Antipsychotic-Induced Remodeling of the Gut Microbiota: Drug-Specific Patterns and Molecular Links to Metabolic Adverse Effects.
6 affiliations
- 1Department of Psychiatry II, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania.
- 2"Dr. Carol Davila" Central Military Emergency University Hospital, 010825 Bucharest, Romania.
- 3Center for Innovation and eHealth, Carol Davila University of Medicine and Pharmacy, 030167 Bucharest, Romania.
- 4Center for Aerospace Medicine Studies (CEMA), University of Lisbon, 1649-004 Lisbon, Portugal.
- 5Space Technology Center, AGH University of Kraków, 30-054 Kraków, Poland.
- 6Discipline of Medical Physiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania.
Abstract
Antipsychotic drugs are essential for the treatment of schizophrenia-spectrum disorders and other severe psychiatric conditions, but several agents produce clinically important metabolic and gastrointestinal adverse effects. Increasing evidence suggests that these outcomes may involve bidirectional interactions between antipsychotics and the gut microbiota. This structured narrative review integrates human, animal, gnotobiotic, in vitro, pharmacokinetic, and multi-omic evidence to examine drug-specific microbiome effects and microbiota-dependent modulation of host responses. Olanzapine has the strongest mechanistic evidence, with germ-free, antibiotic-depletion, colonization, and vagotomy studies supporting a contributory role of the microbiota in weight gain, adiposity, inflammation, altered microbial metabolites, and lipid dysregulation. Risperidone also shows microbiota-dependent metabolic and neurobiological effects, whereas findings for clozapine, quetiapine, aripiprazole, lurasidone, and amisulpride remain more heterogeneous or limited. Across agents, no universal taxonomic pattern has emerged. Functional pathways involving short-chain fatty acids, bile acids, epithelial barrier integrity, immune and neuroendocrine signaling, vagal pathways, and microbial drug metabolism appear more informative than individual taxa or the Firmicutes/Bacteroidota ratio. Current evidence remains limited by methodological heterogeneity, small cohorts, confounding, and predominantly preclinical mechanistic data. Prospective, treatment-naive, drug-specific longitudinal multi-omic studies are required.
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BibTeX
@article{papacocea2026antipsychoticinduced,
title = {{Antipsychotic-Induced Remodeling of the Gut Microbiota: Drug-Specific Patterns and Molecular Links to Metabolic Adverse Effects.}},
author = {Răzvan-Ioan Papacocea and Miculescu Adina Gabriela and Volosin Radu-Ștefan and Thais Russomano and Ioana Raluca Papacocea},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198471},
url = {https://europepmc.org/article/MED/42883721},
note = {CC BY},
}
RIS
TY - JOUR
TI - Antipsychotic-Induced Remodeling of the Gut Microbiota: Drug-Specific Patterns and Molecular Links to Metabolic Adverse Effects.
AU - Răzvan-Ioan Papacocea
AU - Miculescu Adina Gabriela
AU - Volosin Radu-Ștefan
AU - Thais Russomano
AU - Ioana Raluca Papacocea
PY - 2026
DA - 2026/09/23
JO - International journal of molecular sciences
DO - 10.3390/ijms27198471
UR - https://europepmc.org/article/MED/42883721
AB - Antipsychotic drugs are essential for the treatment of schizophrenia-spectrum disorders and other severe psychiatric conditions, but several agents produce clinically important metabolic and gastrointestinal adverse effects. Increasing evidence suggests that these outcomes may involve bidirectional interactions between antipsychotics and the gut microbiota. This structured narrative review integrates human, animal, gnotobiotic, in vitro, pharmacokinetic, and multi-omic evidence to examine drug-specific microbiome effects and microbiota-dependent modulation of host responses. Olanzapine has the strongest mechanistic evidence, with germ-free, antibiotic-depletion, colonization, and vagotomy studies supporting a contributory role of the microbiota in weight gain, adiposity, inflammation, altered microbial metabolites, and lipid dysregulation. Risperidone also shows microbiota-dependent metabolic and neurobiological effects, whereas findings for clozapine, quetiapine, aripiprazole, lurasidone, and amisulpride remain more heterogeneous or limited. Across agents, no universal taxonomic pattern has emerged. Functional pathways involving short-chain fatty acids, bile acids, epithelial barrier integrity, immune and neuroendocrine signaling, vagal pathways, and microbial drug metabolism appear more informative than individual taxa or the Firmicutes/Bacteroidota ratio. Current evidence remains limited by methodological heterogeneity, small cohorts, confounding, and predominantly preclinical mechanistic data. Prospective, treatment-naive, drug-specific longitudinal multi-omic studies are required.
SN - 1422-0067
ER -