Unraveling Gut-Brain Communication Mechanisms using Clinical Phenotype, Microbiome, and Structural MRI Features in Patients with Alcohol Use Disorder

Authors

• U Bocchero
• DA Stacks
• MN Nguyen
• SJ Pittler
• J Pahlberg

Abstract

Background: Alcohol misuse is a public health concern and alcohol use disorder (AUD) contributes to chronic health conditions. Studies suggest the gut microbiome plays a role in AUD and its associated symptoms through gut-brain communication. The objective of this study was to 1) evaluate associations between morphometry of stress-associated areas of the brain and the microbiome and 2) characterize longitudinal relationships between AUD-associated symptoms and the gut microbiome.
Methods: Subjects undergoing inpatient treatment for AUD were studied (n=20, 35% female). Stool specimens and symptoms of anxiety, depression, withdrawal, sleep disturbance and alcohol cravings were collected weekly while inpatient (4 weeks). Structural MRIs (n=16) were obtained at week 2 and morphometry was quantified in brain regions of interest (ROIs) involved in the hypothalamic-pituitary-adrenal axis. Shotgun metagenomics sequencing was performed and the neuroactive potential of predicted metagenomes was tested using gut-brain modules.
Results: Anterior cingulate cortex (ACC) thickness was negatively associated and amygdala volume was positively associated with microbiome alpha diversity (Shannon Index). Several Blautia taxa were associated with amygdala and ACC ROIs, along with AUD-associated symptom severity scores. Longitudinal responses of clinically significant microbiome features will also be presented.
Conclusions: In this cohort of subjects, ACC and amygdala morphometry were associated with microbiome features suggesting gut-brain communication with these brain regions in patients with AUD. Ongoing work will quantify longitudinal responses of bacteria and gut-brain modules associated with symptom severity scores in hopes of providing preliminary data to design future studies aimed at improving mental health symptoms in patients with AUD.

Scientific Focus Area: ACI/IRS

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