Gut microbiota serve as a risk predictor of weight gain in schizophrenia patients with antipsychotic medication

Background:Emerging evidence indicates that gut microbial dysbiosis is associated with the development of antipsychotic-induced overweight/obesity in schizophrenia (SZ). We aim to determine the taxonomic composition and metabolites profiling of “obesogenic” microbiota in SZ patients after chronic antipsychotic medication. Results:Our retrospective survey identified two groups of population separated by BMI, with 1/3 patients developing overweight/obesity after chronic antipsychotics treatment. Then, based on the 16S rRNA sequencing and multi-omics analyses, we found that SZ patients with overweight/obesity had lower relative abundances of the signature bacteria genera such as Bacteroides, Parabacteroides, Akkermansia, and Clostridium when compared to individuals with normal BMI. Further investigation revealed dysregulated energy expenditure and nutritional metabolism coupled with severe clinical indices and decreased levels of beneficial metabolites, e.g. indole-3-carboxylic acid, and propionic acid. The signature bacteria were positively associated with host metabolic homeostasis, according to the redundancy and co-occurrence analysis. Moreover, leveraging the data from first-episode drug-naïve SZ (FSZ) patients at 1-month and 1-year follow-up, both artificial neural network and random forest classifier-based prediction models demonstrated a strong ability of microbial profiles to predict antipsychotic-induced weight gain. Importantly, FSZ patients with a higher relative abundance of Parabacteria distasonisare less susceptible to antipsychotic-induced weight gain. Conclusion: Gut microbiota could serve as a noninvasive approach to predict antipsychotic-induced weight gain, guiding clinical antipsychotics administration and developing novel therapeutic strategies for the weight management in SZ.