---
title: "Antipsychotic Drugs Alter Gut Microbial Metabolism and Raise Enteric Infection Risk in Mice"
id: "biorxiv-17-anti-psychotic-therapeutics-modify-gut-microbial-metabolism-and-modulate"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-17-anti-psychotic-therapeutics-modify-gut-microbial-metabolism-and-modulate"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.15.745804v1?rss=1"
published_at: "2026-09-16T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Antipsychotic Drugs Alter Gut Microbial Metabolism and Raise Enteric Infection Risk in Mice
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-17-anti-psychotic-therapeutics-modify-gut-microbial-metabolism-and-modulate
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.15.745804v1?rss=1)
- **Published At:** 2026-09-16T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Researchers evaluated the effects of four **antipsychotic** drugs (haloperidol, olanzapine, risperidone, quetiapine) in a mouse model to determine impacts on behavior, the gut microbiome, and susceptibility to enteric infection. - Antipsychotic exposure produced persistent behavioral changes and increased vulnerability to infection with **Citrobacter rodentium**, with quetiapine and olanzapine associated with the greatest weight loss following challenge. - Microbiome sequencing showed drug-specific shifts in **beta diversity** but no consistent changes in **alpha diversity** across treatments. - Untargeted metabolomic profiling revealed robust, drug-specific metabolic reprogramming, especially in **lipid and sterol** pathways in the gut metabolome. - Integration of taxonomic and metabolomic data indicated disrupted bacterial taxa–metabolite networks and loss of homeostatic metabolic modules; compositional microbiome changes alone did not fully explain functional outcomes. - The findings support a mechanistic link between antipsychotic-induced microbiome and metabolome disruption and impaired colonization resistance against enteric pathogens. - Funding sources included NIDDK (F30), CDC, NIAID (K23), and institutional CTSA support; authors declared no competing interests. - Data and code availability were referenced via DOIs provided in the source but the source text did not report further methodological or numeric detail beyond these summarized outcomes.
## Clinical Analysis & Structured Key Points
Anti-psychotic therapeutics modify gut microbial metabolism and modulate susceptibility to gastrointestinal infection in mice | bioRxiv Skip to main content New Results Anti-psychotic therapeutics modify gut microbial metabolism and modulate susceptibility to gastrointestinal infection in mice View ORCID Profile Camilo Anthony Gallarde Gacasan , View ORCID Profile Jaclyn Weinberg , Lyndsey Lipson , Gabrielle M Webster , View ORCID Profile Dean P Jones , View ORCID Profile Timothy R Sampson , View ORCID Profile Rheinallt M Jones , View ORCID Profile Michael H Woodworth doi: https://doi.org/10.64898/2026.09.15.745804 Camilo Anthony Gallarde Gacasan 1 Emory University School of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Camilo Anthony Gallarde Gacasan Jaclyn Weinberg 1 Emory University School of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jaclyn Weinberg Lyndsey Lipson 1 Emory University School of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Gabrielle M Webster 1 Emory University School of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Dean P Jones 1 Emory University School of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Dean P Jones Timothy R Sampson 1 Emory University School of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Timothy R Sampson Rheinallt M Jones 1 Emory University School of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Rheinallt M Jones Michael H Woodworth 2 Emory University Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Michael H Woodworth For correspondence: michael.holmes.woodworth{at}emory.edu Abstract Info/History Metrics Data/Code Preview PDF Abstract Antipsychotic medications are widely prescribed and associated with increased infection risk, but underlying mechanisms remain unclear. We examined if antipsychotic-induced microbiome and metabolome alterations impair colonization resistance. Using a murine model, we evaluated haloperidol, olanzapine, risperidone, and quetiapine through longitudinal microbiome profiling, untargeted metabolomic fingerprinting, behavioral testing, and enteric infection challenge. Antipsychotic exposure induced persistent behavioral changes and increased susceptibility to Citrobacter rodentium, with quetiapine and olanzapine producing the greatest weight loss. Microbiome sequencing revealed treatment-specific shifts in beta diversity without consistent alpha diversity changes, while untargeted metabolomic analysis demonstrated robust, drug-specific metabolic reprogramming, particularly in lipid and sterol pathways. Although microbial compositional changes did not fully account for functional outcomes, their integration with metabolomics data revealed disrupted bacterial taxa-metabolite networks and loss of homeostatic metabolic modules. These results provide a potential mechanistic link between the disruptive effects of antipsychotics on the microbiome and impaired colonization resistance. Competing Interest Statement The authors have declared no competing interest. Footnotes https://doi.org/10.5281/zenodo.19337970 https:/doi.org/10.5281/zenodo.19337970 Funder Information Declared National Institute of Diabetes and Digestive and Kidney Diseases , F30 DK139762 Centers for Disease Control and Prevention , U54CK000601 National Institute for Allergy and Infectious Diseases , K23AI144036 Emory School of Medicine and through the Georgia CTSA NIH award , UL1-TR002378 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted September 16, 2026. Download PDF Data/Code Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Anti-psychotic therapeutics modify gut microbial metabolism and modulate susceptibility to gastrointestinal infection in mice Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Anti-psychotic therapeutics modify gut microbial metabolism and modulate susceptibility to gastrointestinal infection in mice Camilo Anthony Gallarde Gacasan , Jaclyn Weinberg , Lyndsey Lipson , Gabrielle M Webster , Dean P Jones , Timothy R Sampson , Rheinallt M Jones , Michael H Woodworth bioRxiv 2026.09.15.745804; doi: https://doi.org/10.64898/2026.09.15.745804 Share This Article: Copy Citation Tools Anti-psychotic therapeutics modify gut microbial metabolism and modulate susceptibility to gastrointestinal infection in mice Camilo Anthony Gallarde Gacasan , Jaclyn Weinberg , Lyndsey Lipson , Gabrielle M Webster , Dean P Jones , Timothy R Sampson , Rheinallt M Jones , Michael H Woodworth bioRxiv 2026.09.15.745804; doi: https://doi.org/10.64898/2026.09.15.745804 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Microbiology Subject Areas All Articles Animal Behavior and Cognition (8003) Biochemistry (18709) Bioengineering (14839) Bioinformatics (44356) Biophysics (22557) Cancer Biology (19680) Cell Biology (26844) Clinical Trials (138) Developmental Biology (13942) Ecology (20969) Epidemiology (2067) Evolutionary Biology (25412) Genetics (16150) Genomics (23476) Immunology (18677) Microbiology (42397) Molecular Biology (18020) Neuroscience (93337) Paleontology (699) Pathology (2977) Pharmacology and Toxicology (5085) Physiology (8105) Plant Biology (15969) Scientific Communication and Education (2094) Synthetic Biology (4549) Systems Biology (10219) Zoology (2384)
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