{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:26:53Z","timestamp":1792895213680,"version":"4.5.0"},"reference-count":67,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009727","name":"Hospital Research Foundation","doi-asserted-by":"publisher","award":["2022\u2010CF\u2010EMCR\u2010004\u201025314"],"award-info":[{"award-number":["2022\u2010CF\u2010EMCR\u2010004\u201025314"]}],"id":[{"id":"10.13039\/100009727","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Antipsychotics such as olanzapine are associated with significant metabolic dysfunction, attributed to gut microbiome dysbiosis. A recent notion that most psychotropics are detrimental to the gut microbiome has arisen from consistent findings of metabolic adverse effects. However, unlike olanzapine, the metabolic effects of lurasidone are conflicting. Thus, this study investigates the contrasting effects of olanzapine and lurasidone on the gut microbiome to explore the hypothesis of \u2018gut neutrality\u2019 for lurasidone exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Using Sprague\u2013Dawley rats, the effects of olanzapine and lurasidone on the gut microbiome were explored. Faecal and blood samples were collected weekly over a 21\u2010day period to analyse changes to the gut microbiome and related metabolic markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Lurasidone triggered no significant weight gain or metabolic alterations, instead positively modulating the gut microbiome through increases in mean operational taxonomical units (OTUs) and alpha diversity. This novel finding suggests an underlying mechanism for lurasidone's metabolic inertia. In contrast, olanzapine triggered a statistically significant decrease in mean OTUs, substantial compositional variation and a depletion in short\u2010chain fatty acid abundance. Microbiome depletion correlated with metabolic dysfunction, producing a 30% increase in weight gain, increased pro\u2010inflammatory cytokine expression, and increased blood glycaemic and triglyceride levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our results challenge the notion that all antipsychotics disrupt the gut microbiome similarly and highlights the potential benefits of gut\u2010neutral antipsychotics, such as lurasidone, in managing metabolic side effects. Further research is warranted to validate these findings in humans to guide personalised pharmacological treatment regimens for schizophrenia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16507","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T03:15:51Z","timestamp":1722309351000},"page":"4531-4545","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The atypical antipsychotics lurasidone and olanzapine exert contrasting effects on the gut microbiome and metabolic function of rats"],"prefix":"10.1111","volume":"181","author":[{"given":"Srinivas","family":"Kamath","sequence":"first","affiliation":[{"name":"Centre for Pharmaceutical Innovation (CPI), UniSA Clinical &amp; Health Sciences University of South Australia  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hunter","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation (CPI), UniSA Clinical &amp; Health Sciences University of South Australia  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Collins","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation (CPI), UniSA Clinical &amp; Health Sciences University of South Australia  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Wignall","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation (CPI), UniSA Clinical &amp; Health Sciences University of South Australia  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-7901","authenticated-orcid":false,"given":"Paul","family":"Joyce","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation (CPI), UniSA Clinical &amp; Health Sciences University of South Australia  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92204-0"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2023.1236417"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2020.110182"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087326"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3746\/pnf.2020.25.2.113"},{"issue":"4","key":"e_1_2_12_8_1","first-page":"28","article-title":"The gut\u2010brain Axis: Influence of microbiota on mood and mental health","volume":"17","author":"Appleton J.","year":"2018","journal-title":"Integrative Medicine: a Clinician's Journal"},{"key":"e_1_2_12_9_1","unstructured":"Australian Institute of Health and Welfare (AIHW) 2024 Medicare Benefits Scheme funded services: Monthly data. 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