Gastrointestinal Insights into Anorexia Nervosa Treatment

This novel project aims to investigate the underexamined, biological mechanisms driving gastroparesis in chronic anorexia nervosa (AN), a severe condition characterized by high morbidity and limited treatment options. Gastroparesis, a condition where the stomach's ability to empty its contents is delayed, is highly prevalent in individuals with chronic AN and may play a key role in perpetuating the disorder. The slowing of gastric emptying contributes to a range of gastrointestinal (GI) symptoms, such as early satiety, nausea, and bloating, which research has shown can heighten fear of eating and reinforce food restriction behaviors. This creates a vicious cycle where AN cognitions and behaviors, along with physiological dysfunction, feed into one another, making it harder to treat the disorder effectively. However, to date, no study has thoroughly attempted to address how gastrointestinal dysfunction may play a role in the maintenance of chronic AN. By focusing on interactions between glucagon-like peptide-1 (GLP-1), gut microbiota dysbiosis, and gastric emptying, we aim to explore how these factors contribute to the persistence of AN. Specifically, we hypothesize that slower gastric emptying correlates with increased selfreported AN symptoms, with gastroparesis partially mediating this relationship. Additionally, we will examine how GLP-1 responsiveness and gut microbial beta-diversity moderate the relationships between gastric emptying, gastroparesis, and AN behaviors. Data will be collected from participants on an inpatient eating disorder unit through laboratory assessments, including gastric emptying evaluations and GLP-1 response measurements, along with ecological momentary assessments (EMA) tracking symptoms over two weeks. A second fecal sample and clinical information collected one month post-discharge will assess changes in gut microbiota diversity and GI distress. By elucidating these mechanisms, this research has the potential to inform novel treatments (i.e., emerging pharmacological interventions such as GLP-1 antagonists) that reduce the chronicity of AN and address the "crisis in care" for individuals with this challenging disorder. Project Number: 5P20GM134969-05 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Joseph Wonderlich | Institution: SANFORD RESEARCH NORTH, FARGO, ND | Award Amount: $291,040 | Activity Code: P20 | Study Section: ZGM1-RCB-2(C1) View on NIH RePORTER: https://reporter.nih.gov/project-details/11471563