The gut microbiota as a contributing factor to antipsychotic-induced weight gain and metabolic dysfunction

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dc.contributor.advisor O'Mahony, Siobhain M. en
dc.contributor.advisor Dinan, Timothy G. en
dc.contributor.advisor Cryan, John F. en Davey, Kieran 2013-10-08T11:04:30Z 2014-10-09T04:00:05Z 2013 2013
dc.identifier.citation Davey, K. 2013. The gut microbiota as a contributing factor to antipsychotic-induced weight gain and metabolic dysfunction. PhD Thesis, University College Cork. en
dc.identifier.endpage 321
dc.description.abstract Schizophrenia represents one of the world’s most devastating illnesses due to its often lifelong course and debilitating nature. The treatment of schizophrenia has vastly improved over recent decades with the discovery of several antipsychotic compounds; however these drugs are not without adverse effects that must be addressed to maximize their therapeutic value. Newer, atypical, antipsychotics are associated with a compilation of serious metabolic side effects including weight gain, insulin resistance, fat deposition, glucose dysregulation and ensuing co-morbidities such as type II diabetes mellitus. The mechanisms underlying these side effects remain to be fully elucidated and adequate interventions are lacking. Further understanding of the factors that contribute these side effects is therefore required in order to develop effective adjunctive therapies and to potentially design antipsychotic drugs in the future with reduced impact on the metabolic health of patients. We investigated if the gut microbiota represented a novel mechanism contributing to the metabolic dysfunction associated with atypical antipsychotics. The gut microbiota comprises the bacteria that exist symbiotically within the gastrointestinal tract, and has been shown in recent years to be involved in several aspects of energy balance and metabolism. We have demonstrated that administration of certain antipsychotics in the rat results in an altered microbiota profile and, moreover, that the microbiota is required for the full scale of metabolic dysfunction to occur. We have further shown that specific antibiotics can attenuate certain aspects of olanzapine and risperidone–induced metabolic dysfunction, in particular fat deposition and adipose tissue inflammation. Mechanisms underlying this novel link appear to involve energy utilization via expression of lipogenic genes as well as reduced inflammatory tone. Taken together, these data indicate that the gut microbiota is an important factor involved in the myriad of metabolic complications associated with antipsychotic therapy. Furthermore, these data support the future investigation of microbial-based therapeutics for not only antipsychotic-induced weight gain but also for tackling the global obesity epidemic. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2013. Kieran Davey en
dc.rights.uri en
dc.subject Microbiota en
dc.subject Metabolic syndrome en
dc.subject Olanzapine en
dc.subject Antipsychotics en
dc.subject.lcsh Obesity en
dc.subject.lcsh Antipsychotic drugs en
dc.subject.lcsh Schizophrenia--Chemotherapy en
dc.subject.lcsh Gastrointestinal system--Microbiology en
dc.title The gut microbiota as a contributing factor to antipsychotic-induced weight gain and metabolic dysfunction en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text not available en Restricted to everyone for one year en
dc.description.version Accepted Version
dc.description.status Not peer reviewed en Alimentary Pharmabotic Centre en Pharmacy en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.entireThesis Entire Thesis Restricted
dc.check.embargoformat E-thesis on CORA only en
dc.internal.conferring Autumn Conferring 2013 en

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