The fecal microbiota transplantation from drug-naïve schizophrenia patients distinctively changes gut microbiome and metabolic profiles in male and female mice

作者：Raghunath Singh, Sandra Pereira, Kristoffer Panganiban, Laurie Hamel, David C. Wright, Thomas D. Prévot, Daniel J. Müller, Gary Remington, Sri Mahavir Agarwal, Přemysl Berčík, Elena F Verdue, Giada De Palma, Margaret Hahn · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.1101/2025.09.13.675957 · 被引用次数：1 · 研究领域：Gut microbiota and health、Clostridium difficile and Clostridium perfringens research、Gastrointestinal motility and disorders

Abstract Background Emerging evidence suggests a role for the gut microbiome in schizophrenia (SCZ) and antipsychotic-induced metabolic perturbations. Using human fecal microbiota transplantation (FMT) in mice, this study investigated the role of gut microbiome in metabolic changes related to SCZ and antipsychotic (olanzapine) treatment. Methods 5-6 weeks old germ-free NIH Swiss mice of both sexes received microbiota from either SCZ patients (SCZ-FMT) or healthy controls (HC-FMT) followed by a diet with or without olanzapine for six-weeks. Food intake and body weight were monitored weekly, and an intraperitoneal glucose tolerance test and open field test were performed. Serum glucose, and insulin were measured. Gut microbiome characterization and short-chain fatty acids (SCFAs) quantification were performed in the cecal samples using 16S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. Results Olanzapine treatment decreased the locomotor activity in the open field test, irrespective of sex or microbiota. Female SCZ-FMT recipient mice exhibited insulin resistance compared to HC-FMT, irrespective of olanzapine treatment. Female SCZ-FMT mice showed significantly lower alpha-diversity compared to HC-FMT, whereas olanzapine treatment increased alpha-diversity. SCZ-FMT and olanzapine treatment differentially altered the microbial abundances, and metabolic pathways in male and female mice. Interestingly, cecal SCFAs, mainly acetate levels, were significan...