History of childhood physical abuse is associated with gut microbiota diversity among adult psychiatric inpatients.

BACKGROUND: Traumatic life events are associated with the development of psychiatric and chronic medical illnesses. This exploratory study examined the relationship between traumatic life events and the gut microbiota among adult psychiatric inpatients. METHODS: 105 adult psychiatric inpatients provided clinical data and a single fecal sample shortly after admission. A modified version of the Stressful Life Events Screening Questionnaire was used to quantify history of traumatic life events. 16S rRNA gene sequencing was used to analyze the gut microbial community. RESULTS: Gut microbiota diversity was not associated with overall trauma score or any of the three trauma factor scores. Upon item-level analysis, history of childhood physical abuse was uniquely associated with beta diversity. Linear Discriminant Analysis Effect Size (LefSe) analyses revealed that childhood physical abuse was associated with abundance of distinct bacterial taxa associated with inflammation. LIMITATIONS: This study did not account for dietary differences, though diet was highly restricted as all participants were psychiatric inpatients. Absolute variance accounted for by the taxa was small though practically meaningful. The study was not powered for full subgroup analysis based on race and ethnicity. CONCLUSIONS: This study is among the first to demonstrate a relationship between childhood physical abuse and gut microbiota composition among adult psychiatric patients. These findings suggest that early childhood adverse events may have long-conferred systemic consequences. Future efforts may target the gut microbiota for the prevention and/or treatment of psychiatric and medical risk associated with traumatic life events.

Differential co-expression networks of the gut microbiota are associated with depression and anxiety treatment resistance among psychiatric inpatients.

BACKGROUND: Comorbid anxiety and depression are common and are associated with greater disease burden than either alone. Our recent efforts have identified an association between gut microbiota dysfunction and severity of anxiety and depression. In this follow-up, we applied Differential Co-Expression Analysis (DiffCoEx) to identify potential gut microbiota biomarker(s) candidates of treatment resistance among psychiatric inpatients. METHODS: In a sample of convenience, 100 psychiatric inpatients provided clinical data at admission and discharge; fecal samples were collected early during the hospitalization. Whole genome shotgun sequencing methods were used to process samples. DiffCoEx was used to identify clusters of microbial features significantly different based on treatment resistance status. Once overlapping features were identified, a knowledge-mining tool was used to review the literature using a list of microbial species/pathways and a select number of medical subject headlines (MeSH) terms relevant for depression, anxiety, and brain-gut-axis dysregulation. Network analysis used overlapping features to identify microbial interactions that could impact treatment resistance. RESULTS: DiffCoEx analyzed 10,403 bacterial features: 43/44 microbial features associated with depression treatment resistance overlapped with 43/114 microbial features associated with anxiety treatment resistance. Network analysis resulted in 8 biological interactions between 16 bacterial species. Clostridium perfringens evidenced the highest connection strength (0.95). Erysipelotrichaceae bacterium 6_1_45 has been most widely examined, is associated with inflammation and dysbiosis, but has not been associated with depression or anxiety. CONCLUSION: DiffCoEx potentially identified gut bacteria biomarker candidates of depression and anxiety treatment-resistance. Future efforts in psychiatric microbiology should examine the mechanistic relationship of identified pro-inflammatory species, potentially contributing to a biomarker-based algorithm for treatment resistance.