Understanding Non-Celiac Wheat Sensitivity and miRNA Expression Patterns
The Role of Wheat in Global Diets
Wheat stands as the most extensively cultivated crop worldwide, forming a staple in various foods such as bread, pasta, noodles, bulgur, and couscous. Gluten, a protein found in wheat, barley, and rye, can provoke severe immune responses in individuals with celiac disease. Celiac disease is an autoimmune condition where gluten ingestion incites an immune reaction that damages the small intestine’s lining, leading to symptoms such as diarrhea, fatigue, weight loss, bloating, and anemia.
Prevalence and Market Trends
In Western nations, the estimated prevalence of celiac disease hovers around 1%. However, an increasing segment of the population is opting for wheat-free diets, contributing to a burgeoning global market for gluten-free products, which was valued at nearly $2.5 billion (US) in 2010. This trend has sparked discussions regarding alternative reactions to gluten beyond celiac disease.
Non-Celiac Wheat Sensitivity: A New Perspective
Recent insights indicate that some adverse reactions to gluten may be neither allergic nor autoimmune. Individuals suffering from gastrointestinal distress after consuming gluten-containing products, yet showing improvement on a gluten-free diet, may have non-celiac wheat sensitivity (NCWS). This newly defined condition exists within the spectrum of gluten-related disorders.
Challenges in Diagnosing NCWS
The pathogenesis of NCWS remains poorly understood, and diagnosing gluten sensitivities poses challenges. Unlike celiac disease, which can be diagnosed through specific serum markers and mucosal changes, no laboratory biomarkers exist for NCWS. Currently, the diagnosis is based on a complex clinical protocol correlating gastrointestinal symptoms with gluten consumption. Patients must demonstrate symptom relief during gluten exclusion, followed by a resurgence of symptoms upon reintroducing gluten.
Research Advancements in NCWS Diagnosis
To enhance diagnostic accuracy for NCWS, researchers from the University of Chieti-Pescara, Italy, employed gene expression profiling. This technique analyzes thousands of genes concurrently to assess gene expression in tissues. The study focused on microRNAs (miRNAs), short non-coding RNA sequences that regulate gene expression. Previous research has linked miRNAs to the development of various autoimmune diseases, including celiac disease. The researchers posited that NCWS might exhibit a distinct miRNA signature, aiding in differentiating gluten-related disorders with overlapping clinical presentations.
Study Methodology and Findings
Patients were recruited from hospitals and clinics in Chieti, Italy, based on referrals for gluten-related gastrointestinal symptoms. Those diagnosed with celiac disease formed a control group, while patients with gastrointestinal distress but a negative celiac diagnosis underwent a six-week gluten exclusion followed by a gluten challenge. Additionally, patients with gluten-independent gastrointestinal issues served as further controls. All participants underwent endoscopy to collect intestinal mucosa samples for miRNA expression evaluation.
The researchers identified a unique miRNA signature in NCWS patients, distinguishing them from control patients with gluten-independent symptoms and those with celiac disease. Specifically, seven miRNAs exhibited differential expression in the intestinal biopsies of NCWS patients. These findings were corroborated in a larger validation cohort comprising 25 control patients and 27 NCWS patients, with six of the identified miRNAs showing overexpression in the intestinal mucosa of NCWS patients. This research has been published in the journal PLOS ONE.
Implications for Future Diagnosis
In light of the absence of laboratory biomarkers for validating NCWS diagnosis, these findings provide an objective miRNA profile that could be applied in clinical practice. The identification of this distinct miRNA pattern, in conjunction with a negative celiac disease diagnosis, may set the groundwork for future NCWS diagnostic protocols.
Written by Cheryl Xia, HBMSc
Reference: Clemente, E. et al. An explorative study identifies miRNA signatures for the diagnosis of non-celiac wheat sensitivity. PLoS ONE 14, e0226478 (2019).
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