The Antipsychotic Olanzapine Interacts with the Gut Microbiome to Cause Weight Gain in Mouse
Publication Date
December 15, 2014
Journal
PLOS ONE
Authors
Andrew P. Morgan, James J. Crowley, Randal J. Nonneman, Corey R. Quackenbush, et al
Volume
9
Issue
12
Pages
e115225
DOI
https://dx.plos.org/10.1371/journal.pone.0115225
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0115225
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/25506936
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266663
Europe PMC
http://europepmc.org/abstract/MED/25506936
Web of Science
000346607100063
Scopus
84919340264
Mendeley
http://www.mendeley.com/research/antipsychotic-olanzapine-interacts-gut-microbiome-cause-weight-gain-mouse
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Mendeley | Further Information

{"title"=>"The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse", "type"=>"journal", "authors"=>[{"first_name"=>"Andrew P.", "last_name"=>"Morgan", "scopus_author_id"=>"56019771200"}, {"first_name"=>"James J.", "last_name"=>"Crowley", "scopus_author_id"=>"55826872700"}, {"first_name"=>"Randal J.", "last_name"=>"Nonneman", "scopus_author_id"=>"23028681900"}, {"first_name"=>"Corey R.", "last_name"=>"Quackenbush", "scopus_author_id"=>"36553055000"}, {"first_name"=>"Cheryl N.", "last_name"=>"Miller", "scopus_author_id"=>"37026740800"}, {"first_name"=>"Allison K.", "last_name"=>"Ryan", "scopus_author_id"=>"56452308800"}, {"first_name"=>"Molly A.", "last_name"=>"Bogue", "scopus_author_id"=>"7004185066"}, {"first_name"=>"Sur Herrera", "last_name"=>"Paredes", "scopus_author_id"=>"55324879800"}, {"first_name"=>"Scott", "last_name"=>"Yourstone", "scopus_author_id"=>"55317443500"}, {"first_name"=>"Ian M.", "last_name"=>"Carroll", "scopus_author_id"=>"6602296610"}, {"first_name"=>"Thomas H.", "last_name"=>"Kawula", "scopus_author_id"=>"6701720885"}, {"first_name"=>"Maureen A.", "last_name"=>"Bower", "scopus_author_id"=>"55842401800"}, {"first_name"=>"R. Balfour", "last_name"=>"Sartor", "scopus_author_id"=>"24282006500"}, {"first_name"=>"Patrick F.", "last_name"=>"Sullivan", "scopus_author_id"=>"7402033718"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"600784667", "sgr"=>"84919340264", "issn"=>"19326203", "pmid"=>"25506936", "scopus"=>"2-s2.0-84919340264", "doi"=>"10.1371/journal.pone.0115225", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)"}, "id"=>"16796d31-1605-3187-97c8-4f7355fa2070", "abstract"=>"The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain in human patients. We investigated the role of the gut microbiota in this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that gut bacteria are necessary and sufficient for weight gain caused by oral delivery of olanzapine. Second, we surveyed fecal microbiota before, during, and after treatment and found that olanzapine potentiated a shift towards an \"obesogenic\" bacterial profile. Finally, we demonstrated that olanzapine has antimicrobial activity in vitro against resident enteric bacterial strains. These results collectively provide strong evidence for a mechanism underlying olanzapine-induced weight gain in mouse and a hypothesis for clinical translation in human patients.", "link"=>"http://www.mendeley.com/research/antipsychotic-olanzapine-interacts-gut-microbiome-cause-weight-gain-mouse", "reader_count"=>65, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>14, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>4, "Student > Master"=>9, "Other"=>5, "Student > Bachelor"=>10, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>14, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>4, "Student > Master"=>9, "Other"=>5, "Student > Bachelor"=>10, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>24, "Medicine and Dentistry"=>20, "Neuroscience"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>7, "Psychology"=>2, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>20}, "Neuroscience"=>{"Neuroscience"=>5}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>7}}, "reader_count_by_country"=>{"New Zealand"=>1, "Republic of Singapore"=>1, "Netherlands"=>1}, "group_count"=>5}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1843438"], "description"=>"<p>Points in the left-hand third represent observations under germ-free conditions. The first dashed line marks the beginning of the drug-free conventionalization period (with colonization by gavage) and the second dashed line marks the resumption of treatment under conventional conditions. Each point represents the mean across 12 mice; error bars are ± 2 standard error.</p>", "links"=>[], "tags"=>["microbiota", "57BL", "Antipsychotic Olanzapine Interacts", "Cause Weight Gain", "gut", "weight gain", "olanzapine"], "article_id"=>1271088, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Andrew P. Morgan", "James J. Crowley", "Randal J. Nonneman", "Corey R. Quackenbush", "Cheryl N. Miller", "Allison K. Ryan", "Molly A. Bogue", "Sur Herrera Paredes", "Scott Yourstone", "Ian M. Carroll", "Thomas H. Kawula", "Maureen A. Bower", "R. Balfour Sartor", "Patrick F. Sullivan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115225.g002", "stats"=>{"downloads"=>2, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_high_fat_diet_plus_olanzapine_OLZ_filled_circles_versus_placebo_PLA_open_circles_on_body_weight_in_germ_free_mice_/1271088", "title"=>"Effect of high-fat diet plus olanzapine (OLZ; filled circles) versus placebo (PLA; open circles) on body weight in germ-free mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-15 02:53:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1843461"], "description"=>"<p>*<b>df</b>, degrees of freedom; <sup>∧</sup><b>SS</b>, Sum of squares; <sup>#</sup><b>F</b>, pseudo-<i>F</i>-statistic.</p><p>PERMANOVA decomposition of β-diversity as measured by UniFrac.</p>", "links"=>[], "tags"=>["microbiota", "57BL", "Antipsychotic Olanzapine Interacts", "Cause Weight Gain", "gut", "weight gain", "olanzapine"], "article_id"=>1271112, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Andrew P. Morgan", "James J. Crowley", "Randal J. Nonneman", "Corey R. Quackenbush", "Cheryl N. Miller", "Allison K. Ryan", "Molly A. Bogue", "Sur Herrera Paredes", "Scott Yourstone", "Ian M. Carroll", "Thomas H. Kawula", "Maureen A. Bower", "R. Balfour Sartor", "Patrick F. Sullivan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115225.t001", "stats"=>{"downloads"=>6, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PERMANOVA_decomposition_of_946_diversity_as_measured_by_UniFrac_/1271112", "title"=>"PERMANOVA decomposition of β-diversity as measured by UniFrac.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-12-15 02:53:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1843458"], "description"=>"<p>Bacterial growth is measured as optical density at 600 nm wavelength. Measurements of growth in rich medium (brain heart infusion, BHI) plus vehicle (dimethylsulfoxide) only is included as a control. Each line represents the mean of three independent experiments.</p>", "links"=>[], "tags"=>["microbiota", "57BL", "Antipsychotic Olanzapine Interacts", "Cause Weight Gain", "gut", "weight gain", "olanzapine"], "article_id"=>1271108, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Andrew P. Morgan", "James J. Crowley", "Randal J. Nonneman", "Corey R. Quackenbush", "Cheryl N. Miller", "Allison K. Ryan", "Molly A. Bogue", "Sur Herrera Paredes", "Scott Yourstone", "Ian M. Carroll", "Thomas H. Kawula", "Maureen A. Bower", "R. Balfour Sartor", "Patrick F. Sullivan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115225.g005", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_olanzapine_OLZ_on_growth_of_Escherichia_coli_NC101_and_Enteroccoccus_faecalis_OGIRF_in_vitro_/1271108", "title"=>"Effect of olanzapine (OLZ) on growth of <i>Escherichia coli</i> NC101 and <i>Enteroccoccus faecalis</i> OGIRF <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-15 02:53:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1843450"], "description"=>"<p>(<b>A</b>) Colored blocks show relative abundance of specific bacterial classes during treatment with OLZ (HFD-OLZ) or placebo (HFD-placebo), pooled across individuals in each of the two study arms (<i>n</i> = 3 time points ×24 subjects). (<b>B</b>) Effect of OLZ on relative abundance of specific taxa, expressed as confidence intervals (at nominal significance level <i>α</i> = 0.05) about the mean fold-change in relative abundance. Taxa with a statistically-significant increase are shown in red, and those with a significant decrease in blue. (<b>C</b>) Effect of relative abundance of specific taxa on weight gain, expressed as confidence intervals (at nominal significance level <i>α</i> = 0.05) about the effect estimate.</p>", "links"=>[], "tags"=>["microbiota", "57BL", "Antipsychotic Olanzapine Interacts", "Cause Weight Gain", "gut", "weight gain", "olanzapine"], "article_id"=>1271100, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Andrew P. Morgan", "James J. Crowley", "Randal J. Nonneman", "Corey R. Quackenbush", "Cheryl N. Miller", "Allison K. Ryan", "Molly A. Bogue", "Sur Herrera Paredes", "Scott Yourstone", "Ian M. Carroll", "Thomas H. Kawula", "Maureen A. Bower", "R. Balfour Sartor", "Patrick F. Sullivan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115225.g004", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Compositional_shifts_in_gut_microbiota_induced_by_high_fat_diet_HFD_and_olanzapine_OLZ_during_crossover_study_/1271100", "title"=>"Compositional shifts in gut microbiota induced by high-fat diet (HFD) and olanzapine (OLZ) during crossover study.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-15 02:53:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1843445"], "description"=>"<p>(<b>A</b>) Within-subject (<i>α</i>) diversity, quantified by Fisher's <i>α</i><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115225#pone.0115225-Fisher1\" target=\"_blank\">[45]</a>; larger values indicate greater diversity (<i>n</i> = 95 samples  = 4 time points ×24 subjects – 1 failed sample). Panels are split by study arm (see <b>Error! Reference source not found</b>.) and points are colored according to diet and treatment status: on regular chow prior to initiation of HFD (regular), during treatment with placebo (HFD-placebo) or during treatment with OLZ (HFD-OLZ). Each point represents a single individual and bars indicate 95% confidence intervals about the point estimates; observations on the same subject are connected by a grey line. (<b>B</b>) Between-subjects (<i>β</i>) diversity (<i>n</i> = 95 samples  = 4 time points ×24 subjects – 1 failed sample). Pairwise distances between samples were calculated using weighted UniFrac and visualized using non-metric multidimensional scaling along two axes, which together explain 98% of between-subjects variance. Observations on the same subject are connected by a grey line.</p>", "links"=>[], "tags"=>["microbiota", "57BL", "Antipsychotic Olanzapine Interacts", "Cause Weight Gain", "gut", "weight gain", "olanzapine"], "article_id"=>1271095, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Andrew P. Morgan", "James J. Crowley", "Randal J. Nonneman", "Corey R. Quackenbush", "Cheryl N. Miller", "Allison K. Ryan", "Molly A. Bogue", "Sur Herrera Paredes", "Scott Yourstone", "Ian M. Carroll", "Thomas H. Kawula", "Maureen A. Bower", "R. Balfour Sartor", "Patrick F. Sullivan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0115225.g003", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_high_fat_diet_HFD_and_olanzapine_OLZ_treatment_on_diversity_of_gut_microbiota_during_crossover_study_/1271095", "title"=>"Effect of high-fat diet (HFD) and olanzapine (OLZ) treatment on diversity of gut microbiota during crossover study.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-12-15 02:53:52"}

PMC Usage Stats | Further Information

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Relative Metric

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