Reduced anti-inflammatory gut microbiota are associated with depression and anhedonia

Introduction: Characterise gut microbiota distributions of participants with co-occurring depression and anxiety, in those with only depression or with anxiety, and determine if gut bacteria differentially correlates with distinct clinical presentations.

Methods: Participants (10 healthy controls [mean age: 33, 60% female] and 60 psychiatric subjects; major depressive disorder (comorbid with anxiety), n = 38 [mean age: 39.2, 82% female], anxiety only, n = 8 [mean age: 40.0, 100% female], depression only without anxiety, n = 14 [mean age: 41.9, 79% female]) were characterized by psychiatric assessments. Quantitative PCR and 16S rRNA sequencing were used to characterize the gut microbiota in stool samples.

Results: Altered microbiota correlated with pre-defined clinical presentation, with Bacteroides (p = 0.011) and the Clostridium leptum subgroup (p = 0.023) significantly different between clinical categories. Cluster analysis of the total sample using weighted UniFrac β-diversity of the gut microbiota identified two different clusters defined by differences in bacterial distribution. Cluster 2 had higher Bacteroides (p = 0.006), and much reduced presence of Clostridales (p<0.001) compared to Cluster 1. Bifidobacterium (p = 0.0173) was also reduced in Cluster 2 compared to Cluster 1. When evaluated for clinical charateristics, anhedonia scores in Cluster 2 were higher than in Cluster 1.

Limitations: The sample is smaller and predominately female.

Conclusions: Reduced or absent Clostridia was consistently seen in those with depression, independent of the presence of anxiety. Conversely, reduced Bacteroides may be more associated with the presence of anxiety, independent of the presence of depression. These differences suggest that gut microbiota distribution could help clarify the underlying pathology of comorbid clinical presentation.