Celiac.com 12/15/2025 - This scientific review explores an unexpected connection between two very different kinds of proteins: those involved in Alzheimer’s disease and those found in wheat gluten. Both types of proteins can form tiny structures called nanostructures, which resist being broken down by normal body processes. These structures can influence how diseases develop, from brain degeneration to intestinal inflammation. The goal of the study is to help scientists from both fields learn from one another to better understand how these tiny assemblies of proteins—called peptides—might drive disease and offer new targets for therapy.

When Proteins Build Themselves Into Harmful Shapes

Proteins are made from chains of smaller molecules called peptides. Under certain conditions, these chains can fold and stick together, forming stable structures that the body cannot easily remove. This process, called self-assembly, can be both useful and dangerous. In healthy systems, self-assembly can create strong, functional materials like hair and collagen. But in disease, the same process can lead to toxic clumps that damage cells.

The study focuses on two examples of this harmful self-assembly: one that occurs naturally inside the brain and one that comes from the food we eat. The first involves amyloid-beta peptides, which are believed to play a key role in Alzheimer’s disease. The second involves gliadin peptides, fragments of the gluten protein that can cause celiac disease and other gluten-related conditions. Although these diseases affect different organs, they share a common theme—tiny, hard-to-destroy peptide structures that trigger inflammation and cell stress.

Amyloid-Beta in Alzheimer’s Disease

In Alzheimer’s disease, certain peptides in the brain—known as amyloid-beta 1–40 and amyloid-beta 1–42—aggregate into fibers and clusters that damage nerve cells. These clusters vary in shape and size, and those variations may explain why the disease progresses differently among patients. Recent research shows that amyloid structures formed in living brain tissue differ from those created in laboratory conditions. This means that researchers must refine their models to better mimic what happens inside the body.

The review emphasizes that understanding how individual amyloid-beta peptides join together is essential. By identifying which specific folding patterns lead to toxic forms, scientists can design drugs that stabilize safer forms or block harmful ones. This molecular-level understanding could pave the way for more effective Alzheimer’s treatments.

Gliadin Peptides in Gluten-Related Disorders

The second focus of the review is on gluten, a major component of wheat and related grains. Gluten is made up of several types of proteins, one of which is gliadin. In people with celiac disease or other gluten-related disorders, the body mistakenly reacts to gliadin as if it were a threat. The immune system’s response damages the small intestine, leading to nutrient deficiencies and digestive distress.

The problem begins with gliadin peptides that resist digestion. These fragments survive stomach acids and enzymes, then travel intact into the small intestine. There, they can form their own nanostructures—tiny but stable assemblies that are difficult for the body to break apart. Because they resemble the persistent structures seen in amyloid diseases, scientists are beginning to study them in similar ways. These gliadin nanostructures might act like nonliving “pathogens,” triggering immune responses and inflammation long after the original food has been digested.

Learning From Alzheimer’s Research to Study Gluten Toxicity

Alzheimer’s researchers have spent decades perfecting laboratory techniques to study how amyloid-beta peptides form toxic clusters. These methods include isolating pure monomers, analyzing their shapes under microscopes, and tracking how they assemble into larger fibers. The review suggests that gluten researchers could adopt similar methods to better understand gliadin’s harmful behavior.

By borrowing these protocols, scientists studying celiac disease can isolate gliadin peptide fragments, observe how they group together, and identify which structures interact most strongly with the immune system. This approach could help explain why some forms of gluten exposure cause mild reactions, while others lead to severe autoimmune damage. The more precisely researchers can characterize these nanostructures, the easier it becomes to develop therapies that disrupt their formation.

Bridging Two Fields Through Nanostructure Research

A key message of the paper is collaboration. Alzheimer’s researchers and gluten scientists rarely interact, yet both study peptides that self-assemble and resist degradation. By pooling knowledge, they can advance faster. Alzheimer’s experts can teach gluten researchers how to identify and stabilize specific peptide forms, while gluten researchers can offer insight into how these structures survive digestion and move through the body.

Understanding how different peptides assemble could also improve models of the “gut–brain axis,” the communication system between the digestive tract and the brain. This concept suggests that what happens in the gut can influence neurological health. If gliadin nanostructures can cross biological barriers or influence inflammation beyond the gut, they might help explain why some people with celiac disease experience neurological symptoms such as brain fog or anxiety.

From Structure to Therapy

One of the main obstacles in treating diseases linked to peptide aggregation is the remarkable stability of these nanostructures. They resist heat, enzymes, and other breakdown processes. By identifying exactly how the peptides arrange themselves—how tightly they bind, what shapes they take, and which parts of the molecule are exposed—scientists can design molecules that interfere with the process. For Alzheimer’s disease, this might mean drugs that prevent amyloid-beta from forming fibers. For celiac disease, it could mean treatments that block gliadin peptides from aggregating or reaching the immune system.

The authors also call for the development of new tools to visualize and measure peptide structures. These tools could include high-resolution imaging, spectroscopy, and computational simulations. With better data, researchers could predict which peptide sequences are most likely to form harmful assemblies and how to neutralize them before they cause damage.

Implications for People With Celiac Disease

For individuals living with celiac disease, this line of research is deeply meaningful. It offers a possible explanation for why even trace amounts of gluten can provoke strong and lasting immune reactions. If gliadin peptides form persistent nanostructures similar to those seen in neurodegenerative diseases, it would explain why the immune system continues attacking long after gluten has left the digestive tract. Understanding these structures could help researchers design enzymes, medications, or supplements that break down gliadin more effectively, reducing the risk of accidental exposure.

It also opens the door to studying potential links between gluten sensitivity and neurological symptoms. If the same types of resistant peptides that harm the intestine can influence brain inflammation or signaling, future therapies could target both gut and brain health at once. Ultimately, these insights could lead to safer food processing methods, better diagnostic tools, and more effective treatments for people who must avoid gluten for life.

Conclusion

This review connects two complex areas of science—Alzheimer’s disease and gluten intolerance—by focusing on a shared molecular phenomenon: peptide self-assembly. Whether inside the brain or the gut, these tiny protein fragments can form stubborn, disease-promoting nanostructures. By studying how they build, stabilize, and interact with cells, scientists can uncover the roots of chronic inflammation and tissue damage. For people with celiac disease, the promise is especially hopeful: a future where gluten reactions can be predicted, prevented, or even neutralized before they cause harm.

Read more at: pubs.acs.org

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Celiac.com 08/08/2025 - Celiac disease is a serious autoimmune condition that causes the body to attack its own small intestine when gluten is consumed. For children diagnosed with celiac disease, following a strict gluten-free diet often leads to improvement in symptoms and a decline in antibodies that indicate inflammation, such as tissue transglutaminase immunoglobulin A. However, not all children experience complete relief. Many continue to have lingering stomach issues even with excellent dietary adherence.

This study focused on understanding why that happens. Specifically, it examined whether disorders of gut–brain interaction—chronic gastrointestinal symptoms with no clear structural cause—were responsible for the ongoing discomfort in these children. The research looked at how common these disorders were in children with managed celiac disease and identified factors that might predict their development.

What Are Gut–Brain Interaction Disorders?

Disorders of gut–brain interaction (formerly called functional gastrointestinal disorders) are conditions where the brain and the digestive system do not work together as they should, leading to symptoms like abdominal pain, constipation, nausea, and bloating. These symptoms can be long-lasting and significantly affect a child's quality of life, even when no physical damage is found during medical tests.

While these conditions are increasingly recognized in the general population, they can be especially hard to detect in people with other known gastrointestinal issues like celiac disease. That's because symptoms overlap—abdominal pain, diarrhea, and fatigue are common to both. This study was the first in the United States to specifically look at these gut–brain disorders in children who have celiac disease and who are otherwise managing the condition well.

Key Findings: Nearly Half Had Gut–Brain Disorders

The researchers studied 191 children between the ages of 4 and 21 who had biopsy-confirmed celiac disease. All of these children were sticking to a gluten-free diet and had improving antibody levels, which suggested that their celiac disease was under control. Despite this, 43 percent of them met the medical criteria for a gut–brain disorder.

The most common types found were:

• Functional constipation (33% of those with a disorder)
• Functional abdominal pain (29%)
• Other types included nausea, irritable bowel syndrome, and delayed stomach emptying.

Interestingly, many children who were still experiencing these symptoms after their celiac diagnosis had shown the same issues even before they started a gluten-free diet. This makes it unclear whether the symptoms were initially caused by celiac disease, a gut–brain disorder, or both.

Early Symptoms and Risk Factors

The study found that certain symptoms and conditions increased the likelihood of developing a gut–brain disorder, even after celiac disease was being properly managed. These included:

• Abdominal pain, vomiting, and constipation at the time of diagnosis
• Nighttime stomach pain
• Joint hypermobility (very flexible joints)
• Frequent headaches and body pain
• Symptoms of anxiety or depression
• Poor growth or low body weight at diagnosis
• More severe small intestine damage (villous blunting) seen during initial biopsy

Children with these issues were more likely to develop ongoing gut-related problems, even when their celiac disease appeared to be under control. This highlights a need for doctors to watch these children more closely after diagnosis and provide support beyond just a gluten-free diet.

Why Gut–Brain Disorders Are Easy to Miss

Diagnosing gut–brain disorders in children with celiac disease is challenging because standard follow-up care often focuses only on antibody levels. These tests are important but not perfect. Some children with normal lab results still have persistent symptoms, which are often brushed off or blamed on gluten exposure.

However, this study suggests that these symptoms may not be from eating gluten at all. Instead, they may come from a gut–brain disorder that needs its own diagnosis and treatment. That means children with celiac disease who continue to feel sick—despite following all the rules—deserve a deeper look and possibly a different kind of care.

What This Means for Families and Healthcare Providers

For families dealing with celiac disease, the results of this study offer both clarity and a new path forward. If a child continues to have digestive issues after switching to a gluten-free diet, it may not mean they’re doing something wrong. Instead, the problem might be a disorder of gut–brain interaction—something that can and should be diagnosed and treated separately.

Healthcare providers should take lingering symptoms seriously and consider screening for gut–brain disorders during follow-up visits. Early diagnosis could help families better understand what’s going on and avoid unnecessary anxiety about hidden gluten or dietary mistakes.

Doctors can also offer more balanced guidance during the initial diagnosis. Letting families know that some symptoms may continue—and that this is not uncommon—can help manage expectations and reduce the fear of long-term damage.

Conclusion: A Broader View of Celiac Disease Management

This study highlights the importance of looking beyond just gluten when managing celiac disease in children. Nearly half of the children in this study experienced ongoing gut problems even though their disease markers were improving. These symptoms were often due to disorders of gut–brain interaction, not continued celiac activity.

Recognizing this opens the door for better care, more accurate diagnosis, and much-needed relief for families. It also suggests that future guidelines for celiac disease management should include screening for gut–brain disorders, especially in children who had severe symptoms at the start or have other related health issues.

In the end, this research shows that managing celiac disease is not just about avoiding gluten—it's about understanding the whole person and treating all of the symptoms, not just the lab results.

Read more at: onlinelibrary.wiley.com

Celiac.com 07/23/2025 - Celiac disease is well-known for its impact on the digestive system, but many patients report symptoms that go beyond the gut—such as brain fog, anxiety, and memory problems. Researchers have long debated whether these cognitive and emotional issues are truly linked to celiac disease or simply coincidental. To address this question, a new study used data from the UK Biobank, a large database of medical information from over half a million people, to investigate whether people with celiac disease show measurable differences in brain function and structure.

This study compared individuals with celiac disease to healthy people of the same age, sex, and general health. It aimed to determine if there were differences in mental performance, emotional well-being, and brain imaging results. The results offer compelling evidence that celiac disease can affect the brain in meaningful ways.

How the Study Was Conducted

The researchers selected 104 adults with celiac disease from the UK Biobank and matched them with 198 individuals who did not have the condition. Both groups were carefully balanced in terms of age, gender, education, body weight, and blood pressure status. Importantly, all participants were otherwise healthy and free from diagnosed neurological diseases.

To assess mental function, both groups completed five different cognitive tests and answered six questions related to mental health. The researchers also analyzed brain scans from all participants using advanced magnetic resonance imaging techniques. These scans were used to look for changes in the brain’s white matter, the part of the brain that helps send messages between different regions.

Key Findings: Slower Thinking and More Emotional Distress

Cognitive Testing Results
One of the most important findings was that people with celiac disease had slower reaction times compared to the control group. Reaction time is a standard way to measure how quickly someone can process and respond to information. Although this may seem like a small difference, slower reaction times are associated with reduced processing speed, which can affect everyday functioning—such as driving, multitasking, and memory.

Mental Health Findings
The emotional health of people with celiac disease was also noticeably different. Participants with celiac disease were more likely to report symptoms of anxiety and depression. They also expressed greater dissatisfaction with their health and, alarmingly, were more likely to report thoughts of self-harm. These findings suggest that the psychological burden of living with celiac disease may be heavier than previously thought, and could also reflect deeper biological changes related to gluten sensitivity.

Brain Imaging Reveals White Matter Changes

Using a special brain imaging technique called diffusion tensor imaging, the researchers identified subtle but widespread changes in the white matter of participants with celiac disease. White matter is critical for fast and efficient brain communication. The most notable change was an increase in what’s known as axial diffusivity, a measure that can signal damage to brain pathways.

This kind of white matter alteration is often seen in conditions like mild traumatic brain injury, stroke, and early forms of cognitive decline. Although these changes didn’t directly correlate with the cognitive test scores, the pattern was strong enough to suggest a biological basis for the mental differences observed.

Interestingly, other forms of brain injury, such as visible lesions or brain atrophy (shrinking), were not found to be significantly different between the groups. This means that while the brain changes were not severe enough to be seen in a basic scan, they were detectable with more sensitive methods and still appear to impact thinking ability.

Why These Results Matter

This study is one of the most rigorous and well-controlled investigations into the brain effects of celiac disease to date. By using a large and relatively healthy population, the researchers avoided many of the biases that can skew results in clinical studies. The findings suggest that even in the absence of visible neurological disease, people with celiac disease may suffer from meaningful brain changes that affect their daily lives.

More importantly, these changes may not go away completely—even when the patient is following a strict gluten-free diet. Previous research has shown that neurological damage caused by gluten may be long-lasting or even permanent in some cases. This underscores the importance of early diagnosis and strict adherence to a gluten-free lifestyle to prevent irreversible harm.

Possible Explanations for Brain Effects

While this study did not directly investigate why these brain changes occur, it builds on earlier research that suggests several possible explanations:

• Immune System Reactions: Gluten can trigger immune responses that affect blood vessels and brain tissue.
• Inflammation: Chronic inflammation from untreated celiac disease may slowly damage brain cells.
• Nutrient Deficiencies: Malabsorption in the gut can lead to deficiencies in essential vitamins and minerals that support brain health.
• Emotional Stress: Living with a chronic illness, especially one that affects eating and social life, can contribute to anxiety and depression.

In reality, it may be a combination of these factors working together to affect brain structure and function.

Limitations of the Study

Like all research, this study has some limitations. Notably, the participants with celiac disease were healthier than average, as those with related conditions were excluded. Also, there was no detailed information on how long participants had been diagnosed, how well they were following a gluten-free diet, or whether they had active symptoms. This makes it difficult to pinpoint exactly when and how brain changes begin or if they can improve over time.

Still, the fact that meaningful differences were found in such a healthy group suggests that the true scale of brain involvement in celiac disease may be even larger than reported.

What This Means for People With Celiac Disease

For individuals living with celiac disease, this study offers both a warning and a call to action. It reinforces the idea that celiac disease is a whole-body condition that extends beyond the gut. Mental fog, mood changes, and slower thinking are not just "in your head"—they may be signs of real brain involvement.

Following a strict gluten-free diet remains the best way to prevent further damage. However, because the brain does not heal as easily as the gut, early diagnosis is crucial. This research may also help patients advocate for better care, including access to mental health support and cognitive assessments.

Conclusion: Celiac Disease Is Not Just a Digestive Condition

In summary, this study confirms that celiac disease can affect both the mind and the brain in measurable ways. People with the condition showed slower reaction times, higher levels of emotional distress, and widespread white matter changes in the brain. These findings validate what many patients have long suspected: that the mental and neurological effects of celiac disease are real, significant, and deserving of more attention.

Understanding this connection may help doctors provide more comprehensive care and encourage patients to stick to the gluten-free diet—not just for digestive health, but for lifelong brain health as well.

Read more at: gastrojournal.org

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Celiac.com 11/06/2023 - Celiac disease is a condition where the body cannot properly process gluten. It is primarily known as a gastrointestinal disorder, but it can also lead to various neurological and psychiatric issues. Often, children receive diagnoses of neurological symptoms, such as epilepsy, attention-deficit hyperactivity disorder (ADHD), restless leg syndrome (RLS), and peripheral neuropathy, without identifying the root cause. 

Recent research delved into the neurological manifestations of gluten-related disorders and the influence of a gluten-free diet on these conditions, with a particular focus on pediatric patients. 

A team of researchers recently set out to review the pathological manifestations of gluten-related neuro-psychiatric disorders, and the impact of gluten-free diet in children. The research team included Prajwala Nagarajappa, Sree Mahathi Chavali, and Maneeth Mylavarapu.

They are variously affiliated with the Department of Public Health, Adelphi University in Garden City, New Jersey, USA; the Department of Pediatrics, Graduate from GSL Medical College, Charlotte, USA; and the Mysore Medical College and Research Institute in Mysore, India.

Many of these pediatric patients experience neuropsychiatric symptoms with no apparent cause. However, these symptoms might be linked to celiac disease, as studies show that antibody levels could be indicators. What's striking is that these neurological manifestations can often be managed, or even eliminated, with a gluten-free diet.

Comprehensive Literature Review on Neuropathological Manifestations and the Impact of a Gluten-Free Diet

To explore these issues, researchers conducted a comprehensive literature review, sourcing studies from major databases like PubMed and Google Scholar. They sought studies providing individual-level data on neuropathological manifestations and the impact of a gluten-free diet on extra-intestinal celiac disease symptoms. Their research protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO).

The inclusion criteria covered prospective studies, observational studies, and case reports on pediatric patients with biopsy-confirmed celiac disease, serologically positive celiac disease, celiac disease with neuropsychiatric symptoms, and research reporting the effects of a gluten-free diet. After a stringent quality assessment to ensure minimal bias, 20 studies were included for discussion.

In six studies, patients with neuropsychiatric symptoms had positive serological findings and more severe biopsy results. Seven studies explored the positive influence of a gluten-free diet, and five of these reported statistically significant results.

The findings of this study underscore the role of gluten in the severity of neuropsychiatric symptoms in celiac disease. The research strongly indicates that a gluten-free diet can significantly impact the prognosis of this disease. Furthermore, neuropsychiatric symptoms without accompanying gastrointestinal manifestations are more frequently observed in pediatric patients. The study provides clear evidence of a substantial association between gluten and various neurological conditions, including neuropathy, ADHD, epilepsy, and RLS. These conditions can potentially benefit from a gluten-free diet.

Given these insights, the study suggests that guidelines should incorporate a combination of serological, biopsy, and imaging techniques for early detection and the initiation of a gluten-free diet.

Moreover, the research supports introducing gluten-free diet as a primary preventive measure in the pediatric population. By addressing the significance of gluten in pediatric neurological conditions, this study aims to raise awareness about this frequently misdiagnosed, but manageable disease.

Read more in DOI: 10.7759/cureus.47062

Celiac.com 10/04/2023 - Neuropathic pain is a challenging condition with complex diagnostic and treatment issues. Although we've made progress in understanding and treating neuropathy, many aspects of this condition remain unclear. One intriguing aspect of neuropathy is that it can cause both sensory loss and pain, despite being driven by abnormal nerve signaling.

Voltage-gated sodium channels, crucial for proper nerve function and communication, can go awry in neuropathy, triggering hyperexcitability and pain. Even with a number of diagnostic tools available, neuropathy patients often face delays in getting an accurate diagnosis for the underlying cause.

The research team included Giustino Varrassi, Stefano Tamburin, Panagiotis Zis, Vittorio A. Guardamagna, Antonella Paladini, and Martina Rekatsina. They are variously affiliated with the department of Pain Medicine, Paolo Procacci Foundation, Rome, ITA; the Department of Neurology, University of Verona, Verona, ITA; the Department of Neurology, University of Cyprus, Nicosia, CYP; the depertment of Anesthesia, IEO, Milano, ITA; the Department of MESVA, University of L'Aquila, L'Aquila, ITA; and the department of Pain Management, Basildon University Hospital, London, GBR.

The prevalence of pain varies depending on the type of neuropathy, with chronic idiopathic axonal polyneuropathy being one of the most painful forms. In fact, more than half of patients with this condition experience pain. 

A newer consideration in the world of neuropathy is gluten neuropathy, a type of peripheral neuropathy. Detecting this condition may require specialized tests, like electrochemical conductance testing of the hands and feet to assess sudomotor dysfunction, aka sweat gland innervation. For people with confirmed gluten sensitivity or celiac disease, gluten neuropathy is a common neurological complication, and adopting a gluten-free diet can help alleviate some of the symptoms.

In Greece, a neuropathic pain registry was established in 2014 to collect real-world data from neuropathic pain patients. While still in its early stages, this registry has already provided valuable demographic and treatment information. Interestingly, the data suggests that many patients are not receiving optimal prescriptions and recommended interventional procedures. 

Many Greek pain clinics are working to raise awareness among people who suffer from neuropathic pain, and to encourage their participation in this crucial registry, which could help to improve the understanding and management of neuropathic pain more broadly.

Read more in Cureus.com

Celiac.com 08/15/2023 - Researchers from the University of Otago in New Zealand recently studied the effects of dietary wheat gluten on the hypothalamus of male mice. The researchers include Mohammed Z. Rizwan, Romy Kerbus, Kaj Kamstra, Pramuk Keerthisinghe, and Alexander Tups. Their findings are intriguing.

The researchers are variously affiliated with the Centre for Neuroendocrinology and Department of Physiology at the University of Otago School of Biomedical Sciences in Dunedin, New Zealand; the Centre for Neuroendocrinology and Department of Anatomy at the University of Otago School of Biomedical Sciences in Dunedin, New Zealand, and the Maurice Wilkins Centre for Molecular Biodiscovery in Auckland, New Zealand.

Gluten is commonly found in wheat, rye, and barley, and is a major dietary component in many western countries. Gluten has been linked to weight gain and peripheral inflammation in mice. This research aimed to understand its impact on central inflammation, particularly in relation to diet-induced obesity.

Low-fat Diet vs. High-fat Diet with Gluten

The study observed that adding gluten to a low-fat diet had no discernible effect, but male mice fed a high-fat diet enriched with gluten exhibited increased body mass and adiposity compared to those on an high-fat diet without gluten. Additionally, when gluten was introduced to the low-fat diet, it led to higher levels of circulating C-reactive protein.

Interestingly, it made no difference whether gluten was added to a low-fat or a high-fat diet. Either way, it triggered a significant increase in the number of microglia and astrocytes in the arcuate nucleus of the hypothalamus. 

These changes were identified using specific markers through immunohistochemistry. Even on an low-fat diet, gluten appeared to replicate the immunogenic effects seen with an high-fat diet, and its inclusion in the latter led to a further rise in the number of reactive immune cells.

Gluten Triggers an Obesity and Injury to the Hypothalamus

Overall, the findings suggested that gluten had a moderate obeso-genic effect, when given to mice exposed to an high-fat diet. 

Moreover, the study reported that gluten triggered the presence of astrocytes and microglia in the hypothalamus, indicating a potential injury to the hypothalamus in rodents. Mice are used in studies to model human disease risk due to genetic similarities, allowing researchers to investigate potential factors and develop treatments in controlled, ethically manageable settings.

This research contributes to our understanding the complex relationship between dietary components, like gluten, and obesity-related inflammation in the brain. It also offers up some exciting areas of further research inquiry into the brain's response to gluten in both mice and humans.

Read more in the Journal of Neuroendocrinology

Celiac.com 07/19/2021 - Many people with celiac disease and non-celiac gluten sensitivity claim to suffer from gluten-induced neuro-cognitive impairment (GINI), often referred to as “celiac fog,” "gluten fog,"or “brain fog,” but there have been no good studies, and so there is very little data about the rates and symptoms associated with GINI.

A team of researchers recently set out to to understand the neuro-cognitive symptoms associated with gluten exposure in individuals with self-reported celiac disease and non-celiac gluten sensitivity (NCGS). For the study the team had 1,143 with people with celiac disease and 253 with NCGS participate in 9-question online survey. 

The survey used both forced choice and free-response to get a description of neuro-cognitive symptoms the participants experienced after gluten ingestion. The team coded free-response answers based on the Health-Related Quality of Life Instrument. 

Nearly nine out of 10 celiacs, and 95% of NCGS sufferers reported symptoms of GINI. In both groups, the most common words used by respondents to describe the symptoms were "difficulty concentrating," "forgetfulness," and "grogginess." Both groups shared similar timing of symptoms, including symptom onset and peak. 

The free responses for both groups showed that respondents most commonly referred to cognitive, physical, psychological, and overall impact on quality of life.

This survey indicates that GINI is common and may be severe in both individuals with celiac disease and NCGS. 

The team speculates that gluten-related cognitive and physical impairment may be similar to that seen in other autoimmune conditions, such as lupus. 

The researchers encourage clinicians to include assessment for GINI symptoms in assessments for all celiac disease and NCGS patients. They also call for additional research which includes the development of a patient-reported outcome measure that notes the patients' perceived neurocognitive effects of gluten exposure.

Read more in the Journal of Clinical Gastroenterology: May 28, 2021

This study was funded in full by Beyond Celiac.

Notes:
J.B.E.G.: has served as an unpaid consultant for Beyond Celiac and Takeda Pharmaceuticals and is an employee of Northeastern University. B.A.: is an employee of Northeastern University. K.N.V.: is an employee of Ultragenyx Pharmaceuticals Inc. and owns stocks and shares in Ultragenyx Pharmaceuticals Inc. J.O.F.: is an employee of Cambridge Health Alliance. K.S: is an employee of Johnson and Johnson and owns stocks and shares in Johnson and Johnson. K.A.: is an employee of Beyond Celiac. A.E.: has served as a speaker for the American Academy of Family Physicians and Pri-Med, served as Chair of the Board of Directors for Beyond Celiac and is an employee of EBSCO Inc. (publisher of Dynamed) and Reliant Medical Group. 

A.B.: has served as a speaker for Takeda Pharmaceutical Company, was an advisory board member for AHRQ, is an employee of Beyond Celiac and owns stocks and shares in Takeda Pharmaceutical Company, Amgen, Pfizer and Merck and Co. 

D.A.L.: has served as an advisory board member for Beyond Celiac, is an employee of Takeda Pharmaceuticals and owns stocks and shares in Takeda Pharmaceuticals. K.Y. declares that there is nothing to disclose.

The research team included Jessica B. Edwards George, PhD; Babatunde Aideyan, MA; Kayla Yates, BS; Kristin N. Voorhees, MA; Jennifer O’Flynn, PhD; Kristen Sweet, PhD; Kate Avery, MPH; Alan Ehrlich MD; Alice Bast BS; and Daniel A. Leffler MD. They are variously affiliated with the Department of Applied Psychology, Bouvé College of Health Sciences, Northeastern University, Boston, MA; Beyond Celiac, Ambler, PA; the Department of Family Medicine and Community Health, University of Massachusetts Medical School, Worcester; Takeda, Cambridge; and the Celiac Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.

Celiac.com 05/06/2021 - Gluten neuropathy is the term used to describe peripheral neuropathy that occurs in patients with gluten sensitivity or celiac disease in the absence of other risk factors.

A team of researchers recently set out to describe the neurophysiological progression rate of gluten neuropathy across time and look into the potential role of genetic susceptibility in its development.

The research team included Panagiotis Zis, Ptolemaios Sarrigiannis, Artemios Artemiadis, David S. Sanders & Marios Hadjivassiliou. They are variously affiliated with the Academic Directorate of Neurosciences, and the Academic Unit of Gastroenterology at Sheffield Teaching Hospitals NHS Foundation Trust in Sheffield, UK, and with the Medical School, University of Cyprus in Nicosia, Cyprus.

The team looked at a group of 45 patients with gluten neuropathy for an average follow-up period of 8 ± 5 years. They gathered clinical and neurophysiological data, along with HLA-DQ genotype information.

Average patient age at diagnosis was 60 ± 12 years. More than 75% of patients had a length-dependent neuropathy, while the rest had sensory ganglionopathy. Sixty percent of patients with positive DQA1*02 suffered from sensory ganglionopathy compared to just under 14% of DQA1*02-negative patients. 

The team also noted a statistically significant detail regarding the DQB1*06 allele and the DQA1*01/DQB1*06 haplotype, which were found more frequently in patients with gluten neuropathy than in healthy control subjects. 

The team found a linear effect of time on the neurophysiological findings, with radial sensory nerve action potential decreasing nearly 2% annually, sural sensory nerve action potential decreasing 3%, and tibial nerve motor compound action potential decreasing 6.5%, independently of age or gender.

Gluten neuropathy is a late manifestation of gluten sensitivity and celiac disease. The majority of patients with gluten neuropathy suffer from length-dependent neuropathy with a linear deterioration over time. 

To help spot patients at risk for developing sensory ganglionopathy, the team recommends HLA genotyping for patients with gluten sensitivity or celiac disease who present with neuropathic symptoms.

Read the full report in the Journal of Neurology volume 268, pages199–205(2021)

Celiac.com 02/18/2021 - There has been some evidence to support the idea that patients with anti-GAD ataxia and no gluten sensitivity may benefit form immunosuppressive drugs.

A team of researchers recently set out to report the clinical characteristics and treatment of patients with progressive cerebellar ataxia associated with anti-GAD antibodies. 

The research team included M. Hadjivassiliou, P. G. Sarrigiannis, P. D. Shanmugarajah, D. S. Sanders, R. A. Grünewald, P. Zis & N. Hoggard. They are variously affiliated with the Academic Department of Neurosciences, and the Academic Department of Neuroradiology at the Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, in Sheffield, UK.

The team conducted a retrospective review of all 50 patients with anti-GAD ataxia treated at the Sheffield Ataxia Centre over the last 25 years.  The rate of anti-GAD ataxia was 2.5% amongst 2,000 patients with progressive ataxia of various causes. Average onset age was 55, with an average duration of 8 years. 

The researchers found gaze-evoked nystagmus in 26% of subjects, cerebellar dysarthria in 26%, limb ataxia in 44% and gait ataxia in all of them.  Nine patients suffered from severe ataxia, 12 from moderate ataxia,  and 29 from mild ataxia. Ninety percent of patients had a history other autoimmune diseases. 

Just over half had a family history of autoimmune diseases. In nearly three out of four patients, baseline MR spectroscopy of the vermis was abnormal at presentation. Thirty-five patients had positive serological evidence of gluten sensitivity. 

All 35 patients began a gluten-free diet (GFD). Eighteen patients, more than half, improved, while 13 patients stabilized, three patients began the GFD too recently to draw conclusions, and one patient got worse. 

Sixteen patients received mycophenolate. Seven patients, nearly 45%, improved, while two patients stabilized, six patients began the medication too recently to draw conclusions, and one did not tolerate the drug. 

There is considerable overlap between anti-GAD ataxia and gluten ataxia. For patients with both conditions, a strict GFD alone is sufficient treatment. 

However, patients with anti-GAD ataxia and no gluten sensitivity respond well to immunosuppression.

Read more in The Cerebellum (2020)

Celiac.com 03/18/2020 - Researchers are still debating the extent to which celiac disease might cause brain damage. Some research has indicated that celiac disease can trigger changes to brain white matter, among other potential issues.

A team of researchers recently set out to validate previous reports, we investigated the prevalence of neuropsychological dysfunction in persons with celiac disease included in the National UK Biobank, which contains experimental medical data from 500,000 adults in the United Kingdom.

The research team included I.D. Croall, D.S. Sanders, M. Hadjivassiliou, and N. Hoggard. They are variously affiliated with the University of Sheffield, Academic Unit of Radiology; the Academic Unit of Gastroenterology; and the Department of Neurology at Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.

The team matched 104 otherwise healthy celiac disease patients with 198 healthy individuals controls, closely matched for age, sex, level of education, body mass index, and diagnosis of hypertension. The researchers then compared scores from five cognitive tests, and multiple-choice responses to six questions about mental health, between groups using t test and χ2 analyses. 

Group analyses of magnetic resonance imaging brain data included a study of diffusion tensor imaging metrics (mean diffusivity, fractional anisotropy, radial diffusivity, axial diffusivity), voxel-based morphometry, and Mann-Whitney U comparisons of Fazekas grades.

Compared to the control subjects, celiac disease patients showed substantially slower reaction times, and markedly higher rates of anxiety, depression, thoughts of self-harm, and health-related unhappiness. 

Tract-based spatial statistical analysis showed sharply higher axial diffusivity in widespread locations, which shows that white matter changes in brains of people with celiac disease. Voxel-based morphometry and Fazekas grade analyses were similar between the groups.

Brain imaging shows that celiac disease patients suffer from cognitive deficit, changes to brain white matter, and reduced mental health, which support the notion that celiac disease is associated with both neurological and psychological features.

Read more in Gastroenterology

Celiac.com 12/02/2019 - Parkinson’s development can take many paths, with factors like genetics, aging, and environmental conditions all playing roles. Most people with Parkinson’s disease experience non-motor-symptoms, such as chronic constipation and/or impairment of gastrointestinal (GI) transit, long before the disease manifests clearly. Researcher Tomasza Brudek recently reviewed available medical literature for a possible link between Inflammatory Bowel Disease (IBD) and Parkinson's Disease.

Brudek is affiliated with both the Research Laboratory for Stereology and Neuroscience, Copenhagen University Hospital, Bispebjerg-Frederiksberg Hospital in Copenhagen, Denmark; and the Copenhagen Center for Translational Research, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark.

Build-up of α-synuclein protein in the form of Lewy bodies and Lewy neurites, and degeneration of substantia nigra dopamine neurons are classic clinical markers of Parkinson's Disease.

Major features of Parkinson's Disease include inflammatory responses manifested by glial reactions, T cell infiltration, and increased expression of inflammatory cytokines, along with other toxic mediators derived from activated glial cells.

Experimental, clinical and epidemiological data suggest that intestinal inflammation influences the development of Parkinson's Disease, while more and more studies suggest that Parkinson's disease may begin in the gut long before any motor symptoms show up.

Patients with inflammatory bowel disease (IBD) have a higher risk of developing Parkinson's Disease compared with non-IBD individuals. Gene association study has found a genetic link between IBD and Parkinson's Disease, and an evidence from animal studies suggests that gut inflammation, similar to that observed in IBD, may induce loss of dopaminergic neurons.

Based on preclinical models of Parkinson's Disease, some clinicians hypothesize that the early stages of early in Parkinson's Disease are marked by enteric microbiome changes, and gut infections triggering α-synuclein release and aggregation.

Because gastrointestinal pathology can play such an important role in Parkinson's Disease development, there's good reason to believe that IBD and IBD treatments can influence Parkinson's Disease risk.

This review underscores how important it is for physicians to be aware of Parkinson's Disease symptoms in IBD patients.

Read more in the Journal of Parkinson's Disease, vol. 9, no. s2, pp. S331-S344, 2019

Celiac.com 08/27/2019 - Patients with gluten neuropathy often have peripheral neuropathic pain, indicating the involvement of small fibers. The most common types of peripheral neuropathy in people with celiac disease and gluten sensitivity are length-dependent symmetrical sensorimotor neuropathies and sensory ganglionopathies. 

A team of researchers recently set out to describe the clinical characteristics of patients with celiac disease or gluten sensitivity and pure small fiber neuropathy (SFN). 

The research team included Pangiotis Zis, PG Sarrigiannis, DG Rao, DS Sanders, and M Hadjivassiliou. They are variously affiliated with the Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; and the Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust in Sheffield, UK.

The research team reviewed the records for all patients referred to the Gluten-Related Neurological Disorders clinic with clinical and neurophysiological evidence of small fiber neuropathy. 

Blood screens indicated that all patients were gluten sensitive prior to starting a gluten-free diet.  The team offered duodenal biopsy to all patients, except those patients with conditions that could cause small fiber neuropathy. 

The researchers found 9 males and 5 females with small fiber neuropathy and gluten sensitivity. Eleven of those patients underwent duodenal biopsy, and ten of those showed evidence of celiac disease enteropathy.  Average age at onset of pain was 53.5 ± 11.4 years, while the average age of celiac disease/gluten sensitivity diagnosis was 50.8 ± 10.4 years. More than six out of ten patients reported feeling pain. 

Neurophysiological assessment suggested a length-dependent small fiber neuropathy in 11 patients, whereas in 2, a non-length dependent pattern was identified, suggesting that the predominant pathology lies in the dorsal root ganglia. 

This study reveals that small fiber neuropathy can be a feature of celiac disease and gluten sensitivity. The team recommends that patients with idiopathic small fiber neuropathy be screened for celiac disease and gluten sensitivity.

Read more in Postgrad Med. 2019 Aug 6:1-5. doi: 10.1080/00325481.2019.1650609.