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
A selection of health news from the University of Chicago and around the globe curated just for you.
Improving care for young hearts
Ivan Moskowitz is investigating the genetic causes of pediatric congenital heart disease (CHD) in an effort to improve diagnosis and treatment of children born with this condition. A recent gift from The Heart of a Child Foundation will help support his research. (Give to Medicine)
Antibiotic treatment alleviates Alzheimer’s disease symptoms in male mice
Researchers at the University of Chicago have demonstrated that the type of bacteria living in the gut can influence the development of Alzheimer’s disease symptoms in mice. Sangram Sisodia featured. (UChicago Medicine)
Addressing social needs and structural inequities to reduce health disparities
“Entering Asian American and Pacific Islander Heritage Month, a cutting-edge issue is addressing social determinants of health, which are especially critical among diverse Asian American ethnic groups that vary in education, income, and acculturation,” writes UChicago Medicine’s Marshall Chin. (NIMHD Insights)
Phage therapy to prevent cholera infections—and possibly those caused by other deadly bacteria
Discovered a little more than 100 years ago, bacteriophages, or phages, are generating renewed interest as potential weapons to fight bacteria that are resistant to multiple antibiotics. (The Conversation)
Common food additive found to affect gut microbiota
Experts call for better regulation of a common additive in foods and medicine, as research reveals it can impact the gut microbiota and contribute to inflammation in the colon, which could trigger diseases such as inflammatory bowel diseases and colorectal cancer. (ScienceDaily)
by Folabomi Oladosu, PhD
Post-doctoral researcher specializing in pain and women’s health at NorthShore University HealthSystem
Every now and again, you wake up to find your arm or leg didn’t quite wake up with you. You dread it, but you wiggle through the pricking, tingling sensations until your once-numb limb is ready to start the day. What if, despite your best efforts, the numbness persists? Numb tingling limbs are one of several hallmark symptoms associated with multiple sclerosis (MS), an autoimmune disorder where the immune system attacks the central nervous system.
Our nerves are somewhat similar to an electrical power cable. The inside of a nerve is made of smaller nerve fibers. These fibers conduct important electrical signals and messages throughout the body. The outside of the fibers are covered by myelin, a fatty material formed by specialized brain cells. Thanks to its insulating properties, myelin speeds the transmission of electrical messages throughout the body.
If you bend any cable too often, eventually the outer plastic coating starts to fray, exposing the inner metal wiring. The cable may still work, but over time, it becomes less and less reliable (raise your hand if you’re on your third phone power cable). A similar phenomenon occurs in MS. The immune system attacks the body’s own cables, damaging the specialized cells and degrading the insulating myelin on nerve fibers. Over time, this demyelination produces a range of symptoms, including fatigue, depression, pain, and movement issues.
First-line treatments for MS aim to dampen the immune system to reduce demyelination. Although effective, these treatments make the body vulnerable to sickness and infection.
What if there was a way to directly protect the cells and the myelin they produce? Brian Popko and his team wanted to know if Sephin1, a small molecule that enhances a cell’s defensive response to environmental stressors, could protect nerve fibers from demyelination.
Popko uses a mouse model where an injection of myelin proteins coupled with a toxin generates an immune response similar to that in MS patients, initiating a MS-like disease in mice. He and his team then injected the mice with Sephin1 and followed the mice’s responses for 35 days. In this mouse model, clinical symptoms usually appear after 11 days and peak on day 17. When given one week after the initial injection to create MS-like symptoms, Sephin1 delayed disease progression, with clinical symptoms peaking on day 26.
The findings suggest that Sephin1 delayed disease progression by boosting the defensive response to insults from the immune system. When compared to control mice, mice that received Sephin1 had more of the specialized brain cells and less demyelination in the spinal cord on day 17. Sephin1 also dampened immune cell activity in the spinal cord.
The team went on to discover that Sephin1 worked even better when it was paired with interferon beta (IFN-β), an anti-viral protein native to the body, also used as a common treatment for MS. Mice that received both Sephin1 and IFN-β showed much slower, less severe disease progression.
This timely translational research from the Popko lab illustrates the promising therapeutic effects of Sephin1 for MS, especially when combined with IFN-β. Its demonstrated efficacy in MS mouse model indicates Sephin1 may help to protect indispensable nerve fibers from demyelination in MS patients. Dr Popko is currently exploring opportunities to assess the therapeutic safety of Sephin1 for MS patients.