Alterations in fatty acid metabolism in patients with schizophrenia in a multi-omics perspective

Recent research has extensively explored the involvement of gut microbes in various fatty acid metabolic processes, elucidating their crucial roles in host energy homeostasis and metabolism. Nevertheless, there remains a dearth of studies examining the comprehensive profile of fatty acid metabolites in schizophrenia and their potential connection to gut microbes.

Conducting a thorough investigation, this study scrutinized the gut microbiome composition of 63 individuals, consisting of 35 schizophrenia (SZ) patients and 28 demographically matched healthy control (HC) subjects. Feces and serum samples were meticulously collected, with stool samples subjected to 16S rRNA sequencing targeting region V4 and untargeted metabolomics analysis, while serum samples underwent untargeted metabolomics assessment.

A total of 21 different genus-level species were identified in the SZ and HC groups. Predictive analysis of gut flora pathways revealed abnormal fatty acid degradation in schizophrenia. Notably, 17 differential fatty acid metabolites were found in feces, whereas 43 were found in serum fatty acid metabolites. A higher proportion of differential fatty acid metabolites were found in serum compared to those in feces. The predominant pathways enriched in fatty acid metabolites included biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and linoleic acid metabolism. Additionally, a significant correlation was noted between intestinal flora and fatty acids, as well as potential interactions between intestinal flora, fecal fatty acids and serum fatty acids.

Our multi-omics study provides new insights into the pathogenesis of schizophrenia, which may inform the treatment of neurodevelopmental disorders by modifying fatty acid metabolism through modulation of the gut microbiota.