Effects of gut microbiota-inflammation axis on brain functional connectivity in patients with acute schizophrenia

ObjectiveTo investigate the potential influence of gut microbiota on neuroimaging alterations in schizophrenia through immune-inflammatory pathways, by integrating gut metagenomic, serum cytokine, and resting-state functional magnetic resonance imaging data.MethodsA total of 65 first-episode or recurrent, untreated acute inpatients with schizophrenia and 44 healthy controls (HC) were enrolled. Functional neuroimaging data were acquired using a 3 T MRI scanner to analyze functional connectivity (FC) between regions of interest. Serum levels of seven cytokines were measured by using ELISA, and gut microbiota were sequenced using metagenomic technology. Correlations among gut metagenomics, serum cytokine levels, and brain FC were analyzed. Mediation analysis was further employed to infer whether serum cytokines, as mediating variables, could explain the relationship between gut microbiota diversity and brain FC.ResultsCompared with healthy controls, patients with schizophrenia exhibited increased FC in the thalamus-occipital lateral cortex ( P=0.027), hippocampus-thalamus ( P=0.049), and thalamus-amygdala ( P=0.013), while FC was decreased in the amygdala-precentral gyrus ( P=0.003), nucleus accumbens-posterior cingulate cortex ( P=0.006), hippocampus-brainstem/parahippocampal gyrus ( P=0.040), and hippocampal entorhinal cortex-lingual gyrus ( P=0.002). These FC alterations were all correlated with interleukin-4 (IL-4) levels ( PConclusionThe gut microbiota-immune-inflammatory axis contributes to the disruption of brain functional connectivity in schizophrenia, providing direct evidence for the gut-brain axis pathogenesis of schizophrenia.