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Stent me once, that’s on me. Stent me twice, that’s on my gut bacteria.

Stent me once, that’s on me. Stent me twice, that’s on my gut bacteria.

by Folabomi Oladosu, PhD
Post-doctoral researcher specializing in pain and women’s health at NorthShore University HealthSystem

At the start of your doctor’s visit, as the nurse checks your pulse and blood pressure, you probably take slow deep breaths, trying to convince your doctor and yourself that you’re cool, calm, and collected. (No? Is that just me?)

Your blood pressure can tell your doctor a lot about you—including your risk for peripheral arterial disease, or PAD. In PAD, arteries that carry blood throughout the body are narrowed by deposits of fat and cholesterol. The disease is common, with more than three million new cases surfacing every year. PAD puts people at increased risk of both heart attack and stroke, so it’s important to treat it quickly and effectively.

When diet, physical activity, or medications are not enough, surgery is the next step to open up the narrowed arteries. Options include an angioplasty, where a tiny balloon is inserted into the blocked artery. The balloon is inflated to crush the plaque deposits and then removed to restore blood flow.

Following surgery, these once clogged arteries should carry red blood cells throughout the body like an amusement park water slide. To your dismay, you find this water park attraction might need more repairs three to 12 months later because of restenosis, the abnormal re-narrowing of arteries following surgery (Get it? Re-stenosis). Restenosis occurs in about 40 percent of patients after angioplasty and is usually treated with yet another surgery.

What causes this re-narrowing? Inserting the balloon and compressing the plaque may cause a mild arterial injury. The immune system responds, sending in white blood cells and platelets to repair the artery. But sometimes the immune system goes overboard and causes scarring instead. This means that the same arteries that were first narrowed by fatty deposits are narrowed yet again because of scarring caused by the immune system.

Why does the immune system to go into hyper-drive following surgery? One contributing factor may be—amazingly—the bacteria living in our gut. Drs. Eugene Chang and Betty Theriault of the University of Chicago collaborated with Dr. Karen Ho of Northwestern University to investigate the role of the gut microbiome on arterial healing following surgery.

Using their extensive knowledge and technical expertise, the team developed a method to study arterial healing in germ-free mice, mice with no gut bacteria. Their work revealed that germ-free mice developed much less arterial scarring following surgery compared to normal mice. Their research also showed that the immune system of germ-free mice was different than normal mice, using different white blood cells less likely to encourage swelling and scarring at the injury site.

All of us have been surrounded by germs since the day we were born. So if we need an angioplasty, we’d be like those normal mice, more likely to have arterial scarring after surgery.

Is there anything we can do to prevent restenosis? Related work by Drs. Ho and Chang suggests yes. A month-long treatment of the antibiotic vancomycin paired with sodium butyrate (a compound that slows cell growth) reduced arterial scarring in rats following an angioplasty. Legumes like beans and peanuts, when digested by gut bacteria, are a common source of sodium butyrate. This suggests that the dietary changes prior to angioplasty may help reduce arterial scarring and restenosis.

This “basic science” research by Drs. Chang, Theriault, and Ho provides great insights for better health. It shows that, despite their microscopic size, gut bacteria can greatly influence how we heal from common surgeries. The humble legume–cheap, tasty, easily stored, and environmentally friendly to grow—may help to keep our internal water slides open for service long after initial repairs.

 

Tracking down the ‘microbial peacekeepers’

Tracking down the ‘microbial peacekeepers’

by Kate Dohner

“When you go to the forest, what do you see?” asks A. Murat Eren, whom everyone calls Meren.

While the trees are the most noticeable, it’s important to pay attention to what’s on the forest floor—shrubs, wildflowers, ferns, and mosses. Without them, Meren points out, there would be no forest at all.

Like the forest, the human gut contains a multitude of organisms—bacteria, fungi, and viruses—collectively known as the human microbiome.

‘If you can observe a forest after a fire, you can see how it renews,” Meren said. “It all starts on the forest floor, led by ‘pioneer’ species like grasses and shrubs.”

Similarly, Meren is studying the human microbiome after a period of disturbance to see which bacteria help return it to a healthy state.

For instance, when the balance of bacteria in the gut is disrupted, a bacterium called Clostridium difficile or C. diff can proliferate. While C. diff sometimes responds well to antibiotics, recurrent, resilient infections are not uncommon. In these instances, patients can benefit from fecal microbiota transplantation or FMT, the transfer of “good bacteria” from a donor’s stool to a recipient. Although FMT is successful in many cases, there are risks, including the unintentional transfer of problematic biological material, such as viruses.

“With FMT today, we essentially gather the entire contents of a healthy forest and dump that ecosystem into a disturbed forest,” Meren explained. “Though that may work, we don’t know how.”

Meren and his team are on the hunt for the specific bacteria that can set up a healthy environment in any distressed digestive system, especially for those battling inflammatory bowel diseases.

“The microbes we’re looking for are like the person who can talk to anyone at a party,” Meren said. “She’s happy anywhere and helps put others at ease.”

Collaborating with world-renowned clinical experts (including Thomas Louie and David Rubin), Meren and his team are studying fecal samples from people around the world to identify these versatile microbes. Using the advanced computational tools they develop, Meren’s team can compare and categorize bacteria found in a variety of people—from infants to adults, to those in industrialized countries versus places like Tanzania.

The goal is to not only advance our understanding of the trillions of bacteria that make up the human microbiome, but to track down the special characters that can make any microbial community thrive.

“We scientists often gravitate toward what is most abundant in an environment—a byproduct of our historical relationship with numbers and the methods we have to make sense of them,” Meren said. “As a trained computer scientist, I recognize that bias and always remind myself that function—how something contributes to its environment—is what we’re really after.”

Meren cites the role of police in society; though they make up a small proportion of the population, they are critically important to how communities function. So it may be with certain bacteria.

“Instead of investigating just any bacteria we find in healthy human guts, we are conducting a systematic study to find microbes that can help microbial ecosystems recover from distress,” Meren said.

The team has already identified some “microbial peacekeepers” and are continuing their search for more, building a comprehensive genomic and culture library to see how each microbe behaves in different experimental settings.

Ultimately, Meren hopes this work will lead to a targeted, reliable microbial therapeutic that will not only help those with C. diff infections, but also people with inflammatory bowel disease and other gastrointestinal problems.

“Although basic science is demanding and even frustrating at times, important insights will only emerge from this type of work. My group and I believe we are on the right track to finding the critical members that keep the microbial forest in our guts healthy.”

“There’s so much more to learn,” added Meren, “but here at the University of Chicago, we have the right tools to recognize and investigate fundamental questions and are surrounded by tremendous expertise in immunology, microbiology, and gastroenterology—collectively offering us a rare opportunity to transform medicine.”

Kate Dohner is a senior writer for the University of Chicago Medicine & Biological Sciences Development office.

News roundup: November 2018

News roundup: November 2018

A selection of health news from the University of Chicago and around the globe curated just for you.

Researchers find promise in new treatment for food allergies
UChicago is part of clinical trial that doctors hope will lead to an FDA-approved medication for people with peanut allergy. Christina Ciaccio featured. (UChicago News)

Save the germs
With modern medicine killing off whole categories of bacteria and viruses—including benign ones that promote health—Jack Gilbert and colleagues propose a way to preserve microbes that may rescue us one day. (The New York Times)

How might the appendix play a key role in Parkinson’s disease?
Those who have their appendixes removed in young adulthood run a nearly 20 percent lower risk of developing the neurodegenerative disorder decades later or not at all, study finds. (Scientific American)

Polsky Center’s Innovation Fund renamed to honor George P. Shultz
The decision to rename the Innovation Fund was the result of a $10 million gift to the Fund from University trustee and Booth alumna Mary A. Tolan, MBA ’92. (Polsky Center)

Jeffrey Hubbell named to National Academy of Medicine
Research by Hubbell—who co-founded UChicago food allergy startup ClostraBio—has led to tools and treatments, including nanoparticle vaccines and drug delivery systems, that combat diseases ranging from influenza and type 1 diabetes to tuberculosis and cancer. (UChicago News)

Going with the flow

Going with the flow

 by Elise Wachspress

If you think the invention of the microscope was a pivotal moment in the development of biological knowledge, you might be pretty impressed with the flow cytometer.

This technology allows scientists to “see” an entire stream of individual cells, detecting the features of each as they rush single file through a tiny tube. A laser (or sometimes several) shines through or bounces off the cells as they pass by. Depending on the specific kinds of fluorescent indicators applied, flow cytometry can efficiently characterize 30 or more factors in hundreds of thousands of individual cells and even sort them as they surge through the tube.

For scientists studying the microbiome, the immune system, and their intersection, flow cytometry—we celebrate its 50th anniversary this year—was a breakthrough. The tool provides an efficient way to both distinguish the various bacteria in a sample and identify human immune cells and the particular antibodies they carry.

Last fall, a team led by Jeffrey Bunker (a student in the University of Chicago’s revered Medical Scientist Training Program) and his mentor, Albert Bendelac, MD, PhD (A.N. Pritzker Professor of Pathology) used flow cytometry to understand an important interaction between the gut and the bacteria that live there.

The gut is the source of large quantities of immunoglobulin A (IgA), the most abundant antibody protein in mammals. In our intestines, where we depend on a diverse community of bacteria to digest our food and make important by-products like vitamins, IgA sticks to the surfaces of the microbes, allowing them do their work while keeping them from settling in on the mucous membranes that line the gut. These membranes are the critical barrier that separates the energy furnace in our intestines from the rest of our bodies.

But how do IgA proteins—which defang bacteria with a kind of key-in-lock technique—recognize the many different kinds of bacterial locks and latch so specifically on to each? Thanks to flow cytometry, the team could identify the many types of bacteria involved, so they knew the complicated job IgA was up against.

What they found was that IgA cells in the gut were “polyreactive”: they could clasp very specifically onto many different types of bacteria. This Swiss-army-knife ability was not the result of intervention by other parts of the immune system or hyperactive mutations within the IgA cells themselves. Even changes in diet (and the presumed alterations in the balance of bacteria induced by these changes) did not significantly affect their ability as quick-change artists.

This research demonstrated that IgAs, part of our adaptive immune system, actually have the innate—born inability to recognize individual types of bacteria, even new ones, and do what they need to do to create the right latch. The takeaway is that the bacteria in our guts and our own immune systems have clearly been evolving together, probably for millennia, and that the immune systems of new humans have innate ability to recognize “old” bacteria—those that have been fellow travelers with the human race for generations.

This is just one more bit of evidence that none of us are truly individuals. Each human being is a colony of species living together in community—communities with very long histories and intense cultures—and we’re wise to go with the flow.

This past summer, Bunker and Bendelac went on to publish a major review article on IgA biology for the journal Immunity. There they presented a new framework integrating two distinct types of immunity that protect the gastrointestinal mucus membranes: the polyreactive IgA described above and much more “bespoke” key-and-lock responses to pathogens and vaccines provided by other kinds of immune cells.

Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office

 

News roundup: October 2018

News roundup: October 2018

A selection of health news from the University of Chicago and around the globe curated just for you.

Three UChicago Scientists Earn NIH Grants to Pursue Innovative Research
Three UChicago scientists—including Jun Huang, who studies the immune system and its role in treating infectious diseases and cancer—each have been awarded $1.5 million grants over five years from the National Institutes of Health in support of their innovative, high-impact biomedical research. (UChicago News)

Noah’s Ark for Microbes
A team of researchers, including Jack Gilbert, is calling for the creation of a global microbiota vault to protect the long-term health of humanity. (Science)

These 19 MassChallenge Startups Just Won $1.65M
Nineteen early-stage startups, including Oxalo Therapeutics, won a total of $1.65 million at Wednesday night’s MassChallenge awards ceremony. (BostInno)

Polsky Opens its High-Profile Accelerator to Alumni Startups
UChicago’s New Venture Challenge, ranked among the top accelerator programs in the country, is launching an alumni track as part of its annual startup competition. (American Inno)

Meet the Carousing, Harmonica-Playing Texan Who Just Won a Nobel for his Cancer Breakthrough
This year, the Nobel Prize was awarded to James Allison, PhD—a colleague, friend, and “The Checkpoints” bandmate of Tom Gajewski—for research that laid the groundwork for the development of checkpoint inhibitor immunotherapies. (WIRED)

 

News roundup: September 2018

News roundup: September 2018

A selection of health news from the University of Chicago and around the globe curated just for you.

The end of an epidemic
The number of people with food allergies has exploded in recent years. A dream team of researchers from UChicago may have figured out why, and now they’re developing therapies that could end the epidemic. Cathy Nagler featured. (Chicago magazine)

UChicago startup gets $2.3 million for kidney stone prevention
Biotechnology startup Oxalo Therapeutics is closer to developing a first-of-its-kind drug to prevent kidney stones thanks to $2.3 million from the National Institutes of Health. Hatim Hassan and Yang Zheng featured. (Crain’s Chicago Business)

Science by the sea
In three weeks, there are just over 500 hours. The students in the Marine Biological Laboratory’s September intensive courses tried to use them all. Jack Gilbert featured. (UChicago Magazine)

Nasal bacteria linked to cold severity
In a study, people with certain bacteria in their noses were more likely to develop more severe cold symptoms. (U.S. News & World Report)

Brain-gut link may be way faster than we thought
New research with mice may upend our understanding of the connection between the gut and the brain, as well as appetite. (Futurity)