Apr 1, 2019 | Microbiome
by Folabomi Oladosu, PhD
Post-doctoral researcher specializing in pain and women’s health at NorthShore University HealthSystem
Holding a newborn for the first time simultaneously conveys the fragility of life and the enormous responsibility of ensuring this tiny person’s progression to adulthood. All the coos, gurgling, and late night cries are important steps in a newborn’s developmental process. These behavioral cues let us know that this baby is growing up exactly as she should.
Unfortunately, newborns born preterm—earlier than expected—are more likely to have developmental delays. Scientists are looking for ways to help reduce or eliminate some of these delays, and recent research indicates that the gut microbiome may be a key factor.
Before emerging into our messy world, a baby lives in an almost microbe-free environment. It’s during birth that most newborns are introduced to a great variety of helpful microorganisms, especially from her mother. The infant meets additional friendly bacteria as she nurses from her mother’s breast. These microbial partners begin teaching the baby’s immune system how to recognize friends—bacterial or chemical—and distinguish them from bad actors in the same way parents teach their children the difference between Aunt Mary and “stranger danger.”
Along with the immune-boosting proteins delivered via breast milk, these helpful bacteria give the newborn’s immune system the time and experience to learn and mature. In fact, most healthy, full-term infants show a pattern of progression where their gut microbiome evolves to look pretty much like an adult’s by about age two and a half.
But preterm newborns are different in several ways. They are more likely to be delivered via Cesarean section, a route that exposes infants to far fewer microbial allies. And because of their size and shortened development in utero, preterm infants usually need to stay in the hospital longer than most newborns, with reduced access to mom’s breast and the helpful microbes and immune-boosting proteins that come along with it. This means the baby’s immature immune system get less expert training and is thus more susceptible to infections.
To prevent these infections, preterm infants are often given antibiotics, a course that can set up additional problems. Antibiotics can kill bad guys but also destabilize the microbial community developing in the gut, interfering with the immune training that helps the baby thrive in the long run. It is thus important to understand the tradeoffs in using antibiotics and choose the best treatments for the long-term health of each little person.
Alyson Yee, a student in UChicago’s Medical Scientist Training Program (an integrated MD/PhD program) and then a member of the lab of Jack Gilbert (now at the University of California San Diego), wanted to consider that issue. “We think there’s a critical window in early life to train the immune system by being exposed to the right microbes,” said Yee. “For example, kids born by Caesarean section, with less exposure to microbes from their mother’s gut and vagina, have a higher lifelong risk for allergy and asthma. Childhood exposures to the environment, especially pets, can also change the microbiome and the immune system. This is why it’s so important to study the microbiome in infancy.”
Of course, the most sensitive infants are the tiniest. So Yee set out to analyze the gut microbiome of infants with very low birth weights by determining how their microbial profiles differed from full-term babies then examining how those differences affected weight and length gain during the first six weeks after birth. For a subset of those babies, she and her team were able to retest the children at two and four years of age.
Her team looked at two specific characteristics of the gut microbiome: the overall diversity, a sign of microbial health, and the rate of microbial turnover, a key measure of progress to microbial maturity.
At six weeks, the team found that very-low-birth-weight babies with greater microbial diversity who received a greater percentage of milk from their mother’s breast were gaining weight somewhat more quickly. But they also found that antibiotic exposure encouraged an abundance of proteobacteria, a kind of resistant microorganism commonly found in hospitals that can become opportunistic pathogens. Together with two other specific types of bacteria found in those on antibiotics, proteobacteria were correlated with poor weight and length gains. In contrast, infants with increased microbial turnover—including those delivered by C-section—tended to have fewer of these bacteria and grew faster during their hospital stay.
The best news is that microbial diversity in most of these very-low-birth-weight babies increased significantly over time. By age four, the baby’s microbial profile was very similar to that of her mom’s, proving yet again the resilience of the human organism.
It’s interesting to note that researchers have found similarities between the preemie microbiome and that of full-term infants who are undernourished—suggesting that therapies developed for one group may be helpful for the other.
Given the relatively small number of very-low-birth-weight babies they followed at six weeks (83) and at four years (25), the researchers suggest continuing expanded studies. UChicago neonatologist Erika Claud is already leading a major study that will follow of thousands of premature babies over five years to understand how the development of the microbiome affects childhood development and even school readiness. Stay tuned for more clarity on how we can promote the greatest health for our littlest fellow humans.
Mar 28, 2019 | Commercialization, Immunology, Microbiome, News Roundup
A selection of health news from the University of Chicago and around the globe curated just for you.
Polsky Center’s Life Science Launchpad partners with faculty to launch startups
The Launchpad bridges the gap between academic research and entrepreneurship by forming hands-on partnerships with life sciences researchers who seek to convert their research products into business ventures. Cathryn Nagler and Eugene Chang featured. (Polsky Center for Entrepreneurship and Innovation)
How the microbiome could be the key to new cancer treatments
The effectiveness of drugs that help the immune system fight cancer cells appears to depend on bacteria in the gut. (Smithsonian magazine)
Training cells to attack
Groundbreaking CAR T-cell therapy engineers cells to target tumors. Michael Bishop featured. (Chicago Health)
How to reduce the chances of being hospitalized for Crohn’s disease
Take these steps to lessen the risk of complications from the inflammatory bowel disease. David Rubin featured. (U.S. News and World Report)
Real innovation is going to be centered on how we collect, standardize, and harmonize data
Bridging the gap between clinical care and research means creating two-way collaboration, and improving the way in which data is collected, organized, shared. Sam Volchenboum featured. (Outsourcing-Pharma.com)
Mar 6, 2019 | Microbiome, Sustainability
by Elise Wachspress
Image courtesy of Regio Energie Solothurn
WellNews usually reports on groundbreaking research on the immune system, genetics, and the microbiome that promotes wellness—at the level of the individual.
Now for something totally different.
Laurens Mets is studying ancient microbes—archaea—as a way of improving human health for everyone in the world, banking on these tiny organisms to help clean up our environment, remove carbon dioxide from the air, and perhaps save the planet.
On the surface, archaea look something like bacteria, with similar shapes and no nuclei. But unlike bacteria, they have some genetic and metabolic similarities to plants and animals—and some traits that make them totally unlike either group. It wasn’t until 1977 that Carl Woese and George E. Fox proved archaea were a totally different domain, with their own separate, major branch on the “tree” of life.
The first archaea discovered were “extremophiles,” organisms that prospered in harsh environments like hot springs and salt lakes. Now they’ve been found everywhere, including in our own bodies. Archaea are amazing life-forms, in that they can live on a huge diversity of energy sources: ammonia, metal ions, even hydrogen gas. Some salt-tolerant types use sunlight as an energy source, and others can fix carbon from the atmosphere. They are particularly numerous in the oceans, and so far, none seem to be pathogenic.
Mets’s idea was to find and optimize archaea that would metabolize the garbage in our landfills and the carbon dioxide in the atmosphere—by-products of our own energy use—and then turn these into fuels. And he’s developed some proprietary strains of archaea (starting from some originally isolated from a hot spring in Iceland) that are already doing just that—in two different ways.
In the case of garbage, the approach is to “gasify” carbon-based trash (which is most of what fills our landfills) at extremely high temperatures, creating a mixture of largely hydrogen, carbon dioxide, and carbon monoxide. That part has been done by several other methods, but with an implicit problem: how do you manage the deadly carbon monoxide? Mets’s process uses archaea as a biocatalyst to turn the entire mixture—including the carbon monoxide—into methane. Methane makes up the bulk of what we call natural gas, a relatively clean fuel that is easily transported and stored through existing systems.
A new approach to carbon capture?
In the second approach, Mets uses archaea to solve two problems with solar and wind power. First, both generate energy as electricity, which currently meets less than 20 percent of the U.S.’s energy needs. Perhaps more important, solar and wind energy are intermittent, tough to store, and poorly matched to variation in demand over daily or yearly cycles. But Mets’s archaea can use energy from excess electricity to convert atmospheric carbon dioxide into methane. Switching from natural gas to electricity and back again would not only mitigate the variabilities in electricity production but also incentivize greater reliance on these renewable energy sources—and reduce net carbon emissions to the atmosphere.
With help from the Polsky Center for Entrepreneurship and Innovation, the University of Chicago has licensed out the early versions of Mets’s archaea technology to a German Company, Electrochaea GmbH. Germany and much of Eastern Europe, famously dependent on Russian fuel, recognize a crucial need for increased energy diversification. As Mich Hein, CEO of Electrochaea (and former entrepreneur in residence at the Polsky Center) pointed out in advance of last year’s Energy Storage Europe conference, the archaea technology can serve as “a drop-in replacement for fossil natural gas that can be stored or transported in existing natural gas infrastructure. The renewable gas product unites different energy sectors and provides economic leverage for owners and operators of existing assets.”
Electrochaea is now a partner in a venture called Store&Go that just opened a new plant in Switzerland, introduced by an absolutely charming spokesmodel: Archie, an archaea who demonstrates just how he cleans up after our own energy expenditures to make more fuels.
Mets, however, believes he can push the technologies much further. While he has developed the most energy-efficient strain of archaea so far, he is convinced that he and his lab can do better. These molecular geneticists want to advance experiments to iteratively select, mutate, and then sequence the genomes of the most carbon monoxide-tolerant archaea and develop microbes that are increasingly efficient at turning our carbon-based waste into storable, transportable fuel.
If archaea technology can create a closed loop for carbon-based fuels, where carbon uptake equals carbon emissions, the world may have reason to heave a sigh of relief. After the past decade of increasing global temperatures and dramatic variations in weather patterns—some costing cities and countries trillions of dollars—it is becoming clear that man-made climate change is threatening millions of lives around the world. Mets’s research (and yes, he is looking for funding support) holds the potential to save both money and the planet. These microbes could indeed help the entire world’s population—and all the other animals who live here—become healthier in many ways.
Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office
Feb 14, 2019 | Microbiome
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.
Jan 25, 2019 | Microbiome
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.
Nov 30, 2018 | Food Allergies, Microbiome, News Roundup
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)
