An official website of the United States government
Accelerating Research in Celiac Disease
When beginning your next investigator-initiated application, consider the following NIH highlighted topic. The area of science described below is of interest to the listed NIH Institutes, Centers, and Offices (ICOs). This is not a notice of funding opportunity (NOFO).
Apply through an appropriate NIH Parent Funding Announcement or another broad NIH opportunity available on Grants.gov. Learn how to interpret and use Highlighted Topics.
Topic Description
Post Date: September 10, 2025
Expiration Date: September 10, 2026
Purpose
This topic encourages applications to accelerate research on the:
- Etiology and pathogenesis of celiac disease
- Reliable diagnostic methods to detect disease early, before significant intestinal pathology occurs
- Identification of therapeutic targets
- development of preventative and therapeutic strategies
Background
Celiac disease is an autoimmune disease that occurs in genetically susceptible individuals, who develop an immune response to dietary gluten resulting in damage to the small intestine. Celiac disease affects over 1% of the U.S. population, with incidence rising over the last several decades, and is diagnosed more frequently in women. The only known treatment is a lifelong, strict avoidance of all forms of gluten, which is present in wheat, rye, and barely. While this diet is an effective treatment for many individuals, up to 50% are poorly responsive or refractory to a gluten-free diet. Moreover, the majority of patients are inadvertently exposed to gluten or report difficulty adhering to a gluten-free diet.
The clinical manifestations of celiac disease are multifaceted and include both gastrointestinal and extraintestinal symptoms. The gastrointestinal manifestations range from severe malabsorption to subclinical damage of the gastrointestinal tract. Additional extraintestinal manifestations include dental enamel defects, dermatitis herpetiformis, and osteoporosis. Although rare, celiac disease is associated with increased risk of gastrointestinal tract cancers and lymphomas. Diagnosis of celiac disease relies on a small intestinal biopsy and serological markers, though some patients do not meet all diagnostic criteria.
The pathogenesis of celiac disease involves a combination of predisposing genes, dietary gluten, and environmental factors. The predominant genetic factors are Human Leukocyte Antigen- DQ8 and/or DQ2 (HLA-DQ2 and/or HLA-DQ8) haplotypes, while dietary gluten is the major trigger for disease. Many other environmental factors influence the development of celiac disease but are less well-defined than gluten. The immune response to gluten fragments occurs at the small intestinal epithelium, involving both innate and adaptive immune responses. The results are characteristic autoantibodies, histologic changes (intraepithelial lymphocytosis, crypt hyperplasia and villous atrophy), and clinical symptoms such as diarrhea, weight loss and iron deficiency anemia.
Significant progress in understanding celiac disease has been achieved in recent years, accompanied by a growing clinical and scientific workforce focused on celiac disease research. Despite this progress, many unmet needs remain, which include fully elucidating disease pathogenesis and developing improved tools and strategies for diagnosis, prevention, and treatment of celiac disease.
Participating ICOs
NIAID encourages applications that enable earlier and more reliable diagnosis of celiac disease, uncover immune mechanisms involved in disease pathogenesis, and that develop immune modulating interventions or other strategies to prevent celiac disease and/or restore gluten tolerance. Areas of interest include defining cellular and molecular mechanisms that drive autoimmunity and tissue damage, identifying triggers of disease onset and progression, and elucidating the link between gluten exposure and immune-mediated pathology. Projects may focus on biomarker discovery for diagnosis and disease monitoring, immune mechanisms underlying variable responses to gluten avoidance, immune modulating interventions to prevent/treat disease. Other areas of interest include the development of novel research models including New Approach Methodologies (NAMs) that accurately model celiac disease immunopathology, and research into shared mechanisms between celiac disease and other immune disorders.
ICO Scientific Contact:Kelly Hudspeth, Ph.D.
[email protected]
For cancer or tumor-associated celiac disease, research may include, but are not limited to:
- Molecular, cellular immune mechanisms, or responses underlying celiac disease and cancer
- Roles of gastrointestinal autoimmunity and/or inflammation in GI or extra-intestinal cancers associated with celiac disease
- Mechanisms to understand how commensal or pathogenic organisms, such as enteric microbiome (including virome), promote or exacerbate celiac disease GI inflammation toward cancer
- Development of tumor model systems to study the effects of gluten and intestinal damage
- Mechanisms of intestinal lining cell biology with celiac disease and cancer
- Characterization of immune checkpoint blockade-induced celiac disease
- Translational, preclinical research, and/or clinical trials of microbiota, natural products, and/or nutrition/diet interventions to treat and/or prevent celiac disease development for cancer
Marco Cardone, Ph.D. (cancer therapeutics)
[email protected]
Cheryl Cero, Ph.D. (cancer cell biology, non-immunology)
[email protected]
Lillian Kuo, Ph.D. (tumor immunology, immune mechanisms)
[email protected]
The National Institute of Arthritis and Musculoskeletal and Skin Diseases mission is to support research into the causes, treatment, and prevention of arthritic, rheumatic, musculoskeletal, and skin diseases. In the context of celiac disease, NIAMS is interested in research related to the symptoms, co-morbidities, and complications of celiac disease focused in NIAMS mission areas (including but not limited to skin conditions, osteoporosis/osteopenia, arthritis, joint inflammation) and the impact of pathways disrupted by celiac disease (e.g., tissue cross-talk, gut microbiome imbalance, etc.) in the development and progression of diseases within the NIAMS mission.
ICO Scientific Contact:Marie Mancini, Ph.D.
[email protected]
NIDCR is interested in research related oral symptoms, co-morbidities, and complications of celiac disease related to dental, oral and craniofacial health and the impact of common pathways disrupted by celiac disease in development and progression of diseases within NIDCR’s mission. Research topics include:
- Mechanistic studies on dental enamel defects in children with celiac disease
- Mechanisms of celiac-related inflammatory symptoms in the mouth like aphthous ulcers, atrophic glossitis, periodontal disease and oral lichen planus in patients
- Role of salivary proteins, salivary gland involvement, xerostomia and autoimmune symptoms in the oral cavity associated with celiac disease
- Oral mucosa-associated immune and microbial dysbiosis mechanisms in celiac disease
- Mechanistic studies focused on establishment and maintenance of the oral microbiome in children with celiac disease to address oral symptoms
- Mechanistic relationship between nutrition and oral health in celiac disease
Preethi Chander, Ph.D.
[email protected]
The NIH Office of Research on Women's Health's (ORWH) areas of interest include:
- Investigate sex-specific factors (genetic, hormonal, environmental) contributing to higher prevalence and unique manifestations of celiac disease in women across the life course, focusing on earlier and more reliable diagnosis.
- Examine the impact of celiac disease on reproductive health, pregnancy outcomes, and bone density in women; develop tailored prevention and treatment strategies.
- Co-occurrence of celiac disease with other autoimmune diseases.
- Mechanisms of autoimmunity, including interactions of genes and the environment.
This office does not award grants. Applications must be relevant to the objectives of at least one of the participating NIH Institutes and Centers listed in this topic.
ICO Scientific Contact:Elena Gorodetsky, M.D., Ph.D.
[email protected]
Victoria Shanmugam, MBBS, MRCP, FACR, CCD
[email protected]
For technical issues E-mail OER Webmaster