Disruption of the gut microbiota-inflammation-brain axis in unmedicated bipolar disorder II depression

The relationships of the gut microbiota-inflammation-brain axis in depressive bipolar disorder (BD) remains under-elaborated. Sixty-five unmedicated depressive patients with BD II and 58 controls (HCs) were prospectively enrolled. Resting-state functional MRI data of static and dynamic amplitude of low-frequency fluctuation (ALFF) was measured, and abnormal ALFF masks were subsequently set as regions of interest to calculate whole-brain static functional connectivity (sFC) and dynamic functional connectivity (dFC). Fecal samples were collected to assess gut diversity and enterotypes using 16S amplicon sequencing. Blood samples were also collected, serum was assayed for levels of cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-α). Patients with BD II exhibited decreased static ALFF values in the left cerebellum Crus II, and decreased cerebellar sFC and dFC to the right inferior parietal lobule and right superior frontal gyrus, respectively. Moreover, higher pro-inflammatory and anti-inflammatory cytokines levels, and increased proinflammatory bacteria and glutamate and gamma-aminobutyric acid metabolism related bacteria were identified in BD II. The interaction of Parabacteroides levels × IL-8 levels was an independent contributor to static ALFF in the left cerebellar Crus II. The findings bridged a gap in the underlying pathophysiological mechanism of the gut microbiota-inflammation-brain axis in BD II depression.