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Kong L, Wang X, Chen G, Zhu Y, Wang L, Yan M, Zeng J, Zhou X, Lui SSY, Chan RCK. Gut microbiome characteristics in individuals across different stages of schizophrenia spectrum disorders: A systematic review and meta-analysis. Neurosci Biobehav Rev 2025; 173:106167. [PMID: 40250540 DOI: 10.1016/j.neubiorev.2025.106167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 04/08/2025] [Accepted: 04/16/2025] [Indexed: 04/20/2025]
Abstract
Schizophrenia (SCZ) is a complex neuropsychiatric disorder with unclear pathogenesis, limiting advances in early diagnosis and targeted interventions. Increasing evidence suggests that the gut microbiome contributed to SCZ pathophysiology, yet comprehensive characterization across illness stages remains lacking. This meta-analysis aimed to characterize gut microbial alterations across the SCZ spectrum disorder, including individuals at ultra-high risk for psychosis, first-episode psychosis (FEP) and chronic SCZ patients. A systematic search of 10 databases identified 91 case-control studies. Gut microbial outcome measures included relative abundance, alpha and beta diversity. Review Manager and R were used to analyze the data. The results showed that patients with SCZ exhibited significantly reduced alpha diversity, particularly in Shannon, Chao1, Observe and Evenness indices, compared to healthy controls. Beta diversity also differed significantly, with 88.5 % of studies reporting distinct microbial profiles across SCZ stages. Quantitative analysis revealed significantly increased relative abundance of Bacteroides and a decrease abundance of Bifidobacterium and Lactobacilli in FEP patients compared to healthy controls. Qualitative analysis further showed increasing abundance in Lactobacillus, Prevotella and Collinsella, but decreasing abundance in Faecalibacterium, Butyricicoccus, and Blautia in SCZ. Bifidobacterium exhibited stage-specific changes, decreasing in first-episode psychosis but increasing in chronic stages, while Bacteroides followed an opposite trajectory. Notably, Lactobacillus demonstrated an early upward tractor in high-risk individuals, persisting to chronic stages. This meta-analysis identified dynamic and consistent alterations in the gut microbial across the SCZ spectrum. These findings implicated the potentials of gut microbes as early indicators for identification and intervention of SCZ.
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Affiliation(s)
- Li Kong
- School of Psychology, Shanghai Normal University, Shanghai, China.
| | - Xingsong Wang
- School of Psychology, Shanghai Normal University, Shanghai, China
| | - Guanlin Chen
- School of Psychology, Shanghai Normal University, Shanghai, China
| | - Yikang Zhu
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lina Wang
- School of Psychology, Shanghai Normal University, Shanghai, China
| | - Miaomiao Yan
- School of Psychology, Shanghai Normal University, Shanghai, China
| | - Jingwen Zeng
- School of Psychology, Shanghai Normal University, Shanghai, China
| | - Xiaoqi Zhou
- Center for Global Change and Ecological Forecasting, School of Ecological and Environmental Sciences, East China Normal University, Shanghai 200241, China
| | - Simon S Y Lui
- Department of Psychiatry, School of Clinical Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Raymond C K Chan
- Neuropsychology and Applied Cognitive Neuroscience Laboratory, State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, the University of Chinese Academy of Sciences, Beijing, China
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Chen L, Wang Z, Wang Y, Jiang H, Ding Y, Xia Q, Cheng X, Zhang X. Alterations in fatty acid metabolism in patients with schizophrenia in a multi-omics perspective. Schizophr Res 2025; 279:94-105. [PMID: 40184646 DOI: 10.1016/j.schres.2025.03.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 03/17/2025] [Accepted: 03/24/2025] [Indexed: 04/07/2025]
Abstract
BACKGROUND Recent research has extensively explored the involvement of gut microbes in various fatty acid metabolic processes, elucidating their crucial roles in host energy homeostasis and metabolism. Nevertheless, there remains a dearth of studies examining the comprehensive profile of fatty acid metabolites in schizophrenia and their potential connection to gut microbes. METHOD Conducting a thorough investigation, this study scrutinized the gut microbiome composition of 63 individuals, consisting of 35 schizophrenia (SZ) patients and 28 demographically matched healthy control (HC) subjects. Feces and serum samples were meticulously collected, with stool samples subjected to 16S rRNA sequencing targeting region V4 and untargeted metabolomics analysis, while serum samples underwent untargeted metabolomics assessment. RESULTS A total of 21 different genus-level species were identified in the SZ and HC groups. Predictive analysis of gut flora pathways revealed abnormal fatty acid degradation in schizophrenia. Notably, 17 differential fatty acid metabolites were found in feces, whereas 43 were found in serum fatty acid metabolites. A higher proportion of differential fatty acid metabolites were found in serum compared to those in feces. The predominant pathways enriched in fatty acid metabolites included biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and linoleic acid metabolism. Additionally, a significant correlation was noted between intestinal flora and fatty acids, as well as potential interactions between intestinal flora, fecal fatty acids and serum fatty acids. CONCLUSIONS Our multi-omics study provides new insights into the pathogenesis of schizophrenia, which may inform the treatment of neurodevelopmental disorders by modifying fatty acid metabolism through modulation of the gut microbiota.
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Affiliation(s)
- Long Chen
- Anhui Clinical Center for mental and psychological diseases, Hefei Fourth People's Hospital, 316 Mei shan Road, Hefei, Anhui 230000, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei 230022, China,; Anhui Mental Health Center, Hefei 230000, China
| | - Zhiqiang Wang
- Anhui Clinical Center for mental and psychological diseases, Hefei Fourth People's Hospital, 316 Mei shan Road, Hefei, Anhui 230000, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei 230022, China,; Anhui Mental Health Center, Hefei 230000, China; School of Mental Health and Psychological Science, Anhui Medical University, Hefei 230022, China
| | - Yanyu Wang
- Anhui Clinical Center for mental and psychological diseases, Hefei Fourth People's Hospital, 316 Mei shan Road, Hefei, Anhui 230000, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei 230022, China,; Anhui Mental Health Center, Hefei 230000, China; School of Mental Health and Psychological Science, Anhui Medical University, Hefei 230022, China
| | - Haonan Jiang
- Anhui Clinical Center for mental and psychological diseases, Hefei Fourth People's Hospital, 316 Mei shan Road, Hefei, Anhui 230000, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei 230022, China,; Anhui Mental Health Center, Hefei 230000, China; School of Mental Health and Psychological Science, Anhui Medical University, Hefei 230022, China
| | - Yuntong Ding
- Anhui Clinical Center for mental and psychological diseases, Hefei Fourth People's Hospital, 316 Mei shan Road, Hefei, Anhui 230000, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei 230022, China,; Anhui Mental Health Center, Hefei 230000, China
| | - Qingrong Xia
- Anhui Clinical Center for mental and psychological diseases, Hefei Fourth People's Hospital, 316 Mei shan Road, Hefei, Anhui 230000, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei 230022, China,; Anhui Mental Health Center, Hefei 230000, China
| | - Xialong Cheng
- Anhui Clinical Center for mental and psychological diseases, Hefei Fourth People's Hospital, 316 Mei shan Road, Hefei, Anhui 230000, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei 230022, China,; Anhui Mental Health Center, Hefei 230000, China
| | - Xulai Zhang
- Anhui Clinical Center for mental and psychological diseases, Hefei Fourth People's Hospital, 316 Mei shan Road, Hefei, Anhui 230000, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei 230022, China,; Anhui Mental Health Center, Hefei 230000, China; School of Mental Health and Psychological Science, Anhui Medical University, Hefei 230022, China.
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Dhieb D, Bastaki K. Pharmaco-Multiomics: A New Frontier in Precision Psychiatry. Int J Mol Sci 2025; 26:1082. [PMID: 39940850 PMCID: PMC11816785 DOI: 10.3390/ijms26031082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/19/2025] [Accepted: 01/21/2025] [Indexed: 02/16/2025] Open
Abstract
The landscape of psychiatric care is poised for transformation through the integration of pharmaco-multiomics, encompassing genomics, proteomics, metabolomics, transcriptomics, epigenomics, and microbiomics. This review discusses how these approaches can revolutionize personalized treatment strategies in psychiatry by providing a nuanced understanding of the molecular bases of psychiatric disorders and individual pharmacotherapy responses. With nearly one billion affected individuals globally, the shortcomings of traditional treatments, characterized by inconsistent efficacy and frequent adverse effects, are increasingly evident. Advanced computational technologies such as artificial intelligence (AI) and machine learning (ML) play crucial roles in processing and integrating complex omics data, enhancing predictive accuracy, and creating tailored therapeutic strategies. To effectively harness the potential of pharmaco-multiomics approaches in psychiatry, it is crucial to address challenges such as high costs, technological demands, and disparate healthcare systems. Additionally, navigating stringent ethical considerations, including data security, potential discrimination, and ensuring equitable access, is essential for the full realization of this approach. This process requires ongoing validation and comprehensive integration efforts. By analyzing recent advances and elucidating how different omic dimensions contribute to therapeutic customization, this review aims to highlight the promising role of pharmaco-multiomics in enhancing patient outcomes and shifting psychiatric treatments from a one-size-fits-all approach towards a more precise and patient-centered model of care.
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Affiliation(s)
| | - Kholoud Bastaki
- Pharmaceutical Sciences Department, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar;
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Spettigue W, Norris ML. Olanzapine use for the treatment of adolescents with anorexia nervosa - reflecting on research and clinical practice. JOURNAL OF THE CANADIAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY = JOURNAL DE L'ACADEMIE CANADIENNE DE PSYCHIATRIE DE L'ENFANT ET DE L'ADOLESCENT 2024; 33:164-170. [PMID: 39534775 PMCID: PMC11552675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 05/29/2024] [Indexed: 11/16/2024]
Abstract
Anorexia nervosa is a complex and potentially devastating mental health (MH) diagnosis that is recognized as having high rates of non-response to treatment, pronounced medical as well as MH morbidity, and elevated mortality rates. Olanzapine is a second-generation atypical antipsychotic that has demonstrated benefit with weight gain in adults with anorexia nervosa (AN), although controlled research involving children and youth remains limited. In this commentary, the authors provide a brief history and review of research relating to olanzapine for the adjunctive treatment of children and adolescents with AN. Although the medication has been used for more than two decades, its mechanism of action remains incompletely understood and is likely multifactorial. Despite a paucity of research to guide clinical decision making, olanzapine prescription among youth with moderate to severe AN appears to be prevalent among eating disorder specialists in Canada. In addition to commenting on gaps and challenges related to controlled randomized research in this area, the authors reflect on factors likely contributing to olanzapine's adoption into clinical practice. Moving forward, it is critical that further research involving olanzapine for the adjunctive treatment of AN in youth be undertaken to better understand efficacy, appropriate indications for use, and safety profile.
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Affiliation(s)
- Wendy Spettigue
- Department of Psychiatry, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario
| | - Mark L Norris
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario
- Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario
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5
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Nakhal MM, Yassin LK, Alyaqoubi R, Saeed S, Alderei A, Alhammadi A, Alshehhi M, Almehairbi A, Al Houqani S, BaniYas S, Qanadilo H, Ali BR, Shehab S, Statsenko Y, Meribout S, Sadek B, Akour A, Hamad MIK. The Microbiota-Gut-Brain Axis and Neurological Disorders: A Comprehensive Review. Life (Basel) 2024; 14:1234. [PMID: 39459534 PMCID: PMC11508655 DOI: 10.3390/life14101234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 09/23/2024] [Accepted: 09/24/2024] [Indexed: 10/28/2024] Open
Abstract
Microbes have inhabited the earth for hundreds of millions of years longer than humans. The microbiota-gut-brain axis (MGBA) represents a bidirectional communication pathway. These communications occur between the central nervous system (CNS), the enteric nervous system (ENS), and the emotional and cognitive centres of the brain. The field of research on the gut-brain axis has grown significantly during the past two decades. Signalling occurs between the gut microbiota and the brain through the neural, endocrine, immune, and humoral pathways. A substantial body of evidence indicates that the MGBA plays a pivotal role in various neurological diseases. These include Alzheimer's disease (AD), autism spectrum disorder (ASD), Rett syndrome, attention deficit hyperactivity disorder (ADHD), non-Alzheimer's neurodegeneration and dementias, fronto-temporal lobe dementia (FTLD), Wilson-Konovalov disease (WD), multisystem atrophy (MSA), Huntington's chorea (HC), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), temporal lobe epilepsy (TLE), depression, and schizophrenia (SCZ). Furthermore, the bidirectional correlation between therapeutics and the gut-brain axis will be discussed. Conversely, the mood of delivery, exercise, psychotropic agents, stress, and neurologic drugs can influence the MGBA. By understanding the MGBA, it may be possible to facilitate research into microbial-based interventions and therapeutic strategies for neurological diseases.
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Affiliation(s)
- Mohammed M. Nakhal
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Lidya K. Yassin
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Rana Alyaqoubi
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Sara Saeed
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Alreem Alderei
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Alya Alhammadi
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Mirah Alshehhi
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Afra Almehairbi
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Shaikha Al Houqani
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Shamsa BaniYas
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Haia Qanadilo
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Bassam R. Ali
- Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates;
| | - Safa Shehab
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
| | - Yauhen Statsenko
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates;
- Neuroscience Platform, ASPIRE Precision Medicine Institute in Abu Dhabi, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - Sarah Meribout
- Internal Medicine Department, Maimonides Medical Center, New York, NY 11219, USA;
| | - Bassem Sadek
- Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Bo Box 15551, United Arab Emirates; (B.S.); (A.A.)
- Zayed Center for Health Sciences, United Arab Emirates University, Al Ain P.O. Box 1551, United Arab Emirates
| | - Amal Akour
- Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Bo Box 15551, United Arab Emirates; (B.S.); (A.A.)
- Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The University of Jordan, Amman 11942, Jordan
| | - Mohammad I. K. Hamad
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates (S.B.); (S.S.)
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Misera A, Marlicz W, Podkówka A, Łoniewski I, Skonieczna-Żydecka K. Possible application of Akkermansia muciniphila in stress management. MICROBIOME RESEARCH REPORTS 2024; 3:48. [PMID: 39741949 PMCID: PMC11684984 DOI: 10.20517/mrr.2023.81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 08/30/2024] [Accepted: 09/02/2024] [Indexed: 01/03/2025]
Abstract
Akkermansia muciniphila (A. muciniphila) is a promising candidate bacterium for stress management due to its beneficial effects on the microbiota-gut-brain axis (MGBA). As a well-known mucin-degrading bacterium in the digestive tract, A. muciniphila has demonstrated significant benefits for host physiology. Recent research highlights its potential in treating several neuropsychiatric disorders. Proposed mechanisms of action include the bacterium's outer membrane protein Amuc_1100 and potentially its extracellular vesicles (EVs), which interact with host immune receptors and influence serotonin pathways, which are crucial for emotional regulation. Despite its potential, the administration of probiotics containing A. muciniphila faces technological challenges, prompting the development of pasteurized forms recognized as safe by the European Food Safety Authority (EFSA). This review systematically examines the existing literature on the role of A. muciniphila in stress management, emphasizing the need for further research to validate its efficacy. The review follows a structured methodology, including comprehensive database searches and thematic data analysis, to provide a detailed understanding of the relationship between stress, microbiota, and A. muciniphila therapeutic potential.
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Affiliation(s)
- Agata Misera
- Department of Psychiatry, Pomeranian Medical University in Szczecin, Szczecin 71-460, Poland
| | - Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Szczecin 71-252, Poland
| | - Albert Podkówka
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, Szczecin 71-460, Poland
| | - Igor Łoniewski
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, Szczecin 71-460, Poland
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Posar A, Visconti P. Gut Microbiota Alterations in Autism Spectrum Disorder. Turk Arch Pediatr 2024; 59:506-507. [PMID: 39440468 PMCID: PMC11391233 DOI: 10.5152/turkarchpediatr.2024.24086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 05/29/2024] [Indexed: 10/25/2024]
Affiliation(s)
- Annio Posar
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOSI Disturbi dello Spettro Autistico, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
| | - Paola Visconti
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOSI Disturbi dello Spettro Autistico, Bologna, Italy
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Misiak B, Pawlak E, Rembacz K, Kotas M, Żebrowska-Różańska P, Kujawa D, Łaczmański Ł, Piotrowski P, Bielawski T, Samochowiec J, Samochowiec A, Karpiński P. Associations of gut microbiota alterations with clinical, metabolic, and immune-inflammatory characteristics of chronic schizophrenia. J Psychiatr Res 2024; 171:152-160. [PMID: 38281465 DOI: 10.1016/j.jpsychires.2024.01.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 12/31/2023] [Accepted: 01/22/2024] [Indexed: 01/30/2024]
Abstract
The present study had the following aims: 1) to compare gut microbiota composition in patients with schizophrenia and controls and 2) to investigate the association of differentially abundant bacterial taxa with markers of inflammation, intestinal permeability, lipid metabolism, and glucose homeostasis as well as clinical manifestation. A total of 115 patients with schizophrenia during remission of positive and disorganization symptoms, and 119 controls were enrolled. Altogether, 32 peripheral blood markers were assessed. A higher abundance of Eisenbergiella, Family XIII AD3011 group, Eggerthella, Hungatella, Lactobacillus, Olsenella, Coprobacillus, Methanobrevibacter, Ligilactobacillus, Eubacterium fissicatena group, and Clostridium innocuum group in patients with schizophrenia was found. The abundance of Paraprevotella and Bacteroides was decreased in patients with schizophrenia. Differentially abundant genera were associated with altered levels of immune-inflammatory markers, zonulin, lipid profile components, and insulin resistance. Moreover, several correlations of differentially abundant genera with cognitive impairment, higher severity of negative symptoms, and worse social functioning were observed. The association of Methanobrevibacter abundance with the level of negative symptoms, cognition, and social functioning appeared to be mediated by the levels of interleukin-6 and RANTES. In turn, the association of Hungatella with the performance of attention was mediated by the levels of zonulin. The findings indicate that compositional alterations of gut microbiota observed in patients with schizophrenia correspond with clinical manifestation, intestinal permeability, subclinical inflammation, lipid profile alterations, and impaired glucose homeostasis. Subclinical inflammation and impaired gut permeability might mediate the association of gut microbiota alterations with psychopathological symptoms and cognitive impairment.
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Affiliation(s)
- Błażej Misiak
- Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland.
| | - Edyta Pawlak
- Laboratory of Immunopathology, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Krzysztof Rembacz
- Laboratory of Immunopathology, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Marek Kotas
- Laboratory of Immunopathology, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Paulina Żebrowska-Różańska
- Laboratory of Genomics & Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Dorota Kujawa
- Laboratory of Genomics & Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Łukasz Łaczmański
- Laboratory of Genomics & Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Patryk Piotrowski
- Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland
| | - Tomasz Bielawski
- Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland
| | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical University, Szczecin, Poland
| | - Agnieszka Samochowiec
- Department of Clinical Psychology, Institute of Psychology, University of Szczecin, Poland
| | - Paweł Karpiński
- Laboratory of Genomics & Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; Department of Genetics, Wroclaw Medical University, Wroclaw, Poland
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9
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Stiernborg M, Prast-Nielsen S, Melas PA, Skott M, Millischer V, Boulund F, Forsell Y, Lavebratt C. Differences in the gut microbiome of young adults with schizophrenia spectrum disorder: using machine learning to distinguish cases from controls. Brain Behav Immun 2024; 117:298-309. [PMID: 38280535 DOI: 10.1016/j.bbi.2024.01.218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 12/27/2023] [Accepted: 01/22/2024] [Indexed: 01/29/2024] Open
Abstract
While an association between the gut microbiome and schizophrenia spectrum disorders (SSD) has been suggested, the existing evidence is still inconclusive. To this end, we analyzed bacteria and bacterial genes in feces from 52 young adult SSD patients and 52 controls using fecal shotgun metagenomic sequencing. Compared to controls, young SSD patients were found to have significantly lower α-diversity and different β-diversity both regarding bacterial species (i.e., taxonomic diversity) and bacterial genes (i.e., functional diversity). Furthermore, the α-diversity measures 'Pielou's evenness' and 'Shannon' were significantly higher for both bacterial species, bacterial genes encoding enzymes and gut brain modules in young SSD patients on antipsychotic treatment (young SSD not on antipsychotics=9 patients, young SSD on antipsychotics=43 patients). We also applied machine learning classifiers to distinguish between young SSD patients and healthy controls based on their gut microbiome. Results showed that taxonomic and functional data classified young SSD individuals with an accuracy of ≥ 70% and with an area under the receiver operating characteristic curve (AUROC) of ≥ 0.75. Differential abundance analysis on the most important features in the classifier models revealed that most of the species with higher abundance in young SSD patients had their natural habitat in the oral cavity. In addition, many of the modules with higher abundance in young SSD patients were amino acid biosynthesis modules. Moreover, the abundances of gut-brain modules of butyrate synthesis and acetate degradation were lower in the SSD patients compared to controls. Collectively, our findings continue to support the presence of gut microbiome alterations in SSD and provide support for the use of machine learning algorithms to distinguish patients from controls based on gut microbiome profiles.
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Affiliation(s)
- Miranda Stiernborg
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden
| | - Stefanie Prast-Nielsen
- Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Philippe A Melas
- Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm, Sweden
| | - Maria Skott
- Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm, Sweden
| | - Vincent Millischer
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Fredrik Boulund
- Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Yvonne Forsell
- Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
| | - Catharina Lavebratt
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
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10
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Sen P, Prandovszky E, Honkanen JK, Chen O, Yolken R, Suvisaari J. Dysregulation of Microbiota in Patients With First-Episode Psychosis Is Associated With Symptom Severity and Treatment Response. Biol Psychiatry 2024; 95:370-379. [PMID: 38061464 DOI: 10.1016/j.biopsych.2023.10.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 08/21/2023] [Accepted: 10/23/2023] [Indexed: 01/16/2024]
Abstract
BACKGROUND The gut microbiome has been implicated in the pathogenesis of mental disorders where the gut-brain axis acts as a bidirectional communication network. METHODS Herein, we investigated the compositional and functional differences of gut microbiome between patients with first-episode psychosis (FEP) (n = 26) and healthy control participants (n = 22) using whole-genome shotgun sequencing. In addition, we assessed the oral microbiome in patients with FEP (n = 13) and listed their taxonomic diversity. RESULTS Our findings suggest that there is a dysbiosis of gut microbiota in patients with FEP. Relative abundance of Bifidobacterium adolescentis, Prevotella copri, and Turicibacter sanguinis was markedly increased (linear discriminant analysis scores [log10] > 1, and Mann-Whitney U test; false discovery rate-adjusted p values < .05) in the FEP group compared with the healthy control participants. Pathway analysis indicated that several metabolic pathways, particularly deoxyribonucleotide biosynthesis, branched-chain amino acid biosynthesis, tricarboxylic acid cycle, and fatty acid elongation and biosynthesis, were dysregulated in the FEP group compared with the healthy control group. In addition, this preliminary study was able to identify specific gut microbes (at baseline) that were predictive of weight gain in the FEP group at a 1-year follow-up. Bacteroides dorei, Bifidobacterium adolescentis, Turicibacter sanguinis, Roseburia spp., and Ruminococcus lactaris were positively associated (eXtreme gradient boosting, XGBoost regression model, Shapley additive explanations, R2 = 0.82) with weight gain. CONCLUSIONS Our findings may suggest the involvement of gut microbiota in the pathogenesis of psychosis. The benefit of modulation of the gut microbiome in the treatment of psychotic disorders should be explored further.
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Affiliation(s)
- Partho Sen
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
| | - Emese Prandovszky
- Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Jarno K Honkanen
- Translational Immunology Program, Research Programs Unit, University of Helsinki, Helsinki, Finland
| | - Ou Chen
- Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Robert Yolken
- Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Jaana Suvisaari
- Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland; Finnish Institute for Health and Welfare, Helsinki, Finland.
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11
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Gonçalves CL, Doifode T, Rezende VL, Costa MA, Rhoads JM, Soutullo CA. The many faces of microbiota-gut-brain axis in autism spectrum disorder. Life Sci 2024; 337:122357. [PMID: 38123016 DOI: 10.1016/j.lfs.2023.122357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 12/02/2023] [Accepted: 12/13/2023] [Indexed: 12/23/2023]
Abstract
The gut-brain axis is gaining more attention in neurodevelopmental disorders, especially autism spectrum disorder (ASD). Many factors can influence microbiota in early life, including host genetics and perinatal events (infections, mode of birth/delivery, medications, nutritional supply, and environmental stressors). The gut microbiome can influence blood-brain barrier (BBB) permeability, drug bioavailability, and social behaviors. Developing microbiota-based interventions such as probiotics, gastrointestinal (GI) microbiota transplantation, or metabolite supplementation may offer an exciting approach to treating ASD. This review highlights that RNA sequencing, metabolomics, and transcriptomics data are needed to understand how microbial modulators can influence ASD pathophysiology. Due to the substantial clinical heterogeneity of ASD, medical caretakers may be unlikely to develop a broad and effective general gut microbiota modulator. However, dietary modulation followed by administration of microbiota modulators is a promising option for treating ASD-related behavioral and gastrointestinal symptoms. Future work should focus on the accuracy of biomarker tests and developing specific psychobiotic agents tailored towards the gut microbiota seen in ASD patients, which may include developing individualized treatment options.
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Affiliation(s)
- Cinara L Gonçalves
- Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
| | - Tejaswini Doifode
- Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health (UTHealth), Houston, TX, USA
| | - Victoria L Rezende
- Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Maiara A Costa
- Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - J Marc Rhoads
- Department of Pediatrics, Division of Pediatric Gastroenterology, McGovern Medical School, The University of Texas Health (UTHealth), Houston, TX, USA
| | - Cesar A Soutullo
- Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health (UTHealth), Houston, TX, USA
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12
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Lin SKK, Chen HC, Chen CH, Chen IM, Lu ML, Hsu CD, Chiu YH, Wang TY, Chen HM, Chung YCE, Kuo PH. Exploring the human gut microbiota targets in relation to the use of contemporary antidepressants. J Affect Disord 2024; 344:473-484. [PMID: 37820962 DOI: 10.1016/j.jad.2023.10.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 09/04/2023] [Accepted: 10/08/2023] [Indexed: 10/13/2023]
Abstract
BACKGROUND Antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed for depression treatment. Animal studies have shown that antidepressants can influence gut microbiota composition and specific bacterial taxa. We aimed to investigate the association between antidepressant use and human gut microbiota composition and functional pathway. METHODS We collected information on antidepressant use, demographic, food patterns, and clinical characteristics through questionnaires and medical records. The gut microbiota profiles of 271 depressive patients were carried out through 16S rRNA gene sequencing. Patients were categorized based on different types of antidepressant use groups for gut microbiota comparisons. MaAsLin2 was performed to evaluate microbiota composition across groups. PICRUSt2 was used to predict microbiota functional pathways. RESULTS Patients taking SSRIs or SNRIs had a lower microbiota diversity. We found seven taxa abundances (Turicibacter, Barnesiella, Lachnospiraceae_ND3007_group, Romboutia, Akkermansia, Dialister, Romboutia and Fusicatenibacter) differed in patients with various types of antidepressants compared with those without antidepressant treatments (p < 0.05). Turicibacter inversely correlated with depression severity in SSRIs or SNRI users (r = -0.43, p < 0.05). Top identified pathways were related to compound fermentation and biosynthesis in microbiota function. CONCLUSION Antidepressant usage, especially SSRIs and SNRIs, associates with changes in gut microbiota composition and specific taxa. Given our study's preliminary cross-sectional nature, further research is warranted to comprehend the relationship between antidepressant use, treatment response, and gut microbiota, aiming to enhance therapeutic interventions in the future.
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Affiliation(s)
- Shih-Kai Kevin Lin
- Department of Public Health, Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Hsi-Chung Chen
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; Department of Psychiatry, Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Hsin Chen
- Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Psychiatric Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - I-Ming Chen
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan
| | - Mong-Liang Lu
- Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Psychiatric Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Cheng-Dien Hsu
- Department of Psychiatry, Taiwan Adventist Hospital, Taipei, Taiwan
| | - Yi-Hang Chiu
- Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan; Psychiatric Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Tsung-Yang Wang
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan
| | - Hui-Mei Chen
- Department of Public Health, Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Yu-Chu Ella Chung
- Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan
| | - Po-Hsiu Kuo
- Department of Public Health, Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; Psychiatric Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
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Kowalski K, Żebrowska-Różańska P, Karpiński P, Kujawa D, Łaczmański Ł, Samochowiec J, Chęć M, Piotrowski P, Misiak B. Profiling gut microbiota signatures associated with the deficit subtype of schizophrenia: Findings from a case-control study. Prog Neuropsychopharmacol Biol Psychiatry 2023; 127:110834. [PMID: 37473955 DOI: 10.1016/j.pnpbp.2023.110834] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/12/2023] [Accepted: 07/17/2023] [Indexed: 07/22/2023]
Abstract
BACKGROUND Previous studies have reported a variety of gut microbiota alterations in patients with schizophrenia. However, none of these studies has investigated gut microbiota in patients with the deficit subtype of schizophrenia (D-SCZ) that can be characterized by primary and enduring negative symptoms. Therefore, in this study we aimed to profile gut microbiota of individuals with D-SCZ, compared to those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs). METHODS A total of 115 outpatients (44 individuals with D-SCZ and 71 individuals with ND-SCZ) during remission of positive and disorganization symptoms as well as 120 HCs were enrolled. Gut microbiota was analyzed using the 16 rRNA amplicon sequencing. Additionally, the levels of C-reactive protein (CRP), glucose and lipid metabolism markers were determined in the peripheral blood samples. RESULTS Altogether 14 genera showed differential abundance in patients with D-SCZ compared to ND-SCZ and HCs, including Candidatus Soleaferrea, Eubacterium, Fusobacterium, Lachnospiraceae UCG-002, Lachnospiraceae UCG-004, Lachnospiraceae UCG-010, Libanicoccus, Limosilactobacillus, Mogibacterium, Peptococcus, Prevotella, Prevotellaceae NK3B31 group, Rikenellaceae RC9 gut group, and Slackia after adjustment for potential confounding factors. Observed alterations were significantly associated with cognitive performance in both groups of patients. Moreover, several significant correlations of differentially abundant genera with the levels of CRP, lipid profile parameters, glucose and insulin were found across all subgroups of participants. CONCLUSION Findings from the present study indicate that individuals with D-SCZ show a distinct profile of gut microbiota alterations that is associated with cognitive performance, metabolic parameters and subclinical inflammation.
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Affiliation(s)
- Krzysztof Kowalski
- Department of Psychiatry, Division of Consultation Psychiatry and Neuroscience, Wroclaw Medical University, Wroclaw, Poland
| | - Paulina Żebrowska-Różańska
- Laboratory of Genomics & Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Paweł Karpiński
- Laboratory of Genomics & Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; Department of Genetics, Wroclaw Medical University, Wroclaw, Poland
| | - Dorota Kujawa
- Laboratory of Genomics & Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Łukasz Łaczmański
- Laboratory of Genomics & Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
| | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical University, Szczecin, Poland
| | - Magdalena Chęć
- Department of Clinical Psychology, Institute of Psychology, University of Szczecin, Szczecin, Poland
| | - Patryk Piotrowski
- Department of Psychiatry, Division of Consultation Psychiatry and Neuroscience, Wroclaw Medical University, Wroclaw, Poland
| | - Błażej Misiak
- Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland.
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Kaźmierczak-Siedlecka K, Bulman N, Ulasiński P, Sobocki BK, Połom K, Marano L, Kalinowski L, Skonieczna-Żydecka K. Pharmacomicrobiomics of cell-cycle specific anti-cancer drugs - is it a new perspective for personalized treatment of cancer patients? Gut Microbes 2023; 15:2281017. [PMID: 37985748 PMCID: PMC10730203 DOI: 10.1080/19490976.2023.2281017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 11/05/2023] [Indexed: 11/22/2023] Open
Abstract
Intestinal bacteria are equipped with an enzyme apparatus that is involved in the active biotransformation of xenobiotics, including drugs. Pharmacomicrobiomics, a new area of pharmacology, analyses interactions between bacteria and xenobiotics. However, there is another side to the coin. Pharmacotherapeutic agents can significantly modify the microbiota, which consequently affects their efficacy. In this review, we comprehensively gathered scientific evidence on the interplay between anticancer therapies and gut microbes. We also underlined how such interactions might impact the host response to a given therapy. We discuss the possibility of modulating the gut microbiota to increase the effectiveness/decrease the incidence of adverse events during tumor therapy. The anticipation of the future brings new evidence that gut microbiota is a target of interest to increase the efficacy of therapy.
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Affiliation(s)
- Karolina Kaźmierczak-Siedlecka
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
| | - Nikola Bulman
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
| | - Paweł Ulasiński
- Unit of Surgery with Unit of Oncological Surgery in Koscierzyna, Kościerzyna, Poland
| | - Bartosz Kamil Sobocki
- Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdańsk, Poland
| | - Karol Połom
- Academy of Medical and Social Applied Sciences, Elbląg, Poland
| | - Luigi Marano
- Academy of Medical and Social Applied Sciences, Elbląg, Poland
| | - Leszek Kalinowski
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
- BioTechMed Centre/Department of Mechanics of Materials and Structures, Gdansk University of Technology, Gdansk, Poland
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15
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Qian L, He X, Liu Y, Gao F, Lu W, Fan Y, Gao Y, Wang W, Zhu F, Wang Y, Ma X. Longitudinal Gut Microbiota Dysbiosis Underlies Olanzapine-Induced Weight Gain. Microbiol Spectr 2023; 11:e0005823. [PMID: 37260381 PMCID: PMC10433857 DOI: 10.1128/spectrum.00058-23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 05/16/2023] [Indexed: 06/02/2023] Open
Abstract
Olanzapine is one of the most effective medicines available for stabilizing schizophrenia spectrum disorders. However, it has been reported to show the greatest propensity for inducing body weight gain and producing metabolic side effects, which cause a great burden in patients with psychiatric disorders. Since the gut microbiota has a profound impact on the initiation and development of metabolic diseases, we conducted a longitudinal study to explore its role in olanzapine-induced obesity and metabolic abnormalities. Female Sprague-Dawley rats were treated with different doses of olanzapine, and metabolic and inflammatory markers were measured. Olanzapine significantly induced body weight gain (up to a 2.1-fold change), which was accompanied by hepatic inflammation and increased plasma triglyceride levels (up to a 2.9-fold change), as well as gut microbiota dysbiosis. Subsequently, fuzzy c-means clustering was used to characterize three clusters of longitudinal trajectories for microbial fluctuations: (i) genera continuing to increase, (ii) genera continuing to decrease, and (iii) genera temporarily changing. Among them, Enterorhabdus (r = 0.38), Parasutterella (r = 0.43), and Prevotellaceae UCG-001 (r = 0.52) positively correlated with body weight gain. In addition, two MetaCyc metabolic pathways were identified as associated with olanzapine-induced body weight gain, including the superpathway of glucose and xylose degradation and the superpathway of l-threonine biosynthesis. In conclusion, we demonstrate that olanzapine can directly alter the gut microbiota and rapidly induce dysbiosis, which is significantly associated with body weight gain. This may suggest gut microbiota targets in future studies on metabolic abnormalities caused by olanzapine. IMPORTANCE Olanzapine is one of the most effective second-generation antipsychotics for stabilizing schizophrenia spectrum disorders. However, olanzapine has multiple drug-induced metabolic side effects, including weight gain. This study provides insight to the gut microbiota target in olanzapine-induced obesity. Specifically, we explored the longitudinal gut microbiota trajectories of female Sprague-Dawley rats undergoing olanzapine treatment. We showed that olanzapine treatment causes a dynamic alteration of gut microbiota diversity. Additionally, we identified three genera, Parasutterella, Enterorhabdus, and Prevotellaceae UCG-001, that may play an important role in olanzapine-induced obesity. In this case, the supply or removal of specific elements of the gut microbiota may represent a promising avenue for treatment of olanzapine-related metabolic side effects.
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Affiliation(s)
- Li Qian
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xiaoyan He
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yixin Liu
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Fengjie Gao
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Wen Lu
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yajuan Fan
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yuan Gao
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Wei Wang
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Feng Zhu
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yanan Wang
- Med-X institute, Center for Immunological and Metabolic Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi’an, China
| | - Xiancang Ma
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Yang F, Gao R, Luo X, Liu R, Xiong D. Berberine influences multiple diseases by modifying gut microbiota. Front Nutr 2023; 10:1187718. [PMID: 37599699 PMCID: PMC10435753 DOI: 10.3389/fnut.2023.1187718] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 07/17/2023] [Indexed: 08/22/2023] Open
Abstract
Berberine (BBR) is an isoquinoline alkaloid that is widely distributed in the plant kingdom and is commonly found in Coptis chinensis Franch. It has low bioavailability, but it can interact with gut microbiota and affect a variety of diseases. The effects of BBR in diabetes, hyperlipidemia, atherosclerosis, liver diseases, intestinal diseases, mental disorders, autoimmune diseases, and other diseases are all thought to be related to gut microbiota. This review systematically and comprehensively summarize these interactions and their effects, and describes the changes of gut microbiota after the intervention of different doses of berberine and its potential clinical consequences, in order to provide a basis for the rational application of BBR in the future clinical treatment.
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Affiliation(s)
- Fujie Yang
- Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Rongmao Gao
- Department of ICU, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiaoxiu Luo
- Department of ICU, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Rongan Liu
- Department of ICU, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Daqian Xiong
- Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Ortega MA, Álvarez-Mon MA, García-Montero C, Fraile-Martínez Ó, Monserrat J, Martinez-Rozas L, Rodríguez-Jiménez R, Álvarez-Mon M, Lahera G. Microbiota-gut-brain axis mechanisms in the complex network of bipolar disorders: potential clinical implications and translational opportunities. Mol Psychiatry 2023; 28:2645-2673. [PMID: 36707651 PMCID: PMC10615769 DOI: 10.1038/s41380-023-01964-w] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 01/02/2023] [Accepted: 01/13/2023] [Indexed: 01/28/2023]
Abstract
Bipolar disorders (BD) represent a severe leading disabling mental condition worldwide characterized by episodic and often progressive mood fluctuations with manic and depressive stages. The biological mechanisms underlying the pathophysiology of BD remain incompletely understood, but it seems that there is a complex picture of genetic and environmental factors implicated. Nowadays, gut microbiota is in the spotlight of new research related to this kind of psychiatric disorder, as it can be consistently related to several pathophysiological events observed in BD. In the context of the so-called microbiota-gut-brain (MGB) axis, it is shown to have a strong influence on host neuromodulation and endocrine functions (i.e., controlling the synthesis of neurotransmitters like serotonin or mediating the activation of the hypothalamic-pituitary-adrenal axis), as well as in modulation of host immune responses, critically regulating intestinal, systemic and brain inflammation (neuroinflammation). The present review aims to elucidate pathophysiological mechanisms derived from the MGB axis disruption and possible therapeutic approaches mainly focusing on gut microbiota in the complex network of BD. Understanding the mechanisms of gut microbiota and its bidirectional communication with the immune and other systems can shed light on the discovery of new therapies for improving the clinical management of these patients. Besides, the effect of psychiatric drugs on gut microbiota currently used in BD patients, together with new therapeutical approaches targeting this ecosystem (dietary patterns, probiotics, prebiotics, and other novelties) will also be contemplated.
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Affiliation(s)
- Miguel A Ortega
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain.
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain.
| | - Miguel Angel Álvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Óscar Fraile-Martínez
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Jorge Monserrat
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Lucia Martinez-Rozas
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Roberto Rodríguez-Jiménez
- Department of Legal Medicine and Psychiatry, Complutense University, Madrid, Spain
- Institute for Health Research 12 de Octubre Hospital, (Imas 12)/CIBERSAM (Biomedical Research Networking Centre in Mental Health), Madrid, Spain
| | - Melchor Álvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine, University Hospital Príncipe de Asturias (CIBEREHD), Alcalá de Henares, Spain
- Psychiatry Service, Center for Biomedical Research in the Mental Health Network, University Hospital Príncipe de Asturias, Alcalá de Henares, Spain
| | - Guillermo Lahera
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Psychiatry Service, Center for Biomedical Research in the Mental Health Network, University Hospital Príncipe de Asturias, Alcalá de Henares, Spain
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Amdanee N, Shao M, Hu X, Fang X, Zhou C, Chen J, Ridwan Chattun M, Wen L, Pan X, Zhang X, Xu Y. Serum Metabolic Profile in Schizophrenia Patients With Antipsychotic-Induced Constipation and Its relationship With Gut Microbiome. Schizophr Bull 2023; 49:646-658. [PMID: 36723169 PMCID: PMC10154739 DOI: 10.1093/schbul/sbac202] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND AND HYPOTHESIS Antipsychotics (APs), the cornerstone of schizophrenia treatment, confer a relatively high risk of constipation. However, the mechanisms underpinning AP-induced constipation are poorly understood. Thus, we hypothesized that (1) schizophrenia patients with AP-induced constipation have distinct metabolic patterns; (2) there is more than one mechanism at play in producing this adverse drug effect; and (3) AP-associated changes in the gut microbiome are related to the altered metabolic profiles. STUDY DESIGN Eighty-eight schizophrenia patients, including 44 with constipation (C) and 44 matched patients without constipation (NC), were enrolled in this study. Constipation was diagnosed by Rome IV criteria for constipation and colonic transit time using radiopaque markers (ROMs) while severity was evaluated with the Bristol Stool Form Scale (BSS) and Constipation Assessment Scale (CAS). Fasting blood samples were drawn from all participants and were subjected to non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. STUDY RESULTS Eleven metabolites were significantly altered in AP-induced constipation which primarily disturbed sphingolipid metabolism, choline metabolism, and sphingolipid signaling pathway (P value < .05, FDR < 0.05). In the C group, changes in the gut bacteria showed a certain degree of correlation with 2 of the significantly altered serum metabolites and were associated with alterations in choline metabolism. CONCLUSIONS Our findings indicated that there were disturbances in distinct metabolic pathways that were associated with AP-induced constipation. In addition, this study presents evidence of a link between alterations in the gut microbiome and host metabolism which provides additional mechanistic insights on AP-induced constipation.
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Affiliation(s)
- Nousayhah Amdanee
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Miaomiao Shao
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
- Department of Psychiatry, The Second People’s Hospital of Jiangning District, Nanjing, Jiangsu, China
| | - Xiuxiu Hu
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
- Department of Psychiatry, The Second People’s Hospital of Jiangning District, Nanjing, Jiangsu, China
| | - Xinyu Fang
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Chao Zhou
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Jiu Chen
- Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Mohammad Ridwan Chattun
- Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Lu Wen
- Department of Psychiatry, The Second People’s Hospital of Jiangning District, Nanjing, Jiangsu, China
| | - Xinming Pan
- Department of Psychiatry, The Second People’s Hospital of Jiangning District, Nanjing, Jiangsu, China
| | - Xiangrong Zhang
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
- The Affiliated Xuzhou Oriental Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yue Xu
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
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Singal P, Nuñez NA, Joseph B, Hassett LC, Seshadri A, Singh B. Efficacy and Safety of Clonidine in the Treatment of Acute Mania in Bipolar Disorder: A Systematic Review. Brain Sci 2023; 13:brainsci13040547. [PMID: 37190511 DOI: 10.3390/brainsci13040547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 03/20/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
Clonidine, an alpha-2 adrenergic agonist, has been proposed as an antimanic agent that acts by reducing noradrenergic transmission. We conducted a systematic review to examine the efficacy and safety of clonidine for acute mania/hypomania. A comprehensive literature search was performed to identify randomized controlled trials (RCT) and non-randomized studies investigating the efficacy and safety of monotherapy/adjuvant treatment with clonidine for acute mania/hypomania in patients with bipolar disorder (BD). Nine studies (n = 222) met our inclusion criteria, including five RCTs (n = 159) and four non-randomized studies (n = 63). Non-randomized studies showed clonidine to help reduce symptoms of mania. However, data from placebo controlled RCTs were inconsistent. One RCT showed adjuvant clonidine as superior to placebo, whereas another RCT reported that clonidine was not better than placebo. In individual RCTs, lithium and valproate offered better antimanic effects compared to clonidine. Studies reported hypotension, depression, and somnolence as common adverse effects. Significant differences in study design and sample size contributed to high heterogeneity. This systematic review suggests low-grade evidence for clonidine as an adjuvant treatment for acute mania with mood stabilizers and inconclusive efficacy as monotherapy, warranting further well-designed RCTs.
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Mruk-Mazurkiewicz H, Kulaszyńska M, Jakubczyk K, Janda-Milczarek K, Czarnecka W, Rębacz-Maron E, Zacha S, Sieńko J, Zeair S, Dalewski B, Marlicz W, Łoniewski I, Skonieczna-Żydecka K. Clinical Relevance of Gut Microbiota Alterations under the Influence of Selected Drugs-Updated Review. Biomedicines 2023; 11:biomedicines11030952. [PMID: 36979931 PMCID: PMC10046554 DOI: 10.3390/biomedicines11030952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/12/2023] [Accepted: 03/14/2023] [Indexed: 03/30/2023] Open
Abstract
As pharmacology and science progress, we discover new generations of medicines. This relationship is a response to the increasing demand for medicaments and is powered by progress in medicine and research about the respective entities. However, we have questions about the efficiency of pharmacotherapy in individual groups of patients. The effectiveness of therapy is controlled by many variables, such as genetic predisposition, age, sex and diet. Therefore, we must also pay attention to the microbiota, which fulfill a lot of functions in the human body. Drugs used in psychiatry, gastroenterology, diabetology and other fields of medicine have been demonstrated to possess much potential to change the composition and probably the function of the intestinal microbiota, which consequently creates long-term risks of developing chronic diseases. The article describes the amazing interactions between gut microbes and drugs currently used in healthcare.
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Affiliation(s)
| | - Monika Kulaszyńska
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland
| | - Karolina Jakubczyk
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland
| | - Katarzyna Janda-Milczarek
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland
| | - Wiktoria Czarnecka
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland
| | - Ewa Rębacz-Maron
- Institute of Biology, Department of Ecology and Anthropology, University of Szczecin, 71-415 Szczecin, Poland
| | - Sławomir Zacha
- Department of Pediatric Orthopedics and Oncology of the Musculoskeletal System, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland
| | - Jerzy Sieńko
- Department of General and Gastroenterology Oncology Surgery, Pomeranian Medical University in Szczecin, 71-899 Szczecin, Poland
- Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland
| | - Samir Zeair
- General and Transplant Surgery Ward with Sub-Departments of Pomeranian Regional Hospital in Szczecin, 71-455 Arkonska, Poland
| | - Bartosz Dalewski
- Department of Dental Prosthetics, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
| | - Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, 71-455 Szczecin, Poland
| | - Igor Łoniewski
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland
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21
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Elwyn R, Mitchell J, Kohn MR, Driver C, Hay P, Lagopoulos J, Hermens DF. Novel ketamine and zinc treatment for anorexia nervosa and the potential beneficial interactions with the gut microbiome. Neurosci Biobehav Rev 2023; 148:105122. [PMID: 36907256 DOI: 10.1016/j.neubiorev.2023.105122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 03/04/2023] [Accepted: 03/07/2023] [Indexed: 03/13/2023]
Abstract
Anorexia nervosa (AN) is a severe illness with diverse aetiological and maintaining contributors including neurobiological, metabolic, psychological, and social determining factors. In addition to nutritional recovery, multiple psychological and pharmacological therapies and brain-based stimulations have been explored; however, existing treatments have limited efficacy. This paper outlines a neurobiological model of glutamatergic and γ-aminobutyric acid (GABA)-ergic dysfunction, exacerbated by chronic gut microbiome dysbiosis and zinc depletion at a brain and gut level. The gut microbiome is established early in development, and early exposure to stress and adversity contribute to gut microbial disturbance in AN, early dysregulation to glutamatergic and GABAergic networks, interoceptive impairment, and inhibited caloric harvest from food (e.g., zinc malabsorption, competition for zinc ions between gut bacteria and host). Zinc is a key part of glutamatergic and GABAergic networks, and also affects leptin and gut microbial function; systems dysregulated in AN. Low doses of ketamine in conjunction with zinc, could provide an efficacious combination to act on NMDA receptors and normalise glutamatergic, GABAergic and gut function in AN.
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Affiliation(s)
- Rosiel Elwyn
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia.
| | - Jules Mitchell
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Michael R Kohn
- AYA Medicine Westmead Hospital, CRASH (Centre for Research into Adolescent's Health) Western Sydney Local Health District, Sydney University, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Christina Driver
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Phillipa Hay
- Translational Health Research Institute (THRI) School of Medicine, Western Sydney University, Campbelltown, NSW, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Jim Lagopoulos
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Daniel F Hermens
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
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22
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Misera A, Łoniewski I, Palma J, Kulaszyńska M, Czarnecka W, Kaczmarczyk M, Liśkiewicz P, Samochowiec J, Skonieczna-Żydecka K. Clinical significance of microbiota changes under the influence of psychotropic drugs. An updated narrative review. Front Microbiol 2023; 14:1125022. [PMID: 36937257 PMCID: PMC10014913 DOI: 10.3389/fmicb.2023.1125022] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 02/13/2023] [Indexed: 03/05/2023] Open
Abstract
Relationship between drugs and microbiota is bilateral. Proper composition thus function of microbiota is a key to some medications used in modern medicine. However, there is also the other side of the coin. Pharmacotherapeutic agents can modify the microbiota significantly, which consequently affects its function. A recently published study showed that nearly 25% of drugs administered to humans have antimicrobial effects. Multiple antidepressants are antimicrobials,. and antibiotics with proven antidepressant effects do exist. On the other hand, antibiotics (e.g., isoniaside, minocycline) confer mental phenotype changes, and adverse effects caused by some antibiotics include neurological and psychological symptoms which further supports the hypothesis that intestinal microbiota may affect the function of the central nervous system. Here we gathered comprehensively data on drugs used in psychiatry regarding their antimicrobial properties. We believe our data has strong implications for the treatment of psychiatric entities. Nevertheless the study of ours highlights the need for more well-designed trials aimed at analysis of gut microbiota function.
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Affiliation(s)
- Agata Misera
- Department of Psychiatry, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Igor Łoniewski
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, Szczecin, Poland
- Sanprobi sp. z o.o. sp.k., Szczecin, Poland
| | - Joanna Palma
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Monika Kulaszyńska
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Wiktoria Czarnecka
- Department of Biochemical Science, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | | | - Paweł Liśkiewicz
- Department of Psychiatry, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical University in Szczecin, Szczecin, Poland
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Chen H, Cao T, Zhang B, Cai H. The regulatory effects of second-generation antipsychotics on lipid metabolism: Potential mechanisms mediated by the gut microbiota and therapeutic implications. Front Pharmacol 2023; 14:1097284. [PMID: 36762113 PMCID: PMC9905135 DOI: 10.3389/fphar.2023.1097284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Accepted: 01/12/2023] [Indexed: 01/26/2023] Open
Abstract
Second-generation antipsychotics (SGAs) are the mainstay of treatment for schizophrenia and other neuropsychiatric diseases but cause a high risk of disruption to lipid metabolism, which is an intractable therapeutic challenge worldwide. Although the exact mechanisms underlying this lipid disturbance are complex, an increasing body of evidence has suggested the involvement of the gut microbiota in SGA-induced lipid dysregulation since SGA treatment may alter the abundance and composition of the intestinal microflora. The subsequent effects involve the generation of different categories of signaling molecules by gut microbes such as endogenous cannabinoids, cholesterol, short-chain fatty acids (SCFAs), bile acids (BAs), and gut hormones that regulate lipid metabolism. On the one hand, these signaling molecules can directly activate the vagus nerve or be transported into the brain to influence appetite via the gut-brain axis. On the other hand, these molecules can also regulate related lipid metabolism via peripheral signaling pathways. Interestingly, therapeutic strategies directly targeting the gut microbiota and related metabolites seem to have promising efficacy in the treatment of SGA-induced lipid disturbances. Thus, this review provides a comprehensive understanding of how SGAs can induce disturbances in lipid metabolism by altering the gut microbiota.
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Affiliation(s)
- Hui Chen
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China,Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China,Institute of Clinical Pharmacy, Central South University, Changsha, China,International Research Center for Precision Medicine, Transformative Technology and Software Services, Changsha, Hunan, China
| | - Ting Cao
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China,Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China,Institute of Clinical Pharmacy, Central South University, Changsha, China,International Research Center for Precision Medicine, Transformative Technology and Software Services, Changsha, Hunan, China
| | - Bikui Zhang
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China,Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China,Institute of Clinical Pharmacy, Central South University, Changsha, China,International Research Center for Precision Medicine, Transformative Technology and Software Services, Changsha, Hunan, China,*Correspondence: Bikui Zhang, ; Hualin Cai,
| | - Hualin Cai
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China,Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China,Institute of Clinical Pharmacy, Central South University, Changsha, China,International Research Center for Precision Medicine, Transformative Technology and Software Services, Changsha, Hunan, China,*Correspondence: Bikui Zhang, ; Hualin Cai,
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24
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Zhao K, Ni Z, Qin Y, Zhu R, Yu Z, Ma Y, Chen W, Sun Q, Wang Z, Liu Y, Zhao J, Peng W, Hu S, Shi J, Lu L, Sun H. Disrupted diurnal oscillations of the gut microbiota in patients with alcohol dependence. Front Cell Infect Microbiol 2023; 13:1127011. [PMID: 36875518 PMCID: PMC9983756 DOI: 10.3389/fcimb.2023.1127011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/08/2023] [Indexed: 02/19/2023] Open
Abstract
Background Patients with alcohol dependence (AD) can exhibit gut dysbacteria. Dysbacteria may co-occur with disruptions of circadian rhythmicity of the gut flora, which can aggravate AD. Herein, this study aimed to investigate diurnal oscillations of the gut microbiota in AD patients. Methods Thirty-two patients with AD, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 20 healthy subjects were enrolled in this study. Demographic and clinical data were collected by self-report questionnaires. Fecal samples at 7:00 AM, 11:00 AM, 3:00 PM, and 7:00 PM were collected from each subject. 16S rDNA sequencing was conducted. Wilcoxon and Kruskal-Wallis tests were performed to characterize alterations and oscillations of the gut microbiota. Results We found that β-diversity of the gut microbiota in AD patients oscillated diurnally compared with healthy subjects (p = 0.01). Additionally, 0.66% of operational taxonomic units oscillated diurnally in AD patients versus 1.68% in healthy subjects. At different taxonomic levels, bacterial abundance oscillated diurnally in both groups, such as Pseudomonas and Prevotella pallens (all p < 0.05). β-diversity of the gut microbiota in AD patients with high daily alcohol consumption, high-level cravings, short AD durations, and mild withdrawal symptoms oscillated diurnally compared with other AD patients (all p < 0.05). Conclusion The gut microbiota in AD patients exhibits disruptions of diurnal oscillation, which may provide novel insights into mechanisms of AD and the development of therapeutic strategies.
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Affiliation(s)
- Kangqing Zhao
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Zhaojun Ni
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Ying Qin
- Addiction Medicine Department, The Second People’s Hospital of Guizhou Province, Guizhou, China
| | - Ran Zhu
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Zhoulong Yu
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Yundong Ma
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Wenhao Chen
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Qiqing Sun
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Zhong Wang
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Yanjing Liu
- Addiction Medicine Department, The Second People’s Hospital of Guizhou Province, Guizhou, China
| | - Jingwen Zhao
- Addiction Medicine Department, The Second People’s Hospital of Guizhou Province, Guizhou, China
| | - Wenjuan Peng
- Addiction Medicine Department, The Second People’s Hospital of Guizhou Province, Guizhou, China
| | - Sifan Hu
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Jie Shi
- National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China
- The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China
- The Key Laboratory for Neuroscience of the Ministry of Education and Health, Peking University, Beijing, China
| | - Lin Lu
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Hongqiang Sun
- NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
- *Correspondence: Hongqiang Sun,
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Gangopadhyay A, Ibrahim R, Theberge K, May M, Houseknecht KL. Non-alcoholic fatty liver disease (NAFLD) and mental illness: Mechanisms linking mood, metabolism and medicines. Front Neurosci 2022; 16:1042442. [PMID: 36458039 PMCID: PMC9707801 DOI: 10.3389/fnins.2022.1042442] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/21/2022] [Indexed: 09/26/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world and one of the leading indications for liver transplantation. It is one of the many manifestations of insulin resistance and metabolic syndrome as well as an independent risk factor for cardiovascular disease. There is growing evidence linking the incidence of NAFLD with psychiatric illnesses such as schizophrenia, bipolar disorder and depression mechanistically via genetic, metabolic, inflammatory and environmental factors including smoking and psychiatric medications. Indeed, patients prescribed antipsychotic medications, regardless of diagnosis, have higher incidence of NAFLD than population norms. The mechanistic pharmacology of antipsychotic-associated NAFLD is beginning to emerge. In this review, we aim to discuss the pathophysiology of NAFLD including its risk factors, insulin resistance and systemic inflammation as well as its intersection with psychiatric illnesses.
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Affiliation(s)
| | | | | | | | - Karen L. Houseknecht
- Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME, United States
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26
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O’Donnell M, Teasdale SB, Chua XY, Hardman J, Wu N, Curtis J, Samaras K, Bolton P, Morris MJ, Shannon Weickert C, Purves-Tyson T, El-Assaad F, Jiang XT, Hold GL, El-Omar E. The Role of the Microbiome in the Metabolic Health of People with Schizophrenia and Related Psychoses: Cross-Sectional and Pre-Post Lifestyle Intervention Analyses. Pathogens 2022; 11:1279. [PMID: 36365032 PMCID: PMC9695516 DOI: 10.3390/pathogens11111279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/19/2022] [Accepted: 10/24/2022] [Indexed: 03/20/2024] Open
Abstract
The microbiome has been implicated in the development of metabolic conditions which occur at high rates in people with schizophrenia and related psychoses. This exploratory proof-of-concept study aimed to: (i) characterize the gut microbiota in antipsychotic naïve or quasi-naïve people with first-episode psychosis, and people with established schizophrenia receiving clozapine therapy; (ii) test for microbiome changes following a lifestyle intervention which included diet and exercise education and physical activity. Participants were recruited from the Eastern Suburbs Mental Health Service, Sydney, Australia. Anthropometric, lifestyle and gut microbiota data were collected at baseline and following a 12-week lifestyle intervention. Stool samples underwent 16S rRNA sequencing to analyse microbiota diversity and composition. Seventeen people with established schizophrenia and five people with first-episode psychosis were recruited and matched with 22 age-sex, BMI and ethnicity matched controls from a concurrent study for baseline comparisons. There was no difference in α-diversity between groups at baseline, but microbial composition differed by 21 taxa between the established schizophrenia group and controls. In people with established illness pre-post comparison of α-diversity showed significant increases after the 12-week lifestyle intervention. This pilot study adds to the current literature that detail compositional differences in the gut microbiota of people with schizophrenia compared to those without mental illness and suggests that lifestyle interventions may increase gut microbial diversity in patients with established illness. These results show that microbiome studies are feasible in patients with established schizophrenia and larger studies are warranted to validate microbial signatures and understand the relevance of lifestyle change in the development of metabolic conditions in this population.
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Affiliation(s)
- Maryanne O’Donnell
- Discipline of Psychiatry and Mental Health, School of Medicine and Health, University of New South Wales, Kensington 2033, Australia
- Eastern Suburbs Mental Health Service, South Eastern Sydney Local Health District, Randwick 2031, Australia
| | - Scott B. Teasdale
- Discipline of Psychiatry and Mental Health, School of Medicine and Health, University of New South Wales, Kensington 2033, Australia
- Mindgardens Neuroscience Network, Sydney 2033, Australia
| | - Xin-Yi Chua
- Microbiome Research Centre, St George and Sutherland Clinical Campuses, University of New South Wales, Kogarah 2217, Australia
| | - Jamie Hardman
- Eastern Suburbs Mental Health Service, South Eastern Sydney Local Health District, Randwick 2031, Australia
| | - Nan Wu
- Microbiome Research Centre, St George and Sutherland Clinical Campuses, University of New South Wales, Kogarah 2217, Australia
- Department of Gastroenterology, The Sutherland Hospital, Caringbah 2229, Australia
| | - Jackie Curtis
- Discipline of Psychiatry and Mental Health, School of Medicine and Health, University of New South Wales, Kensington 2033, Australia
- Eastern Suburbs Mental Health Service, South Eastern Sydney Local Health District, Randwick 2031, Australia
- Mindgardens Neuroscience Network, Sydney 2033, Australia
| | - Katherine Samaras
- Department of Endocrinology, St Vincent’s Hospital Sydney, Victoria St, Darlinghurst 2010, Australia
- Clinical Obesity, Nutrition and Adipose Biology Lab, 384 Garvan Institute of Medical Research, Victoria St, Darlinghurst 2010, Australia
- School of Clinical Medicine, St Vincent’s Healthcare Clinical Campus, University of New South Wales, Darlinghurst 2010, Australia
| | - Patrick Bolton
- Eastern Suburbs Mental Health Service, South Eastern Sydney Local Health District, Randwick 2031, Australia
- School of Public Health, University of New South Wales, Kensington 2033, Australia
| | - Margaret J. Morris
- School of Medical Sciences, University of New South Wales, Kensington 2033, Australia
| | - Cyndi Shannon Weickert
- Discipline of Psychiatry and Mental Health, School of Medicine and Health, University of New South Wales, Kensington 2033, Australia
- Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney 2033, Australia
- Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY 13210, USA
| | - Tertia Purves-Tyson
- Discipline of Psychiatry and Mental Health, School of Medicine and Health, University of New South Wales, Kensington 2033, Australia
- Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney 2033, Australia
| | - Fatima El-Assaad
- Microbiome Research Centre, St George and Sutherland Clinical Campuses, University of New South Wales, Kogarah 2217, Australia
| | - Xiao-Tao Jiang
- Microbiome Research Centre, St George and Sutherland Clinical Campuses, University of New South Wales, Kogarah 2217, Australia
| | - Georgina L. Hold
- Microbiome Research Centre, St George and Sutherland Clinical Campuses, University of New South Wales, Kogarah 2217, Australia
| | - Emad El-Omar
- Microbiome Research Centre, St George and Sutherland Clinical Campuses, University of New South Wales, Kogarah 2217, Australia
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Zhu Z, Gu Y, Zeng C, Yang M, Yu H, Chen H, Zhang B, Cai H. Olanzapine-induced lipid disturbances: A potential mechanism through the gut microbiota-brain axis. Front Pharmacol 2022; 13:897926. [PMID: 35991866 PMCID: PMC9388751 DOI: 10.3389/fphar.2022.897926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 07/07/2022] [Indexed: 11/13/2022] Open
Abstract
Objective: Long-term use of olanzapine can induce various side effects such as lipid metabolic disorders, but the mechanism remains to be elucidated. The gut microbiota-brain axis plays an important role in lipid metabolism, and may be related to the metabolic side effects of olanzapine. Therefore, we explored the mechanism by which olanzapine-induced lipid disturbances through the gut microbiota-brain axis. Methods: Sprague Dawley rats were randomly divided into two groups, which underwent subphrenic vagotomy and sham surgery. Then the two groups were further randomly divided into two subgroups, one was administered olanzapine (10 mg/kg/day) by intragastric administration, and the other was administered normal saline by intragastric administration (4 ml/kg/day) for 2 weeks. The final changes in lipid parameters, gut microbes and their metabolites, and orexin-related neuropeptides in the hypothalamus were investigated among the different groups. Results: Olanzapine induced lipid disturbances as indicated by increased weight gain, elevated ratio of white adipose tissue to brown adipose tissue, as well as increased triglyceride and total cholesterol. Olanzapine also increased the Firmicutes/Bacteroides (F/B) ratio in the gut, which was even aggravated by subphrenic vagotomy. In addition, olanzapine reduced the abundance of short-chain fatty acids (SCFAs) metabolism related microbiome and 5-hydroxytryptamine (5-HT) levels in the rat cecum, and increased the gene and protein expression of the appetite-related neuropeptide Y/agouti-related peptide (NPY/AgRP) in the hypothalamus. Conclusion: The abnormal lipid metabolism caused by olanzapine may be closely related to the vagus nerve-mediated gut microbiota-brain axis.
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Affiliation(s)
- Zhenyu Zhu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
- International Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, China
| | - Yuxiu Gu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
- International Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, China
| | - Cuirong Zeng
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
- International Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, China
| | - Man Yang
- School of Pharmacy, Changsha Medical University, Changsha, China
| | - Hao Yu
- School of Pharmacy, Hunan University of Medicine, Changsha, China
| | - Hui Chen
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
- International Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, China
| | - Bikui Zhang
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
- International Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, China
- *Correspondence: Bikui Zhang, ; Hualin Cai,
| | - Hualin Cai
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
- International Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, China
- *Correspondence: Bikui Zhang, ; Hualin Cai,
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Singh R, Stogios N, Smith E, Lee J, Maksyutynsk K, Au E, Wright DC, De Palma G, Graff-Guerrero A, Gerretsen P, Müller DJ, Remington G, Hahn M, Agarwal SM. Gut microbiome in schizophrenia and antipsychotic-induced metabolic alterations: a scoping review. Ther Adv Psychopharmacol 2022; 12:20451253221096525. [PMID: 35600753 PMCID: PMC9118432 DOI: 10.1177/20451253221096525] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 04/07/2022] [Indexed: 12/11/2022] Open
Abstract
Schizophrenia (SCZ) is a severe mental disorder with high morbidity and lifetime disability rates. Patients with SCZ have a higher risk of developing metabolic comorbidities such as obesity and diabetes mellitus, leading to increased mortality. Antipsychotics (APs), which are the mainstay in the treatment of SCZ, increase the risk of these metabolic perturbations. Despite extensive research, the mechanism underlying SCZ pathophysiology and associated metabolic comorbidities remains unclear. In recent years, gut microbiota (GMB) has been regarded as a 'chamber of secrets', particularly in the context of severe mental illnesses such as SCZ, depression, and bipolar disorder. In this scoping review, we aimed to investigate the underlying role of GMB in the pathophysiology of SCZ and metabolic alterations associated with APs. Furthermore, we also explored the therapeutic benefits of prebiotic and probiotic formulations in managing SCZ and AP-induced metabolic alterations. A systematic literature search yielded 46 studies from both preclinical and clinical settings that met inclusion criteria for qualitative synthesis. Preliminary evidence from preclinical and clinical studies indicates that GMB composition changes are associated with SCZ pathogenesis and AP-induced metabolic perturbations. Fecal microbiota transplantation from SCZ patients to mice has been shown to induce SCZ-like behavioral phenotypes, further supporting the plausible role of GMB in SCZ pathogenesis. This scoping review recapitulates the preclinical and clinical evidence suggesting the role of GMB in SCZ symptomatology and metabolic adverse effects associated with APs. Moreover, this scoping review also discusses the therapeutic potentials of prebiotic/probiotic formulations in improving SCZ symptoms and attenuating metabolic alterations related to APs.
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Affiliation(s)
- Raghunath Singh
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - Nicolette Stogios
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Emily Smith
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Jiwon Lee
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Kateryna Maksyutynsk
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Emily Au
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - David C. Wright
- Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada
| | - Giada De Palma
- Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Ariel Graff-Guerrero
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Philip Gerretsen
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - Daniel J. Müller
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Gary Remington
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - Margaret Hahn
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - Sri Mahavir Agarwal
- Staff Psychiatrist and Clinician-Scientist, Medical Head, Clinical Research, Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), 1051 Queen Street W, Toronto, ON M6J 1H3, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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29
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Gebrayel P, Nicco C, Al Khodor S, Bilinski J, Caselli E, Comelli EM, Egert M, Giaroni C, Karpinski TM, Loniewski I, Mulak A, Reygner J, Samczuk P, Serino M, Sikora M, Terranegra A, Ufnal M, Villeger R, Pichon C, Konturek P, Edeas M. Microbiota medicine: towards clinical revolution. J Transl Med 2022; 20:111. [PMID: 35255932 PMCID: PMC8900094 DOI: 10.1186/s12967-022-03296-9] [Citation(s) in RCA: 128] [Impact Index Per Article: 42.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 02/03/2022] [Indexed: 02/07/2023] Open
Abstract
The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge.
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Affiliation(s)
| | - Carole Nicco
- Department Endocrinology, Metabolism and Diabetes, Faculté de Médecine Cochin-Port Royal, Université de Paris, INSERM U1016, Institut Cochin, 24 Rue du Faubourg St Jacques, 75014, Paris, France
- Laboratory of Excellence GR-Ex, Paris, France
| | - Souhaila Al Khodor
- Maternal and Child Health Department, Research Branch, Sidra Medicine, Doha, Qatar
| | | | | | | | | | - Cristina Giaroni
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | | | | | | | | | - Paulina Samczuk
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Matteo Serino
- IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, Toulouse, France
| | - Mariusz Sikora
- National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland
| | - Annalisa Terranegra
- Maternal and Child Health Department, Research Branch, Sidra Medicine, Doha, Qatar
| | | | | | - Chantal Pichon
- Center for Molecular Biophysics CNRS UPR 4301, University of Orléans, Orléans, France
| | - Peter Konturek
- Teaching Hospital of the University of Jena, Jena, Germany
| | - Marvin Edeas
- Department Endocrinology, Metabolism and Diabetes, Faculté de Médecine Cochin-Port Royal, Université de Paris, INSERM U1016, Institut Cochin, 24 Rue du Faubourg St Jacques, 75014, Paris, France.
- Laboratory of Excellence GR-Ex, Paris, France.
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Menon V, Ransing R, Praharaj SK. Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases. Indian J Psychiatry 2022; 64:S379-S393. [PMID: 35602369 PMCID: PMC9122174 DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_18_22] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 01/04/2022] [Accepted: 01/05/2022] [Indexed: 12/01/2022] Open
Affiliation(s)
- Vikas Menon
- Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Ramdas Ransing
- Department of Psychiatry, BKL Walalwalkar Rural Medical College, Ratnagiri, Maharashtra, India
| | - Samir Kumar Praharaj
- Department of Psychiatry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India E-mail:
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Ahmadpanah M, Pezeshki R, Soltanian AR, Jahangard L, Dürsteler KM, Keshavarzi A, Brand S. Influence of adjuvant clonidine on mania, sleep disturbances and cognitive performance - Results from a double-blind and placebo-controlled randomized study in individuals with bipolar I disorder during their manic phase. J Psychiatr Res 2022; 146:163-171. [PMID: 34990968 DOI: 10.1016/j.jpsychires.2021.12.035] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 12/10/2021] [Accepted: 12/17/2021] [Indexed: 12/31/2022]
Abstract
BACKGROUND While the favorable effect of adjuvant clonidine in the treatment of acute mania has been observed already about 40 years ago, this line of treatment has not been further investigated. Here, we resumed this topic, and we tested the effect of adjuvant clonidine, an antihypertensive stimulating the alpha-2 central adrenergic receptor, on symptoms of mania, cognitive performance, and subjective sleep. To this end, we performed a randomized, double-blind and placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania. METHODS A total of 70 inpatients (mean age: 37.40 years; 15.7% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant clonidine (0.2 mg/d to a maximum of 0.6 mg/d) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants' acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants' cognitive performance was assessed at baseline and at day 24 at the end of the study. RESULTS Over time, mania scores significantly decreased (large effect size), but more so in the clonidine condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the clonidine, compared to the placebo condition (medium effect size). Over time, cognitive performance improved (medium effect size), irrespective from the study condition. CONCLUSIONS Compared to placebo, adjuvant clonidine to lithium improved symptoms of mania, as rated by experts', and subjective sleep quality. Adjuvant clonidine had no further favorable (or detrimental) impact on cognitive performance.
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Affiliation(s)
- Mohammad Ahmadpanah
- Research Center for Behavioral Disorders and Substances Abuse, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Rana Pezeshki
- Research Center for Behavioral Disorders and Substances Abuse, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ali Reza Soltanian
- Modeling of Non-Communicable Diseases Research Center, Department of Biostatistics, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Leila Jahangard
- Research Center for Behavioral Disorders and Substances Abuse, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Kenneth M Dürsteler
- Psychiatric Clinics of the University of Basel, Division of Substance Use Disorders, University of Basel, Basel, Switzerland; Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
| | - Amir Keshavarzi
- Research Center for Behavioral Disorders and Substances Abuse, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Serge Brand
- Center for Affective, Stress and Sleep Disorders (ZASS), Psychiatric University Hospital Basel, 4002 Basel, Switzerland; Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Substance Abuse Prevention Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Sport, Exercise and Health, Division of Sport Science and Psychosocial Health, University of Basel, Basel, Switzerland; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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32
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Pu Z, Sun Y, Jiang H, Hou Q, Yan H, Wen H, Li G. Effects of Berberine on Gut Microbiota in Patients with Mild Metabolic Disorders Induced by Olanzapine. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2022; 49:1949-1963. [PMID: 34961418 DOI: 10.1142/s0192415x21500920] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Secondary metabolic disturbances in patients with schizophrenia or bipolar disorder may be attributed to olanzapine. It is important to prevent mild metabolic disorders progressing to metabolic syndrome. This study aims to investigate the effects of berberine on intestinal flora in patients with mild metabolic disorders induced by olanzapine. A total of 132 patients with schizophrenia, bipolar disorder, or schizoaffective psychosis that had been treated with olanzapine for at least 9 months were randomly assigned ([Formula: see text] = 66 each) to receive berberine or placebo tablets for 12 weeks. Metabolic assessments and intestinal flora were quantified at baseline and after 4, 8, and 12 weeks of treatment. Incidence rates of adverse reactions were recorded. FPG, FPI, HOMA-IR, HbA1, TG, BMI, and WC were significantly lower in patients who received berberine compared to placebo after 12 weeks of treatment ([Formula: see text]< 0.05). The abundance of firmicutes and coliform were significantly lower and the abundance of bacteroides significantly higher in patients who received berberine compared to placebo after 12 weeks of treatment ([Formula: see text]< 0.05). In patients who received berberine, the abundance of firmicutes was significantly decreased, and the abundance of bacteroides was significantly increased, and in patients who received placebo, the abundance of firmicutes was significantly increased post-treatment, compared to baseline (both [Formula: see text]< 0.05). In conclusions, berberine may regulate intestinal flora and metabolism in patients with schizophrenia or bipolar disorder and mild metabolic disturbances induced by olanzapine.
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Affiliation(s)
- Zhengping Pu
- Shanghai Mental Health Center, Shanghai Jiao Tong, University School of Medicine, Xuhui 200030, Shanghai, P. R. China.,Department of Psychiatry, Kangci Hospital of Jiaxing, Tongxiang 314500, Zhejiang, P. R. China
| | - Yunying Sun
- Endocrinology Department, First People's Hospital of Haining, Haining 314400, Zhejiang, P. R. China
| | - Hongxia Jiang
- Department of Psychiatry, Kangci Hospital of Jiaxing, Tongxiang 314500, Zhejiang, P. R. China
| | - Qingmei Hou
- Department of Clinical Psychology, The Second Specialized Hospital of Hegang, Hegang 154102, Heilongjiang, P. R. China
| | - Hui Yan
- Department of Psychiatry, Second People's Hospital of Taizhou, Tiantai 317200, Zhejiang, P. R. China
| | - Hui Wen
- Department of Traditional Chinese Medicine, Second People's Hospital of Tongxiang, Tongxiang 314500, Zhejiang, P. R. China
| | - Guorong Li
- Department of Psychiatry, Kangci Hospital of Jiaxing, Tongxiang 314500, Zhejiang, P. R. China
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Safadi JM, Quinton AMG, Lennox BR, Burnet PWJ, Minichino A. Gut dysbiosis in severe mental illness and chronic fatigue: a novel trans-diagnostic construct? A systematic review and meta-analysis. Mol Psychiatry 2022; 27:141-153. [PMID: 33558650 PMCID: PMC8960409 DOI: 10.1038/s41380-021-01032-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 12/18/2020] [Accepted: 01/13/2021] [Indexed: 01/30/2023]
Abstract
Reduced gut-microbial diversity ("gut dysbiosis") has been associated with an anhedonic/amotivational syndrome ("sickness behavior") that manifests across severe mental disorders and represent the key clinical feature of chronic fatigue. In this systematic review and meta-analysis, we investigated differences in proxy biomarkers of gut dysbiosis in patients with severe mental illness and chronic fatigue vs. controls and the association of these biomarkers with sickness behavior across diagnostic categories. Following PRISMA guidelines, we searched from inception to April 2020 for all the studies investigating proxy biomarkers of gut dysbiosis in patients with severe mental illness and chronic fatigue. Data were independently extracted by multiple observers, and a random-mixed model was used for the analysis. Heterogeneity was assessed with the I2 index. Thirty-three studies were included in the systematic review; nineteen in the meta-analysis (N = 2758 patients and N = 1847 healthy controls). When compared to controls, patients showed increased levels of zonulin (four studies reporting data on bipolar disorder and depression, SMD = 0.97; 95% Cl = 0.10-1.85; P = 0.03, I2 = 86.61%), lipopolysaccharide (two studies reporting data on chronic fatigue and depression, SMD = 0.77; 95% Cl = 0.42-1.12; P < 0.01; I2 = 0%), antibodies against endotoxin (seven studies reporting data on bipolar disorder, depression, schizophrenia, and chronic fatigue, SMD = 0.99; 95% CI = 0.27-1.70; P < 0.01, I2 = 97.14%), sCD14 (six studies reporting data on bipolar disorder, depression, schizophrenia, and chronic fatigue, SMD = 0.54; 95% Cl 0.16-0.81; P < 0.01, I2 = 90.68%), LBP (LBP, two studies reporting data on chronic fatigue and depression, SMD = 0.87; 95% Cl = 0.25-1.48; P < 0.01; I2 = 56.80%), alpha-1-antitripsin (six studies reporting data on bipolar disorder, depression, and schizophrenia, SMD = 1.23; 95% Cl = 0.57-1.88; P < 0.01, I2: 89.25%). Elevated levels of gut dysbiosis markers positively correlated with severity of sickness behavior in patients with severe mental illness and chronic fatigue. Our findings suggest that gut dysbiosis may underlie symptoms of sickness behavior across traditional diagnostic boundaries. Future investigations should validate these findings comparing the performances of the trans-diagnostic vs. categorical approach. This will facilitate treatment breakthrough in an area of unmet clinical need.
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Affiliation(s)
- Jenelle Marcelle Safadi
- grid.5386.8000000041936877XCornell University, Ithaca, NY USA ,grid.4991.50000 0004 1936 8948Department of Psychiatry, University of Oxford, Oxford, UK
| | - Alice M. G. Quinton
- grid.4991.50000 0004 1936 8948Department of Psychiatry, University of Oxford, Oxford, UK
| | - Belinda R. Lennox
- grid.4991.50000 0004 1936 8948Department of Psychiatry, University of Oxford, Oxford, UK
| | - Philip W. J. Burnet
- grid.4991.50000 0004 1936 8948Department of Psychiatry, University of Oxford, Oxford, UK
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Yang C, Lin X, Wang X, Liu H, Huang J, Wang S. The schizophrenia and gut microbiota: A bibliometric and visual analysis. Front Psychiatry 2022; 13:1022472. [PMID: 36458121 PMCID: PMC9705344 DOI: 10.3389/fpsyt.2022.1022472] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 10/24/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Many studies have explored the link between the gut microbiota and schizophrenia. To date, there have been no bibliometric analyses to summarize the association between the gut microbiota and schizophrenia. We aimed to conduct a bibliometric study of this association to determine the current status and areas for advancement in this field. MATERIALS AND METHODS Publications related to the gut microbiota and schizophrenia were retrieved from the Web of Science Core Collection (WoSCC). The WoSCC literature analysis wire and VOSviewer 1.6.16 were used to conduct the analysis. RESULTS In total, 162 publications were included in our study. The publications generally showed an upward trend from 2014. A total of 873 authors from 355 organizations and 40 countries/regions contributed to this field. The leading authors were Timothy Dinan, John F Cryan, and Emily Severance. The leading institutions were Johns Hopkins University, the University College Cork, and the University of Toronto. The most productive countries were the United States (US), China, and Canada. In total, 95 journals contributed to this field. Among them, the top three productive journals were Schizophrenia Research, Progress in Neuro Psychopharmacology Biological Psychiatry, and Frontiers in Psychiatry. The important keywords in the clusters were gut microbiome, bipolar disorder, schizophrenia, antipsychotics, weight gain, metabolic syndrome, gut-brain axis, autism, depression, inflammation, and brain. CONCLUSION The main research hotspots involving the connection between schizophrenia and the gut microbiota were the characteristics of the microbiota composition in schizophrenia patients, the gut-brain axis, and microbial-based interventions for schizophrenia. The studies about the association between gut microbiota and schizophrenia are limited, and more studies are needed to provide new insights into the gut microbiota in the pathogenesis and treatment of schizophrenia.
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Affiliation(s)
- Chao Yang
- Department of Psychiatry, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Xiaoxiao Lin
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xianteng Wang
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, China.,Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, International Cancer Center of Shenzhen University, Shenzhen, China
| | - Huanzhong Liu
- Department of Psychiatry, Chaohu Hospital, Anhui Medical University, Chaohu, China
| | - Jinyu Huang
- Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shuai Wang
- Department of Translation Medicine Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Mikrobiota jelitowa a leki. Interakcje wpływające na skuteczność i bezpieczeństwo farmakoterapii. POSTEP HIG MED DOSW 2021. [DOI: 10.2478/ahem-2021-0009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstrakt
Mikrobiota jelitowa stanowi nieodłączny element organizmu umożliwiający jego prawidłowe funkcjonowanie. Dzięki mikroorganizmom jelitowym możliwa jest stymulacja układu odpornościowego, synteza witamin czy poprawa wchłaniania składników odżywczych. Jednak jej aktywność może również niekorzystnie działać na organizm, m.in. z powodu przetwarzania treści jelitowej. Opisywana w artykule interakcja mikrobiota–lek uwzględnia pozytywny i negatywny wpływ mikroorganizmów jelitowych na farmakoterapię poprzez bezpośrednie i pośrednie oddziaływanie na lek w organizmie. Ze względu na to, że mikrobiom stanowi nieodłączny element organizmu, ingerencja nawet w jego niewielką część może doprowadzić do wystąpienia daleko idących, czasami niespodziewanych skutków. Stąd w celu poprawy skuteczności i bezpieczeństwa farmakoterapii konieczne jest wyjaśnienie mechanizmów oddziaływania mikrobioty na lek w organizmie.
W artykule podsumowano obecną wiedzę na temat biologicznej aktywności mikrobioty jelitowej, a zwłaszcza oddziaływań mikrobiota–leki determinujących skuteczność i bezpieczeństwo farmakoterapii. Wyszukiwanie przeprowadzono we wrześniu 2020 r. w bazach danych PubMed, Scopus, Web of Science, Cochrane Library i powszechnie dostępnej literaturze z użyciem terminów: „mikrobiota jelitowa”, „mikrobiom”, „metabolizm leku”, „interakcje mikrobiota–lek”. W artykule omówiono interakcje między mikrobiotą a lekami m.in. z grupy antybiotyków, inhibitorów pompy protonowej, sulfonamidów, pochodnych kwasu 5-aminosalicylowego, niesteroidowych leków przeciwzapalnych, przeciwnowotworowych, statyn czy metforminą.
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Caffeine consumption and schizophrenia: A highlight on adenosine receptor-independent mechanisms. Curr Opin Pharmacol 2021; 61:106-113. [PMID: 34688994 DOI: 10.1016/j.coph.2021.09.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Revised: 09/02/2021] [Accepted: 09/06/2021] [Indexed: 12/13/2022]
Abstract
Schizophrenia is a common psychiatric disorder which affects approximately 1% of the population worldwide. However, the complexity of etiology, treatment resistance and side effects induced by current antipsychotics, relapse prevention, and psychosocial rehabilitation are still to be uncovered. Caffeine, as the world's most widely consumed psychoactive drug, plays a crucial role in daily life. Plenty of preclinical and clinical evidence has illustrated that caffeine consumption could have a beneficial effect on schizophrenia. In this review, we firstly summarize the factors associated with the caffeine-induced beneficial effect. Then, a variety of mechanism of actions independent of adenosine receptor signaling will be discussed with an emphasis on the potential contribution of the microbiome-gut-brain axis to provide more possibilities for future therapeutic, prognosis, and social rehabilitation strategy.
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Chang SC, Goh KK, Lu ML. Metabolic disturbances associated with antipsychotic drug treatment in patients with schizophrenia: State-of-the-art and future perspectives. World J Psychiatry 2021; 11:696-710. [PMID: 34733637 PMCID: PMC8546772 DOI: 10.5498/wjp.v11.i10.696] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/16/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
Metabolic disturbances and obesity are major cardiovascular risk factors in patients with schizophrenia, resulting in a higher mortality rate and shorter life expectancy compared with those in the general population. Although schizophrenia and metabolic disturbances may share certain genetic or pathobiological risks, antipsychotics, particularly those of second generation, may further increase the risk of weight gain and metabolic disturbances in patients with schizophrenia. This review included articles on weight gain and metabolic disturbances related to antipsychotics and their mechanisms, monitoring guidelines, and interventions. Nearly all antipsychotics are associated with weight gain, but the degree of the weight gain varies considerably. Although certain neurotransmitter receptor-binding affinities and hormones are correlated with weight gain and specific metabolic abnormalities, the precise mechanisms underlying antipsychotic-induced weight gain and metabolic disturbances remain unclear. Emerging evidence indicates the role of genetic polymorphisms associated with antipsychotic-induced weight gain and antipsychotic-induced metabolic disturbances. Although many guidelines for screening and monitoring antipsychotic-induced metabolic disturbances have been developed, they are not routinely implemented in clinical care. Numerous studies have also investigated strategies for managing antipsychotic-induced metabolic disturbances. Thus, patients and their caregivers must be educated and motivated to pursue a healthier life through smoking cessation and dietary and physical activity programs. If lifestyle intervention fails, switching to another antipsychotic drug with a lower metabolic risk or adding adjunctive medication to mitigate weight gain should be considered. Antipsychotic medications are essential for schizophrenia treatment, hence clinicians should monitor and manage the resulting weight gain and metabolic disturbances.
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Affiliation(s)
- Shen-Chieh Chang
- Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
| | - Kah Kheng Goh
- Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei 116, Taiwan
| | - Mong-Liang Lu
- Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei 116, Taiwan
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Abstract
PURPOSE OF REVIEW Accumulating evidence indicates that there are bidirectional interactions between the gut microbiota and functioning of the central nervous system. Consequently, it has been proposed that gut microbiota alterations might play an important role in the pathophysiology of schizophrenia. Therefore, in this article, we aimed to perform a narrative review of studies addressing gut microbiota alterations in patients with schizophrenia that were published in the years 2019-2020. RECENT FINDINGS Several studies have shown a number of gut microbiota alterations at various stages of schizophrenia. Some of them can be associated with neurostructural abnormalities, psychopathological symptoms, subclinical inflammation and cardiovascular risk. Experimental studies clearly show that transplantation of gut microbiota from unmedicated patients with schizophrenia to germ-free mice results in a number of behavioural impairments accompanied by altered neurotransmission. However, findings from clinical trials do not support the use of probiotics as add-on treatments in schizophrenia. SUMMARY Gut microbiota alterations are widely observed in patients with schizophrenia and might account for various biological alterations involved in the cause of psychosis. However, longitudinal studies are still needed to conclude regarding causal associations. Well designed clinical trials are needed to investigate safety and efficacy of probiotics and prebiotics in schizophrenia.
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Affiliation(s)
| | - Błażej Misiak
- Department of Psychiatry, Division of Consultation Psychiatry and Neuroscience, Wroclaw Medical University, Wroclaw, Poland
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Chen LL, Abbaspour A, Mkoma GF, Bulik CM, Rück C, Djurfeldt D. Gut Microbiota in Psychiatric Disorders: A Systematic Review. Psychosom Med 2021; 83:679-692. [PMID: 34117156 PMCID: PMC8428865 DOI: 10.1097/psy.0000000000000959] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 02/04/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVE This systematic review sought to comprehensively summarize gut microbiota research in psychiatric disorders following PRISMA guidelines. METHODS Literature searches were performed on databases using keywords involving gut microbiota and psychiatric disorders. Articles in English with human participants up until February 13, 2020, were reviewed. Risk of bias was assessed using a modified Newcastle-Ottawa Scale for microbiota studies. RESULTS Sixty-nine of 4231 identified studies met the inclusion criteria for extraction. In most studies, gut microbiota composition differed between individuals with psychiatric disorders and healthy controls; however, limited consistency was observed in the taxonomic profiles. At the genus level, the most replicated findings were higher abundance of Bifidobacterium and lower abundance of Roseburia and Faecalibacterium among patients with psychiatric disorders. CONCLUSIONS Gut bacteria that produce short-chain fatty acids, such as Roseburia and Faecalibacterium, could be less abundant in patients with psychiatric disorders, whereas commensal genera, for example, Bifidobacterium, might be more abundant compared with healthy controls. However, most included studies were hampered by methodological shortcomings including small sample size, unclear diagnostics, failure to address confounding factors, and inadequate bioinformatic processing, which might contribute to inconsistent results. Based on our findings, we provide recommendations to improve quality and comparability of future microbiota studies in psychiatry.
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Gawlik-Kotelnicka O, Skowrońska A, Margulska A, Czarnecka-Chrebelska KH, Łoniewski I, Skonieczna-Żydecka K, Strzelecki D. The Influence of Probiotic Supplementation on Depressive Symptoms, Inflammation, and Oxidative Stress Parameters and Fecal Microbiota in Patients with Depression Depending on Metabolic Syndrome Comorbidity-PRO-DEMET Randomized Study Protocol. J Clin Med 2021; 10:jcm10071342. [PMID: 33804999 PMCID: PMC8036404 DOI: 10.3390/jcm10071342] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 03/17/2021] [Accepted: 03/20/2021] [Indexed: 12/14/2022] Open
Abstract
There is a huge need to search for new treatment options and potential biomarkers of therapeutic response to antidepressant treatment. Depression and metabolic syndrome often coexist, while a pathophysiological overlap, including microbiota changes, may play a role. The paper presents a study protocol that aims to assess the effect of probiotic supplementation on symptoms of depression, anxiety and stress, metabolic parameters, inflammatory and oxidative stress markers, as well as fecal microbiota in adult patients with depressive disorders depending on the co-occurrence of metabolic syndrome. The trial will be a four-arm, parallel-group, prospective, randomized, double-blind, controlled design that will include 200 participants and will last 20 weeks (ClinicalTrials.gov identifier: NCT04756544). The probiotic preparation will contain Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175. We will assess the level of depression, anxiety and stress, quality of life, blood pressure, body mass index and waist circumference, white blood cells count, serum levels of C-reactive protein, high-density lipoprotein (HDL) cholesterol, triglycerides, fasting glucose, fecal microbiota composition and the level of some fecal microbiota metabolites, as well as serum inflammatory markers and oxidative stress parameters. The proposed trial may establish a safe and easy-to-use adjunctive treatment option in a subpopulation of depressive patients only partially responsive to pharmacologic therapy.
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Affiliation(s)
- Oliwia Gawlik-Kotelnicka
- Department of Affective and Psychotic Disorders, Medical University of Lodz, 92-216 Lodz, Poland; (A.S.); (D.S.)
- Correspondence:
| | - Anna Skowrońska
- Department of Affective and Psychotic Disorders, Medical University of Lodz, 92-216 Lodz, Poland; (A.S.); (D.S.)
| | - Aleksandra Margulska
- Admission Department, Central Teaching Hospital of Medical University of Lodz, 92-216 Lodz, Poland;
| | | | - Igor Łoniewski
- Department of Biochemical Sciences, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (I.Ł.); (K.S.-Ż.)
| | - Karolina Skonieczna-Żydecka
- Department of Biochemical Sciences, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (I.Ł.); (K.S.-Ż.)
| | - Dominik Strzelecki
- Department of Affective and Psychotic Disorders, Medical University of Lodz, 92-216 Lodz, Poland; (A.S.); (D.S.)
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Libowitz MR, Nurmi EL. The Burden of Antipsychotic-Induced Weight Gain and Metabolic Syndrome in Children. Front Psychiatry 2021; 12:623681. [PMID: 33776816 PMCID: PMC7994286 DOI: 10.3389/fpsyt.2021.623681] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 02/17/2021] [Indexed: 12/13/2022] Open
Abstract
Antipsychotic medications are critical to child and adolescent psychiatry, from the stabilization of psychotic disorders like schizophrenia, bipolar disorder, and psychotic depression to behavioral treatment of autism spectrum disorder, tic disorders, and pediatric aggression. While effective, these medications carry serious risk of adverse events-most commonly, weight gain and cardiometabolic abnormalities. Negative metabolic consequences affect up to 60% of patients and present a major obstacle to long-term treatment. Since antipsychotics are often chronically prescribed beginning in childhood, cardiometabolic risk accumulates. An increased susceptibility to antipsychotic-induced weight gain (AIWG) has been repeatedly documented in children, particularly rapid weight gain. Associated cardiometabolic abnormalities include central obesity, insulin resistance, dyslipidemia, and systemic inflammation. Lifestyle interventions and medications such as metformin have been proposed to reduce risk but remain limited in efficacy. Furthermore, antipsychotic medications touted to be weight-neutral in adults can cause substantial weight gain in children. A better understanding of the biological underpinnings of AIWG could inform targeted and potentially more fruitful treatments; however, little is known about the underlying mechanism. As yet, modest genetic studies have nominated a few risk genes that explain only a small percentage of the risk. Recent investigations have begun to explore novel potential mechanisms of AIWG, including a role for gut microbiota and microbial metabolites. This article reviews the problem of AIWG and AP metabolic side effects in pediatric populations, proposed mechanisms underlying this serious side effect, and strategies to mitigate adverse impact. We suggest future directions for research efforts that may advance the field and lead to improved clinical interventions.
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Affiliation(s)
| | - Erika L. Nurmi
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, United States
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Zeng C, Yang P, Cao T, Gu Y, Li N, Zhang B, Xu P, Liu Y, Luo Z, Cai H. Gut microbiota: An intermediary between metabolic syndrome and cognitive deficits in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2021; 106:110097. [PMID: 32916223 DOI: 10.1016/j.pnpbp.2020.110097] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 08/29/2020] [Accepted: 09/01/2020] [Indexed: 12/12/2022]
Abstract
Gut microbiome interacts with the central nervous system tract through the gut-brain axis. Such communication involves neuronal, endocrine, and immunological mechanisms, which allows for the microbiota to affect and respond to various behaviors and psychiatric conditions. In addition, the use of atypical antipsychotic drugs (AAPDs) may interact with and even change the abundance of microbiome to potentially cause adverse effects or aggravate the disorders inherent in the disease. The regulate effects of gut microbiome has been described in several psychiatric disorders including anxiety and depression, but only a few reports have discussed the role of microbiota in AAPDs-induced Metabolic syndrome (MetS) and cognitive disorders. The following review systematically summarizes current knowledge about the gut microbiota in behavior and psychiatric illness, with the emphasis of an important role of the microbiome in the metabolism of schizophrenia and the potential for AAPDs to change the gut microbiota to promote adverse events. Prebiotics and probiotics are microbiota-management tools with documented efficacy for metabolic disturbances and cognitive deficits. Novel therapies for targeting microbiota for alleviating AAPDs-induced adverse effects are also under fast development.
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Affiliation(s)
- CuiRong Zeng
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China; The Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan Province, China
| | - Ping Yang
- Department of Psychiatry, The Second People's Hospital of Hunan Province, Changsha 410007, Hunan Province, China
| | - Ting Cao
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China; The Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan Province, China
| | - YuXiu Gu
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China; The Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan Province, China
| | - NaNa Li
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China; The Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan Province, China
| | - BiKui Zhang
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China; The Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan Province, China
| | - Ping Xu
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China; The Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan Province, China
| | - YiPing Liu
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China; The Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan Province, China
| | - ZhiYing Luo
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China; The Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan Province, China
| | - HuaLin Cai
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China; The Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan Province, China.
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Verhaegen AA, Van Gaal LF. Drugs Affecting Body Weight, Body Fat Distribution, and Metabolic Function-Mechanisms and Possible Therapeutic or Preventive Measures: an Update. Curr Obes Rep 2021; 10:1-13. [PMID: 33400222 DOI: 10.1007/s13679-020-00419-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/17/2020] [Indexed: 01/06/2023]
Abstract
PURPOSE OF REVIEW Weight gain and body fat redistribution are common side effects of many widely used drugs. We summarize recent literature on prevalence data and mechanisms associated with drug-induced body fat changes and mechanisms to prevent or treat metabolic side effects. RECENT FINDINGS The highest prevalence of metabolic complications is seen with antipsychotics and antiretroviral drugs used in the treatment of HIV and may, at least partly, be responsible for the increased risk for co-morbid diseases such as diabetes, steatosis of the liver, and cardiovascular disease. The pathogenetic mechanisms leading to weight gain from antipsychotics are increasingly known and help to unravel the complex interaction that exists between psychopathology and metabolic complications. Although the classic lipodystrophy mainly occurred with older HIV drugs, also with the newer HIV treatment, weight gain seems to be a major side effect. Early detection of the metabolic consequences of drugs can lead to an early diagnosis of the complications and their treatment. Different medications, including the newer antidiabetics, are being studied in the therapy of drug-induced obesity. Future research should focus on identifying individuals at risk for metabolic side effects and on early markers to identify individuals with side effects so that timely treatment of metabolic complications can be initiated.
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Affiliation(s)
- Ann A Verhaegen
- Department of Endocrinology, Diabetes and Metabolism, Antwerp University Hospital, Drie Eikenstraat 655, 2650, Edegem, Belgium.
- Department of Endocrinology, ZNA - Jan Palfijn, Lange Bremstraat 70,, 2170, Merksem, Belgium.
| | - Luc F Van Gaal
- Department of Endocrinology, Diabetes and Metabolism, Antwerp University Hospital, Drie Eikenstraat 655, 2650, Edegem, Belgium
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Luo C, Wang X, Huang HX, Mao XY, Zhou HH, Liu ZQ. Coadministration of metformin prevents olanzapine-induced metabolic dysfunction and regulates the gut-liver axis in rats. Psychopharmacology (Berl) 2021; 238:239-248. [PMID: 33095288 DOI: 10.1007/s00213-020-05677-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 10/05/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Olanzapine is widely prescribed for patients with mental disorders; however, it may induce metabolic dysfunction. Metformin is an efficient adjuvant for preventing olanzapine-induced metabolic dysfunction in clinical practice. Although the mechanism of how metformin prevents this metabolic dysfunction remains unknown, changes in the gut-liver axis are considered a potential explanation. METHODS Forty-eight male rats were gavaged with olanzapine and/or metformin for 35 consecutive days. Body weight, food intake, and water intake were measured daily. Histopathological and biochemical tests were performed to evaluate the metabolic dysfunction. The 16S rRNA obtained from fecal bacterial DNA was assessed. RESULTS Olanzapine treatment increased the body weight, blood glucose and triglyceride levels, and the number of adipocytes in the liver. While coadministration of metformin, there was a dose-dependent reverse of the abnormal changes induced by olanzapine treatment. Both olanzapine and metformin treatments altered the composition of the gut microbiota. Bacteroides acidifaciens and Lactobacillus gasseri were possibly played a positive role in metformin-mediated olanzapine-induced metabolic dysfunction prevention. CONCLUSION Metformin prevented olanzapine-induced metabolic dysfunction and regulated the gut microbiota in a dose-dependent manner.
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Affiliation(s)
- Chao Luo
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.,School of Life Sciences, Central South University, Changsha, 410078, Hunan, China
| | - Xu Wang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China
| | - Han-Xue Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China
| | - Xiao-Yuan Mao
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China
| | - Hong-Hao Zhou
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China
| | - Zhao-Qian Liu
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China. .,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.
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Seeman MV. The gut microbiome and antipsychotic treatment response. Behav Brain Res 2021; 396:112886. [PMID: 32890599 DOI: 10.1016/j.bbr.2020.112886] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 06/21/2020] [Accepted: 08/24/2020] [Indexed: 12/12/2022]
Abstract
Patients with psychosis usually respond to one antipsychotic drug and not to another; one third fail to respond to any. Some patients, who initially do well, stop responding. Some develop serious side effects even at low doses. While several of the reasons for this variability are known, many are not. The aim of this review is to explore the potential role of intestinal organisms in response/non-response to antipsychotics. Much of the literature in this field is relatively new and still, for the most part, theoretical. A growing number of animal experiments and clinical trials are starting to point, however, to substantial effects of antipsychotics on the composition of gut bacteria and, reciprocally, to the effects of microbiota on the pharmacokinetics of antipsychotic medication. Because so many factors influence the constituents of the human intestine, it is difficult, at present, to sort out how much one or more either enhance or dampen the benefits of antipsychotics or the character/severity of the adverse effects they induce. Dietary and other therapies are being devised to reverse dysbiosis. If successful, such therapies plus the modification of factors that, together, are known to determine the composition of microbiota could help to maximize the effectiveness of currently available antipsychotic therapy.
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Affiliation(s)
- Mary V Seeman
- Department of Psychiatry, University pf Toronto, Suite #605 260 Heath St. West, Toronto, Ontario, M5P 3L6, Canada.
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The Differences between Gluten Sensitivity, Intestinal Biomarkers and Immune Biomarkers in Patients with First-Episode and Chronic Schizophrenia. J Clin Med 2020; 9:jcm9113707. [PMID: 33218214 PMCID: PMC7699286 DOI: 10.3390/jcm9113707] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/13/2020] [Accepted: 11/16/2020] [Indexed: 12/15/2022] Open
Abstract
Schizophrenia is a heterogeneous disorder without a fully elucidated etiology and mechanisms. One likely explanation for the development of schizophrenia is low-grade inflammation, possibly caused by processes in the gastrointestinal tract related to gluten sensitivity. The aims of this study were to: (1) compare levels of markers of gluten sensitivity, inflammation and gut permeability, and (2) determine associations between gluten sensitivity, inflammation, and intestinal permeability in patients with first-episode/chronic (FS/CS) schizophrenia and healthy individuals (HC). The total sample comprised 162 individuals (52 FS; 50 CS, and 60 HC). The examination included clinical variables, nutritional assessment, and serum concentrations of: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), anti-Saccharomyces cerevisiae antibody (ASCA), antigliadin antibodies (AGA) IgA/IgG, antibodies against tissue transglutaminase 2 (anti-tTG) IgA, anti-deamidated gliadin peptides (anti-DGP) IgG. A significant difference between groups was found in sCD14, ASCA, hs-CRP, IL-6 and AGA IgA levels. AGA IgG/IgA levels were higher in the FS (11.54%; 30.77%) and CS (26%; 20%) groups compared to HC. The association between intestinal permeability and inflammation in the schizophrenic patients only was noted. The risk for developing schizophrenia was odds ratio (OR) = 4.35 (95% confidence interval (CI 1.23-15.39) for AGA IgA and 3.08 (95% CI 1.19-7.99) for positive AGA IgG. Inflammation and food hypersensitivity reactions initiated by increased intestinal permeability may contribute to the pathophysiology of schizophrenia. The immune response to gluten in FS differs from that found in CS.
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Skonieczna-Żydecka K, Jakubczyk K, Maciejewska-Markiewicz D, Janda K, Kaźmierczak-Siedlecka K, Kaczmarczyk M, Łoniewski I, Marlicz W. Gut Biofactory-Neurocompetent Metabolites within the Gastrointestinal Tract. A Scoping Review. Nutrients 2020; 12:E3369. [PMID: 33139656 PMCID: PMC7693392 DOI: 10.3390/nu12113369] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/27/2020] [Accepted: 10/29/2020] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota have gained much scientific attention recently. Apart from unravelling the taxonomic data, we should understand how the altered microbiota structure corresponds to functions of this complex ecosystem. The metabolites of intestinal microorganisms, especially bacteria, exert pleiotropic effects on the human organism and contribute to the host systemic balance. These molecules play key roles in regulating immune and metabolic processes. A subset of them affect the gut brain axis signaling and balance the mental wellbeing. Neurotransmitters, short chain fatty acids, tryptophan catabolites, bile acids and phosphatidylcholine, choline, serotonin, and L-carnitine metabolites possess high neuroactive potential. A scoping literature search in PubMed/Embase was conducted up until 20 June 2020, using three major search terms "microbiota metabolites" AND "gut brain axis" AND "mental health". This review aimed to enhance our knowledge regarding the gut microbiota functional capacity, and support current and future attempts to create new compounds for future clinical interventions.
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Affiliation(s)
- Karolina Skonieczna-Żydecka
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (K.S.-Ż.); (K.J.); (D.M.-M.); (K.J.)
| | - Karolina Jakubczyk
- Department of Surgical Oncology, Medical University of Gdansk, Smoluchowskiego 17, 80-214 Gdańsk, Poland;
| | - Dominika Maciejewska-Markiewicz
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (K.S.-Ż.); (K.J.); (D.M.-M.); (K.J.)
| | - Katarzyna Janda
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (K.S.-Ż.); (K.J.); (D.M.-M.); (K.J.)
| | | | - Mariusz Kaczmarczyk
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland;
| | - Igor Łoniewski
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (K.S.-Ż.); (K.J.); (D.M.-M.); (K.J.)
| | - Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University, 71-252 Szczecin, Poland
- The Centre for Digestive Diseases Endoklinika, 70-535 Szczecin, Poland
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Gubert C, Kong G, Uzungil V, Zeleznikow-Johnston AM, Burrows EL, Renoir T, Hannan AJ. Microbiome Profiling Reveals Gut Dysbiosis in the Metabotropic Glutamate Receptor 5 Knockout Mouse Model of Schizophrenia. Front Cell Dev Biol 2020; 8:582320. [PMID: 33195226 PMCID: PMC7658610 DOI: 10.3389/fcell.2020.582320] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 10/08/2020] [Indexed: 01/03/2023] Open
Abstract
Schizophrenia (SZ) is a psychiatric disorder that constitutes one of the top 10 global causes of disability. More recently, a potential pathogenic role for the gut microbial community (microbiota) has been highlighted, with numerous studies describing dysregulated microbial profiles in SZ patients when compared to healthy controls. However, no animal model of SZ has previously recapitulated the gut dysbiosis observed clinically. Since the metabotropic glutamate receptor 5 (mGlu5) knockout mice provide a preclinical model of SZ with strong face and predictive validity, in the present study we performed gut microbiome profiling of mGlu5 knockout (KO) and wild-type (WT) mice by 16S rRNA sequencing of bacterial genomic DNA from fecal samples, analyzing bacterial diversity and taxonomic composition, as well as gastrointestinal parameters as indicators of gut function. We found a significant genotype difference in microbial beta diversity. Analysis of composition of microbiomes (ANCOM) models were performed to evaluate microbiota compositions, which identified a decreased relative abundance of the Erysipelotrichaceae family and Allobaculum genus in this mouse model of SZ. We also identified a signature of bacteria discriminating between the genotypes (KO and WT), consisting of the Erysipelotrichales, Bacteroidales, and Clostridiales orders and macroscopic gut differences. We thus uncovered global differential community composition in the gut microbiota profile between mGlu5 KO and WT mice, outlining the first evidence for gut dysbiosis in a genetic animal model of SZ. Our findings suggest that this widely used preclinical model of SZ also has substantial utility for investigations of gut dysbiosis and associated signaling via the microbiota-gut-brain axis, as potential modulators of SZ pathogenesis. Our discovery opens up new avenues to explore gut dysbiosis and its proposed links to brain dysfunction in SZ, as well as novel therapeutic approaches to this devastating disorder.
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Affiliation(s)
- Carolina Gubert
- Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
| | - Geraldine Kong
- Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
| | - Volkan Uzungil
- Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
| | | | - Emma L. Burrows
- Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
| | - Thibault Renoir
- Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
| | - Anthony J. Hannan
- Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
- Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia
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49
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Sridhar GR. On Psychology and Psychiatry in Diabetes. Indian J Endocrinol Metab 2020; 24:387-395. [PMID: 33489842 PMCID: PMC7810053 DOI: 10.4103/ijem.ijem_188_20] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 05/08/2020] [Accepted: 06/06/2020] [Indexed: 12/16/2022] Open
Abstract
Managing diabetes requires dealing with diet, medications, and self-monitoring, besides other pressures of daily living. It, therefore, requires collaboration among individuals with diabetes, their families, and significant others including the social milieu in which they reside. Psychological stress plays critical role in the cause and course of diabetes, particularly in mastering various self-management skills, which are essential for adequate management of diabetes. It is possible to measure and to resolve such stressors. Besides the patient and the family, the built environment which the person occupies must be conducive for healthy living. This is a key component in providing an appropriate physical and psychosocial environment. Lacunae in any of the built environmental parameters compromise social and psychological well-being. Psychiatric conditions are also common in diabetes. Both depression and distress are bi-directionally associated with diabetes. The presence of one condition increases the risk of developing the other. In addition, medications used for the treatment of psychiatric conditions have adverse effects on body weight and insulin sensitivity. One must carefully weigh the risk and benefit of the drug class with potential adverse effects. Therefore, identification and management of psychological and psyciatric aspects in subjects with diabetes is an integral and critical component in treating subjects with diabetes.
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50
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The HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota? Prog Neuropsychopharmacol Biol Psychiatry 2020; 102:109951. [PMID: 32335265 DOI: 10.1016/j.pnpbp.2020.109951] [Citation(s) in RCA: 198] [Impact Index Per Article: 39.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/15/2020] [Accepted: 04/21/2020] [Indexed: 12/12/2022]
Abstract
Accumulating evidence indicates that patients with severe mental disorders, including major depression, bipolar disorder and schizophrenia present with various alterations of the gut microbiota and increased intestinal permeability. In addition, the hypothalamic-pituitary-adrenal (HPA) axis dysregulation and subclinical inflammation have been reported in this group of patients. Although it has been found that the HPA axis dysregulation appears as a consequence of psychosocial stress, especially traumatic life events, the exact mechanisms of this observation remain unclear. Animal model studies have unraveled several mechanisms linking the gut microbiota with the HPA axis dysfunction. Indeed, the gut microbiota can activate the HPA axis through several mediators that cross the blood-brain barrier and include microbial antigens, cytokines and prostaglandins. There is also evidence that various microbial species can affect ileal corticosterone production that may impact the activity of the HPA axis. However, some metabolites released by various microbes, e.g., short-chain fatty acids, can attenuate the HPA axis response. Moreover, several bacteria release neurotransmitters that can directly interact with vagal afferents. It has been postulated that the HPA axis activation can impact the gut microbiota and intestinal permeability. In this article, we discuss various mechanisms linking the gut microbiota with the HPA axis activity and summarize current evidence for a cross-talk between the gut-brain axis and the HPA axis from studies of patients with mood and psychotic disorders. Finally, we show potential clinical implications that can arise from future studies investigating the HPA axis activity with respect to the gut microbiota in severe mental disorders.
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