Shotgun metagenomics reveals abnormal short-chain fatty acid-producing bacteria and glucose and lipid metabolism of the gut microbiota in patients with schizophrenia

Evidence has shown that the gut microbiota is closely related to the pathogenesis of schizophrenia, but temporal changes in the gut microbiota of patients with schizophrenia (SZ) during treatment remain unclear. Here, to evaluate temporal changes in the gut microbiota in schizophrenia, we performed whole-genome shotgun metagenomics on fecal samples from 36 healthy controls (HCs) and 19 baseline-period patients, and followed up with patients upon treatment. Compared to that in HCs, beta diversity in SZ was significantly distinct. The genera Bacteroides, Prevotella and Clostridium were the top 3 altered genera between SZ and HCs, and the BacteroidesPrevotella ratio was significantly increased in SZ. Thirty-three percent of differentially abundant species were short-chain fatty acid (SCFA)-producing bacteria. Functional analysis showed that glucose and lipid metabolism of the gut microbiota was decreased in SZ compared with those in HCs. The abundances of two rate-limiting enzymes in glucose and lipid metabolism, phosphofructokinase (PFK) and acetyl-CoA carboxylase (ACC), were significantly decreased in SZ, and differentially abundant metabolism-related enzymes were significantly associated with SCFA-producing bacteria. Next, we found that the abundance of SCFA-producing bacteria also changed after treatment and that Clostridium was significantly negatively correlated with the total positive and negative syndrome scale (PANSS) score in patients. Functional analysis showed that glycoside hydrolase family 30 incrementally increased in abundance during treatment and were significantly associated with SCFAproducing bacteria. Our findings help to provide evidence for the role of gut microbiota in the occurrence and development of schizophrenia.