P4061 - Metabolomic Profiling Reveals Alterations in Butyrate Metabolism Associated With Anxiety in Working Adults

Brent J. Gawey, MD, MSc¹, Matthew R. Smith, PhD², Yagmur Y. Comba, MD¹, Andrew S. Neish, MD², Dean P. Jones, PhD², Thomas R. Ziegler, MD, MSc^2
1Mayo Clinic, Rochester, MN; ²Emory University School of Medicine, Atlanta, GA

Introduction: Anxiety disorders are highly prevalent and often co-occur with gastrointestinal conditions. Butyrate, a short-chain fatty acid produced by gut microbiota, has been implicated in various psychiatric diseases and may play a role in anxiety disorders. This study used high-resolution metabolomics (HRM) to investigate the relationship between butyrate metabolism and clinical anxiety scores in working adults.

Methods: Fasting plasma from 179 adults (mean age 49.5 ± 10.3 years; 64% female) was analyzed using HRM. Clinical severity of anxiety was quantified using the General Anxiety Disorder-7 (GAD-7) questionnaire. Multiple linear regression analyses were used to identify metabolic features that were significantly associated (p < 0.05) with GAD-7 scores. Significant metabolites were used as input for pathway analysis using the mummichog bioinformatics package.

Results: A total of 5,471 metabolic features were identified, of which 494 were significantly associated with GAD-7 scores (p < 0.05). Pathway analysis revealed significant overlap (p = 0.04) with butyrate metabolism. Specifically, succinate (β = -1.03, SE ± 0.44, p = 0.02) and 5-aminopentanoate (β = 0.65, SE ± 0.30, p = 0.03) were associated with GAD-7 scores.

Discussion: The findings suggest that alterations in butyrate metabolism, specifically involving succinate and 5-aminopentanoate, are associated with clinically validated measures of anxiety in working adults. These metabolic changes may reflect dysregulation in gut microbial communities or host metabolic pathways related to butyrate production and utilization. The results provide pathway-level insights into the potential role of butyrate metabolism in anxiety disorders and highlight the need for further investigation into the implications of the gut-brain axis in mental health.


Disclosures:


Brent J. Gawey, MD, MSc¹, Matthew R. Smith, PhD², Yagmur Y. Comba, MD¹, Andrew S. Neish, MD², Dean P. Jones, PhD², Thomas R. Ziegler, MD, MSc². P4061 - Metabolomic Profiling Reveals Alterations in Butyrate Metabolism Associated With Anxiety in Working Adults, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.