(P27-025-23) The Gut Microbiome in Psychiatric Disorders: A Transdiagnostic Perspective

Objectives: Recent research has implicated the gut microbiome in the development and perpetuation of several psychiatric disorders. Changes in microbiota composition show overlap between disorders, potentially indicating a common mechanism. Here, we investigated the cross-disorder associations between the gut microbiota and psychiatric symptoms in a highly comorbid psychiatric cohort (MIND-Se).

Methods: The MIND-Set cohort included 272 patients with a mood, anxiety, attention deficit/hyperactivity, autism spectrum, and/or a substance use disorder and 97 unaffected individuals. Of all patients, 55% fell into at least two diagnostic categories. Cross-disorder symptom domains were obtained using principal component analysis (PCA) on the subscales of 8 questionnaires (31 subscales), measuring psychiatric symptoms, psychological constructs, and personality traits. Microbiota abundances (16S gene sequences) were CLR-transformed at the genus level, and a randomized lasso was used to select genera with the highest informative value. Multiple linear regression (adjusted for age, sex, and the number of diagnoses) was used to assess associations between the selected genera and PCA-based symptom domains. Diet, medication, and genetic covariates were additionally entered into the model in a stepwise fashion.

Results: Four symptom domains (negative valence, social processes, cognition and regulation/inhibition) were extracted from the PCA. We identified several significant associations between the symptom domains and CLR-adjusted genus abundance, including associations between negative valence and Sellimonas, CHKCI001, Clostridium_sensu_stricto_1, Oscillibacter, and Flavonifractor; social processes and Sellimonas; cognitive systems and Allisonella, Sporobacter, and Hungatella, and regulation/inhibition and Ruminococcus_torques_group (all p<sub>FDR < .044). Most associations persisted after adjustment for additional covariates. Moreover, associations were symptom domain specific and existed across psychiatric disorders.

Conclusions: We demonstrated cross-disorder associations between the gut microbiota and psychiatric symptom domains, which could potentially be used in biologically informed disease subtyping or as target for symptom reduction.

Funding Sources: European Horizon 2020
National Institute of Mental Health (NIH)