¹Hyogo Medical University, Neuropsychiatry, Nishinomiya, Japan

Background: Gluten sensitivity is characterized by a range of gluten-induced physical and psychological symptoms, including abdominal pain, diarrhea, fatigue, anxiety, and depressive mood. Increasing evidence has linked gluten-related disorders to various psychiatric conditions; however, their relationship with eating disorders remains poorly understood. At CINP 2025, we reported a high prevalence of immunological gluten sensitivity among eating-disorder patients presenting with chronic diarrhea, suggesting the existence of a clinically relevant subgroup in which gluten-related immune activation contributes to gastrointestinal distress and nutritional instability. Building on these findings, the present report describes two patients with anorexia nervosa (AN) in whom immunological gluten sensitivity was identified and gluten restriction was associated with meaningful weight restoration.

Aims & Objectives: The aim of this report was to explore the potential clinical relevance of immunological gluten sensitivity in patients with anorexia nervosa. Specifically, we sought to describe the clinical course of two patients with treatment-refractory AN in whom immunological gluten sensitivity was confirmed, and to examine the impact of gluten restriction on gastrointestinal symptoms and longitudinal weight outcomes. Through these cases, we aimed to highlight an underrecognized pathway by which gluten-related immune responses may exacerbate low weight, food avoidance, and nutritional instability in a subset of patients with AN.

Method: Two female patients diagnosed with anorexia nervosa underwent immunological evaluation for gluten sensitivity as part of their clinical assessment due to persistent gastrointestinal symptoms. Both patients provided written informed consent for case presentation, and identifying details were modified to protect privacy. Immunological gluten sensitivity was confirmed by positive anti-gliadin IgG antibodies. Gluten restriction was subsequently introduced in an outpatient treatment setting. Clinical data, including body mass index (BMI), gastrointestinal symptoms, and longitudinal weight changes, were reviewed retrospectively to evaluate clinical outcomes following dietary modification.

Results: Case 1: A 34-year-old woman with restrictive-type AN (onset at age 22) remained persistently underweight (BMI 12–13 kg/m²) despite prolonged outpatient treatment. She exhibited marked fear of weight gain and chew-and-spit behavior. Without laxative misuse, chronic diarrhea impaired dietary tolerance. Following confirmation of gluten sensitivity and initiation of gluten restriction, gastrointestinal symptoms gradually improved, enabling increased oral intake. Her BMI rose to 20.3 kg/m² after one year. She subsequently achieved pregnancy and childbirth and has maintained a normal BMI.
Case 2: A 29-year-old woman with binge–purge-type AN (onset at age 20) similarly maintained a BMI of 12–13 kg/m² despite multiple treatment attempts. She experienced diarrhea and abdominal bloating without laxative misuse. After gluten sensitivity was confirmed, gluten restriction led to improvement in gastrointestinal symptoms. Her BMI increased to 16 kg/m² after one year and to 18 kg/m² after two years.

Discussion & Conclusions: In both cases, gluten restriction was associated with improvement in gastrointestinal symptoms and sustained weight gain. These findings suggest that immunological gluten sensitivity may contribute to persistent low weight, meal-related distress, and avoidance of wheat-containing carbohydrates in a subgroup of patients with AN, particularly those with chronic diarrhea. Screening for immunological gluten sensitivity may therefore be clinically valuable, and targeted dietary interventions could support symptom relief and facilitate weight restoration in treatment-refractory AN.