Unravelling the role of the gut microbiome in antipsychotic-induced weight gain and metabolic dysfunction in humans and rodents: A systematic review

Second-generation antipsychotics are frequently linked to weight gain and metabolic dysfunction, yet the mechanisms driving these effects remain elusive. The gut microbiome has been proposed as a potential mediator of these adverse outcomes. This study aimed to investigate the role of the gut microbiota in antipsychotic-induced weight gain. A systematic search of PubMed and Embase was conducted. In total, 24 publications were included in this review, including clinical and preclinical observational and intervention studies. Collectively, there is strong evidence that atypical antipsychotic-induced weight gain and metabolic dysfunction is accompanied by microbiota alterations. However, there is a lack of consensus with regards to the exact mechanisms and involvement of the microbiome in antipsychotic-induced weight gain. Nevertheless, a few patterns and common observations were found across studies, such as reduced diversity, increased Firmicutes/Bacteroidetes ratio and a reduction in Akkermansia species. While microbiota-targeted interventions had generally weak effects on weight gain and metabolic dysfunction in clinical cohorts, the use of specific probiotic strains and microbiota metabolites showed promise in preclinical studies. Thus, while the relationship between antipsychotic-induced weight gain, metabolic dysfunction, and changes in the gut microbiome are evident, further research is warranted to establish definitive causal relationships and to aid in the development of precision microbiota-targeted interventions to counteract these adverse effects.