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Zolotareva D, Zazybin A, Belyankova Y, Bayazit S, Dauletbakov A, Seilkhanov T, Kemelbekov U, Aydemir M. Heterocyclic Antidepressants with Antimicrobial and Fungicide Activity. Molecules 2025; 30:1102. [PMID: 40076325 PMCID: PMC11902072 DOI: 10.3390/molecules30051102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 02/24/2025] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
In this review, the presence of antimicrobial and fungicidal activity in heterocyclic antidepressants was investigated. The already proven connection between the intestinal microbiome and mental health prompted the idea of whether these drugs disrupt the normal intestinal microflora. In addition, there is a serious problem of increasing resistance of microorganisms to antibiotics. In this article, we found that almost all of the antidepressants considered (except moclobemide, haloperidol, and doxepin) have antimicrobial activity and can suppress the growth of not only pathogenic microorganisms but also the growth of bacteria that directly affect mental health (such as Lactobacillus, Lactococcus, Streptococcus, Enterococcus, and Bifidobacterium).
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Affiliation(s)
- Darya Zolotareva
- School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan; (D.Z.); (Y.B.); (S.B.); (A.D.)
| | - Alexey Zazybin
- School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan; (D.Z.); (Y.B.); (S.B.); (A.D.)
| | - Yelizaveta Belyankova
- School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan; (D.Z.); (Y.B.); (S.B.); (A.D.)
| | - Sarah Bayazit
- School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan; (D.Z.); (Y.B.); (S.B.); (A.D.)
| | - Anuar Dauletbakov
- School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan; (D.Z.); (Y.B.); (S.B.); (A.D.)
| | - Tulegen Seilkhanov
- Laboratory of Engineering Profile NMR Spectroscopy, Sh. Ualikhanov Kokshetau University, 76 Abay Str., Kokshetau 020000, Kazakhstan;
| | - Ulan Kemelbekov
- South Kazakhstan Medical Academy, 1 Al-Farabi Square, Shymkent 160019, Kazakhstan;
| | - Murat Aydemir
- Faculty of Science, Department of Chemistry, Dicle University, Diyarbakır 21280, Turkey;
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2
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Degner KN, Bell JL, Jones SD, Won H. Just a SNP away: The future of in vivo massively parallel reporter assay. CELL INSIGHT 2025; 4:100214. [PMID: 39618480 PMCID: PMC11607654 DOI: 10.1016/j.cellin.2024.100214] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 10/03/2024] [Accepted: 10/06/2024] [Indexed: 04/03/2025]
Abstract
The human genome is largely noncoding, yet the field is still grasping to understand how noncoding variants impact transcription and contribute to disease etiology. The massively parallel reporter assay (MPRA) has been employed to characterize the function of noncoding variants at unprecedented scales, but its application has been largely limited by the in vitro context. The field will benefit from establishing a systemic platform to study noncoding variant function across multiple tissue types under physiologically relevant conditions. However, to date, MPRA has been applied to only a handful of in vivo conditions. Given the complexity of the central nervous system and its widespread interactions with all other organ systems, our understanding of neuropsychiatric disorder-associated noncoding variants would be greatly advanced by studying their functional impact in the intact brain. In this review, we discuss the importance, technical considerations, and future applications of implementing MPRA in the in vivo space with the focus on neuropsychiatric disorders.
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Affiliation(s)
- Katherine N. Degner
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Jessica L. Bell
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Sean D. Jones
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Hyejung Won
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Jadhav G, Dudhabhate BB, Kokare DM, Sakharkar AJ. Gut Microbiota Regulates Epigenetic Remodelling in the Amygdala: A Role in Repeated Mild Traumatic Brain Injury (rMTBI)-Induced Anxiety. Mol Neurobiol 2024; 61:9892-9914. [PMID: 37872356 DOI: 10.1007/s12035-023-03697-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 10/05/2023] [Indexed: 10/25/2023]
Abstract
Gut microbiota serves in the development and maintenance of phenotype. However, the underlying mechanisms are still in its infancy. The current study shows epigenetic remodelling in the brain as a causal mechanism in the gut microbiota-brain axis. Like in trauma patients, gut dysbiosis and anxiety were comorbid in adult male Wistar rats subjected to repeated mild traumatic brain injuries (rMTBI). rMTBI caused epigenetic dysregulation of brain-derived neurotrophic factor (Bdnf) expression in the amygdala, owing to the formation of transcriptional co-repressor complex due to dynamic interaction between histone deacetylase and DNA methylation modification at the Bdnf gene promoter. The probiosis after faecal microbiota transplantation (FMT) from healthy naïve rats or by administration of single strain probiotic (SSP), Lactobacillus rhamnosus GG (LGG), recuperated rMTBI-induced anxiety. Concurrently, LGG infusion or naïve FMT also dislodged rMTBI-induced co-repressor complex resulting in the normalization of Bdnf expression and neuronal plasticity as measured by Golgi-Cox staining. Furthermore, sodium butyrate, a short-chain fatty acid, produced neurobehavioural effects similar to naïve FMT or LGG administration. Interestingly, the gut microbiota from rMTBI-exposed rats per se was able to provoke anxiety in naïve rats in parallel with BDNF deficits. Therefore, gut microbiota seems to be causally linked with the chromatin remodelling necessary for neuroadaptations via neuronal plasticity which drives experience-dependent behavioural manifestations.
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Affiliation(s)
- Gouri Jadhav
- Department of Biotechnology, Savitribai Phule Pune University, Pune, 411 007, Maharashtra, India
| | - Biru B Dudhabhate
- Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, 440 033, Maharashtra, India
| | - Dadasaheb M Kokare
- Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, 440 033, Maharashtra, India
| | - Amul J Sakharkar
- Department of Biotechnology, Savitribai Phule Pune University, Pune, 411 007, Maharashtra, India.
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4
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Gustafson KL, Busi SB, McAdams ZL, McCorkle RE, Khodakivskyi P, Bivens NJ, Davis DJ, Raju M, Coghill LM, Goun EA, Amos-Landgraf J, Franklin CL, Wilmes P, Cortese R, Ericsson AC. Fetal programming by the parental microbiome of offspring behavior, and DNA methylation and gene expression within the hippocampus. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.04.12.589237. [PMID: 39484583 PMCID: PMC11526851 DOI: 10.1101/2024.04.12.589237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Abstract
Background The microorganisms colonizing the gastrointestinal tract of animals, collectively referred to as the gut microbiome, affect numerous host behaviors dependent on the central nervous system (CNS). Studies comparing germ-free mice to normally colonized mice have demonstrated influences of the microbiome on anxiety-related behaviors, voluntary activity, and gene expression in the CNS. Additionally, there is epidemiologic evidence supporting an intergenerational influence of the maternal microbiome on neurodevelopment of offspring and behavior later in life. There is limited experimental evidence however directly linking the maternal microbiome to long-term neurodevelopmental outcomes, or knowledge regarding mechanisms responsible for such effects. Results Here we show that that the maternal microbiome has a dominant influence on several offspring phenotypes including anxiety-related behavior, voluntary activity, and body weight. Adverse outcomes in offspring were associated with features of the maternal microbiome including bile salt hydrolase activity gene expression (bsh), abundance of certain bile acids, and hepatic expression of Slc10a1. In cross-foster experiments, offspring resembled their birth dam phenotypically, despite faithful colonization in the postnatal period with the surrogate dam microbiome. Genome-wide methylation analysis of hippocampal DNA identified microbiome-associated differences in methylation of 196 loci in total, 176 of which show conserved profiles between mother and offspring. Further, single-cell transcriptional analysis revealed accompanying differences in expression of several differentially methylated genes within certain hippocampal cell clusters, and vascular expression of genes associated with bile acid transport. Inferred cell-to-cell communication in the hippocampus based on coordinated ligand-receptor expression revealed differences in expression of neuropeptides associated with satiety. Conclusions Collectively, these data provide proof-of-principle that the maternal gut microbiome has a dominant influence on the neurodevelopment underlying certain offspring behaviors and activities, and selectively affects genome methylation and gene expression in the offspring CNS in conjunction with that neurodevelopment.
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Affiliation(s)
- Kevin L Gustafson
- Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65201, USA
| | - Susheel Bhanu Busi
- UK Centre for Ecology and Hydrology, Wallingford, Oxfordshire, OX10 8BB, UK
| | - Zachary L McAdams
- Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65201, USA
| | - Rachael E McCorkle
- College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA
| | - Pavlo Khodakivskyi
- Department of Chemistry, College of Arts and Science, University of Missouri, Columbia, MO, 65211, USA
| | - Nathan J Bivens
- University of Missouri Genomics Technology Core, University of Missouri, Columbia, MO, 65211, USA
| | - Daniel J Davis
- Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65201, USA
| | - Murugesan Raju
- University of Missouri Bioinformatics and Analytics Core, University of Missouri, Columbia, MO, 65211, USA
| | - Lyndon M Coghill
- University of Missouri Bioinformatics and Analytics Core, University of Missouri, Columbia, MO, 65211, USA
| | - Elena A Goun
- Department of Chemistry, College of Arts and Science, University of Missouri, Columbia, MO, 65211, USA
| | - James Amos-Landgraf
- Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65201, USA
| | - Craig L Franklin
- Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65201, USA
| | - Paul Wilmes
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, L-4362 Esch-sur-Alzette, Luxembourg
| | - Rene Cortese
- Department of Child Health & Obstetrics, Gynecology, and Women's Health, School of Medicine, University of Missouri, Columbia, MO, 65212, USA
| | - Aaron C Ericsson
- Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65201, USA
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Katimbwa DA, Kim Y, Kim MJ, Jeong M, Lim J. Solubilized β-Glucan Supplementation in C57BL/6J Mice Dams Augments Neurodevelopment and Cognition in the Offspring Driven by Gut Microbiome Remodeling. Foods 2024; 13:3102. [PMID: 39410136 PMCID: PMC11476385 DOI: 10.3390/foods13193102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 09/23/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
A maternal diet rich in dietary fiber, such as β-glucan, plays a crucial role in the offspring's acquisition of gut microbiota and the subsequent shaping of its microbiome profile and metabolome. This in turn has been shown to aid in neurodevelopmental processes, including early microglial maturation and immunomodulation via metabolites like short chain fatty acids (SCFAs). This study aimed to investigate the effects of oat β-glucan supplementation, solubilized by citric acid hydrolysis, from gestation to adulthood. Female C57BL/6J mice were orally supplemented with soluble oat β-glucan (ObG) or carboxymethyl cellulose (CMC) via drinking water at 200 mg/kg body weight during breeding while the control group received 50 mg/kg body weight of carboxymethyl cellulose. ObG supplementation increased butyrate production in the guts of both dams and 4-week-old pups, attributing to alterations in the gut microbiota profile. One-week-old pups from the ObG group showed increased neurodevelopmental markers similar to four-week-old pups that also exhibited alterations in serum markers of metabolism and anti-inflammatory cytokines. Notably, at 8 weeks, ObG-supplemented pups exhibited the highest levels of spatial memory and cognition compared to the control and CMC groups. These findings suggest a potential enhancement of neonatal neurodevelopment via shaping of early-life gut microbiome profile, and the subsequent increased later-life cognitive function.
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Affiliation(s)
- Dorsilla A. Katimbwa
- Department of Food Biomaterials, Kyungpook National University, Daegu 41566, Republic of Korea;
| | - Yoonsu Kim
- Department of Integrative Biology, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Min Jeong Kim
- School of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Minsoo Jeong
- Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Jinkyu Lim
- Department of Food Biomaterials, Kyungpook National University, Daegu 41566, Republic of Korea;
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Lin K, Peng F, He K, Qian Z, Mei X, Su Z, Wujimaiti Y, Xia X, Zhang T. Research progress on intestinal microbiota regulating cognitive function through the gut-brain axis. Neurol Sci 2024; 45:3711-3721. [PMID: 38632176 DOI: 10.1007/s10072-024-07525-5] [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: 11/28/2023] [Accepted: 04/05/2024] [Indexed: 04/19/2024]
Abstract
The intestinal microbiota community is a fundamental component of the human body and plays a significant regulatory role in maintaining overall health and in the management disease states.The intestinal microbiota-gut-brain axis represents a vital connection in the cognitive regulation of the central nervous system by the intestinal microbiota.The impact of intestinal microbiota on cognitive function is hypothesized to manifest through both the nervous system and circulatory system. Imbalances in intestinal microbiota during the perioperative period could potentially contribute to perioperative neurocognitive dysfunction. This article concentrates on a review of existing literature to explore the potential influence of intestinal microbiota on brain and cognitive functions via the nervous and circulatory systems.Additionally, it summarizes recent findings on the impact of perioperative intestinal dysbacteriosis on perioperative neurocognitive dysfunction and suggests novel approaches for prevention and treatment of this condition.
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Affiliation(s)
- Kaijie Lin
- School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China
| | - Feng Peng
- School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China
- The First Affiliated Hospital Of Chengdu Medical College, Chengdu, Sichuan, China
| | - Kunyang He
- School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China
| | - Zhengyu Qian
- School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China
| | - Xuan Mei
- School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China
| | - Zhikun Su
- School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China
| | | | - Xun Xia
- School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China.
- The First Affiliated Hospital Of Chengdu Medical College, Chengdu, Sichuan, China.
| | - Tianyao Zhang
- School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China.
- The First Affiliated Hospital Of Chengdu Medical College, Chengdu, Sichuan, China.
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Singh J, Vanlallawmzuali, Singh A, Biswal S, Zomuansangi R, Lalbiaktluangi C, Singh BP, Singh PK, Vellingiri B, Iyer M, Ram H, Udey B, Yadav MK. Microbiota-brain axis: Exploring the role of gut microbiota in psychiatric disorders - A comprehensive review. Asian J Psychiatr 2024; 97:104068. [PMID: 38776563 DOI: 10.1016/j.ajp.2024.104068] [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: 11/22/2023] [Revised: 02/28/2024] [Accepted: 05/01/2024] [Indexed: 05/25/2024]
Abstract
Mental illness is a hidden epidemic in modern science that has gradually spread worldwide. According to estimates from the World Health Organization (WHO), approximately 10% of the world's population suffers from various mental diseases each year. Worldwide, financial and health burdens on society are increasing annually. Therefore, understanding the different factors that can influence mental illness is required to formulate novel and effective treatments and interventions to combat mental illness. Gut microbiota, consisting of diverse microbial communities residing in the gastrointestinal tract, exert profound effects on the central nervous system through the gut-brain axis. The gut-brain axis serves as a conduit for bidirectional communication between the two systems, enabling the gut microbiota to affect emotional and cognitive functions. Dysbiosis, or an imbalance in the gut microbiota, is associated with an increased susceptibility to mental health disorders and psychiatric illnesses. Gut microbiota is one of the most diverse and abundant groups of microbes that have been found to interact with the central nervous system and play important physiological functions in the human gut, thus greatly affecting the development of mental illnesses. The interaction between gut microbiota and mental health-related illnesses is a multifaceted and promising field of study. This review explores the mechanisms by which gut microbiota influences mental health, encompassing the modulation of neurotransmitter production, neuroinflammation, and integrity of the gut barrier. In addition, it emphasizes a thorough understanding of how the gut microbiome affects various psychiatric conditions.
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Affiliation(s)
- Jawahar Singh
- Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), Bathinda, Punjab, India
| | - Vanlallawmzuali
- Department of Biotechnology, Mizoram Central University, Pachhunga University College Campus, Aizawl, Mizoram, India
| | - Amit Singh
- Department of Microbiology Central University of Punjab, Bathinda 151401, India
| | - Suryanarayan Biswal
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda 151401, India
| | - Ruth Zomuansangi
- Department of Microbiology Central University of Punjab, Bathinda 151401, India
| | - C Lalbiaktluangi
- Department of Microbiology Central University of Punjab, Bathinda 151401, India
| | - Bhim Pratap Singh
- Department of Agriculture and Environmental Sciences (AES), National Institute of Food Technology Entrepreneurship and Management (NIFTEM), Sonepat, Haryana, India
| | - Prashant Kumar Singh
- Department of Biotechnology, Pachhunga University College Campus, Mizoram University (A Central University), Aizawl 796001, Mizoram, India
| | - Balachandar Vellingiri
- Stem cell and Regenerative Medicine/Translational Research, Department of Zoology, School of Basic Sciences, Central University of Punjab (CUPB), Bathinda, Punjab 151401, India
| | - Mahalaxmi Iyer
- Department of Microbiology Central University of Punjab, Bathinda 151401, India
| | - Heera Ram
- Department of Zoology, Jai Narain Vyas University, Jodhpur, Rajasthan 342001, India
| | - Bharat Udey
- Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), Bathinda, Punjab, India
| | - Mukesh Kumar Yadav
- Department of Microbiology Central University of Punjab, Bathinda 151401, India.
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Li Z, Tao X, Wang D, Pu J, Liu Y, Gui S, Zhong X, Yang D, Zhou H, Tao W, Chen W, Chen X, Chen Y, Chen X, Xie P. Alterations of the gut microbiota in patients with schizophrenia. Front Psychiatry 2024; 15:1366311. [PMID: 38596637 PMCID: PMC11002218 DOI: 10.3389/fpsyt.2024.1366311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 03/13/2024] [Indexed: 04/11/2024] Open
Abstract
Introduction Schizophrenia is a complex psychiatric disorder, of which molecular pathogenesis remains largely unknown. Accumulating evidence suggest that gut microbiota may affect brain function via the complex gut-brain axis, which may be a potential contributor to schizophrenia. However, the alteration of gut microbiota showed high heterogeneity across different studies. Therefore, this study aims to identify the consistently altered gut microbial taxa associated with schizophrenia. Methods We conducted a systematic search and synthesis of the up-to-date human gut microbiome studies on schizophrenia, and performed vote counting analyses to identify consistently changed microbiota. Further, we investigated the effects of potential confounders on the alteration of gut microbiota. Results We obtained 30 available clinical studies, and found that there was no strong evidence to support significant differences in α-diversity and β-diversity between schizophrenic patients and healthy controls. Among 428 differential gut microbial taxa collected from original studies, we found that 8 gut microbial taxa were consistently up-regulated in schizophrenic patients, including Proteobacteria, Gammaproteobacteria, Lactobacillaceae, Enterobacteriaceae, Lactobacillus, Succinivibrio, Prevotella and Acidaminococcus. While 5 taxa were consistently down-regulated in schizophrenia, including Fusicatenibacter, Faecalibacterium, Roseburia, Coprococcus and Anaerostipes. Discussion These findings suggested that gut microbial changes in patients with schizophrenia were characterized by the depletion of anti-inflammatory butyrate-producing genera, and the enrichment of certain opportunistic bacteria genera and probiotics. This study contributes to further understanding the role of gut microbiota in schizophrenia, and developing microbiota-based diagnosis and therapy for schizophrenia.
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Affiliation(s)
- Zhuocan Li
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiangkun Tao
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dongfang Wang
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Jinfeng Laboratory, Chongqing, China
- Chongqing Institute for Brain and Intelligence, Chongqing, China
| | - Juncai Pu
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Jinfeng Laboratory, Chongqing, China
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yiyun Liu
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Jinfeng Laboratory, Chongqing, China
- Chongqing Institute for Brain and Intelligence, Chongqing, China
| | - Siwen Gui
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Jinfeng Laboratory, Chongqing, China
- Chongqing Institute for Brain and Intelligence, Chongqing, China
| | - Xiaogang Zhong
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Jinfeng Laboratory, Chongqing, China
- College of Basic Medicine, Chongqing Medical University, Chongqing, China
| | - Dan Yang
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Haipeng Zhou
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Tao
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Weiyi Chen
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaopeng Chen
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yue Chen
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiang Chen
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Xie
- National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Jinfeng Laboratory, Chongqing, China
- Chongqing Institute for Brain and Intelligence, Chongqing, China
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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9
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Borrego-Ruiz A, Borrego JJ. An updated overview on the relationship between human gut microbiome dysbiosis and psychiatric and psychological disorders. Prog Neuropsychopharmacol Biol Psychiatry 2024; 128:110861. [PMID: 37690584 DOI: 10.1016/j.pnpbp.2023.110861] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 09/06/2023] [Accepted: 09/06/2023] [Indexed: 09/12/2023]
Abstract
There is a lot of evidence establishing that nervous system development is related to the composition and functions of the gut microbiome. In addition, the central nervous system (CNS) controls the imbalance of the intestinal microbiota, constituting a bidirectional communication system. At present, various gut-brain crosstalk routes have been described, including immune, endocrine and neural circuits via the vagal pathway. Several empirical data have associated gut microbiota alterations (dysbiosis) with neuropsychiatric diseases, such as Alzheimer's disease, autism and Parkinson's disease, and with other psychological disorders, like anxiety and depression. Fecal microbiota transplantation (FMT) therapy has shown that the gut microbiota can transfer behavioral features to recipient animals, which provides strong evidence to establish a causal-effect relationship. Interventions, based on prebiotics, probiotics or synbiotics, have demonstrated an important influence of microbiota on neurological disorders by the synthesis of neuroactive compounds that interact with the nervous system and by the regulation of inflammatory and endocrine processes. Further research is needed to demonstrate the influence of gut microbiota dysbiosis on psychiatric and psychological disorders, and how microbiota-based interventions may be used as potential therapeutic tools.
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Affiliation(s)
- Alejandro Borrego-Ruiz
- Departamento de Psicología Social y de las Organizaciones, Facultad de Psicología, UNED, Madrid, Spain
| | - Juan J Borrego
- Departamento de Microbiología, Universidad de Málaga, Málaga, Spain.
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10
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Zhang Z, Sun J, Li Y, Yang K, Wei G, Zhang S. Ameliorative effects of pine nut peptide-zinc chelate (Korean pine) on a mouse model of Alzheimer's disease. Exp Gerontol 2023; 183:112308. [PMID: 37821052 DOI: 10.1016/j.exger.2023.112308] [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: 06/11/2023] [Revised: 09/17/2023] [Accepted: 10/07/2023] [Indexed: 10/13/2023]
Abstract
In this study, 50 SD adult male mice were used to create an Alzheimer's disease model. The mice's learning and memory abilities were evaluated using an eight-arm radial maze experiment, and changes in body weight and food intake were noted. This helped to better validate the improvement of Alzheimer's disease caused by pine nut peptide-zinc chelate (Korean pine). For a more thorough investigation, mice's brains were dissected, Endogenous mercaptan antioxidants (enzymes), which are markers of brain tissue, were assessed, and mouse gut flora was analyzed. The findings demonstrated that pine nut peptide-zinc chelate (Korean pine) can improve learning and memory, stop brain aging and damage, and control gut flora in mice. It may exert its effects by ameliorating decreased AChE levels and increased ChAT levels in the central cholinergic system, endogenous thiol antioxidants (enzymes) in the cerebral cortex, and by controlling the bacterial flora in the gut.
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Affiliation(s)
- Zhi Zhang
- College of Life Sciences, Northeast Forestry University
| | - Jiajia Sun
- College of Forestry, Northeast Forestry University.
| | - Yanxia Li
- Forestry Research Institute of Heilongjiang Province.
| | - Kexin Yang
- College of Forestry, Northeast Forestry University
| | - Gang Wei
- College of Forestry, Northeast Forestry University
| | - Shenglong Zhang
- Heilongjiang Guohong Energy Saving and Environmental Protection Co
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11
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Tao Q, Zhang ZD, Lu XR, Qin Z, Liu XW, Li SH, Bai LX, Ge BW, Li JY, Yang YJ. Multi-omics reveals aspirin eugenol ester alleviates neurological disease. Biomed Pharmacother 2023; 166:115311. [PMID: 37572635 DOI: 10.1016/j.biopha.2023.115311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 08/06/2023] [Accepted: 08/07/2023] [Indexed: 08/14/2023] Open
Abstract
BACKGROUND Exosomes play an essential role in maintaining normal brain function due to their ability to cross the blood-brain barrier. Aspirin eugenol ester (AEE) is a new medicinal compound synthesized by the esterification of aspirin with eugenol using the prodrug principle. Aspirin has been reported to have neuroprotective effects and may be effective against neurodegenerative diseases. PURPOSE This study wanted to investigate how AEE affected neurological diseases in vivo and in vitro. EXPERIMENTAL APPROACH A multi-omics approach was used to explore the effects of AEE on the nervous system. Gene and protein expression changes of BDNF and NEFM in SY5Y cells after AEE treatment were detected using RT-qPCR and Western Blot. KEY RESULTS The multi-omics results showed that AEE could regulate neuronal synapses, neuronal axons, neuronal migration, and neuropeptide signaling by affecting transport, inflammatory response, and regulating apoptosis. Exosomes secreted by AEE-treated Caco-2 cells could promote the growth of neurofilaments in SY5Y cells and increased the expression of BDNF and NEFM proteins in SY5Y cells. miRNAs in the exosomes of AEE-treated Caco-2 cells may play an important role in the activation of SY5Y neuronal cells. CONCLUSIONS In conclusion, AEE could play positive effects on neurological-related diseases.
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Affiliation(s)
- Qi Tao
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Zhen-Dong Zhang
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Xiao-Rong Lu
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Zhe Qin
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Xi-Wang Liu
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Shi-Hong Li
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Li-Xia Bai
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Bo-Wen Ge
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Jian-Yong Li
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China.
| | - Ya-Jun Yang
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China.
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12
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Murphy CL, Zulquernain SA, Shanahan F. Faecal microbiota transplantation (FMT): classical bedside-to-bench clinical research. QJM 2023; 116:641-643. [PMID: 31297516 DOI: 10.1093/qjmed/hcz181] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 07/01/2019] [Accepted: 07/02/2019] [Indexed: 12/14/2022] Open
Affiliation(s)
- C L Murphy
- From the APC Microbiome Ireland and Department of Medicine, University College Cork, National University of Ireland
- Department of Gastroenterology, Cork University Hospital, Cork, Ireland
| | - S A Zulquernain
- From the APC Microbiome Ireland and Department of Medicine, University College Cork, National University of Ireland
- Department of Gastroenterology, Cork University Hospital, Cork, Ireland
| | - F Shanahan
- From the APC Microbiome Ireland and Department of Medicine, University College Cork, National University of Ireland
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13
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Gu X, Chen ZH, Zhang SC. Fecal microbiota transplantation in childhood: past, present, and future. World J Pediatr 2023; 19:813-822. [PMID: 36484871 PMCID: PMC9734408 DOI: 10.1007/s12519-022-00655-w] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 11/13/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) has been well described in the treatment of pediatric diseases; however, the latest updates regarding its use in children are unclear and the concepts involved need to be revisited. DATA SOURCES We performed advanced searches in the MEDLINE, EMBASE, and Cochrane databases using the keywords "Fecal microbiota transplantation OR Fecal microbiota transfer" in the [Title/Abstract] to identify relevant articles published in English within the last five years. To identify additional studies, reference lists of review articles and included studies were manually searched. Retrieved manuscripts (case reports, reviews, and abstracts) were assessed by the authors. RESULTS Among the articles, studies were based on the mechanism (n = 28), sample preparation (n = 9), delivery approaches (n = 23), safety (n = 26), and indications (n = 67), including Clostridium difficile infection (CDI) and recurrent C. difficile infection (rCDI; n = 21), non-alcoholic fatty liver disease (NAFLD; n = 10), irritable bowel syndrome (IBS; n = 5), inflammatory bowel disease (IBD; n = 15), diabetes (n = 5), functional constipation (FC; n = 4), and autism spectrum disorder (ASD; n = 7). CONCLUSIONS Concepts of FMT in pediatric diseases have been updated with respect to underlying mechanisms, methodology, indications, and safety. Evidence-based clinical trials for the use of FMT in pediatric diseases should be introduced to resolve the challenges of dosage, duration, initiation, and the end point of treatment.
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Affiliation(s)
- Xu Gu
- Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street Heping District, Shenyang, 110004, China
| | - Zhao-Hong Chen
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shu-Cheng Zhang
- Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street Heping District, Shenyang, 110004, China.
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14
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Sha H, He X, Yan K, Li J, Li X, Xie Y, Yang Y, Deng Y, Li G, Yang J. Blocking coprophagy increases the levels of inflammation and depression in healthy mice as well as mice receiving fecal microbiota transplantation from disease model mice donors. APMIS 2023. [PMID: 37145345 DOI: 10.1111/apm.13326] [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: 04/17/2022] [Accepted: 04/18/2023] [Indexed: 05/06/2023]
Abstract
Rodents have been extensively used as animal models in microbiome studies. However, all rodents have a habitual nature called coprophagy, a phenomenon that they self-reinoculate feces into their gastrointestinal tract. Recent studies have shown that blocking coprophagy can alter rodents' diversity of gut microbiota, metabolism, neurochemistry, and cognitive behavior. However, whether rodents' coprophagy behavior affects the levels of inflammation and depression is unclear. In order to address this problem, we first blocked coprophagy in healthy mice. It displayed an increase in the levels of depression, verified by depressive-like behaviors and mood-related indicators, and inflammation, verified by the increased levels of the pro-inflammatory cytokine, in coprophagy-blocked mice. Furthermore, we transplanted fecal microbiota from chronic restraint stress (CRS) depression model mice and lipopolysaccharide (LPS) inflammation model mice to healthy recipient mice, respectively. It showed that the disease-like phenotypes in the coprophagy-blocked group were worse than those in the coprophagy-unblocked group, including severer depressive symptoms and higher levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and IFN-γ) in serum, prefrontal cortex (PFC), and hippocampus (HIP). These findings showed that blocking coprophagy in mice not only increased the levels of inflammation and depression in healthy mice but also aggravated inflammation and depression induced by fecal microbiota from disease donors. The discovery may provide a vital reference for future research involving FMT in rodents.
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Affiliation(s)
- Haoran Sha
- Grade 2020, School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xiaoyi He
- Department of Anatomy, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Kai Yan
- Department of Anatomy, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Jiakang Li
- Grade 2017, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xu Li
- Grade 2018, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Yinyin Xie
- Grade 2018, School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Yousheng Yang
- Grade 2018, School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Yajuan Deng
- Grade 2018, School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Guoying Li
- Guangdong Medical Association, Guangzhou, Guangdong, China
| | - Junhua Yang
- Department of Anatomy, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Bioactive Drug Research, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
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15
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Lactobacillus rhamnosus GG treatment potentiates ethanol-induced behavioral changes through modulation of intestinal epithelium in Danio rerio. INTERNATIONAL MICROBIOLOGY : THE OFFICIAL JOURNAL OF THE SPANISH SOCIETY FOR MICROBIOLOGY 2023:10.1007/s10123-022-00320-2. [PMID: 36656417 DOI: 10.1007/s10123-022-00320-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 12/28/2022] [Accepted: 12/30/2022] [Indexed: 01/20/2023]
Abstract
The gut-brain axis directly regulates the brain homeostatic environment; an imbalance in gut microbial composition following ethanol exposure is maleficent. In this context, involvement of probiotics as prophylactic intervention against ethanol-induced neurotoxicity is elusive in the literature. Therefore, the present study was aimed to determine the impact of chronic ethanol exposure on the neurobehavioral response of zebrafish and possible neuroprotection through co-supplementation of probiotic Lactobacillus rhamnosus GG (LGG). Zebrafish were divided into naive, control, ethanol (0.01% v/v), LGG, and ethanol co-supplemented with LGG groups. Neurobehavioral assessment was performed after 7 days of chronic waterborne exposure to ethanol with LGG co-supplementation followed by histopathological studies. The findings indicated that there was a clear alteration in locomotor activity and habitat preference, with animals preferentially migrating toward altered zones on exposure to ethanol. However, co-supplementation of LGG showed restoration against ethanol-induced neurobehavioral and cognitive dysfunction. Brain tissue pyknosis and intestinal epithelial disruption were significantly mitigated on LGG co-supplementation against ethanol in zebrafish. The present study provides a novel approach toward supplementation of probiotics such as LGG in modulation of gut commensal microbiota influencing zebrafish behavior. Moreover, the findings delineate the possible role of probiotics as a curative administration to counter ethanol-persuaded neurological outcomes.
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16
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Vasiliu O. Is fecal microbiota transplantation a useful therapeutic intervention for psychiatric disorders? A narrative review of clinical and preclinical evidence. Curr Med Res Opin 2023; 39:161-177. [PMID: 36094098 DOI: 10.1080/03007995.2022.2124071] [Citation(s) in RCA: 10] [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] [Indexed: 01/03/2023]
Abstract
The therapeutic management of psychiatric disorders is currently confronted with a critical need to find new therapeutic interventions due to the high rates of non-responsivity or low responsivity in the key pathologies, e.g. schizophrenia spectrum disorders, alcohol use disorders, or major depressive disorder. The modulation of intestinal microbiota has been explored in various organic and psychiatric dysfunctions, with different degrees of success. However, this type of intervention may represent a helpful add-on at a conceptual level since it does not associate negative pharmacokinetics interactions, significant adverse events, or risk for non-adherence in the long term. Oral administration of pre-, pro-, or synbiotics, and especially the treatment with fecal microbiota transplantation (FMT), are methods still in their early research phase for patients with psychiatric disorders, therefore an exploration of data regarding the potential benefits and adverse events of FMT was considered necessary. In order to accomplish this purpose, the available results of research dedicated to each category of psychiatric disorders, starting with depressive and anxiety disorders, continuing with schizophrenia, substance use disorders, and finishing with disorders diagnosed during childhood, were presented in this paper. Seven clinical trials, 16 preclinical studies, three meta-analyses/systematic reviews, and six case reports, all of these representing ten distinct categories of psychiatric disorders or manifestations, have been reviewed. Mood disorders, anxiety disorders, and alcohol dependence have been the most extensively investigated clinical entities from the FMT efficacy and tolerability perspective, and reviewed data are generally promising. Based on the current status of research, FMT may be considered a helpful intervention in specific psychiatric pathologies. Still, this review showed that most of the information is derived from entirely preclinical studies. Therefore, clinical trials with sound methodology and more participants are needed to clarify FMT's benefits and risks in psychiatric disorders.
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Affiliation(s)
- Octavian Vasiliu
- Spitalul Universitar de Urgenţă Militar Central Dr Carol Davila Ringgold standard institution, Bucuresti, Romania
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17
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The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders. Cells 2022; 12:cells12010054. [PMID: 36611848 PMCID: PMC9818777 DOI: 10.3390/cells12010054] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/09/2022] [Accepted: 12/14/2022] [Indexed: 12/25/2022] Open
Abstract
Mounting evidence shows that the complex gut microbial ecosystem in the human gastrointestinal (GI) tract regulates the physiology of the central nervous system (CNS) via microbiota and the gut-brain (MGB) axis. The GI microbial ecosystem communicates with the brain through the neuroendocrine, immune, and autonomic nervous systems. Recent studies have bolstered the involvement of dysfunctional MGB axis signaling in the pathophysiology of several neurodegenerative, neurodevelopmental, and neuropsychiatric disorders (NPDs). Several investigations on the dynamic microbial system and genetic-environmental interactions with the gut microbiota (GM) have shown that changes in the composition, diversity and/or functions of gut microbes (termed "gut dysbiosis" (GD)) affect neuropsychiatric health by inducing alterations in the signaling pathways of the MGB axis. Interestingly, both preclinical and clinical evidence shows a positive correlation between GD and the pathogenesis and progression of NPDs. Long-term GD leads to overstimulation of hypothalamic-pituitary-adrenal (HPA) axis and the neuroimmune system, along with altered neurotransmitter levels, resulting in dysfunctional signal transduction, inflammation, increased oxidative stress (OS), mitochondrial dysfunction, and neuronal death. Further studies on the MGB axis have highlighted the significance of GM in the development of brain regions specific to stress-related behaviors, including depression and anxiety, and the immune system in the early life. GD-mediated deregulation of the MGB axis imbalances host homeostasis significantly by disrupting the integrity of the intestinal and blood-brain barrier (BBB), mucus secretion, and gut immune and brain immune functions. This review collates evidence on the potential interaction between GD and NPDs from preclinical and clinical data. Additionally, we summarize the use of non-therapeutic modulators such as pro-, pre-, syn- and post-biotics, and specific diets or fecal microbiota transplantation (FMT), which are promising targets for the management of NPDs.
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18
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The Role of the Gut Microbiome in Psychiatric Disorders. Microorganisms 2022; 10:microorganisms10122436. [PMID: 36557689 PMCID: PMC9786082 DOI: 10.3390/microorganisms10122436] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 11/20/2022] [Accepted: 11/24/2022] [Indexed: 12/13/2022] Open
Abstract
The role of the gut microbiome in mental health has been of great interest in the past years, with several breakthroughs happening in the last decade. Its implications in several psychiatric disorders, namely anxiety, depression, autism and schizophrenia, are highlighted. In this review were included relevant studies on rodents, as well as human studies. There seems to be a connection between the gut microbiome and these pathologies, the link being emphasized both in rodents and humans. The results obtained in murine models align with the results acquired from patients; however, fewer studies regarding anxiety were conducted on humans. The process of sequencing and analyzing the microbiome has been conducted in humans for several other pathologies mentioned above. Additionally, the possible beneficial role of probiotics and postbiotics administered as an aid to the psychiatric medication was analyzed.
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19
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Transfer efficiency and impact on disease phenotype of differing methods of gut microbiota transfer. Sci Rep 2022; 12:19621. [PMID: 36380056 PMCID: PMC9666633 DOI: 10.1038/s41598-022-24014-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 11/08/2022] [Indexed: 11/16/2022] Open
Abstract
To test causal relationships between complex gut microbiota (GM) and host outcomes, researchers frequently transfer GM between donor and recipient mice via embryo transfer (ET) rederivation, cross-fostering (CF), and co-housing. In this study, we assess the influence of the transfer method and the differences in baseline donor and recipient microbiota richness, on transfer efficiency. Additionally, recipient mice were subjected to DSS-induced chronic colitis to determine whether disease severity was affected by GM transfer efficiency or features within the GM. We found that the recipient's genetic background, the baseline richness of donor and recipient GM, and the transfer method all influenced the GM transfer efficiency. Recipient genetic background and GM both had significant effects on DSS colitis severity and, unexpectedly, the transfer method was strongly associated with differential disease severity regardless of the other factors.
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20
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Chichlowski M, Cotter J, Fawkes N, Pandey N. Feed your microbiome and improve sleep, stress resilience, and cognition. EXPLORATION OF MEDICINE 2022. [DOI: 10.37349/emed.2022.00097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
The brain and gut are connected both physically and biochemically. The gut-brain axis includes the central nervous system, neuroendocrine and neuroimmune systems, the enteric nervous system and vagus nerve, and the gut microbiome. It can influence brain function and even behavior, suggesting that dietary interventions may help enhance and protect mental health and cognitive performance. This review focuses on the role of the microbiome and its metabolites in sleep regulation, neurodegenerative disorders, mechanisms of stress, and mood. It also provides examples of nutritional interventions which can restore healthy gut microbiota and aid with risk reduction and management of many disorders related to mental and cognitive health. Evidence suggests a shift in the gut microbiota towards a balanced composition could be a target to maintain brain health, reduce stress and improve quality of life.
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Affiliation(s)
- Maciej Chichlowski
- Medical and Scientific Affairs, Reckitt/Mead Johnson Nutrition Institute, Evansville, IN 47712, USA
| | - Jack Cotter
- Medical and Scientific Affairs, Reckitt/Mead Johnson Nutrition Institute, SL1 3UH Slough, UK
| | - Neil Fawkes
- Medical and Scientific Affairs, Reckitt/Mead Johnson Nutrition Institute, SL1 3UH Slough, UK
| | - Neeraj Pandey
- Medical and Scientific Affairs, Reckitt/Mead Johnson Nutrition Institute, SL1 3UH Slough, UK
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21
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Shobeiri P, Kalantari A, Teixeira AL, Rezaei N. Shedding light on biological sex differences and microbiota-gut-brain axis: a comprehensive review of its roles in neuropsychiatric disorders. Biol Sex Differ 2022; 13:12. [PMID: 35337376 PMCID: PMC8949832 DOI: 10.1186/s13293-022-00422-6] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 03/14/2022] [Indexed: 12/15/2022] Open
Abstract
Women and men are suggested to have differences in vulnerability to neuropsychiatric disorders, including major depressive disorder (MDD), generalized anxiety disorder (GAD), schizophrenia, eating disorders, including anorexia nervosa, and bulimia nervosa, neurodevelopmental disorders, such as autism spectrum disorder (ASD), and neurodegenerative disorders including Alzheimer's disease, Parkinson's disease. Genetic factors and sex hormones are apparently the main mediators of these differences. Recent evidence uncovers that reciprocal interactions between sex-related features (e.g., sex hormones and sex differences in the brain) and gut microbiota could play a role in the development of neuropsychiatric disorders via influencing the gut-brain axis. It is increasingly evident that sex-microbiota-brain interactions take part in the occurrence of neurologic and psychiatric disorders. Accordingly, integrating the existing evidence might help to enlighten the fundamental roles of these interactions in the pathogenesis of neuropsychiatric disorders. In addition, an increased understanding of the biological sex differences on the microbiota-brain may lead to advances in the treatment of neuropsychiatric disorders and increase the potential for precision medicine. This review discusses the effects of sex differences on the brain and gut microbiota and the putative underlying mechanisms of action. Additionally, we discuss the consequences of interactions between sex differences and gut microbiota on the emergence of particular neuropsychiatric disorders.
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Affiliation(s)
- Parnian Shobeiri
- School of Medicine, Tehran University of Medical Sciences (TUMS), Children's Medical Center Hospital, Dr. Qarib St., Keshavarz Blvd, 14194, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Dr. Gharib St, Keshavarz Blvd, Tehran, Iran
| | - Amirali Kalantari
- School of Medicine, Tehran University of Medical Sciences (TUMS), Children's Medical Center Hospital, Dr. Qarib St., Keshavarz Blvd, 14194, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Antônio L Teixeira
- Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Nima Rezaei
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Dr. Gharib St, Keshavarz Blvd, Tehran, Iran.
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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22
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Gut Microbiota Dysbiosis: Triggers, Consequences, Diagnostic and Therapeutic Options. Microorganisms 2022; 10:microorganisms10030578. [PMID: 35336153 PMCID: PMC8954387 DOI: 10.3390/microorganisms10030578] [Citation(s) in RCA: 141] [Impact Index Per Article: 47.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 02/07/2022] [Accepted: 02/28/2022] [Indexed: 12/12/2022] Open
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23
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Kundu P, Stagaman K, Kasschau K, Holden S, Shulzhenko N, Sharpton TJ, Raber J. Fecal Implants From App NL-G-F and App NL-G-F/E4 Donor Mice Sufficient to Induce Behavioral Phenotypes in Germ-Free Mice. Front Behav Neurosci 2022; 16:791128. [PMID: 35210996 PMCID: PMC8860839 DOI: 10.3389/fnbeh.2022.791128] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 01/11/2022] [Indexed: 12/12/2022] Open
Abstract
The gut microbiome and the gut brain axis are potential determinants of Alzheimer's disease (AD) etiology or severity and gut microbiota might coordinate with the gut-brain axis to regulate behavioral phenotypes in AD mouse models. Using 6-month-old human amyloid precursor protein (hAPP) knock-in (KI) mice, which contain the Swedish and Iberian mutations [APP NL-F (App NL-F)] or the Arctic mutation as third mutation [APP NL-G-F (App NL-G-F)], behavioral and cognitive performance is associated with the gut microbiome and APP genotype modulates this association. In this study, we determined the feasibility of behavioral testing of mice in a biosafety cabinet and whether stool from 6-month-old App NL-G-F mice or App NL-G-F crossed with human apoE4 targeted replacement mice is sufficient to induce behavioral phenotypes in 4-5 month-old germ-free C57BL/6J mice 4 weeks following inoculation. We also compared the behavioral phenotypes of the recipient mice with that of the donor mice. Finally, we assessed cortical Aβ levels and analyzed the gut microbiome in the recipient mice. These results show that it is feasible to behaviorally test germ-free mice inside a biosafety cabinet. However, the host genotype was critical in modulating the pattern of induced behavioral phenotypes as compared to those seen in the genotype- and sex-match donor mice. Male mice that received stool from App NL-G-F and App NL-G-F/E4 donor genotypes tended to have lower body weight as compared to wild type, an effect not observed among donor mice. Additionally, App NL-G-F/E4 recipient males, but not females, showed impaired object recognition. Insoluble Aβ40 levels were detected in App NL-G-F and App NL-G-F/E4 recipient mice. Recipients of App NL-G-F, but not App NL-G-F/E4, donor mice carried cortical insoluble Aβ40 levels that positively correlated with activity levels on the first and second day of open field testing. For recipient mice, the interaction between donor genotype and several behavioral scores predicted gut microbiome alpha-diversity. Similarly, two behavioral performance scores predicted microbiome composition in recipient mice, but this association was dependent on the donor genotype. These data suggest that genotypes of the donor and recipient might need to be considered for developing novel therapeutic strategies targeting the gut microbiome in AD and other neurodegenerative disorders.
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Affiliation(s)
- Payel Kundu
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States
| | - Keaton Stagaman
- Department of Microbiology, Oregon State University, Corvallis, OR, United States
| | - Kristin Kasschau
- Department of Microbiology, Oregon State University, Corvallis, OR, United States
| | - Sarah Holden
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States
| | - Natalia Shulzhenko
- Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, United States
| | - Thomas J. Sharpton
- Department of Microbiology, Oregon State University, Corvallis, OR, United States
- Department of Statistics, Oregon State University, Corvallis, OR, United States
| | - Jacob Raber
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States
- Division of Neuroscience ONPRC, Department of Neurology, Psychiatry, and Radiation Medicine, Oregon Health & Science University, Portland, OR, United States
- College of Pharmacy, Oregon State University, Corvallis, OR, United States
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Healy DB, Ryan CA, Ross RP, Stanton C, Dempsey EM. Clinical implications of preterm infant gut microbiome development. Nat Microbiol 2022; 7:22-33. [PMID: 34949830 DOI: 10.1038/s41564-021-01025-4] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 11/12/2021] [Indexed: 12/12/2022]
Abstract
Perturbations to the infant gut microbiome during the first weeks to months of life affect growth, development and health. In particular, assembly of an altered intestinal microbiota during infant development results in an increased risk of immune and metabolic diseases that can persist into childhood and potentially into adulthood. Most research into gut microbiome development has focused on full-term babies, but health-related outcomes are also important for preterm babies. The systemic physiological immaturity of very preterm gestation babies (born earlier than 32 weeks gestation) results in numerous other microbiome-organ interactions, the mechanisms of which have yet to be fully elucidated or in some cases even considered. In this Perspective, we compare assembly of the intestinal microbiome in preterm and term infants. We focus in particular on the clinical implications of preterm infant gut microbiome composition and discuss the prospects for microbiome diagnostics and interventions to improve the health of preterm babies.
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Affiliation(s)
- David B Healy
- APC Microbiome Ireland, University College Cork, Cork, Ireland. .,Department of Paediatrics and Child Health, University College Cork, Cork, Ireland.
| | - C Anthony Ryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - R Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Ireland
| | - Eugene M Dempsey
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Paediatrics and Child Health, University College Cork, Cork, Ireland.,INFANT Research Centre, Cork University Hospital, Cork, Ireland
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Predictive Value of Gut Microbiome for Cognitive Impairment in Patients with Hypertension. DISEASE MARKERS 2021; 2021:1683981. [PMID: 34659587 PMCID: PMC8514967 DOI: 10.1155/2021/1683981] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/06/2021] [Accepted: 09/09/2021] [Indexed: 12/20/2022]
Abstract
A connection exists between hypertension (HTN) and cognitive impairment (CI) or gut microbiota (GM) and neuropsychiatric disease. However, the link between GM and HTNCI has not been illustrated. This study endeavoured to profile the landscape of GM in HTNCI patients and evaluate the value of GM as HTNCI biomarkers. We recruited 128 patients with hypertension and assigned them to two groups of different MoCA scores. Clinical and biological data were recorded. GM composition was illustrated with 16S ribosomal RNA sequencing, and the dominant species were identified by linear discriminant analysis Effect Size (LEfSe). It showed higher abundance of TM7 and lower abundances of Veillonella and Peptoniphilus in the HTNCI group than in the HTN without cognitive impairment (HTNnCI) group. We next clarified the link between GM and MoCA scores or HTNCI factors. KEGG analysis revealed the involvement of decreased bile secretion. An evident correlation showed up between HTNCI and Veillonella abundance (P = 0.0340). We concluded that some representative GM species, especially Veillonella, could predict cognitive impairment in hypertension patients, making them potential benchmarks of HTNCI.
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Dawidowski B, Górniak A, Podwalski P, Lebiecka Z, Misiak B, Samochowiec J. The Role of Cytokines in the Pathogenesis of Schizophrenia. J Clin Med 2021; 10:jcm10173849. [PMID: 34501305 PMCID: PMC8432006 DOI: 10.3390/jcm10173849] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 08/21/2021] [Accepted: 08/24/2021] [Indexed: 02/07/2023] Open
Abstract
Schizophrenia is a chronic mental illness of unknown etiology. A growing and compelling body of evidence implicates immunologic dysfunction as the key element in its pathomechanism. Cytokines, whose altered levels have been increasingly reported in various patient populations, are the major mediators involved in the coordination of the immune system. The available literature reports both elevated levels of proinflammatory as well as reduced levels of anti-inflammatory cytokines, and their effects on clinical status and neuroimaging changes. There is evidence of at least a partial genetic basis for the association between cytokine alterations and schizophrenia. Two other factors implicated in its development include early childhood trauma and disturbances in the gut microbiome. Moreover, its various subtypes, characterized by individual symptom severity and course, such as deficit schizophrenia, seem to differ in terms of changes in peripheral cytokine levels. While the use of a systematic review methodology could be difficult due to the breadth and diversity of the issues covered in this review, the applied narrative approach allows for a more holistic presentation. The aim of this narrative review was to present up-to-date evidence on cytokine dysregulation in schizophrenia, its effect on the psychopathological presentation, and links with antipsychotic medication. We also attempted to summarize its postulated underpinnings, including early childhood trauma and gut microbiome disturbances, and propose trait and state markers of schizophrenia.
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Affiliation(s)
- Bartosz Dawidowski
- Department of Psychiatry, Pomeranian Medical University, 71-460 Szczecin, Poland; (B.D.); (A.G.); (J.S.)
| | - Adrianna Górniak
- Department of Psychiatry, Pomeranian Medical University, 71-460 Szczecin, Poland; (B.D.); (A.G.); (J.S.)
| | - Piotr Podwalski
- Department of Psychiatry, Pomeranian Medical University, 71-460 Szczecin, Poland; (B.D.); (A.G.); (J.S.)
- Correspondence: ; Tel.: +48-510-091-466
| | - Zofia Lebiecka
- Department of Health Psychology, Pomeranian Medical University, 71-210 Szczecin, Poland;
| | - Błażej Misiak
- Department of Psychiatry, Division of Consultation Psychiatry and Neuroscience, Medical University, 50-367 Wroclaw, Poland;
| | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical University, 71-460 Szczecin, Poland; (B.D.); (A.G.); (J.S.)
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Eastwood J, Walton G, Van Hemert S, Williams C, Lamport D. The effect of probiotics on cognitive function across the human lifespan: A systematic review. Neurosci Biobehav Rev 2021; 128:311-327. [PMID: 34171323 DOI: 10.1016/j.neubiorev.2021.06.032] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 06/18/2021] [Accepted: 06/20/2021] [Indexed: 12/14/2022]
Abstract
Recently the scientific community has seen a growing interest in the role of the gut-brain axis and, in particular, how probiotic supplementation may influence neural function and behaviour via manipulation of the gut microbiota. The purpose of this review was to systematically review the current literature exploring the effect of probiotic intervention on cognitive function. PsychINFO, Web of Science, PubMed and Google Scholar were searched for human trials. Studies selected for inclusion administered a probiotic intervention and included at least one behavioural measure of cognitive performance. A total of 30 experimental papers were included, exploring the effect of probiotics across a variety of ages, populations and cognitive domains. The evidence suggests there may be potential for probiotics to enhance cognitive function or attenuate cognitive decline, particularly in clinically relevant adult populations for whom cognitive dysfunction may be present. However, the limited number of studies and the quality of the existing research makes it challenging to interpret the data. Further research is clearly warranted. PROSPERO: CRD42020164820.
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Affiliation(s)
- Jessica Eastwood
- School of Psychology and Clinical Language Sciences, University of Reading, Earley Gate, Reading, RG6 6BZ, UK
| | - Gemma Walton
- Food Microbial Sciences Unit, Department of Food and Nutritional Sciences, University of Reading, Reading, RG6 6AP, UK
| | - Saskia Van Hemert
- Winclove Probiotics, Hulstweg 11, 1032LB, Amsterdam, the Netherlands
| | - Claire Williams
- School of Psychology and Clinical Language Sciences, University of Reading, Earley Gate, Reading, RG6 6BZ, UK
| | - Daniel Lamport
- School of Psychology and Clinical Language Sciences, University of Reading, Earley Gate, Reading, RG6 6BZ, UK.
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Supplier-origin mouse microbiomes significantly influence locomotor and anxiety-related behavior, body morphology, and metabolism. Commun Biol 2021; 4:716. [PMID: 34112927 PMCID: PMC8192786 DOI: 10.1038/s42003-021-02249-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 05/20/2021] [Indexed: 12/26/2022] Open
Abstract
The mouse is the most commonly used model species in biomedical research. Just as human physical and mental health are influenced by the commensal gut bacteria, mouse models of disease are influenced by the fecal microbiome (FM). The source of mice represents one of the strongest influences on the FM and can influence the phenotype of disease models. The FM influences behavior in mice leading to the hypothesis that mice of the same genetic background from different vendors, will have different behavioral phenotypes. To test this hypothesis, colonies of CD-1 mice, rederived via embryo transfer into surrogate dams from four different suppliers, were subjected to phenotyping assays assessing behavior and physiological parameters. Significant differences in behavior, growth rate, metabolism, and hematological parameters were observed. Collectively, these findings show the profound influence of supplier-origin FMs on host behavior and physiology in healthy, genetically similar, wild-type mice maintained in identical environments.
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Bhargava A, Arnold AP, Bangasser DA, Denton KM, Gupta A, Hilliard Krause LM, Mayer EA, McCarthy M, Miller WL, Raznahan A, Verma R. Considering Sex as a Biological Variable in Basic and Clinical Studies: An Endocrine Society Scientific Statement. Endocr Rev 2021; 42:219-258. [PMID: 33704446 PMCID: PMC8348944 DOI: 10.1210/endrev/bnaa034] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Indexed: 02/08/2023]
Abstract
In May 2014, the National Institutes of Health (NIH) stated its intent to "require applicants to consider sex as a biological variable (SABV) in the design and analysis of NIH-funded research involving animals and cells." Since then, proposed research plans that include animals routinely state that both sexes/genders will be used; however, in many instances, researchers and reviewers are at a loss about the issue of sex differences. Moreover, the terms sex and gender are used interchangeably by many researchers, further complicating the issue. In addition, the sex or gender of the researcher might influence study outcomes, especially those concerning behavioral studies, in both animals and humans. The act of observation may change the outcome (the "observer effect") and any experimental manipulation, no matter how well-controlled, is subject to it. This is nowhere more applicable than in physiology and behavior. The sex of established cultured cell lines is another issue, in addition to aneuploidy; chromosomal numbers can change as cells are passaged. Additionally, culture medium contains steroids, growth hormone, and insulin that might influence expression of various genes. These issues often are not taken into account, determined, or even considered. Issues pertaining to the "sex" of cultured cells are beyond the scope of this Statement. However, we will discuss the factors that influence sex and gender in both basic research (that using animal models) and clinical research (that involving human subjects), as well as in some areas of science where sex differences are routinely studied. Sex differences in baseline physiology and associated mechanisms form the foundation for understanding sex differences in diseases pathology, treatments, and outcomes. The purpose of this Statement is to highlight lessons learned, caveats, and what to consider when evaluating data pertaining to sex differences, using 3 areas of research as examples; it is not intended to serve as a guideline for research design.
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Affiliation(s)
- Aditi Bhargava
- Center for Reproductive Sciences, San Francisco, CA, USA
- Department of Obstetrics and Gynecology, University of California, San Francisco, CA, USA
| | - Arthur P Arnold
- Department of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Debra A Bangasser
- Department of Psychology and Neuroscience Program, Temple University, Philadelphia, PA, USA
| | - Kate M Denton
- Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia
| | - Arpana Gupta
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, CA, USA
| | - Lucinda M Hilliard Krause
- Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia
| | - Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, CA, USA
| | - Margaret McCarthy
- Department of Pharmacology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Walter L Miller
- Center for Reproductive Sciences, San Francisco, CA, USA
- Department of Pediatrics, University of California, San Francisco, CA, USA
| | - Armin Raznahan
- Section on Developmental Neurogenomics, Human Genetics Branch, National Institutes of Mental Health, Intramural Research Program, Bethesda, MD, USA
| | - Ragini Verma
- Diffusion and Connectomics In Precision Healthcare Research (DiCIPHR) lab, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Cannas S, Tonini B, Belà B, Di Prinzio R, Pignataro G, Di Simone D, Gramenzi A. Effect of a novel nutraceutical supplement (Relaxigen Pet dog) on the fecal microbiome and stress-related behaviors in dogs: A pilot study. J Vet Behav 2021. [DOI: 10.1016/j.jveb.2020.09.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Lin MH, Chiu SY, Ho WC, Huang HY. Application of the Ottawa Charter Five Priority Areas of Action for Public Health to an Institution-Wide Diabetes Care Promotion. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18041543. [PMID: 33562885 PMCID: PMC7914748 DOI: 10.3390/ijerph18041543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/22/2021] [Accepted: 02/02/2021] [Indexed: 11/18/2022]
Abstract
This study was the first institution-wide health promotion program in Taiwan to apply the five priority areas for taking action in public health highlighted in the Ottawa Charter for diabetes patients. We aimed to improve the quality of home care received by diabetic patients by training health care professionals in health promotion. This program consisted of developing personal skills, reorienting health services, strengthening community actions, creating supportive environments, and building healthy public policy. It was applied in the Yunlin Christian Hospital located in central Taiwan from August 2011 to November 2011. A health-promoting education course consisting of weight control, diabetes care, and quality management for diabetes was developed and applied to all 323 hospital staff. Then, hospital staff volunteers and diabetes patients were recruited to participate in the program. A total of 61 staff volunteers and 90 diabetes patients were involved in this study. Staff volunteers were trained to participate in communities to provide care and guidance to patients with diabetes. The World Health Organization Quality of Life(WHOQOL)-BREF-Taiwan Version questionnaires were investigated before and after implementation of this program for the patients. A health-promoting lifestyle profile questionnaire was filled by the staff. The investigation data were then analyzed by statistical methods. The diabetes patients experienced a significant increase in their satisfaction with health and health-related quality of life as well as significant improvements in health-promotion and self-management behaviors (p < 0.05). In addition, staff volunteers significantly consumes food from the five major groups than the other staff (p < 0.05). Various improvements in health-promoting behaviors were observed amongst the hospital staff and the diabetic patients. Our project could be a reference for other medical organizations to implement an institution-wide health-promotion program for diabetic patients.
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Affiliation(s)
- Min-Hua Lin
- Department of Nutrition, China Medical University, Taichung 40402, Taiwan; (M.-H.L.); (H.-Y.H.)
- Department of Dietetics, Yunlin Christian Hospital, No. 375, Shichang S. Rd.Xiluo Township, Yunlin 64866, Taiwan
| | - She-Yu Chiu
- Institute of Population Health Sciences, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 35053, Taiwan;
| | - Wen-Chao Ho
- College of Public Health, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan
- Department of Nursing & Graduate Institute of Nursing, Asia University, No. 500, Lioufeng Road, Wufeng, Taichung 41354, Taiwan
- Correspondence:
| | - Hui-Ying Huang
- Department of Nutrition, China Medical University, Taichung 40402, Taiwan; (M.-H.L.); (H.-Y.H.)
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Ericsson AC, Franklin CL. The gut microbiome of laboratory mice: considerations and best practices for translational research. Mamm Genome 2021; 32:239-250. [PMID: 33689000 PMCID: PMC8295156 DOI: 10.1007/s00335-021-09863-7] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 02/18/2021] [Indexed: 12/14/2022]
Abstract
Just as the gut microbiota (GM) is now recognized as an integral mediator of environmental influences on human physiology, susceptibility to disease, and response to pharmacological intervention, so too does the GM of laboratory mice affect the phenotype of research using mouse models. Multiple experimental factors have been shown to affect the composition of the GM in research mice, as well as the model phenotype, suggesting that the GM represents a major component in experimental reproducibility. Moreover, several recent studies suggest that manipulation of the GM of laboratory mice can substantially improve the predictive power or translatability of data generated in mouse models to the human conditions under investigation. This review provides readers with information related to these various factors and practices, and recommendations regarding methods by which issues with poor reproducibility or translatability can be transformed into discoveries.
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Affiliation(s)
- Aaron C Ericsson
- University of Missouri Metagenomics Center (MUMC), MU Mutant Mouse Resource and Research Center (MU MMRRC), Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
| | - Craig L Franklin
- University of Missouri Metagenomics Center (MUMC), MU Mutant Mouse Resource and Research Center (MU MMRRC), Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA
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Basson AR, Zhou Y, Seo B, Rodriguez-Palacios A, Cominelli F. Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease. Transl Res 2020; 226:1-11. [PMID: 32585148 PMCID: PMC7308243 DOI: 10.1016/j.trsl.2020.05.008] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 05/20/2020] [Accepted: 05/23/2020] [Indexed: 12/12/2022]
Abstract
The term autologous fecal microbiota transplantation (a-FMT) refers herein to the use of one's feces during a healthy state for later use to restore gut microbial communities after perturbations. Generally, heterologous fecal microbiota transplantation (h-FMT), where feces from a ``healthy" donor is transplanted into a person with illness, has been used to treat infectious diseases such as recurrent Clostridioides difficile infection (CDI), with cure rates of up to 90%. In humans, due to limited response to medicines, h-FMT has become a hallmark intervention to treat CDI. Extrapolating the benefits from CDI, h-FMT has been attempted in various diseases, including inflammatory bowel disease (IBD), but clinical response has been variable and less effective (ranging between 24% and 50%). Differences in h-FMT clinical response could be because CDI is caused by a Clostridial infection, whereas IBD is a complex, microbiome-driven immunological inflammatory disorder that presents predominantly within the gut wall of genetically-susceptible hosts. FMT response variability could also be due to differences in microbiome composition between donors, recipients, and within individuals, which vary with diet, and environments, across regions. While donor selection has emerged as a key factor in FMT success, the use of heterologous donor stool still places the recipient at risk of exposure to infectious/pathogenic microorganisms. As an implementable solution, herein we review the available literature on a-FMT, and list some considerations on the benefits of a-FMT for IBD.
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Key Words
- a-fmt, autologous fecal microbiota transplantation
- cd, crohn's disease
- cdi, clostridium difficile infection
- ci, confidence interval
- fmt, fecal microbiota transplantation
- hgm, human gut microbiota
- h-fmt, heterologous fecal microbiota transplantation
- ibd, inflammatory bowel disease
- ibs, irritable bowel syndrome
- rct, randomized controlled trial
- uc, ulcerative colitis
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Affiliation(s)
- Abigail R Basson
- Division of Gastroenterology & Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio; Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Yibing Zhou
- Division of Gastroenterology & Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Brian Seo
- Division of Gastroenterology & Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Alexander Rodriguez-Palacios
- Division of Gastroenterology & Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio; Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Fabio Cominelli
- Division of Gastroenterology & Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio; Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
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Ballini A, Scacco S, Boccellino M, Santacroce L, Arrigoni R. Microbiota and Obesity: Where Are We Now? BIOLOGY 2020; 9:biology9120415. [PMID: 33255588 PMCID: PMC7761345 DOI: 10.3390/biology9120415] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/14/2020] [Accepted: 11/24/2020] [Indexed: 02/06/2023]
Abstract
Simple Summary Emerging new data reported in the international scientific literature show that specific alterations in the human gut microbiota are characteristic in obesity and obesity-related metabolic diseases. Obesity is conditioned by a multitude of factors, and the microbiota is certainly an important player. The analysis of the data obtained from experimental studies allow us to hypothesize that changes in the composition of the microbiota may be the cause, and not simply the consequence, of alterations in human metabolism. Clinical trials on wide samples that investigate the role of diet-induced modulation of the gut microbiota on the host metabolism are needed to understand the interactions at the molecular level for the observed correlations between metabolism and microbiota changes. Abstract Genetic and environmental factors are underlying causes of obesity and other metabolic diseases, so it is therefore difficult to find suitable and effective medical treatments. However, without a doubt, the gut microbiota—and also the bacteria present in the oral cavity—act as key factors in the development of these pathologies, yet the mechanisms have not been fully described. Certainly, a more detailed knowledge of the structure of the microbiota—composition, intra- and inter-species relationships, metabolic functions—could be of great help in counteracting the onset of obesity. Identifying key bacterial species will allow us to create a database of “healthy” bacteria, making it possible to manipulate the bacterial community according to metabolic and clinical needs. Targeting gut microbiota in clinical care as treatment for obesity and health-related complications—even just for weight loss has become a real possibility. In this topical review we provide an overview of the role of the microbiota on host energy homeostasis and obesity-related metabolic diseases, therefore addressing the therapeutic potential of novel and existing strategies (impact of nutrition/dietary modulation, and fecal microbiota transplantation) in the treatment of metabolic disease.
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Affiliation(s)
- Andrea Ballini
- Department of Biosciences, Biotechnologies and Biopharmaceutics, Campus Universitario, University of Bari “Aldo Moro”, 70125 Bari, Italy;
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, 70121 Bari, Italy
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Salvatore Scacco
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, 70121 Bari, Italy
- Correspondence: (S.S.); (M.B.); (R.A.)
| | - Mariarosaria Boccellino
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
- Correspondence: (S.S.); (M.B.); (R.A.)
| | - Luigi Santacroce
- Microbiology and Virology Laboratory, Ionian Department, Policlinico University Hospital, University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Roberto Arrigoni
- CNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), 70124 Bari, Italy
- Correspondence: (S.S.); (M.B.); (R.A.)
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Ling Y, Gong T, Zhang J, Gu Q, Gao X, Weng X, Liu J, Sun J. Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke. Front Aging Neurosci 2020; 12:511562. [PMID: 33192448 PMCID: PMC7645221 DOI: 10.3389/fnagi.2020.511562] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 08/24/2020] [Indexed: 12/15/2022] Open
Abstract
Post-stroke cognitive impairment (PSCI) is a common neuropsychiatric complication of stroke. Mounting evidence has demonstrated a connection between gut microbiota (GM) and neuropsychiatric disease. Our previous study revealed the changes in the GM in a mouse model of vascular dementia. However, the characteristic GM of PSCI remains unclear. This study aimed to characterize the GM of PSCI and explored the potential of GM as PSCI biomarkers. A total of 93 patients with ischemic stroke were enrolled in this study. The patients were divided into two groups according to their MoCA scores 3 months after stroke onset. Clinical data and biological variables were recorded. GM composition was analyzed using 16S ribosomal RNA sequencing, and the characteristic GM was identified by linear discriminant analysis Effect Size (Lefse). Our results showed that Proteobacteria was highly increased in the PSCI group compared with the post-stroke non-cognitive impairment (PSNCI) group, the similar alterations were also observed at the class, order, family, and genus levels of Proteobacteria. After age adjustments, the abundance of Firmicutes, and its members, including Clostridia, Clostridiales, Lachnospiraceae, and Lachnospiraceae_other, were significantly decreased in the age-matched PSCI group compared with the PSNCI group. Besides, the GM was closely associated with MoCA scores and the risk factors for PSCI, including higher baseline National Institute of Health Stroke Scale score, higher homocysteine (Hcy) level, higher prevalence of stroke recurrence, leukoaraiosis, and brain atrophy. The KEGG results showed the enriched module for folding, sorting and degradation (chaperones and folding catalysts) and the decreased modules related to metabolisms of cofactors and vitamins, amino acid, and lipid in PSCI patients. A significant correlation was observed between PSCI and the abundance of Enterobacteriaceae after adjustments (P = 0.035). Moreover, the receiver operating characteristic (ROC) models based on the characteristic GM and Enterobacteriaceae could distinguish PSCI patients from PSNCI patients [area under the curve (AUC) = 0.840, 0.629, respectively]. Our findings demonstrated that the characteristic GM, especially Enterobacteriaceae, might have the ability to predict PSCI in post-stroke patients, which are expected to be used as clinical biomarkers of PSCI.
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Affiliation(s)
- Yi Ling
- Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Tianyu Gong
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China
| | - Junmei Zhang
- Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Qilu Gu
- Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xinxin Gao
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China
| | - Xiongpeng Weng
- Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jiaming Liu
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China
| | - Jing Sun
- Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
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Mediavilla C. Bidirectional gut-brain communication: A role for orexin-A. Neurochem Int 2020; 141:104882. [PMID: 33068686 DOI: 10.1016/j.neuint.2020.104882] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 10/02/2020] [Accepted: 10/11/2020] [Indexed: 02/06/2023]
Abstract
It is increasingly evident that bidirectional gut-brain signaling provides a communication pathway that uses neural, hormonal, and immunological routes to regulate homeostatic mechanisms such as hunger/satiety as well as emotions and inflammation. Hence, disruption of the gut-brain axis can cause numerous pathophysiologies, including obesity and intestinal inflammatory diseases. One chemical mediator in the gut-brain axis is orexin-A, given that hypothalamic orexin-A affects gastrointestinal motility and secretion, and peripheral orexin in the intestinal mucosa can modulate brain functions, making possible an orexinergic gut-brain network. It has been proposed that orexin-A acts on this axis to regulate nutritional processes, such as short-term intake, gastric acid secretion, and motor activity associated with the cephalic phase of feeding. Orexin-A has also been related to stress systems and stress responses via the hypothalamic-pituitary-adrenal axis. Recent studies on the relationship of orexin with immune system-brain communications in an animal model of colitis suggested an immunomodulatory role for orexin-A in signaling and responding to infection by reducing the production of pro-inflammatory cytokines (e.g., tumor necrosis factor α, interleukin-6, and monocyte chemoattractant protein-1). These studies suggested that orexin administration might be of potential therapeutic value in irritable bowel syndrome or chronic intestinal inflammatory diseases, in which gastrointestinal symptoms frequently coexist with behavioral disorders, including loss of appetite, anxiety, depression, and sleeping disorders. Interventions in the orexinergic system have been proposed as a therapeutic approach to these diseases and for the treatment of chemotherapeutic drug-related hyperalgesia and fatigue in cancer patients.
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Affiliation(s)
- Cristina Mediavilla
- Department of Psychobiology, and Mind, Brain, and Behavior Research Center (CIMCYC), University of Granada, Spain.
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Kwon HJ, Mohammed AE, Eltom KH, Albrahim JS, Alburae NA. Evaluation of antibiotic-induced behavioral changes in mice. Physiol Behav 2020; 223:113015. [PMID: 32553641 DOI: 10.1016/j.physbeh.2020.113015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 06/03/2020] [Accepted: 06/12/2020] [Indexed: 12/20/2022]
Abstract
Gut microbiota (GM) plays a critical role in health maintenance. Previous reports connected GM with metabolic, immunologic and neurologic pathways. The main purpose of the current investigation was to study whether antibiotic-induced disturbances of GM affects psychological or behavioral conditions on mice as animal model. Mice were exposed to clindamycin or amoxicillin, and their behaviors were evaluated. Antibiotic-treated groups displayed reduced recognition memory and increased depression. No significant changes in the locomotor activity and anxiety were observed. Our data suggested that changes in GM composition by antibiotics may lead to the cognitive and behavioral deficit.
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Affiliation(s)
- Hye-Joo Kwon
- Biology Department, Faculty of Science, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi Arabia; The University of Utah Asia Campus, Incheon, Korea
| | - Afrah E Mohammed
- Biology Department, Faculty of Science, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi Arabia.
| | - Kamal H Eltom
- Unit of Animal Health and Safety of Animal Products, Institute for Studies and Promotion of Animal Exports, University of Khartoum, Shambat Postal Code 13314, Khartoum North, Sudan
| | - Jehan S Albrahim
- Biology Department, Faculty of Science, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi Arabia
| | - Najla Ali Alburae
- Department of Biology, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
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Analysis of the diversity of intestinal microbiome and its potential value as a biomarker in patients with schizophrenia: A cohort study. Psychiatry Res 2020; 291:113260. [PMID: 32763534 DOI: 10.1016/j.psychres.2020.113260] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 05/15/2020] [Accepted: 06/26/2020] [Indexed: 02/08/2023]
Abstract
Exploring the gut microbiota characteristics of patients with acute and remission schizophrenia (SCZ) and evaluating the potential of the gut microbiome as a non-invasive biomarker for SCZ. A total of 87 fecal samples were collected, including a total of 58 samples from 29 SCZ patients over two different periods (remission and onset period) and 29 samples from the control group for 16S rRNA Miseq.The changes of intestinal microbiota in SCZ patients from remission to onset were analyzed, and a random forest model was constructed to recognize biomarkers. The optimal three genus-level diagnosis biomarkers were identified through an AUC validation on a random forest model, furthermore, an AUC of 0.76 (95% CI (0.63, 0.89)) was achieved between 29 aSCZ and 29 HCs. Compared with the control group, the first 11 OUT-level' biomarkers were identified in rSCZ group. As a status marker of the disease, the AUC of 0.7 (95% CI (0.56, 0.84)) was achieved between 29 rSCZ and 29 HCs. There were differences between SCZ patients and HCs, acute and remission patients as well, suggesting that the potential of the gut microbiota as a non-invasive diagnostic tool. Moreover, the features of the gut microbiome of SCZ provide clues for disease prognosis assessment and targeted intervention.
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Mind and gut: Associations between mood and gastrointestinal distress in children exposed to adversity. Dev Psychopathol 2020; 32:309-328. [PMID: 30919798 DOI: 10.1017/s0954579419000087] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastrointestinal and mental disorders are highly comorbid, and animal models have shown that both can be caused by early adversity (e.g., parental deprivation). Interactions between the brain and bacteria that live within the gastrointestinal system (the microbiome) underlie adversity-gastrointestinal-anxiety interactions, but these links have not been investigated during human development. In this study, we utilized data from a population of 344 youth (3-18 years old) who were raised with their biological parents or were exposed to early adverse caregiving experiences (i.e., institutional or foster care followed by international adoption) to explore adversity-gastrointestinal-anxiety associations. In Study 1, we demonstrated that previous adverse care experiences were associated with increased incidence of gastrointestinal symptoms in youth. Gastrointestinal symptoms were also associated with concurrent and future anxiety (measured across 5 years), and those gastrointestinal symptoms mediated the adversity-anxiety association at Time 1. In a subsample of children who provided both stool samples and functional magnetic resonance imaging of the brain (Study 2, which was a "proof-of-principle"), adversity was associated with changes in diversity (both alpha and beta) of microbial communities, and bacteria levels (adversity-associated and adversity-independent) were correlated with prefrontal cortex activation to emotional faces. Implications of these data for supporting youth mental health are discussed.
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Benhaïm D, Leblanc CA, Horri K, Mannion K, Galloway M, Leeper A, Knobloch S, Sigurgeirsson Ó, Thorarensen H. The effect of triploidy on the performance, gut microbiome and behaviour of juvenile Atlantic salmon (Salmo salar) raised at low temperature. Appl Anim Behav Sci 2020. [DOI: 10.1016/j.applanim.2020.105031] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Identifying mechanisms that predict weight trajectory after bariatric surgery: rationale and design of the biobehavioral trial. Surg Obes Relat Dis 2020; 16:1816-1826. [PMID: 32768295 DOI: 10.1016/j.soard.2020.06.020] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 05/15/2020] [Accepted: 06/11/2020] [Indexed: 02/07/2023]
Abstract
Bariatric surgery is currently the most efficacious and durable intervention for severe obesity. The most commonly performed procedures in the United States are the Roux-en-Y gastric bypass and the sleeve gastrectomy, which involve significant anatomic and physiologic alterations that lead to changes in behavior and biology. Unfortunately, many patients experience suboptimal weight loss and/or substantial weight regain. Eating and physical activity/sedentary behaviors, mood, cognition, and the gut microbiome all change postoperatively and have an association with weight change. The longitudinal relationship between changes in the gut microbiome and postoperative weight trajectory has not been explored thoroughly, and the interactive associations among the gut microbiome and the other variables that impact weight have been similarly understudied. The following is a methods and design description for a prospective, 24-month longitudinal study of 144 bariatric surgery patients, at 2 sites, that aimed to identify predictors of weight loss trajectories over 24 months after Roux-en-Y gastric bypass and the sleeve gastrectomy. Specifically, the study will examine the relationships between empirically supported behavioral and biological variables and their combined impact on postoperative weight trajectories. Novel data collection will include intensive measurement of problematic eating behaviors and diet and physical activity postoperatively, which may be altered in parallel with, or in response to, changes observed in the gut microbiota. Identifying postoperative predictors of weight loss and co-morbidity resolution should inform development of novel interventions that are tailored to individual patients' risk profiles to optimize and sustain more favorable weight trajectories.
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42
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Wang Y, Ren R, Sun G, Peng L, Tian Y, Yang Y. Pilot study of cytokine changes evaluation after fecal microbiota transplantation in patients with ulcerative colitis. Int Immunopharmacol 2020; 85:106661. [PMID: 32563025 DOI: 10.1016/j.intimp.2020.106661] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/27/2020] [Accepted: 05/31/2020] [Indexed: 02/07/2023]
Abstract
AIMS To evaluate the changes of serum cytokines levels after fecal microbiota transplantation (FMT) in patients with active ulcerative colitis (UC) and the correlation with UC disease activity. METHODS Patients with active UC who meet the inclusion and exclusion criteria were recruited, and received FMT from a single donor for three times with an interval of 2-3 months. Serum samples were collected before every FMT. Clinical responses to FMT were assessed according to the criteria of Mayo score. 41 serum cytokines, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were quantitatively detected. Changes in serum cytokines levels after FMT and their correlation with CRP, ESR and Mayo scores were investigated. RESULTS 16 active UC patients were enrolled, and 14(87.5%) patients achieved clinical response to FMT. Compared with those before FMT, serum concentrations of IL-1Ra, IL-6, IP-10 and ENA-78 decreased significantly after the second FMT (P < 0.05), and serum concentrations of MEC, VCAM-1 and G-CSF decreased significantly after both the first and second FMT (P < 0.05). Serum levels of IL-6, IL-1Ra and VCAM-1 were all significantly positively correlated with CRP and ESR. Serum level of IP-10 was significantly positively correlated with CRP, ESR and Mayo score. Serum level of G-CSF was significantly positively correlated with Mayo score. CONCLUSIONS FMT may play a therapeutic role partly through modulating the host immune response. IL-6, IL-1Ra, IP-10, VCAM-1 and G-CSF may be biomarkers to evaluate the effect of FMT on UC.
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Affiliation(s)
- Yanzhi Wang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China; Medical Laboratory Center, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Rongrong Ren
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Gang Sun
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Lihua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Yaping Tian
- Medical Laboratory Center, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China; Translational Medicine Research Center, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
| | - Yunsheng Yang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
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43
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The role of the gut microbiota in the pathophysiology of mental and neurological disorders. Psychiatr Genet 2020; 30:87-100. [DOI: 10.1097/ypg.0000000000000255] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Mohanta L, Das BC, Patri M. Microbial communities modulating brain functioning and behaviors in zebrafish: A mechanistic approach. Microb Pathog 2020; 145:104251. [PMID: 32418919 DOI: 10.1016/j.micpath.2020.104251] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 05/05/2020] [Accepted: 05/06/2020] [Indexed: 12/20/2022]
Abstract
Microbiota plays a vital role in maintaining their host's physiology, development, reproduction, immune system, nutrient metabolism, brain chemistry and its behavior. How the gut microbiota modulates the brain function altering cognitive and fundamental behavior patterns related to specific functional changes is unclear. Recent studies provide holistic approaches which show gut microbiota can greatly sway all aspects of physiology including gut-brain communication, brain function and behavior by establishing a bi-directional link between the gut and brain. Among these studies, to our knowledge, the present review focus on the new mechanistic basis that relates the microbiota of the intestine with diseases of the nervous system causing behavioral alteration in zebrafish (Danio rerio) during development. The current review on microbiota-gut-brain axis communication showed a high instability of the microbiome at early stage of development in zebrafish. Probiotics restore the composition of the gut microbiota by producing neuroactive compounds and introduce beneficial functions to gut microbial communities, resulting in amelioration of gut inflammation and other intestinal disease phenotypes. Therefore, the present review mainly highlights the mechanistic way of gut-brain function, including neuronal, hormonal, immunological signaling with production of bacterial metabolites. This study consider current knowledge that may enable us to increase our understanding to know how the gut microbiota establishes a connection with brain modulating the gut-brain signaling by alteration of the neurochemistry such as GABA and serotonin levels in brain to control host behavior. Further studies are needed to define the exact microbial and host mechanism in GI disease states and functional syndromes.
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Affiliation(s)
- Larica Mohanta
- Neurobiology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, Cuttack, 753003, Odisha, India
| | - Bhaskar C Das
- Departments of Medicine and Pharmacological Sciences, Icahn School of Medicine, Mount Sinai, Annenberg, 19-201, New York, USA
| | - Manorama Patri
- Neurobiology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, Cuttack, 753003, Odisha, India.
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Peterson VL, Richards JB, Meyer PJ, Cabrera-Rubio R, Tripi JA, King CP, Polesskaya O, Baud A, Chitre AS, Bastiaanssen TFS, Woods LS, Crispie F, Dinan TG, Cotter PD, Palmer AA, Cryan JF. Sex-dependent associations between addiction-related behaviors and the microbiome in outbred rats. EBioMedicine 2020; 55:102769. [PMID: 32403084 PMCID: PMC7218262 DOI: 10.1016/j.ebiom.2020.102769] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 04/06/2020] [Accepted: 04/14/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Multiple factors contribute to the etiology of addiction, including genetics, sex, and a number of addiction-related behavioral traits. One behavioral trait where individuals assign incentive salience to food stimuli ("sign-trackers", ST) are more impulsive compared to those that do not ("goal-trackers", GT), as well as more sensitive to drugs and drug stimuli. Furthermore, this GT/ST phenotype predicts differences in other behavioral measures. Recent studies have implicated the gut microbiota as a key regulator of brain and behavior, and have shown that many microbiota-associated changes occur in a sex-dependent manner. However, few studies have examined how the microbiome might influence addiction-related behaviors. To this end, we sought to determine if gut microbiome composition was correlated with addiction-related behaviors determined by the GT/ST phenotype. METHODS Outbred male (N=101) and female (N=101) heterogeneous stock rats underwent a series of behavioral tests measuring impulsivity, attention, reward-learning, incentive salience, and locomotor response. Cecal microbiome composition was estimated using 16S rRNA gene amplicon sequencing. Behavior and microbiome were characterized and correlated with behavioral phenotypes. Robust sex differences were observed in both behavior and microbiome; further analyses were conducted within sex using the pre-established goal/sign-tracking (GT/ST) phenotype and partial least squares differential analysis (PLS-DA) clustered behavioral phenotype. RESULTS Overall microbiome composition was not associated to the GT/ST phenotype. However, microbial alpha diversity was significantly decreased in female STs. On the other hand, a measure of impulsivity had many significant correlations to microbiome in both males and females. Several measures of impulsivity were correlated with the genus Barnesiella in females. Female STs had notable correlations between microbiome and attentional deficient. In both males and females, many measures were correlated with the bacterial families Ruminocococcaceae and Lachnospiraceae. CONCLUSIONS These data demonstrate correlations between several addiction-related behaviors and the microbiome specific to sex.
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Affiliation(s)
- Veronica L Peterson
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Room 2.33, 2nd Floor, Western Gateway Building, Cork, Ireland
| | - Jerry B Richards
- Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, USA
| | - Paul J Meyer
- Department of Psychology, University at Buffalo, Buffalo, NY, USA
| | - Raul Cabrera-Rubio
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Jordan A Tripi
- Department of Psychology, University at Buffalo, Buffalo, NY, USA
| | | | - Oksana Polesskaya
- Department of Psychiatry, University of California San Diego, CA, USA
| | - Amelie Baud
- Department of Psychiatry, University of California San Diego, CA, USA
| | - Apurva S Chitre
- Department of Psychiatry, University of California San Diego, CA, USA
| | - Thomaz F S Bastiaanssen
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Room 2.33, 2nd Floor, Western Gateway Building, Cork, Ireland
| | | | - Fiona Crispie
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Timothy G Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Paul D Cotter
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Abraham A Palmer
- Department of Psychiatry, University of California San Diego, CA, USA; Institute for Genomic Medicine, University of California San Diego, CA, USA; Center for Microbiome Innovation, University of California San Diego, CA, USA
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Room 2.33, 2nd Floor, Western Gateway Building, Cork, Ireland.
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Sinagra E, Utzeri E, Morreale GC, Fabbri C, Pace F, Anderloni A. Microbiota-gut-brain axis and its affect inflammatory bowel disease: Pathophysiological concepts and insights for clinicians. World J Clin Cases 2020; 8:1013-1025. [PMID: 32258072 PMCID: PMC7103973 DOI: 10.12998/wjcc.v8.i6.1013] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/14/2020] [Accepted: 03/05/2020] [Indexed: 02/05/2023] Open
Abstract
Despite the bi-directional interaction between gut microbiota and the brain not being fully understood, there is increasing evidence arising from animal and human studies that show how this intricate relationship may facilitate inflammatory bowel disease (IBD) pathogenesis, with consequent important implications on the possibility to improve the clinical outcomes of the diseases themselves, by acting on the different components of this system, mainly by modifying the microbiota. With the emergence of precision medicine, strategies in which patients with IBD might be categorized other than for standard gut symptom complexes could offer the opportunity to tailor therapies to individual patients. The aim of this narrative review is to elaborate on the concept of the gut-brain-microbiota axis and its clinical significance regarding IBD on the basis of recent scientific literature, and finally to focus on pharmacological therapies that could allow us to favorably modify the function of this complex system.
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Affiliation(s)
- Emanuele Sinagra
- Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, Cefalù 90015, Italy
- Euro-Mediterranean Institute of Science and Technology, Palermo 90100, Italy
| | - Erika Utzeri
- Nuova Casa di Cura di Decimomannu, Cagliari 09100, Italy
| | | | - Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena, Azienda USL Romagna, Forlì 47121, Italy
| | - Fabio Pace
- Unit of Gastroenterology, Bolognini Hospital, Bergamo 24100, Italy
| | - Andrea Anderloni
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Italy
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Abstract
Investigation of gut microbiome composition and diversity with respect to human personality. Analyses targeted bacterial genera linked to behaviour in animal and human psychiatric studies. Bacterial genera were modelled (using negative binomial regression) with respect to personality. Genera linked to autism are also related to social behaviour in the general population. Sociability is associated with higher diversity, and anxiety and stress with reduced diversity. The gut microbiome has a measurable impact on the brain, influencing stress, anxiety, depressive symptoms and social behaviour. This microbiome–gut–brain axis may be mediated by various mechanisms including neural, immune and endocrine signalling. To date, the majority of research has been conducted in animal models, while the limited number of human studies has focused on psychiatric conditions. Here the composition and diversity of the gut microbiome is investigated with respect to human personality. Using regression models to control for possible confounding factors, the abundances of specific bacterial genera are shown to be significantly predicted by personality traits. Diversity analyses of the gut microbiome reveal that people with larger social networks tend to have a more diverse microbiome, suggesting that social interactions may shape the microbial community of the human gut. In contrast, anxiety and stress are linked to reduced diversity and an altered microbiome composition. Together, these results add a new dimension to our understanding of personality and reveal that the microbiome–gut–brain axis may also be relevant to behavioural variation in the general population as well as to cases of psychiatric disorders.
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van der Eijk JAJ, Rodenburg TB, de Vries H, Kjaer JB, Smidt H, Naguib M, Kemp B, Lammers A. Early-life microbiota transplantation affects behavioural responses, serotonin and immune characteristics in chicken lines divergently selected on feather pecking. Sci Rep 2020; 10:2750. [PMID: 32066789 PMCID: PMC7026165 DOI: 10.1038/s41598-020-59125-w] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 01/17/2020] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota influences host behaviour and physiology, such as anxiety, stress, serotonergic and immune systems. These behavioural and physiological characteristics are related to feather pecking (FP), a damaging behaviour in chickens that reduces animal welfare and productivity. Moreover, high FP (HFP) and low FP (LFP) lines differed in microbiota composition. However, it is unknown whether microbiota can influence the development of FP. For the first time, we identified the effects of microbiota transplantation on FP, and behavioural and physiological characteristics related to FP. HFP and LFP chicks received sterile saline (control), HFP or LFP microbiota transplantation during the first two weeks post-hatch. Microbiota transplantation influenced behavioural responses of the HFP line during treatment and of the LFP line after treatment. In both lines, homologous microbiota transplantation (i.e., receiving microbiota from their line) resulted in more active behavioural responses. Furthermore, microbiota transplantation influenced immune characteristics (natural antibodies) in both lines and peripheral serotonin in the LFP line. However, limited effects on microbiota composition, stress response (corticosterone) and FP were noted. Thus, early-life microbiota transplantation had immediate and long-term effects on behavioural responses and long-term effects on immune characteristics and peripheral serotonin; however, the effects were dependent on host genotype. Since early-life microbiota transplantation influenced behavioural and physiological characteristics that are related to FP, it could thus influence the development of FP later in life.
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Affiliation(s)
- Jerine A J van der Eijk
- Behavioural Ecology Group, Department of Animal Sciences, Wageningen University and Research, Wageningen, the Netherlands.
- Adaptation Physiology Group, Department of Animal Sciences, Wageningen University and Research, Wageningen, the Netherlands.
| | - T Bas Rodenburg
- Adaptation Physiology Group, Department of Animal Sciences, Wageningen University and Research, Wageningen, the Netherlands
- Department of Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands
| | - Hugo de Vries
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, the Netherlands
| | - Joergen B Kjaer
- Friedrich-Loeffler-Institut, Institute of Animal Welfare and Animal Husbandry, Celle, Germany
| | - Hauke Smidt
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, the Netherlands
| | - Marc Naguib
- Behavioural Ecology Group, Department of Animal Sciences, Wageningen University and Research, Wageningen, the Netherlands
| | - Bas Kemp
- Adaptation Physiology Group, Department of Animal Sciences, Wageningen University and Research, Wageningen, the Netherlands
| | - Aart Lammers
- Adaptation Physiology Group, Department of Animal Sciences, Wageningen University and Research, Wageningen, the Netherlands
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Flux MC, Lowry CA. Finding intestinal fortitude: Integrating the microbiome into a holistic view of depression mechanisms, treatment, and resilience. Neurobiol Dis 2020; 135:104578. [PMID: 31454550 PMCID: PMC6995775 DOI: 10.1016/j.nbd.2019.104578] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 06/27/2019] [Accepted: 08/14/2019] [Indexed: 02/07/2023] Open
Abstract
Depression affects at least 322 million people globally, or approximately 4.4% of the world's population. While the earnestness of researchers and clinicians to understand and treat depression is not waning, the number of individuals suffering from depression continues to increase over and above the rate of global population growth. There is a sincere need for a paradigm shift. Research in the past decade is beginning to take a more holistic approach to understanding depression etiology and treatment, integrating multiple body systems into whole-body conceptualizations of this mental health affliction. Evidence supports the hypothesis that the gut microbiome, or the collective trillions of microbes inhabiting the gastrointestinal tract, is an important factor determining both the risk of development of depression and persistence of depressive symptoms. This review discusses recent advances in both rodent and human research that explore bidirectional communication between the gut microbiome and the immune, endocrine, and central nervous systems implicated in the etiology and pathophysiology of depression. Through interactions with circulating inflammatory markers and hormones, afferent and efferent neural systems, and other, more niche, pathways, the gut microbiome can affect behavior to facilitate the development of depression, exacerbate current symptoms, or contribute to treatment and resilience. While the challenge of depression may be the direst mental health crisis of our age, new discoveries in the gut microbiome, when integrated into a holistic perspective, hold great promise for the future of positive mental health.
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Affiliation(s)
- M C Flux
- Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Christopher A Lowry
- Department of Integrative Physiology, Center for Neuroscience, and Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO 80309, USA; Department of Physical Medicine & Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Veterans Health Administration, Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Rocky Mountain Regional Veterans Affairs Medical Center (RMRVAMC), Aurora, CO 80045, USA; Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Aurora, CO 80045, USA; Senior Fellow, VIVO Planetary Health, Worldwide Universities Network (WUN), West New York, NJ 07093, USA.
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Saniotis A, Grantham JP, Kumaratilake J, Henneberg M. Neuro-hormonal Regulation Is a Better Indicator of Human Cognitive Abilities Than Brain Anatomy: The Need for a New Paradigm. Front Neuroanat 2020; 13:101. [PMID: 31998082 PMCID: PMC6962128 DOI: 10.3389/fnana.2019.00101] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 12/04/2019] [Indexed: 12/31/2022] Open
Affiliation(s)
- Arthur Saniotis
- Department of Medical Laboratory Science, Knowledge University, Erbil, Iraq
- Biological Anthropology and Comparative Anatomy Research Unit (BACARU), Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
- *Correspondence: Arthur Saniotis
| | - James P. Grantham
- Biological Anthropology and Comparative Anatomy Research Unit (BACARU), Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
- Institute of Evolutionary Medicine, Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Jaliya Kumaratilake
- Biological Anthropology and Comparative Anatomy Research Unit (BACARU), Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
| | - Maciej Henneberg
- Biological Anthropology and Comparative Anatomy Research Unit (BACARU), Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
- Institute of Evolutionary Medicine, Faculty of Medicine, University of Zurich, Zurich, Switzerland
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