BACKGROUND: Obesity is prevalent among schizophrenia (SZ) patients receiving long-term antipsychotic treatment, yet a subset of patients remains lean or maintains a normal weight. While prior studies have linked the gut microbiome to antipsychotic-induced weight gain, its role in maintaining weight stability among non-obese SZ patients remains largely unexplored. STUDY DESIGN: We recruited 177 participants for the discovery cohort, including chronically antipsychotic-treated SZ patients with or without obesity, as well as healthy controls (HCs) matched by weight status. Additionally, we enrolled 20 first-episode, drug-naïve SZ (FSZ) patients with normal weight to assess their weight changes during one year of antipsychotic treatment. Fecal 16S rRNA sequencing, combined with untargeted metabolomics, was conducted to characterize gut microbiota and metabolite profiles in non-obese SZ patients, and to investigate their association with antipsychotic-induced weight changes. STUDY RESULTS: In total, 15 bacterial genera were identified. Among them, the genera Bacteroides, Dialister, and Pseudomonas exhibited the lowest abundance in non-obese SZ patients, whereas the genus Oscillospira showed the highest abundance. Notably, Desulfovibrio was more abundant in non-obese SZ patients and HCs than in their obese counterparts. This microbial profile was accompanied by enhanced tryptophan metabolism. In FSZ patients, higher baseline levels of Desulfovibrio were linked to less weight gain after 1 year of antipsychotic treatment. Moreover, Desulfovibrio abundance correlated positively with fecal indoleacetic acid levels and inversely with serum tryptophan concentrations. CONCLUSIONS: These findings suggest a potential protective role of genus Desulfovibrio against antipsychotic-induced weight gain, possibly through modulation of tryptophan metabolism.
Wu et al. (Tue,) studied this question.