the fight against cystic fibrosis — not to mention a few mice dining on peanut butter or prunes.
If you're looking for a thread tying these diverse research projects together, the answer can be found spelled out, literally, across the lab's first-floor windows in multi-colored, foot-high letters: M I C R O B I O M E
Quinn, an Associate Professor in MSU's Department of Biochemistry and Molecular Biology, is an expert in the vast and surprising wilderness of microbial life that has an outsized impact on an organism's health.
In particular he's redefining scientific understanding of the microbes who call our very own gastrointestinal tracts home, and the myriad ways they contribute to serious disease and everyday well-being.
Confined to the lower intestines, these microbes in their teeming trillions help break down nutrients during the final steps of digestion, cooking up a kaleidoscopic array of beneficial chemical compounds in the process.
"The microbiome is essentially another organ," Quinn explained. "The thousands of species of bacteria living inside us help digest our food, keep away pathogens and talk to our body through small molecule chemistry."
Imbalances in gut flora can contribute to ailments such as Crohn's disease, ulcerative colitis, chronic inflammation and diabetes to name just a few. Reaching beyond the GI tract, these same microbes play major roles in our mental health and even a well-maintained immune system.
The technology that allowed microbiome science to flourish is now commonplace on university campuses and research institutes. Rob Quinn Associate Professor, Biochemistry and Molecular Biology
By better characterizing the microbial chemistry occurring in the gut, Quinn and his team are paving the way for improved understanding of diseases and helping shape the microbiome into a powerful, precise tool that benefits human health.
Professor Rob Quinn (right) and postdoctoral fellow Cely Gonzalez analyze a culture of a bacterium isolated from the human gut microbiome.
It's a big club
With trillions of organisms in play, trying to visualize this microbial landscape is no small task. One popular fact you'll find brought up by researchers or perhaps at your local bar trivia is that there are more microbes in our bodies than human cells, with most of these calling the gut home.
Ask Quinn for the most exciting bit of microbiome data, however, and he'll tell you it's all in the genes.
"Sure, there are more microbial cells in our body than human cells — or its maybe a 1 to 1 ratio — but there is 30 times more genetic diversity in our microbiome than there is in our own genes," he explained.
Micro-medicine
Produced in the liver and stored in the gallbladder, bile acids are some of the most abundant and well-studied molecules in our guts (their discovery nearly a century ago was a Nobel Prize-sized breakthrough).
"They act as detergents, not unlike soap," Quinn said. "So, when you're having your nacho cheese or a hot dog at the game while watching the Spartans play, they'll solubilize those fats and help you absorb them."
For decades, researchers knew that our livers conjugated bile acids by adding two specific amino acids to the mix before releasing them to do their work.
Imagine the scientific community's surprise when Quinn's lab demonstrated gut microbes could conjugate them, too, adding entirely new combinations into the mix. Double that surprise after the team showed these microbially conjugated bile acids, or MCBAs, were created by a well-studied enzyme that until then was best known for breaking them down.
These findings — each part of a massive, interlocking chemical puzzle — are perfect examples of how the microbiome is becoming a life-changing tool at the meeting place of science and medicine.
In addition to first-of-their kind biochemistry discoveries, Quinn is finding ways to ensure his lab's research makes a timely difference where it matters most: in the hands of healthcare professionals.
Thanks to advances in bioinformatics, a patient's gut microbiome sample can be analyzed and transformed into usable clinical data in as little as 48 hours.
These results provide vital information when it comes to diagnosing microbiome-related diseases, as well as learning how to manipulate gut chemistry as a means of treatment.
"The technology that allowed microbiome science to flourish is now commonplace on university campuses and research institutes. Soon it will be at the bedside in clinics and hospitals, in some places it already is." Quinn said.
