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The connection between hierarchy and health

The connection between hierarchy and health

by Elise Wachspress

After phenomenal increases in lifespans over the past century, longevity in the US has begun to head in the wrong direction. Since 2014, average life expectancy has ticked downward, from a high of 78.9 years to 78.6 last year—placing us 37th among the world’s countries, tied with Albania and more than five years behind long-lived Japan (83.7 years).

The American Academy for Family Medicine cites several causes: the opioid epidemic, increasing suicide rate, and a rise in maternal mortality. Behind these specific threats lurks a shadowy but more endemic source of reduced life expectancy: growing inequality.

As long ago as the first century, the natural philosopher Pliny the Elder recognized a connection between socioeconomic status and lifespan, citing kings, senators, consuls, priests, and performers who lived to a remarkably old age. Some reasons for the perceived disparity seem pretty obvious: lack of food, shelter, hygiene, and medical care have put poor and less educated people at a disadvantage. But the data show that social status also significantly predicts longevity. For instance, despite war and the treacherous travel involved in their diplomatic missions, our first three presidents lived to ages 67, 90, and 83 respectively, when the average US resident could expect to reach only 37. And a survey of the Academy Award nominees shows that those who won the Oscars lived four years longer than those who didn’t.

How does social adversity get inside our skin? One theory is that low social status revs up genes that control the immune response, perhaps preparing lower-status members of a community to fight infections—but at the same time making them more vulnerable to conditions caused or exacerbated by inflammation, like heart disease, cancer, diabetes, and many others.

To investigate how status might influence the immune system, a group of scientists from the US and Canada studied a population of 45 rhesus monkeys, a highly hierarchical species relatively close to us on the evolutionary “tree.” They divided the monkeys into nine groups of five, observed them over a year as rank was established within each group, then re-sorted them into new groups, placing those of similar social rank together—thus forcing an abrupt change in the individual rank of most of the monkeys.

To see how the change in social status affected the animals’ immune states, the researchers took blood samples from each. They found that the lower the social status of each monkey, the stronger was the inflammatory response engaged by their immune system.

The researchers’ clever experimental design also allowed them to see how past social status affected the monkeys’ later immune states. The researchers found that animals at the bottom of the pecking order in the first year of the study still showed immunological traces of past low status, despite their improved social position in their second communities. And though the correlation was weaker, those who enjoyed high rank the first year also suffered immunologically when resorting forced them into a lower social position.

So no matter how each of these primates started in life, being at the bottom of the social ladder was demonstrably detrimental to their immunological state, even with sufficient food, housing, and care.

Research like this is a good example of how the Duchossois Family Institute (DFI), focused on understanding how to maximize health for the greatest number of people, can help us think more deeply and productively about wellness and what it will take for all to thrive.

This work is also an illustration of the approach to training and collaboration central to the organization of the DFI. The lead authors of the paper, Jenny Tung, PhD, and Luis Barreiro, PhD, both did critical postdoctoral training at UChicago early in their still-youthful careers—much like the cross-disciplinary postdocs that will now be supported through the DFI. Though Tung (a 2019 MacArthur Fellow) is now on faculty at Duke University and Barreiro (after an appointment at the University of Montreal) is now a professor at UChicago, they continue to collaborate closely and productively.

And building on that training and collaborative spirit, they are now leading a new generation of graduate and postdoctoral students to uncover how scientific research can improve health for many across the world.

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

 

News roundup: December 2019

News roundup: December 2019

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

Microbes living in the tons of plastics in the oceans
Jessica Mark Welch and colleagues at UChicago’s Marine Biological Laboratory at Woods Hole, MA, aim their new microscopy technique at microplastic samples from the ocean to characterize the extensive biofilms on ocean plastic. (Agro Ecology Innovations)

Staph vaccines likely to work better if administered earlier
Research by former UChicago faculty member Julian Bubeck-Wardenburg, now at Washington University in St. Louis, suggests that vaccinating infants before their first encounter staph, either just after birth or via their mothers during pregnancy, would likely generate a stronger immune response. (Futurity)

Microbial inequity
To the host of ways people experience inequity, add the microbiome: A University of Maine scientist argues that access to fibrous foods, parks, good air quality, other infrastructure affect the development of a healthy microbiome. (The Conversation)

UChicago faculty lauded yet again
Thomas Gajewski, MD, PhD, Abbvie Foundation Professor of Cancer Immunotherapy, is honored with the 2019 Award for Immuno-Oncology from the European Society for Medical Oncology (Healio)

Gut neurons are anti-salmonella warriors
Research from Harvard Medical School have found that nerves in the gut not only regulate the cellular gates that admit microorganisms, but actively boost the number of protective microbes there. (ScienceBlog)

 

Do cultural practices influence the immune system?

Do cultural practices influence the immune system?

by Paulette Krishack
Post-doctoral fellow in the University of Chicago’s Department of Medicine

Around 10,000 years ago, our ancestors began establishing the first permanent settlements. The dawn of agriculture provided a stable food supply, and those who had once hunted and gathered for sustenance could settle down to a more rooted lifestyle and greater investment in shelter, clothing, even political and artistic endeavors.

But every lifestyle has its challenges. The change to a more permanent settlement seems to have been accompanied by an increase in infectious diseases, like measles and plague, that only take hold when there is a critical mass of infected people. Anthropologists and others have theorized that farming made it easier for diseases to spread from soil, insects, and larger animals to humans, and that the larger, denser communities fostered through agriculture encouraged transmission between humans.

UChicago evolutionary biologist Luis Barreiro, PhD, Pennsylvania State anthropologist George H. Perry, PhD, McGill University geneticist and their team set out to test this idea. They wanted to determine if and how the immune system evolved in response to a move from a hunter/gatherer to an agricultural lifestyle. Perhaps they would show that agriculturalists’ immune system had adapted to the spread of infectious diseases via evolution, positively selecting genetic variants that helped them survive in the face of communicable diseases.

The researchers focused on two different Ugandan communities, the Batwa (hunter/gatherers) and the Bakiga (agriculturalists), located near each other but isolated for thousands of years. The research team collected and genotyped whole blood samples from each. They also incubated circulating white blood cells from individuals in both communities with viral and bacterial agents, to understand how immune responses differed between the two communities.

The team found that each community did have a unique immune profile and that natural selection has contributed to differences in immune responses between the two groups. Yet, their results do not support the long-standing hypothesis that pathogens exerted selective pressure on agriculturalist populations. Instead, Barreiro, Perry, and Harrison’s work, documented in Nature Ecology and Evolution, demonstrated that there were more selective differences in immune responses in the hunter-gatherer population. The study also suggest that differences in exposure to viruses might have been the primary driver of adaptive evolution in both populations.

While the authors offer the caveat that their sample size (just over 100 people) was small, they have provided the first genome-wide comparison of immune variation between hunter/gatherer and agricultural populations in Africa—an issue that seems important to understanding man’s relationship to both the environment and food production. By learning how we have adapted to our changing surroundings over time, we can better fine-tune our lives and systems to support greater health in the future.

 

News roundup: November 2019

News roundup: November 2019

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

The community in your mouth
Marine Biological Laboratory and DFI researcher Jessica Mark Welch, PhD, shares her research into oral microbiome, and what we can learn about healthy and diseased states from microbes’ relationships and interactions. (Smithsonian Magazine)

Common drugs linked with microbiome alterations
Patients who used drugs from 18 common drug classifications—including proton pump inhibitors, metformin, antibiotics, laxatives, and others—showed extensive changes in their gut microbiomes. (MedPage Today)

DFI researcher Tatyana Golovkina, PhD, named AAAS fellow
UChicago professors Melina Hale, PhD, and Margaret Beale Spencer, PhD’76, were also honored by the American Association for the Advancement of the Sciences—the world’s largest general scientific society. (UChicago News)

Urine microbiome predicts cancer immunotherapy response
UChicago physician-scientist Randy Sweis, MD, demonstrated that the presence of certain strains of bacteria could tell us which bladder cancer patients would face recurrence after immunotherapy treatment. (Healio)

Diets high in fiber and yogurt cut lung cancer risk
By collecting data from several lung cancer studies involving more than 1.4 million adults from the US, Europe, and Asia, researchers showed that high-fiber, high-yogurt diets reduced lung cancer risk by one third. (Futurity)

 

Can autoimmunity cause neurological problems?

Can autoimmunity cause neurological problems?

by Elise Wachspress

Celiac disease is a serious autoimmune disorder. When those with celiac eat gluten—a group of proteins found in cereal grains like wheat and barley—their immune systems respond by inflaming and damaging the little “fingers” of tissue that absorb food nutrients in the small intestine.

About one in every 100 Americans has celiac, but many don’t realize it. The disease can be hard to diagnose, because symptoms are so diffuse: anemia, osteoporosis, loss of dental enamel, heartburn, headaches, tingling hands, joint pain, a blistery skin rash, etc. Children may suffer vomiting, diarrhea, poor appetite, muscle wasting, and even failure to thrive; adolescents may be abnormally small for their age, with delayed puberty.

Among the hardest symptoms to pinpoint and link to celiac is what some patients call “brain fog.” Those with the disease often report episodes of headaches, depression, moodiness, difficulty concentrating, fumbling to choose words, and/or feeling tired even though they just got out of bed. Sometimes only when people are diagnosed with celiac, change to a gluten-free diet, and then find these symptoms disappear do they realize how celiac inflammation affected the clarity of their neural processing.

The problem is, total gluten elimination is hard to accomplish. While gluten-free foods and restaurants are becoming increasingly common, food is fundamental to most social relationships, and it’s hard to manage every interaction without seeming prickly or oversensitive.

And many “non-food” products use gluten as an edible “glue” to bind mixtures together, including some vitamins, medications, lipsticks and lip balms, even bouillon cubes. Then there are the products one might never suspect involve gluten, like pickles, hot cocoa mix (Celiac patients often make their own), and soy sauce (One can substitute the safer tamari).

So what happens when a patient with celiac has an inadvertent exposed to gluten? Or the pizza shows up in your child’s school and resistance is low? Some people find themselves living through several days when their brains just don’t seem to function. Work and school become a challenge, even for people who are normally bright and creative. People accidentally exposed to gluten report symptoms from irritability to anxiety to full-blown panic attacks.

Bana Jabri, MD, PhD, has long been interested in understanding the neurological distress that sometimes follows accidental gluten exposure. She wants to find out if immune factors called cytokines, released in response to gluten exposure, affect brain chemistry and the nerve centers feeding back to the gut. Understanding the relationship would provide a better understanding not only the neurological mechanisms involved in celiac disease, but also in other autoimmune conditions, like multiple sclerosis and rheumatoid arthritis, in which patients also report similarly diffuse cognitive impairment.

Jabri has established a collaboration with Jean Decety, PhD, a UChicago neuroscientist internationally recognized for his work in using fMRI (functional magnetic resonance imaging) to understand affective behavior. While a handful of case studies have used fMRI to study extremely serious neurological symptoms in individual patients with celiac disease, no one has yet undertaken a larger study of how celiac creates the “brain fog” that seems such a common complaint.

The plan is to have patients undergo fMRI, immunological, and other testing before and after a controlled gluten ingestion, to map the changes in all these factors. Jabri and Decety hope the results will help generate novel insights into the neurological impact of the disease and potential therapeutic avenues to prevent these negative outcomes.

Right now they are searching for funding to support these studies. But what they find may make life a lot easier for the three million Americans living with celiac disease, some living in fear that they may accidentally ingest something that will put them in a fog for days.

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

 

Engineering the immune system to fight breast cancer

Engineering the immune system to fight breast cancer

by Paulette Krishack
Post-doctoral fellow in the University of Chicago’s Department of Medicine

Breast cancer is one of the most commonly diagnosed cancers in women. Approximately one in eight will develop the disease in their lifetime, and over 40,000 in the U.S. will die from it this year. While genetics plays a role, 85 percent of women diagnosed with breast cancer have no family history, and effective prevention and treatment depends on identifying the other factors involved.

Clinicians break down breast cancers into at least five types, based on the molecular features present in the tumor cell. Several types are known to show hormone “receptors” (most commonly estrogen, progesterone, and a protein called HER-2) which offer targets for treatment.

But in one type, triple negative breast cancer (TNBC), tumor cells lack the hormone receptors and HER-2 protein known to fuel breast cancer. Finding a way to specifically target TNBC, a particularly aggressive form of cancer, is critical.

Obesity is known as a risk factor for breast cancer incidence and progression. Because obesity can cause chronic, systemic inflammation, Lev Becker, PhD, Marsha Rosner, PhD, and Payal Tiwari, PhD, were interested in finding out how the immune system might be involved in TNBC.

Becker has dedicated his laboratory and career to studying macrophages, the “big eaters” of the immune system, while Rosner specializes in cancer therapeutics. Although macrophages are powerful fighters of viruses and bacteria, they can also be called in to engulf the saturated fatty acids found in many high-fat foods, causing high-fat induced inflammation in the tissues they invade. Becker, Rosner, and Tiwari wanted to see if these obesity-associated macrophages were involved in TNBC.

Using a mouse model of TNBC, they found that the most common macrophages in the breast fat tissue of obese mice were a type specifically activated by a high-fat diet. These macrophages produced a pro-inflammatory protein, a cytokine called IL-6, which created a nurturing environment for TNBC tumors to grow. The team also found that switching the obese mice to a low-fat diet slowed tumor development. Studies also showed human tumor tissue with similar results: there were fewer macrophages present in tissues from lean patients than obese ones.

These studies suggest that immunotherapy—treatments targeting the immune response that is activated by macrophages—may offer innovative care for patients with TNBC, especially if they are obese. They may also offer potential strategies for treating other diseases linked to obesity, particularly those that involve macrophages, such as cardiovascular disease.

Most importantly, this research demonstrates the value of diet in maintaining health. A third of American adults are obese and another third overweight. Now that we know the toll a high-fat diet exerts on molecules in our body, we can embrace the mission of the Duchossois Family Institute: Use the knowledge we develop to improve our health and all those with whom we share the planet.