Medication Use is Associated with Distinct Microbial Features in Anxiety and Depression

Abstract This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by DSM-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing and shallow shotgun sequencing were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and NeuroMAP CoBRE cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. The findings suggest that future research on the gut microbiota’s role in NPD and its interactions with pharmacological treatments are needed. Competing Interest Statement Daniel McDonald is a consultant for, and has equity in, BiomeSense, Inc. Mehrbod Estaki is the chief science officer and has equity at Innovate Phytoceuticals Inc. He is a scientific advisor and holds equity at Melius Microbiomics Inc. Rima Kaddurah-Daouk is an inventor on key patents in the field of Metabolomics and holds equity in Metabolon. In addition, she holds patents licensed to Chymia LLC and PsyProtix with royalties and ownership. Rob Knight is a scientific advisory board member, and consultant for BiomeSense, Inc., has equity and receives income. He is a scientific advisory board member and has equity in GenCirq. He is a consultant and scientific advisory board member for DayTwo, and receives income. He has equity in and acts as a consultant for Cybele. He is a co-founder of Biota, Inc., and has equity. He is a cofounder of Micronoma, and has equity and is a scientific advisory board member. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. The companies listed here had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the paper; and decision to submit the paper for publication. Pieter Dorrestein (of the AGMP consortium) is an advisor and holds equity in Cybele and Sirenas and a Scientific co-founder, advisor and holds equity to Ometa, Enveda, and Arome with prior approval by UC San Diego. Pieter Dorrestein also consulted for DSM animal health in 2023.