The role of the gut microbiome in weight-gain in schizophrenia patients treated with atypical antipsychotics: Evidence based on altered composition and function in a cross-sectional study

•Atypical antipsychotics are associated with weight gain and obesity-related metabolic disorders in schizophrenia patients.•Altered gut microbiome may be involved in the pathogenesis of atypical antipsychotic-induced weight-gain in schizophrenia.•The regulation of gut microbiome may be a novel therapeutic strategy to manage the weight gain caused by atypical antipsychotics in schizophrenia. We aimed to explore the interconnection between the weight-gain in schizophrenia patients with atypical antipsychotic treatment and gut microbiome. This study employed a cross-sectional design, encompassing a total of 88 schizophrenia patients with long-term atypical antipsychotic treatment. The 16S rRNA gene sequencing was used to identify gut microbiome contents. No significant differences in alpha diversity between normal-weight and overweight schizophrenia treated with atypical antipsychotics. The beta diversity analysis showed that overweight patients clustered tightly while normal-weight patients clustered widely. For taxonomic composition, overweight patients had a lower relative abundance in Porphyromonadaceae at family level and Butyrivibrio at genus level, but higher relative abundance in Ruminococcus2 and Clostridium_XIVa at genus level than normal-weight patients. Function prediction revelated that four pathways (including Cell cycle, Non-homologous end-joining, Vibrio cholerae infection and Meiosis-yeast) were significantly different between groups. Correlation analysis indicated that Klebsiella, Butyrivibrio, Unassigned, Methanosphaera, Holdemania, Anaerotruncus were negatively, while Veillonella was positively correlated with BMI in patients. Our findings offer evidence that perturbations in the gut microbiome composition, encompassing taxa such as Porphyromonadaceae, Butyrivibrio, Ruminococcus2, and Clostridium_XIVa, in conjunction with distinct functional pathways including Cell cycle, Non-homologous end-joining, Vibrio cholerae infection, and Meiosis-yeast, might contribute to the weight-gain in schizophrenia treated with atypical antipsychotics.