Research Suggests that Iron Deficiency Anemia May Cause Celiac Disease: A Causal Relationship Should Now Be Confirmed with Clinical Trials

Jon Bari
11 hours ago
9 min read

"All disease begins in the gut" -- Hippocrates

Patient History

In August 2018, Jax was 5-years old and poised to start Kindergarten. Then our whole world changed when he was diagnosed with Celiac Disease. We learned that Jax was anemic, and he had Marsh 3 level damage to his small intestine. We were advised that they only see Marsh 4 level damage during an autopsy. It was really bad.

Some things started to make sense. At age 5, Jax's anemia and short stature appeared to be a function of his body's inability to absorb nutrients. But, many other things did not make sense. We had so many unanswered questions. How did Jax get Celiac? it doesn't run in our family. When did he develop Celiac? How did we not know? And so our journey began.

Back to school in 2018 was filled with so many new challenges including starting Kindergarten and transitioning Jax to a strict Gluten Free diet. As Jax learned to read, he started with fairy tales and food labels, which are confusing and incomplete. We learned the hard way that Celiac is a disease, not a diet! And there are no breaks from Celiac, ever! There is so much that is not understood about Celiac, and there is so much that is misunderstood. Celiac has really tested our grit and resilience. That said, Jax has been a rock star in navigating this dreaded disease and advocating for increasing government funding for research to find a treatment or a cure and requiring the labeling of Gluten as a Major Food Allergen in the U.S., just like Gluten must be declared on all food labels in 87 other countries.

Even on a strict Gluten Free diet which included iron fortified foods and iron supplements, Jax has remained iron deficient and anemic. Jax has needed to get two iron infusions, the first in 2022 and then again in 2025. We believe that those have been beneficial to his health and well-being.

In the world of autoimmune and digestive diseases, there is a common school of thought that Celiac and Inflammatory Bowel Disease (IBD) can each cause anemia due to villous atrophy. However, new research from the University of Washington and University of Florida suggests that anemia may not necessarily be the downstream consequence of Celiac and/or IBD, but could in fact trigger Celiac Disease and/or IBD.

Along the lines of the chicken and the egg enigma, I started reviewing research on whether Celiac Disease causes anemia or whether anemia may cause Celiac (there is not a lot of research on this), which can then in turn exacerbate the iron deficiency anemia in a viscous cycle. In other words, iron deficiency anemia appears to be a consequence of Celiac, but iron deficiency anemia may also be a cause of Celiac Disease.

To that end, if recent research now suggests that iron deficiency anemia may potentially play a role in the pathogenesis of Celiac Disease, could that have been the case with Jax and others similarly situated? A review of Jax's medical records shows that he had a routine Complete Blood Count (CBC) with automated differential completed in June 2014 just before he was 14 months old. Below are the abnormal results.

CBC (INCLUDES DIFF/PLT)	In Range	Out of Range	Reference Range
White Blood Cell Count		5.6 Low	6.0-17.0 Thousand/uL
Red Blood Cell Count		3.69 Low	3.90-5.50 Million/uL
Hemoglobin		10.5 Low	11.3-14.1 g/dL
Hematocrit		30.8 Low	31.0-41.0 %
Absolute Lymphocytes		3304 Low	4000-10500 (cells/uL)

According to the American Academy of Pediatrics, "Anemia: A hemoglobin (Hb) concentration 2 SDs [standard deviations] below the mean Hb concentration for a normal population of the same gender and age range, as defined by the World Health Organization, the United Nations Children's Fund, and United Nations University. On the basis of the1999-2002 US National Health and Nutrition Examination Survey, anemia is defined as a Hb concentration of less than 11.0 g/dL for both male and female children aged 12 through 35 months."

Unfortunately, the medical records reflect that Jax's iron deficiency anemia was for all intents and purposes ignored since it was left unchecked and unmonitored for more than four years from about 14 months old until his Celiac diagnosis at age 5 years and 5 months old in August 2018.

Prior to July 2018, there was no repeat CBC ever done. Prior to July 2018, there was no meaningful assessment ever done for dietary risk factors including insufficient iron in foods and excessive intake of cow's milk. The first record of Jax consuming cow's milk was on 7/14/2014, and the medical records reflect that he drank on average 20-25 ounces of cow's milk per day, which can interfere with iron absorption. Prior to July 2018, there were no risk assessments ever done for disorders with GI blood loss (i.e., inflammatory bowel disease, or chronic gastritis) or malabsorptive disease (i.e.,, Celiac Disease, or chronic intestinal infections). Prior to 2018, there was never any meaningful clinical suspicion of any of these individual symptoms, let alone any clinical suspicion of this constellation of symptoms including: declining growth rates, night sweats, sleep disturbances and insomnia, frequent respiratory illnesses with coughs requiring antibiotics (anemia can suppress the immune system), possible heart murmur, pallor, etc.

On March 12, 2014, Joseph Murray, M.D., a Gastroenterologist and Celiac Disease Expert at the Mayo Clinic, discussed research published in the Archives of Diseases in Childhood that proposed a scenario of screening children with iron deficiency for Celiac Disease.

Iron Deficiency Can Have Important Consequences to Health & Development

According to an article in Clinical Gastroenterology and Hepatology by Peter Green, M.D. and Benjamin Lebwohl, M.D. at the Celiac Disease Center at Columbia University, "Patients presenting with anemia may have more severe disease expression (as measured by the degree of villous atrophy and the presence of metabolic bone disease) than patients presenting with diarrhea." This correlates with why iron deficiency anemia must be investigated as well as why children must be re-screened and followed over time, none of which happened in our case. This could help to prevent the onset of lifelong chronic disease and other debilitating adverse health effects.

According to Jacquelyn Powers, M.D., MS, Associate Professor of Pediatrics, Baylor College of Medicine and UpToDate author, "Iron deficiency is the most common nutritional deficiency in children. The global prevalence of anemia in 2010 was 32.9 percent, with the highest burden in children less than five years of age… In the United States and other resource-abundant settings, rates of iron deficiency are substantially lower, yet iron deficiency is still common and can have important consequences to health and development."

Iron Deficiency May Contribute to the Development of IBD and Other Immunological Disorders

I recently read an interesting article about how University of Florida researchers including Liang Zhou, M.D., Ph.D. (UF College of Veterinary Medicine) discovered that iron plays a key role in immune system health. Specifically, I was intrigued to learn more about this area of anemia potentially being the causal agent of inflammatory bowel disease as opposed to the downstream consequence of IBD. According to UFHealth News,

"For years, iron deficiency was considered a consequence of inflammatory bowel disease, or IBD, which affects one in every 100 Americans, resulting from chronic blood loss and impaired iron absorption. However, this discovery by UF scientists, reported in Nature Immunology, suggests that iron deficiency may contribute to the development of IBD and other immunological disorders."

Similar to Dr. Zhou's research, iron deficiency anemia has long been been considered a downstream consequence of Celiac Disease, resulting from villous atrophy in the small intestine and impaired iron absorption. That is how it was explained to us, and up until 2025, I was not aware of anyone suggesting otherwise.

However, could iron deficiency anemia contribute by itself or with other factors to the development or activation of Celiac Disease in genetically predisposed individuals, which could then lead to a vicious cycle of Celiac Disease damaging the small intestine and causing and/or exacerbating iron deficiency anemia.

Research Suggests that Iron Deficiency May Play a Role in the Pathogenesis of Celiac Disease Development

As reported by HCP Live, Iron Deficiency May Elevate Risk of Celiac Disease Development. Dr. Isabel Hujoel at the University of Washington recently published research which focused on whether iron deficiency may elevate the risk of Celiac Disease development.

Dr. Hujoel is a Clinical Assistant Professor with the University of Washington Division of Gastroenterology, and she also serves as Clinic Director, Celiac Disease Center. Dr. Hujoel's research was published in BMJ Open Gastroenterol 2024, "Investigating the role of iron status in the development of coeliac disease: a Mendelian randomisation study."

"This study suggests that iron deficiency may play a role in coeliac disease development. A causal relationship should ideally be confirmed with clinical trials, and if affirmative, should be followed by prevention studies. More broadly, this study raises questions of the potential ties between iron deficiency and gluten-sensitivity, and the potential implications of dietary restrictions and avoidant restrictive food intake disorders which are common in coeliac disease, inflammatory bowel disease, and irritable bowel syndrome."

CD71 is a Compensatory Mechanism in Anemia and a Transporter of Gluten Across the Gut Barrier in Celiac

CD71 is the official name for the transferrin receptor, an integral membrane protein that facilitates the uptake of iron into cells by binding to iron-loaded transferrin and undergoing receptor-mediated endocytosis.

CD71 is elevated as a compensatory mechanism in people with iron deficiency anemia. CD71 is also the transporter of Gliadin (Gluten) across the gut barrier through leaky gut syndrome.

The intestinal lining is composed of millions of cells that connect to form a tight barrier, like a security system, that controls what is absorbed into the bloodstream and what is kept out.

Further research is needed to understand how anemia may accelerate or precipitate Celiac Disease by increasing CD71 which in turn increases exposure of the body's immune system to Gluten peptides. In other words, we need to understand how anemia might contribute to leaky gut, which increases the permeability of the intestinal lining. Leaky gut allows food -- such as Gluten that should normally stay within the gut -- to pass into the bloodstream, potentially triggering the immune system to mistakenly identify Gluten as harmful.

Decreased ILC3 Cells May Also Play a Role

There is also the direct impact of iron metabolism on the immune system. Anemia can result in decreased ILC3 cells, and these cells mediate immune tolerance to the gut microbiome. This may be more relevant in IBD than Celiac since Celiac occurs in the region of the gut with less microbes. But decreased ILC3 my still play a role in Celiac Disease. To that end, in his PhD thesis work, Dr. Francisco Leon (who now runs Tolerance Bio) observed a decrease in cells consistent with ILC3 phenotype in Celiac Disease.

Autoimmunity as a Risk Factor for Other Comorbid Conditions

According to the National Institutes of Health, "the effects of autoimmunity are numerous and can have wide-reaching consequences. For example, chronic inflammation, part of the pathophysiology of many autoimmune diseases, is an independent risk factor for cardiovascular disease. In addition, many people with autoimmune diseases develop mental health disorders such as depression and anxiety. Data increasingly signal that these comorbidities are not simply related to the difficulties of living with a chronic disease; rather, inflammation may contribute to the development of systemic complications."

High Risk of Digestive Cancers in Patients With Celiac Disease

In December 2024, the journal "Clinical Gastroenterology and Hepatology" published in-depth research that confirms high risks of lymphoma and small bowel cancer in Celiac patients, as well as indicate increased risks of pancreatic, esophageal, gastric, and colonic cancers. Additionally, the research demonstrated significantly increased risk for Celiacs to develop Type 1 diabetes, thyroiditis, rheumatoid arthritis and osteoporosis. The research also found that patients with Celiac had a higher risk for pernicious anemia, Crohn's disease, ulcerative colitis and noninfectious enterocolitis, which included microscopic colitis as well as nonalcoholic chronic pancreatitis.

The study examined data from 27,114 hospitalized Celiac patients over a nine-year period. When compared to non-Celiac controls, individuals with Celiac Disease had significantly higher risks for small bowel cancer, non-Hodgkin lymphoma, pancreatic cancer, esophageal cancer, colon cancer and gastric cancer.

Given the potentially life-threatening nature of Celiac Disease, it is paramount that more research is done to understand whether iron deficiency anemia could be the activating cause of Celiac Disease in some patients. If we can prevent Celiac Disease from activating by meaningfully and proactively addressing iron deficiency anemia, then these efforts must be undertaken.

NOURISH (Nutrition for OUR Immune System Health): Autoimmunity Challenge

The Trump Administration's Make Our Children Healthy Again Strategy Report included bold initiatives including food allergies and Celiac Disease:

"Food Allergies: FDA will develop guidance on diagnostics and treatments for food allergies. FDA will also make recommendations about requiring transparency in disclosures of ingredients that impact certain health conditions, such as gluten for those with Celiac disease, and other established food allergens."

To that end, the NIH's Nutrition for OUR Immune System Health (NOURISH): Autoimmunity Challenge aligns with the MAHA Strategy Report and with pursuing research opportunities to better understand any causal connection between anemia and Celiac. Based on our experience, there are various potential research areas including:

The role diet plays in the autoimmune prodrome and autoimmune disease inception
How diet and nutrition contribute to autoimmune disease progression and flares
The role that diet may play in autoimmune disease symptom management.

Could anemia be the environmental factor to disrupt the intestinal barrier, increasing its permeability and allowing potential antigens (like Gluten peptides) to come into contact with the immune system?

If the initial research from Dr. Hujoel and Dr. Zhou proves correct about anemia as a causal agent, this opens new areas of treatment along with the possible prevention of a potentially deadly, life-changing diagnosis with Celiac Disease and/or IBD.

Let's go!