Leveraging the microbiome to understand clinical heterogeneity in depression: findings from the T-RAD study

Abstract

Alterations in the gut microbiome have been linked to a variety of mental illnesses including anxiety and depression. This study utilized advanced bioinformatics tools that integrated both the compositional and community nature of gut microbiota to investigate how gut microbiota influence clinical symptoms in a sample of participants with depression. Gut microbiota of 179 participants with major depressive disorder (MDD) in the Texas Resilience Against Depression (T-RAD) study were analyzed by 16S rRNA gene sequencing of stool samples. Severity of anxiety, depression, and anhedonia symptoms were assessed with General Anxiety Disorder – 7 item scale, Patient Health 9-item Questionnaire, and Dimensional Anhedonia Rating Scale, respectively. Using weighted correlation network analysis, a data-driven approach, three co-occurrence networks of bacterial taxa were identified. One of these co-occurrence networks was significantly associated with clinical features including depression and anxiety. The hub taxa associated with this co-occurrence module –one Ruminococcaceae family taxon, one Clostridiales vadinBB60 group family taxon, and one Christencenellaceae family taxon– were connected to several additional butyrate-producing bacteria suggesting that deficits in butyrate production may contribute to clinical symptoms. Therefore, by considering the community nature of the gut microbiome in a real world clinical sample, this study identified a gut microbial co-occurrence network that was significantly associated with clinical anxiety in a cohort of depressed individuals.

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

“…These results support the findings of several other studies that there is a unique microbiota signature associated with ANXD and MDD. For example, the Texas Resilience Against Depression identified a network of microbes that commonly co-occur in participants with MDD (54). These signatures are not exclusive to the stool microbiota: another study identified negative associations between the Bacteroidaceae family and Bacteroides genus with depression symptoms, along with positive associations between the Desulfovibrionaceae family and Clostridiales Family XIII with anxiety symptoms in the serum microbiota, while another found links between members of the oral microbiota and MDD (55,56).…”

Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites

“…The genus Ruminococcaceae UCG011 and genus Ruminococcaceae UCG010 , belonging to family Ruminococcaceae , have been reported as associated with some diseases such as leukemia ( Chen et al, 2023 ), type 2 diabetes ( Li and Li, 2023 ), and esophageal cancer ( Wang et al, 2024 ), but they have yet to be studies in the context of mental health disorders. However, multiple clinical studies have demonstrated that psychological distress and mental illness, such as depression and anxiety, are associated with alterations in the abundance of Ruminococcaceae family members ( Chen et al, 2021 ; Chin Fatt et al, 2023 ), and animal studies have suggested that regulating the abundance of Ruminococcaceae family members with various interventions can promote the production of SCFAs and other neurochemical-related metabolites. These metabolites, in turn, modulate neurotransmitter-associated metabolism, inflammation, and the microbiota-gut-brain axis, thereby alleviating depressive and anxiety-like behaviors in different mouse models of chronic stress ( Chen Y. et al, 2022 ; Zhou et al, 2022 ).…”

Causal effects of gut microbiota on multiple sclerosis: A two‐sample Mendelian randomization study

“…The potential protective mechanisms of Ruminococcaceae and Anaerotruncus against MS might be associated with their role in increasing the production of butyrate in the gut (Bianchimano et al., 2022 ; Chin Fatt et al., 2023 ; Lee et al., 2023 ). Butyrate, acting as an inducer of Tregs (Haghikia et al., 2015 ), has been shown to promote oligodendrocyte differentiation, inhibit demyelination, and stimulate remyelination, reducing the risk of MS relapses and the emergence/extension of magnetic resonance imaging lesions (Chen et al., 2019 ; Horton et al., 2021 ).…”