A cross-sectional study on the link between gut microbiota and inflammation in bipolar depression

Depressed BD patients present significant alterations in the taxonomic compositions of their gut microbiota, and this may be related to inflammatory pathways and depression severity.
Table of Contents

What is already known
Recent findings provide evidence for the involvement of the brain-gut-microbiota (MGB) axis in bipolar disorder (BD). The gut microbiota is thought to have a significant impact in this regard, primarly due to its connection with immune function. Therefore, gut dysbiosis is likely a crucial element contributing to the impaired immune response observed in individuals with BD.

What this research adds
Researchers investigated the traits of gut microbiota in individuals with BD who experience depression, and examined the relationship between gut microbiota and markers of inflammation. By analyzing blood and faeces samples from BD patients and healthy individuals, the authors found a higher levels of inflammatory markers as well as higher abundance of Bacilli, Lactobacillales and genus Veillonella in BD patients than in controls. Moreover, bacterial genera’ abundance in BD patients was strongly correlated with the severity of depression and inflammatory markers.

Conclusions
Individuals with both depression and BD present alterations in the gut microbiota and these changes potentially contribute to the severity of depression symptoms and the inflammatory pathways.

Bipolar disorder (BD) is a debilitating mood disorder that leads to substantial impairments in social functioning. It is characterized by recurrent episodes of either manic/hypomanic or depressive states. Although research in this field is progressing, the pathophysiology of BD remains uncertain, which poses challenges for clinical diagnosis and the need to further elucidate the underlying mechanisms and identify biomarkers associated with BD.

Recently, there has been growing interest in exploring the role of the microbiota-gut-brain (MGB) axis, the complex network that facilitates reciprocal communication between the brain and gut microbiota, in mental illness. Indeed, preliminary studies have shown that the gut microbiota plays a significant role in BD. 

A recent cross-sectional study from Xie and colleagues, published in Annals of General Psychiatry Journal, examined the characteristics of gut microbiota in individuals with BD experiencing depression as well as in healthy controls, and its relation to inflammation and clinical parameters

Blood and faeces samples were taken from 72 depressed BD patients and 16 controls and 16S-ribosomal RNA gene sequencing was used to examine the gut microbiota characteristics. Correlation analysis was then used to assess the relationship between the gut microbiota and clinical parameters.

BD patients present high levels of serum inflammatory markers and changes in gut microbiota composition 

Serum analysis revealed higher levels of inflammatory cytokines in the blood of BD patients compared to healthy controls. Species richness and the overall bacterial community heterogeneity were assessed in depressed BD patients and healthy controls, but no significant difference was observed in terms of heterogeneity in the gut of BD patients compared to controls. 

However, a further analysis of bacterial species revealed an increased abundance of Bacilli, Lactobacillales and Veillonella in BD patients, while the genus Dorea was more abundant in healthy controls. 

Gut microbiota alterations is associated with clinical parameters

The authors next examined the correlation between gut microbiota and clinical parameters and found a strong association between the severity of depression, inflammatory markers, and the abundance rates of specific bacterial genera in depressed BD patients. 

For instance, serum levels of the inflammatory cytokine IL-6 were positively correlated with Enterobacter, Pseudomonas and Leuconostoc abundance, but negatively associated with Cloacibacillus abundance; whereas TNF-α levels correlated positively with Parabacteroides, Clostridium IV and Bilophila abundance but negatively with Prevotella abundance. 

Furthermore, serum CRP levels were positively correlated with Prevotella abundance, but negatively associated with Butyricicoccus, Lachnospiraceae incertae sedis and Dorea abundance. These findings suggest a correlation between an inflammatory status and changes in gut microbiota in BD patients.

Overall, this study provides evidence that depressed BD patients present significant alterations in the taxonomic compositions of their gut microbiota, and this may be related to inflammatory pathways and depression severity. Although these are preliminary findings and further research is needed, it can be hypothesized that the gut microbiota and inflammatory processes may have an impact on the neurobiology of BD.