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Dilmore AH, Kuplicki R, McDonald D, Kumar M, Estaki M, Youngblut N, Tyakht A, Ackermann G, Blach C, MahmoudianDehkordi S, Dunlop BW, Bhattacharyya S, Guinjoan S, Mandaviya P, Ley RE, Kaddaruh-Dauok R, Paulus MP, Knight R. Medication use is associated with distinct microbial features in anxiety and depression. Mol Psychiatry 2025; 30:2545-2557. [PMID: 39794490 DOI: 10.1038/s41380-024-02857-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 11/11/2024] [Accepted: 11/22/2024] [Indexed: 01/13/2025]
Abstract
This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing (16S) and shallow shotgun sequencing (WGS) were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and Neurocomputational Mechanisms of Affiliation and Personality Study Center for Biomedical Research Excellence (NeuroMAP CoBRE) cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. Though the effect sizes were larger in females than males, similar trends emerged for both sexes. These findings encourage future research on the gut microbiota's role in NPD and its interactions with pharmacological treatments.
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Affiliation(s)
- Amanda Hazel Dilmore
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA
| | | | - Daniel McDonald
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Megha Kumar
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Mehrbod Estaki
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Nicholas Youngblut
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Alexander Tyakht
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Gail Ackermann
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Colette Blach
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
- Department of Medicine, Duke University, Durham, NC, USA
- Duke Institute of Brain Sciences, Duke University, Durham, NC, USA
| | | | - Boadie W Dunlop
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Sudeepa Bhattacharyya
- Department of Biological Sciences, Arkansas Biosciences Institute, Arkansas State University, Jonesboro, AR, USA
| | | | - Pooja Mandaviya
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Ruth E Ley
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Rima Kaddaruh-Dauok
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
- Department of Medicine, Duke University, Durham, NC, USA
- Duke Institute of Brain Sciences, Duke University, Durham, NC, USA
| | | | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
- Department of Computer Science & Engineering, University of California San Diego, La Jolla, CA, USA.
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
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Gamboa J, Le GH, Wong S, Alteza EAI, Zachos KA, Teopiz KM, McIntyre RS. Impact of antidepressants on the composition of the gut microbiome: A systematic review and meta-analysis of in vivo studies. J Affect Disord 2025; 369:819-833. [PMID: 39424151 DOI: 10.1016/j.jad.2024.10.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 09/12/2024] [Accepted: 10/09/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND There is a growing body of evidence suggesting that antidepressant drugs (ADs) alter the gut microbiome of persons with depressive disorders. Herein, we aim to investigate the gut microbial profile of AD-treated animal models of depression (MoD) and persons with major depressive disorder (MDD). METHODS We conducted a systematic review and meta-analysis investigating the gut microbiome community-level diversity and relative abundance of microbial taxa in AD-treated animal MoD and persons with MDD. RESULTS 24 human studies (898 participants) and 48 animal studies (849 subjects) were identified. Nonsignificant differences in gut microbial richness were observed between AD-treated and nonmedicated animals and humans. Beta diversity analysis in animals shows that AD intake is linked to a distinct gut microbial profile, a result not observed in humans. Consistent depletion of the genera Faecalibacterium and Parasutterella, along with enrichment of Bifidobacterium, was observed in AD-treated persons with MDD. In AD-treated animals, AD intake was associated with depletion of Flavobacterium and Adlercreutzia, and enrichment of Parabacteroides. LIMITATIONS The studies in our review were heterogeneous in their participant population, dietary intake, type of ADs used, length and dosing of AD treatment, and frequency and time of fecal sample collection. CONCLUSION ADs are associated with some changes to the gut microbiome. Future studies should evaluate the gut microbiome profiles between depressive disorder diagnoses that may reveal potential differences and predictors of AD response, as well as new combinatorial therapeutics with agents (e.g., specific-strain probiotic adjunctive treatment) that can ameliorate micro-composition gut dysbiosis.
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Affiliation(s)
- Jann Gamboa
- Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
| | - Gia Han Le
- Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada
| | - Sabrina Wong
- Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada
| | | | - Kassandra A Zachos
- Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada
| | - Kayla M Teopiz
- Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada
| | - Roger S McIntyre
- Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada.
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3
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Green M, Trivedi MH, Foster JA. Microbes and mood: innovative biomarker approaches in depression. Trends Mol Med 2025; 31:50-63. [PMID: 39353744 DOI: 10.1016/j.molmed.2024.09.002] [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: 05/14/2024] [Revised: 08/18/2024] [Accepted: 09/09/2024] [Indexed: 10/04/2024]
Abstract
Although the field of psychiatry has made gains in biomarker discovery, our ability to change long-term outcomes remains inadequate. Matching individuals to the best treatment for them is a persistent clinical challenge. Moreover, the development of novel treatments has been hampered in part due to a limited understanding of the biological mechanisms underlying individual differences that contribute to clinical heterogeneity. The gut microbiome has become an area of intensive research in conditions ranging from metabolic disorders to cancer. Innovation in these spaces has led to translational breakthroughs, offering novel microbiome-informed approaches that may improve patient outcomes. In this review we examine how translational microbiome research is poised to advance biomarker discovery in mental health, with a focus on depression.
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Affiliation(s)
- Miranda Green
- Department of Psychiatry and Behavioural Neuroscience, McMaster University, Hamilton, ON, Canada
| | - Madhukar H Trivedi
- Center for Depression Research and Clinical Care, Department of Psychiatry and Peter O'Donnell Jr Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA
| | - Jane A Foster
- Department of Psychiatry and Behavioural Neuroscience, McMaster University, Hamilton, ON, Canada; Center for Depression Research and Clinical Care, Department of Psychiatry and Peter O'Donnell Jr Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA.
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Segura D, Sharma D, Espin-Garcia O. Comparing subsampling strategies for metagenomic analysis in microbial studies using amplicon sequence variants versus operational taxonomic units. PLoS One 2024; 19:e0315720. [PMID: 39774426 PMCID: PMC11684612 DOI: 10.1371/journal.pone.0315720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 11/29/2024] [Indexed: 01/11/2025] Open
Abstract
The microbiome is increasingly regarded as a key component of human health, and analysis of microbiome data can aid in the development of precision medicine. Due to the high cost of shotgun metagenomic sequencing (SM-seq), microbiome analyses can be done cost-effectively in two phases: Phase 1-sequencing of 16S ribosomal RNA, and Phase 2-SM-seq of an informative subsample. Existing research suggests strategies to select the subsample based on biological diversity and dissimilarity metrics calculated using operational taxonomic units (OTUs). However, the microbiome field has progressed towards amplicon sequencing variants (ASVs), as they provide more precise microbe identification and sample diversity information. The aim of this work is to compare the subsampling strategies for two-phase metagenomic studies when using ASVs instead of OTUs, and to propose data driven strategies for subsample selection through dimension reduction techniques. We used 199 samples of infant-gut microbiome data from the DIABIMMUNE project to generate ASVs and OTUs, then generated subsamples based on five existing biologically driven subsampling methods and two data driven methods. Linear discriminant analysis Effect Size (LEfSe) was used to assess differential representation of taxa between the subsamples and the overall sample. The use of ASVs showed a 50-93% agreement in the subsample selection with the use of OTUs for the subsampling methods evaluated, and showed a similar bacterial representation across all methods. Although sampling using ASVs and OTUs typically lead to similar results for each subsample, ASVs had more clades that differed in expression levels between allergic and non-allergic individuals across all sample sizes compared to OTUs, and led to more biomarkers discovered at Phase 2-SM-seq level.
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Affiliation(s)
- Daniel Segura
- Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
- Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada
| | - Divya Sharma
- Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Department of Biostatistics, University Health Network, Toronto, Ontario, Canada
| | - Osvaldo Espin-Garcia
- Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Department of Biostatistics, University Health Network, Toronto, Ontario, Canada
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Stevens BR, Roesch LFW. Interplay of human ABCC11 transporter gene variants with axillary skin microbiome functional genomics. Sci Rep 2024; 14:28037. [PMID: 39543265 PMCID: PMC11564711 DOI: 10.1038/s41598-024-78711-w] [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: 08/08/2024] [Accepted: 11/04/2024] [Indexed: 11/17/2024] Open
Abstract
The human armpit microbiome is metabolically entangled with skin cell physiology. This "meta-organism" symbiotic mutualism results in sweat either with or without odor (osmidrosis), depending on host ABCC11 gene haplotypes. Apocrine metabolism produces odorless S-glutathione conjugate that is transferred by ABCC11 transporters into secretory vesicles, deglutamylated to S-Cys-Gly-3M3SH thiol, and exuded to skin surface. An anthropogenic clade of skin bacteria then takes up the thiol and bioconverts it to malodorous 3-methyl-3-sulfanylhexan-1-ol (3M3SH). We hypothesized a familial meta-organism association of human ABCC11 gene non-synonymous SNP rs17822931 interplaying with skin microbiome 3M3SH biosynthesis. Subjects were genotyped for ABCC11 SNPs, and their haplotypes were correlated with axilla microbiome DNA sequencing profiles and predicted metagenome functions. A multigeneration family pedigree revealed a Mendelian autosomal recessive pattern: the C allele of ABCC11 correlated with bacterial Cys-S-conjugate β-lyase (PatB) gene known for Staphylococcus hominis biosynthesis of 3M3SH from human precursor; PatB was rescinded in hosts with homozygous TT alleles encoding ABCC11 loss-of-function mutation. We posit that a C allele encoding functional ABCC11 is key to delivering host conjugate precursors that shape heritable skin niche conditions favorable to harboring Staphylococcus having genomics of odor thiol production. This provides existential insights into human evolution and global regional population ancestries.
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Affiliation(s)
- Bruce R Stevens
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
| | - Luiz F W Roesch
- Department of Microbiology and Cell Science, College of Agriculture and Life Sciences, University of Florida, Gainesville, FL, 32611, USA
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Luo T, Che Q, Guo Z, Song T, Zhao J, Xu D. Modulatory effects of traditional Chinese medicines on gut microbiota and the microbiota-gut-x axis. Front Pharmacol 2024; 15:1442854. [PMID: 39444598 PMCID: PMC11497133 DOI: 10.3389/fphar.2024.1442854] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 09/26/2024] [Indexed: 10/25/2024] Open
Abstract
The gut microbiota offers numerous benefits to the human body, including the promotion of nutrient absorption, participation in metabolic processes, and enhancement of immune function. Recent studies have introduced the concept of the gut-organ axis, which encompasses interactions such as the gut-brain axis, gut-liver axis, and gut-lung axis. This concept underscores the complex interplay between gut microbiota and various organs and tissues, including the brain, heart, lungs, liver, kidneys, muscles, and bones. Growing evidence indicates that gut microbiota can influence the onset and progression of multi-organ system diseases through their effects on the gut-organ axis. Traditional Chinese medicine has demonstrated significant efficacy in regulating the gastrointestinal system, leveraging its unique advantages. Considerable advancements have been made in understanding the role of gut microbiota and the gut-organ axis within the mechanisms of action of traditional Chinese medicine. This review aims to elucidate the roles of gut microbiota and the gut-organ axis in human health, explore the potential connections between traditional Chinese medicine and gut microbiota, and examine the therapeutic effects of traditional Chinese medicine on the microbiota-gut-organ axis. Furthermore, the review addresses the limitations and challenges present in current research while proposing potential directions for future investigations in this area.
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Affiliation(s)
- Tingting Luo
- Department of Medical Instrumental Analysis, Zunyi Medical University, Zunyi, China
| | - Qingya Che
- Department of Medical Instrumental Analysis, Zunyi Medical University, Zunyi, China
| | - Ziyi Guo
- Department of Medical Instrumental Analysis, Zunyi Medical University, Zunyi, China
- Department of Cell Biology, Zunyi Medical University, Zunyi, China
| | - Tingxia Song
- Department of Medical Instrumental Analysis, Zunyi Medical University, Zunyi, China
| | - Juanjuan Zhao
- Department of Immunology, Zunyi Medical University, Zunyi, China
| | - Delin Xu
- Department of Medical Instrumental Analysis, Zunyi Medical University, Zunyi, China
- Department of Cell Biology, Zunyi Medical University, Zunyi, China
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Wang Q, Zhao Y, Qin X, Tian J. Deciphering relationship between depression and microbial molecules based on multi-omics: A case study of Chaigui Granules. CHINESE HERBAL MEDICINES 2024; 16:612-621. [PMID: 39606256 PMCID: PMC11589482 DOI: 10.1016/j.chmed.2023.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 10/04/2023] [Accepted: 12/16/2023] [Indexed: 11/29/2024] Open
Abstract
Objective To decipher the antidepression effect of Chaigui Granules (CGKL) from the relationship between depression and microbial molecules based on multi-omics. Methods Male SD rats were subjected to chronic unpredictable mild stress (CUMS) for seven weeks. The antidepressants CGKL extract and CGKL were administered for the following four weeks. The behavior test and the content of monoamine neurotransmitters were used to evaluate the efficacy of CGKL. The 16S rRNA sequencing, LC-MS technology and molecular biological techniques were used to explore the pharmacological mechanism of CGKL. Results CGKL treatment obviously alleviated the depressive behavioral indicators and regulated the content of monoamine neurotransmitters, and presented dose-dependent manner. CGKL could also improve the arginine metabolism disorder of gut microbiota in the jejunum. Meanwhile, the contents of arginine and its metabolites in the serum and hippocampus were regulated to normal levels. Further investigation indicated that the expression of related rate-limiting enzyme genes and proteins in the hippocampus was validated by qRT-PCR and Western blotting. The results showed that the gut microbiota, metabolites, and genes or proteins of rate-limiting enzymes involved in the arginine pathway were significantly regulated by CGKL. Conclusion The present study demonstrates that CGKL might exert antidepressant effects through regulating arginine metabolism, and its mechanism may be related to modulating the gut microbiota and related metabolic enzyme.
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Affiliation(s)
- Qi Wang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan 030006, China
| | - Yingxia Zhao
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan 030006, China
| | - Xuemei Qin
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan 030006, China
| | - Junsheng Tian
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan 030006, China
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Kolobaric A, Andreescu C, Jašarević E, Hong CH, Roh HW, Cheong JY, Kim YK, Shin TS, Kang CS, Kwon CO, Yoon SY, Hong SW, Aizenstein HJ, Karim HT, Son SJ. Gut microbiome predicts cognitive function and depressive symptoms in late life. Mol Psychiatry 2024; 29:3064-3075. [PMID: 38664490 PMCID: PMC11449789 DOI: 10.1038/s41380-024-02551-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 03/29/2024] [Accepted: 04/03/2024] [Indexed: 10/05/2024]
Abstract
Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.
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Affiliation(s)
- A Kolobaric
- Center for Neuroscience, University of Pittsburgh, Pittsburgh, USA
| | - C Andreescu
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA
| | - E Jašarević
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, USA
- Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, USA
- Magee-Womens Research Institute, Pittsburgh, USA
| | - C H Hong
- Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea
| | - H W Roh
- Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea
| | - J Y Cheong
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Y K Kim
- Institute of MD Healthcare Inc, Seoul, Republic of Korea
| | - T S Shin
- Institute of MD Healthcare Inc, Seoul, Republic of Korea
| | - C S Kang
- Institute of MD Healthcare Inc, Seoul, Republic of Korea
| | - C O Kwon
- Institute of MD Healthcare Inc, Seoul, Republic of Korea
| | - S Y Yoon
- Institute of MD Healthcare Inc, Seoul, Republic of Korea
| | - S W Hong
- Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea
| | - H J Aizenstein
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA
- Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, USA
| | - H T Karim
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
- Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, USA.
| | - S J Son
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
- Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea.
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Taylor B, Hobensack M, Niño de Rivera S, Zhao Y, Masterson Creber R, Cato K. Identifying Depression Through Machine Learning Analysis of Omics Data: Scoping Review. JMIR Nurs 2024; 7:e54810. [PMID: 39028994 PMCID: PMC11297379 DOI: 10.2196/54810] [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: 11/22/2023] [Revised: 04/16/2024] [Accepted: 04/22/2024] [Indexed: 07/21/2024] Open
Abstract
BACKGROUND Depression is one of the most common mental disorders that affects >300 million people worldwide. There is a shortage of providers trained in the provision of mental health care, and the nursing workforce is essential in filling this gap. The diagnosis of depression relies heavily on self-reported symptoms and clinical interviews, which are subject to implicit biases. The omics methods, including genomics, transcriptomics, epigenomics, and microbiomics, are novel methods for identifying the biological underpinnings of depression. Machine learning is used to analyze genomic data that includes large, heterogeneous, and multidimensional data sets. OBJECTIVE This scoping review aims to review the existing literature on machine learning methods for omics data analysis to identify individuals with depression, with the goal of providing insight into alternative objective and driven insights into the diagnostic process for depression. METHODS This scoping review was reported following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. Searches were conducted in 3 databases to identify relevant publications. A total of 3 independent researchers performed screening, and discrepancies were resolved by consensus. Critical appraisal was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. RESULTS The screening process identified 15 relevant papers. The omics methods included genomics, transcriptomics, epigenomics, multiomics, and microbiomics, and machine learning methods included random forest, support vector machine, k-nearest neighbor, and artificial neural network. CONCLUSIONS The findings of this scoping review indicate that the omics methods had similar performance in identifying omics variants associated with depression. All machine learning methods performed well based on their performance metrics. When variants in omics data are associated with an increased risk of depression, the important next step is for clinicians, especially nurses, to assess individuals for symptoms of depression and provide a diagnosis and any necessary treatment.
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Affiliation(s)
- Brittany Taylor
- School of Nursing, Columbia University, New York, NY, United States
| | - Mollie Hobensack
- Brookdale Department of Geriatrics and Palliative Care, Icahn School of Medicine, Mount Sinai Health System, New York, NY, United States
| | | | - Yihong Zhao
- School of Nursing, Columbia University, New York, NY, United States
| | | | - Kenrick Cato
- School of Nursing, University of Pennsylvania, Philadelphia, PA, United States
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10
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Dascălu RC, Bărbulescu AL, Stoica LE, Dinescu ȘC, Biță CE, Popoviciu HV, Ionescu RA, Vreju FA. Review: A Contemporary, Multifaced Insight into Psoriasis Pathogenesis. J Pers Med 2024; 14:535. [PMID: 38793117 PMCID: PMC11122105 DOI: 10.3390/jpm14050535] [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: 03/26/2024] [Revised: 05/09/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
Psoriasis is a chronic recurrent inflammatory autoimmune pathology with a significant genetic component and several interferences of immunological cells and their cytokines. The complex orchestration of psoriasis pathogenesis is related to the synergic effect of immune cells, polygenic alterations, autoantigens, and several other external factors. The major act of the IL-23/IL-17 axis, strongly influencing the inflammatory pattern established during the disease activity, is visible as a continuous perpetuation of the pro-inflammatory response and keratinocyte activation and proliferation, leading to the development of psoriatic lesions. Genome-wide association studies (GWASs) offer a better view of psoriasis pathogenic pathways, with approximately one-third of psoriasis's genetic impact on psoriasis development associated with the MHC region, with genetic loci located on chromosome 6. The most eloquent genetic factor of psoriasis, PSORS1, was identified in the MHC I site. Among the several factors involved in its complex etiology, dysbiosis, due to genetic or external stimulus, induces a burst of pro-inflammatory consequences; both the cutaneous and gut microbiome get involved in the psoriasis pathogenic process. Cutting-edge research studies and comprehensive insights into psoriasis pathogenesis, fostering novel genetic, epigenetic, and immunological factors, have generated a spectacular improvement over the past decades, securing the path toward a specific and targeted immunotherapeutic approach and delayed progression to inflammatory arthritis. This review aimed to offer insight into various domains that underline the pathogenesis of psoriasis and how they influence disease development and evolution. The pathogenesis mechanism of psoriasis is multifaceted and involves an interplay of cellular and humoral immunity, which affects susceptible microbiota and the genetic background. An in-depth understanding of the role of pathogenic factors forms the basis for developing novel and individualized therapeutic targets that can improve disease management.
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Affiliation(s)
- Rucsandra Cristina Dascălu
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (R.C.D.); (C.E.B.); (F.A.V.)
| | - Andreea Lili Bărbulescu
- Department of Pharmacology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Loredana Elena Stoica
- Department of Dermatology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Ștefan Cristian Dinescu
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (R.C.D.); (C.E.B.); (F.A.V.)
| | - Cristina Elena Biță
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (R.C.D.); (C.E.B.); (F.A.V.)
| | - Horațiu Valeriu Popoviciu
- Department of Rheumatology, BFK and Medical Rehabilitation, University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Mures, Romania;
| | - Răzvan Adrian Ionescu
- Third Internal Medicine Department, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania;
| | - Florentin Ananu Vreju
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (R.C.D.); (C.E.B.); (F.A.V.)
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11
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Wei JQ, Bai J, Zhou CH, Yu H, Zhang W, Xue F, He H. Electroacupuncture intervention alleviates depressive-like behaviors and regulates gut microbiome in a mouse model of depression. Heliyon 2024; 10:e30014. [PMID: 38699009 PMCID: PMC11064442 DOI: 10.1016/j.heliyon.2024.e30014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 04/07/2024] [Accepted: 04/18/2024] [Indexed: 05/05/2024] Open
Abstract
Electroacupuncture (EA) is a neuroregulatory therapy for depression. Nonetheless, the effects of EA on the gut microbiome in mice models of depression are not well established. Here, using a chronic unpredictable mild stress (CUMS) model in mice, we evaluated the antidepressant effects of EA and changes in gut microbiota with behavioral tests and 16S rRNA gene sequencing. The results found that EA increased the time spent in the center area of the open-field test and the percentage of sucrose preference and reduced the immobility time in the tail suspension test in CUMS-treated mice. Furthermore, the genus Lachnoclostridium, Ruminococcaceae_UCG-002 and Rikenellaceae_RC9_gut_group were enriched in the CUMS group, which was positively correlated with depressive-like behaviors. Whereas phylum Actinobacteria and genus Allobaculum, Bifidobacterium, Dubosiella, Rikenella and Ileibacterium were enriched in the EA and CUMS + EA groups, all of which were negatively correlated with depressive-like behaviors. This study characterizes gut microbiota under EA treatment and provides new insights into the association of anti-depressive-like effects of EA and gut microbiota.
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Affiliation(s)
- Jia-quan Wei
- Department of Psychiatry, Xi'an Gaoxin Hospital, Xi'an, 710077, China
| | - Jie Bai
- Department of Psychiatry, Xi'an Gaoxin Hospital, Xi'an, 710077, China
| | - Cui-hong Zhou
- Department of Psychiatry, Xijing Hospital, Xi'an, 710032, China
| | - Huan Yu
- Department of Psychiatry, Xijing Hospital, Xi'an, 710032, China
| | - Wen Zhang
- Department of Psychiatry, Xi'an Gaoxin Hospital, Xi'an, 710077, China
| | - Fen Xue
- Department of Psychiatry, Xi'an Gaoxin Hospital, Xi'an, 710077, China
| | - Hong He
- Department of Psychiatry, Xi'an Gaoxin Hospital, Xi'an, 710077, China
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12
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Warren A, Nyavor Y, Beguelin A, Frame LA. Dangers of the chronic stress response in the context of the microbiota-gut-immune-brain axis and mental health: a narrative review. Front Immunol 2024; 15:1365871. [PMID: 38756771 PMCID: PMC11096445 DOI: 10.3389/fimmu.2024.1365871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 04/22/2024] [Indexed: 05/18/2024] Open
Abstract
More than 20% of American adults live with a mental disorder, many of whom are treatment resistant or continue to experience symptoms. Other approaches are needed to improve mental health care, including prevention. The role of the microbiome has emerged as a central tenet in mental and physical health and their interconnectedness (well-being). Under normal conditions, a healthy microbiome promotes homeostasis within the host by maintaining intestinal and brain barrier integrity, thereby facilitating host well-being. Owing to the multidirectional crosstalk between the microbiome and neuro-endocrine-immune systems, dysbiosis within the microbiome is a main driver of immune-mediated systemic and neural inflammation that can promote disease progression and is detrimental to well-being broadly and mental health in particular. In predisposed individuals, immune dysregulation can shift to autoimmunity, especially in the presence of physical or psychological triggers. The chronic stress response involves the immune system, which is intimately involved with the gut microbiome, particularly in the process of immune education. This interconnection forms the microbiota-gut-immune-brain axis and promotes mental health or disorders. In this brief review, we aim to highlight the relationships between stress, mental health, and the gut microbiome, along with the ways in which dysbiosis and a dysregulated immune system can shift to an autoimmune response with concomitant neuropsychological consequences in the context of the microbiota-gut-immune-brain axis. Finally, we aim to review evidenced-based prevention strategies and potential therapeutic targets.
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Affiliation(s)
- Alison Warren
- The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
| | - Yvonne Nyavor
- Department of Biotechnology, Harrisburg University of Science and Technology, Harrisburg, PA, United States
| | - Aaron Beguelin
- The Department of Biotechnology, Johns Hopkins University, Baltimore, MD, United States
| | - Leigh A. Frame
- The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
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13
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Bai Y, Shu C, Hou Y, Wang GH. Adverse childhood experience and depression: the role of gut microbiota. Front Psychiatry 2024; 15:1309022. [PMID: 38628262 PMCID: PMC11019508 DOI: 10.3389/fpsyt.2024.1309022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 03/18/2024] [Indexed: 04/19/2024] Open
Abstract
Depression is the most common psychiatric disorder that burdens modern society heavily. Numerous studies have shown that adverse childhood experiences can increase susceptibility to depression, and depression with adverse childhood experiences has specific clinical-biological features. However, the specific neurobiological mechanisms are not yet precise. Recent studies suggest that the gut microbiota can influence brain function and behavior associated with depression through the "microbe-gut-brain axis" and that the composition and function of the gut microbiota are influenced by early stress. These studies offer a possibility that gut microbiota mediates the relationship between adverse childhood experiences and depression. However, few studies directly link adverse childhood experiences, gut microbiota, and depression. This article reviews recent studies on the relationship among adverse childhood experiences, gut microbiota, and depression, intending to provide insights for new research.
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Affiliation(s)
- Yu Bai
- Department of Psychiatry, Renmin Hospital of Wuhan University, Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Chang Shu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Ying Hou
- Peking University China-Japan Friendship School of Clinical Medicine, Department of Neurology, Beijing, China
| | - Gao-Hua Wang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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14
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Braga JD, Thongngam M, Kumrungsee T. Gamma-aminobutyric acid as a potential postbiotic mediator in the gut-brain axis. NPJ Sci Food 2024; 8:16. [PMID: 38565567 PMCID: PMC10987602 DOI: 10.1038/s41538-024-00253-2] [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: 07/26/2023] [Accepted: 02/01/2024] [Indexed: 04/04/2024] Open
Abstract
Gamma-aminobutyric acid (GABA) plays a crucial role in the central nervous system as an inhibitory neurotransmitter. Imbalances of this neurotransmitter are associated with neurological diseases, such as Alzheimer's and Parkinson's disease, and psychological disorders, including anxiety, depression, and stress. Since GABA has long been believed to not cross the blood-brain barrier, the effects of circulating GABA on the brain are neglected. However, emerging evidence has demonstrated that changes in both circulating and brain levels of GABA are associated with changes in gut microbiota composition and that changes in GABA levels and microbiota composition play a role in modulating mental health. This recent research has raised the possibility that GABA may be a potent mediator of the gut-brain axis. This review article will cover up-to-date information about GABA-producing microorganisms isolated from human gut and food sources, explanation why those microorganisms produce GABA, food factors inducing gut-GABA production, evidence suggesting GABA as a mediator linking between gut microbiota and mental health, including anxiety, depression, stress, epilepsy, autism spectrum disorder, and attention deficit hyperactivity disorder, and novel information regarding homocarnosine-a predominant brain peptide that is a putative downstream mediator of GABA in regulating brain functions. This review will help us to understand how the gut microbiota and GABA-homocarnosine metabolism play a significant role in brain functions. Nonetheless, it could support further research on the use of GABA production-inducing microorganisms and food factors as agents to treat neurological and psychological disorders.
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Affiliation(s)
- Jason D Braga
- Laboratory of Molecular Nutrition, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, 739-8527, Japan
- Institute of Food Science and Technology, College of Agriculture, Food, Environment and Natural Resources, Cavite State University, Indang, Cavite, 4122, Philippines
| | - Masubon Thongngam
- Department of Food Science and Technology, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900, Thailand
| | - Thanutchaporn Kumrungsee
- Laboratory of Molecular Nutrition, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, 739-8527, Japan.
- Smart Agriculture, Graduate School of Innovation and Practice for Smart Society, Hiroshima University, Hiroshima, 739-8527, Japan.
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15
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Dilmore AH, Kuplicki R, McDonald D, Kumar M, Estaki M, Youngblut N, Tyakht A, Ackermann G, Blach C, MahmoudianDehkordi S, Dunlop BW, Bhattacharyya S, Guinjoan S, Mandaviya P, Ley RE, Kaddaruh-Dauok R, Paulus MP, Knight R, Alzheimer Gut Microbiome Project Consortium. Medication Use is Associated with Distinct Microbial Features in Anxiety and Depression. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.03.19.585820. [PMID: 38562901 PMCID: PMC10983923 DOI: 10.1101/2024.03.19.585820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by DSM-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing and shallow shotgun sequencing were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and NeuroMAP CoBRE cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. The findings suggest that future research on the gut microbiota's role in NPD and its interactions with pharmacological treatments are needed.
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Affiliation(s)
- Amanda Hazel Dilmore
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
| | - Rayus Kuplicki
- Laureate Institute for Brain Research, Tulsa, Oklahoma, USA
| | - Daniel McDonald
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Megha Kumar
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Mehrbod Estaki
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Nicholas Youngblut
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Alexander Tyakht
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Gail Ackermann
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Colette Blach
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA
- Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Institute of Brain Sciences, Duke University, Durham, North Carolina, USA
| | | | - Boadie W. Dunlop
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Sudeepa Bhattacharyya
- Department of Biological Sciences, Arkansas Biosciences Institute, Arkansas State University, Jonesboro, AR, USA
| | | | - Pooja Mandaviya
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Ruth E. Ley
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Rima Kaddaruh-Dauok
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA
- Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Institute of Brain Sciences, Duke University, Durham, North Carolina, USA
| | | | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Department of Computer Science & Engineering, University of California San Diego, La Jolla, California, USA
- Department of Bioengineering, University of California San Diego, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
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16
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Matin S, Dadkhah M. BDNF/CREB signaling pathway contribution in depression pathogenesis: A survey on the non-pharmacological therapeutic opportunities for gut microbiota dysbiosis. Brain Res Bull 2024; 207:110882. [PMID: 38244808 DOI: 10.1016/j.brainresbull.2024.110882] [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: 10/02/2023] [Revised: 12/04/2023] [Accepted: 01/15/2024] [Indexed: 01/22/2024]
Abstract
Emerging evidence supports the gut microbiota and the brain communication in general health. This axis may affect behavior through modulating neurotransmission, and thereby involve in the pathogenesis and/or progression of different neuropsychiatric disorders such as depression. Brain-derived neurotrophic factor and cAMP response element-binding protein known as CREB/BDNF pathway plays have critical functions in the pathogenesis of depression as the same of mechanisms related to antidepressants. However, the putative causal significance of the CREB/BDNF signaling cascade in the gut-brain axis in depression remains unknown. Also interventions such as probiotics supplementation and exercise can influence microbiome also improve bidirectional communication of gut and brain. In this review we aim to explain the BDNF/CREB signaling pathway and gut microbiota dysfunction and then evaluate the potential role of probiotics, prebiotics, and exercise as a therapeutic target in the gut microbiota dysfunction induced depression. The current narrative review will specifically focus on the impact of exercise and diet on the intestinal microbiota component, as well as the effect that these therapies may have on the microbiota to alleviate depressive symptoms. Finally, we look at how BDNF/CREB signaling pathway may exert distinct effects on depression and gut microbiota dysfunction.
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Affiliation(s)
- Somaieh Matin
- Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Masoomeh Dadkhah
- Pharmaceutical Sciences Research center, Ardabil University of Medical Sciences, Ardabil, Iran.
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17
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Badrulhisham F, Pogatzki-Zahn E, Segelcke D, Spisak T, Vollert J. Machine learning and artificial intelligence in neuroscience: A primer for researchers. Brain Behav Immun 2024; 115:470-479. [PMID: 37972877 DOI: 10.1016/j.bbi.2023.11.005] [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: 04/26/2023] [Revised: 10/16/2023] [Accepted: 11/08/2023] [Indexed: 11/19/2023] Open
Abstract
Artificial intelligence (AI) is often used to describe the automation of complex tasks that we would attribute intelligence to. Machine learning (ML) is commonly understood as a set of methods used to develop an AI. Both have seen a recent boom in usage, both in scientific and commercial fields. For the scientific community, ML can solve bottle necks created by complex, multi-dimensional data generated, for example, by functional brain imaging or *omics approaches. ML can here identify patterns that could not have been found using traditional statistic approaches. However, ML comes with serious limitations that need to be kept in mind: their tendency to optimise solutions for the input data means it is of crucial importance to externally validate any findings before considering them more than a hypothesis. Their black-box nature implies that their decisions usually cannot be understood, which renders their use in medical decision making problematic and can lead to ethical issues. Here, we present an introduction for the curious to the field of ML/AI. We explain the principles as commonly used methods as well as recent methodological advancements before we discuss risks and what we see as future directions of the field. Finally, we show practical examples of neuroscience to illustrate the use and limitations of ML.
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Affiliation(s)
| | - Esther Pogatzki-Zahn
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany
| | - Daniel Segelcke
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany
| | - Tamas Spisak
- Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Medicine Essen, Essen, Germany; Center for Translational Neuro- and Behavioral Sciences, Department of Neurology, University Medicine Essen, Essen, Germany
| | - Jan Vollert
- Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, United Kingdom; Pain Research, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
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18
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Gao M, Wang J, Liu P, Tu H, Zhang R, Zhang Y, Sun N, Zhang K. Gut microbiota composition in depressive disorder: a systematic review, meta-analysis, and meta-regression. Transl Psychiatry 2023; 13:379. [PMID: 38065935 PMCID: PMC10709466 DOI: 10.1038/s41398-023-02670-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 10/22/2023] [Accepted: 11/17/2023] [Indexed: 12/18/2023] Open
Abstract
Studies investigating gut microbiota composition in depressive disorder have yielded mixed results. The aim of our study was to compare gut microbiome between people with depressive disorder and healthy controls. We did a meta-analysis and meta-regression of studies by searching PubMed, Web of Science, Embase, Scopus, Ovid, Cochrane Library, ProQuest, and PsycINFO for articles published from database inception to March 07, 2022. Search strategies were then re-run on 12 March 2023 for an update. We undertook meta-analyses whenever values of alpha diversity and Firmicutes, Bacteroidetes (relative abundance) were available in two or more studies. A random-effects model with restricted maximum-likelihood estimator was used to synthesize the effect size (assessed by standardized mean difference [SMD]) across studies. We identified 44 studies representing 2091 patients and 2792 controls. Our study found that there were no significant differences in patients with depressive disorder on alpha diversity indices, Firmicutes and Bacteroidetes compared with healthy controls. In subgroup analyses with regional variations(east/west) as a predictor, patients who were in the West had a lower Chao1 level (SMD -0.42[-0.74 to -0.10]). Subgroup meta-analysis showed Firmicutes level was decreased in patients with depressive disorder who were medication-free (SMD -1.54[-2.36 to -0.72]), but Bacteroidetes level was increased (SMD -0.90[0.07 to 1.72]). In the meta-regression analysis, six variables cannot explain the 100% heterogeneity of the studies assessing by Chao1, Shannon index, Firmicutes, and Bacteroidetes. Depleted levels of Butyricicoccus, Coprococcus, Faecalibacterium, Fusicatenibacter, Romboutsia, and enriched levels of Eggerthella, Enterococcus, Flavonifractor, Holdemania, Streptococcus were consistently shared in depressive disorder. This systematic review and meta-analysis found that psychotropic medication and dietary habit may influence microbiota. There is reliable evidence for differences in the phylogenetic relationship in depressive disorder compared with controls, however, method of measurement and method of patient classification (symptom vs diagnosis based) may affect findings. Depressive disorder is characterized by an increase of pro-inflammatory bacteria, while anti-inflammatory butyrate-producing genera are depleted.
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Affiliation(s)
- Mingxue Gao
- Department of Psychiatry, First Hospital of Shanxi Medical University, 030001, Taiyuan, China
- First Clinical Medical College, Shanxi Medical University, 030001, Taiyuan, China
| | - Jizhi Wang
- Department of Psychiatry, First Hospital of Shanxi Medical University, 030001, Taiyuan, China
- First Clinical Medical College, Shanxi Medical University, 030001, Taiyuan, China
| | - Penghong Liu
- Department of Psychiatry, First Hospital of Shanxi Medical University, 030001, Taiyuan, China
- First Clinical Medical College, Shanxi Medical University, 030001, Taiyuan, China
| | - Hongwei Tu
- Department of Psychiatry, First Hospital of Shanxi Medical University, 030001, Taiyuan, China
- First Clinical Medical College, Shanxi Medical University, 030001, Taiyuan, China
| | - Ruiyu Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, 030001, Taiyuan, China
- First Clinical Medical College, Shanxi Medical University, 030001, Taiyuan, China
| | - Yanyan Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, 030001, Taiyuan, China
- Basic Medical College, Shanxi Medical University, 030001, Taiyuan, China
| | - Ning Sun
- Department of Psychiatry, First Hospital of Shanxi Medical University, 030001, Taiyuan, China.
- First Clinical Medical College, Shanxi Medical University, 030001, Taiyuan, China.
| | - Kerang Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, 030001, Taiyuan, China.
- First Clinical Medical College, Shanxi Medical University, 030001, Taiyuan, China.
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19
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Zhou C, Chen Y, Xue S, Shi Q, Guo L, Yu H, Xue F, Cai M, Wang H, Peng Z. rTMS ameliorates depressive-like behaviors and regulates the gut microbiome and medium- and long-chain fatty acids in mice exposed to chronic unpredictable mild stress. CNS Neurosci Ther 2023; 29:3549-3566. [PMID: 37269082 PMCID: PMC10580350 DOI: 10.1111/cns.14287] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 04/18/2023] [Accepted: 05/23/2023] [Indexed: 06/04/2023] Open
Abstract
INTRODUCTION Repetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established. METHODS Mice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive-like behaviors, the composition of gut microbiota of stool samples, as well as medium- and long-chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated. RESULTS CUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive-like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC. CONCLUSION These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS.
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Affiliation(s)
- Cui‐Hong Zhou
- Department of Psychiatry, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Yi‐Huan Chen
- Department of Psychiatry, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Shan‐Shan Xue
- Department of Psychiatry, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Qing‐Qing Shi
- Department of Psychiatry, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Lin Guo
- Department of PsychiatryChang'an HospitalXi'anChina
| | - Huan Yu
- Department of Psychiatry, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Fen Xue
- Department of Psychiatry, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Min Cai
- Department of Psychiatry, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Hua‐Ning Wang
- Department of Psychiatry, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Zheng‐Wu Peng
- Department of Psychiatry, Xijing HospitalAir Force Medical UniversityXi'anChina
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20
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Kouraki A, Kelly A, Vijay A, Gohir S, Astbury S, Georgopoulos V, Millar B, Walsh DA, Ferguson E, Menni C, Valdes AM. Reproducible microbiome composition signatures of anxiety and depressive symptoms. Comput Struct Biotechnol J 2023; 21:5326-5336. [PMID: 37954149 PMCID: PMC10637863 DOI: 10.1016/j.csbj.2023.10.035] [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: 06/13/2023] [Revised: 10/17/2023] [Accepted: 10/17/2023] [Indexed: 11/14/2023] Open
Abstract
The gut microbiome is a significant contributor to mental health, with growing evidence linking its composition to anxiety and depressive disorders. Gut microbiome composition is associated with signs of anxiety and depression both in clinically diagnosed mood disorders and subclinically in the general population and may be influenced by dietary fibre intake and the presence of chronic pain. We provide an update of current evidence on the role of gut microbiome composition in depressive and anxiety disorders or symptoms by reviewing available studies. Analysing data from three independent cohorts (osteoarthritis 1 (OA1); n = 46, osteoarthritis 2 (OA2); n = 58, and healthy controls (CON); n = 67), we identified microbial composition signatures of anxiety and depressive symptoms at genus level and cross-validated our findings performing meta-analyses of our results with results from previously published studies. The genera Bifidobacterium (fixed-effect beta (95% CI) = -0.22 (-0.34, -0.10), p = 3.90e-04) and Lachnospiraceae NK4A136 group (fixed-effect beta (95% CI) = -0.09 (-0.13, -0.05), p = 2.53e-06) were found to be the best predictors of anxiety and depressive symptoms, respectively, across our three cohorts and published literature taking into account demographic and lifestyle covariates, such as fibre intake. The association with anxiety was robust in accounting for heterogeneity between cohorts and supports previous observations of the potential prophylactic effect of Bifidobacterium against anxiety symptoms.
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Affiliation(s)
- Afroditi Kouraki
- Academic Unit of Injury, Recovery and Inflammation Sciences, Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Anthony Kelly
- Academic Unit of Injury, Recovery and Inflammation Sciences, Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Amrita Vijay
- Academic Unit of Injury, Recovery and Inflammation Sciences, Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK
| | - Sameer Gohir
- Academic Unit of Injury, Recovery and Inflammation Sciences, Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Stuart Astbury
- Academic Unit of Injury, Recovery and Inflammation Sciences, Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
| | - Vasileios Georgopoulos
- Academic Unit of Injury, Recovery and Inflammation Sciences, Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK
- Pain Centre Versus Arthritis, University of Nottingham, Nottingham, UK
| | - Bonnie Millar
- Academic Unit of Injury, Recovery and Inflammation Sciences, Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Pain Centre Versus Arthritis, University of Nottingham, Nottingham, UK
| | - David Andrew Walsh
- Academic Unit of Injury, Recovery and Inflammation Sciences, Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Pain Centre Versus Arthritis, University of Nottingham, Nottingham, UK
| | - Eamonn Ferguson
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Pain Centre Versus Arthritis, University of Nottingham, Nottingham, UK
- School of Psychology, University of Nottingham, University Park, Nottingham, UK
- National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Cristina Menni
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK
| | - Ana M. Valdes
- Academic Unit of Injury, Recovery and Inflammation Sciences, Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Pain Centre Versus Arthritis, University of Nottingham, Nottingham, UK
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21
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Constantin C, Surcel M, Munteanu A, Neagu M. Insights into Nutritional Strategies in Psoriasis. Nutrients 2023; 15:3528. [PMID: 37630719 PMCID: PMC10458768 DOI: 10.3390/nu15163528] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/18/2023] [Accepted: 07/26/2023] [Indexed: 08/27/2023] Open
Abstract
Psoriasis, an autoimmune chronic inflammatory skin condition, has a high incidence in the general population, reaching 2-4%. Its pathogenesis involves an interplay of genetic factors, immune disturbances, and environmental factors. Within the environmental factors that aid the appearance of this autoimmune skin disease, the Western lifestyle and overall diet play important roles in the steady growth in psoriasis prevalence. Furthermore, psoriasis is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, and obesity. Accumulating evidence suggests that obesity is an important risk factor for psoriasis. Moreover, obesity aggravates established psoriasis, and a reduction in the body mass index can improve the clinical outcomes of psoriasis and increase the efficacy of standard psoriasis therapies. The possible connection between this autoimmune disease and obesity relies on the fact that white adipose tissue is an essential endocrine organ that secretes an array of immune mediators and inflammatory and metabolic factors with pro-inflammatory action. Thus, immune-mediated mechanisms in both psoriasis and obesity conditions are common factors. This paper describes the factors that link obesity with skin autoimmune disease and highlights the importance of the stimulatory or regulatory effects of nutrients and food in psoriasis and the possible improvement of psoriasis through nutritional strategies.
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Affiliation(s)
- Carolina Constantin
- Immunology Department, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania; (C.C.); (M.S.); (A.M.)
- Pathology Department, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Mihaela Surcel
- Immunology Department, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania; (C.C.); (M.S.); (A.M.)
| | - Adriana Munteanu
- Immunology Department, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania; (C.C.); (M.S.); (A.M.)
| | - Monica Neagu
- Immunology Department, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania; (C.C.); (M.S.); (A.M.)
- Pathology Department, Colentina Clinical Hospital, 020125 Bucharest, Romania
- Doctoral School, Faculty of Biology, University of Bucharest, 050107 Bucharest, Romania
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22
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Chang J, Huang K, Wang W. The influence of parenting style in childhood on adult depressed patients' interpersonal relationships in the period of youth. Front Psychol 2023; 14:1169311. [PMID: 37583608 PMCID: PMC10425184 DOI: 10.3389/fpsyg.2023.1169311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 05/02/2023] [Indexed: 08/17/2023] Open
Abstract
Objective The objective of this study was to explore the mediating effect of adolescent self and courage on the relationship between parenting style in childhood and adult depressed patients' interpersonal relationships in the period of youth. Methods The study analyzed data from 651 depressed individuals using the Wang Weidong memory-tracing personality developmental inventory (WMPI) from the psychology department of Guang'anmen Hospital. Results The results of the study show a significant positive correlation between parenting style in childhood, adolescent self, courage, and adult depressed patients' interpersonal relationships in the period of youth. Parenting style in childhood has a direct positive predictive effect on adult depressed patients' interpersonal relationships in the period of youth. It also has an indirect effect on interpersonal relationships in the period of youth through three indirect pathways: the independent mediating effect of adolescent self, the independent mediating effect of adolescent courage, and the chain mediating effect of adolescent self and courage. Conclusion The findings of this study suggest that parenting style in childhood plays an important role in shaping adult depressed patients' interpersonal relationships in the period of youth. The relationship between parenting style in childhood and interpersonal relationships in the period of youth is influenced by the independent mediating effect of adolescent self and courage, as well as the chain mediating effect of adolescent self and courage. These findings have implications for the development of interventions and programs aimed at improving the mental health and well-being of depressed patients.
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Affiliation(s)
- Jingjing Chang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Qinhuangdao Beidaihe Hospital, Hebei, China
| | - Kaiyi Huang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Weidong Wang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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23
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Chen MM, Wang P, Xie XH, Nie Z, Xu SX, Zhang N, Wang W, Yao L, Liu Z. Young adults with major depression show altered microbiome. Neuroscience 2023; 522:23-32. [PMID: 37169166 DOI: 10.1016/j.neuroscience.2023.05.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 04/26/2023] [Accepted: 05/02/2023] [Indexed: 05/13/2023]
Abstract
There is growing basic and clinical evidence that major depressive disorder (MDD) is associated with gut microbiome alterations, but clinical studies have tended not to adjust for confounding factors. And few studies on the gut microbiome focused on young adults with MDD. Here we performed a pilot study to compare the gut microbiome of young adults with MDD with healthy controls. Shotgun metagenomic sequencing was performed on stool samples obtained from 40 young adults with MDD and 42 healthy controls. After controlling for confounding factors including sex, age, BMI, alcohol or cigarette consumption, bowel movement quality, exercise or defecation frequency, we compared microbiome diversity between groups, identified differentially abundant taxa, and further compared functional differences through gut-brain and gut-metabolic module analysis. There were no significant differences in overall gut microbiome structure and function in young adults with MDD compared with controls. Abundance of Sutterellaceae and species belonging to Clostridium, Eubacterium, and Ruminococcus were significantly different between groups. The cysteine degradation I pathway was increased in MDD. After controlling for most confounding factors, this pilot study provides new evidence on the specific, often subtle gut dysbiosis affecting young adults with depression.
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Affiliation(s)
- Mian-Mian Chen
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Peilin Wang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Xin-Hui Xie
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Zhaowen Nie
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Shu-Xian Xu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Nan Zhang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Wei Wang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Lihua Yao
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Zhongchun Liu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China.
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24
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Chin Fatt CR, Asbury S, Jha MK, Minhajuddin A, Sethuram S, Mayes T, Kennedy SH, Foster JA, Trivedi MH. Leveraging the microbiome to understand clinical heterogeneity in depression: findings from the T-RAD study. Transl Psychiatry 2023; 13:139. [PMID: 37117195 PMCID: PMC10147668 DOI: 10.1038/s41398-023-02416-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 01/25/2023] [Accepted: 03/24/2023] [Indexed: 04/30/2023] Open
Abstract
Alterations in the gut microbiome have been linked to a variety of mental illnesses including anxiety and depression. This study utilized advanced bioinformatics tools that integrated both the compositional and community nature of gut microbiota to investigate how gut microbiota influence clinical symptoms in a sample of participants with depression. Gut microbiota of 179 participants with major depressive disorder (MDD) in the Texas Resilience Against Depression (T-RAD) study were analyzed by 16S rRNA gene sequencing of stool samples. Severity of anxiety, depression, and anhedonia symptoms were assessed with General Anxiety Disorder - 7 item scale, Patient Health 9-item Questionnaire, and Dimensional Anhedonia Rating Scale, respectively. Using weighted correlation network analysis, a data-driven approach, three co-occurrence networks of bacterial taxa were identified. One of these co-occurrence networks was significantly associated with clinical features including depression and anxiety. The hub taxa associated with this co-occurrence module -one Ruminococcaceae family taxon, one Clostridiales vadinBB60 group family taxon, and one Christencenellaceae family taxon- were connected to several additional butyrate-producing bacteria suggesting that deficits in butyrate production may contribute to clinical symptoms. Therefore, by considering the community nature of the gut microbiome in a real world clinical sample, this study identified a gut microbial co-occurrence network that was significantly associated with clinical anxiety in a cohort of depressed individuals.
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Affiliation(s)
- Cherise R Chin Fatt
- Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Sarah Asbury
- Department of Psychiatry & Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada
| | - Manish K Jha
- Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Abu Minhajuddin
- Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Sangita Sethuram
- Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Taryn Mayes
- Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Sidney H Kennedy
- Department of Psychiatry, University of Toronto and Centre for Depression and Suicide Studies, Unity Health, Toronto, ON, Canada
| | - Jane A Foster
- Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
- Department of Psychiatry & Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
| | - Madhukar H Trivedi
- Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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25
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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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26
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Bosch JA, Nieuwdorp M, Zwinderman AH, Deschasaux M, Radjabzadeh D, Kraaij R, Davids M, de Rooij SR, Lok A. The gut microbiota and depressive symptoms across ethnic groups. Nat Commun 2022; 13:7129. [PMID: 36473853 PMCID: PMC9726934 DOI: 10.1038/s41467-022-34504-1] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 10/27/2022] [Indexed: 12/12/2022] Open
Abstract
The gut microbiome is thought to play a role in depressive disorders, which makes it an attractive target for interventions. Both the microbiome and depressive symptom levels vary substantially across ethnic groups. Thus, any intervention for depression targeting the microbiome requires understanding of microbiome-depression associations across ethnicities. Analysing data from the HELIUS cohort, we characterize the gut microbiota and its associations with depressive symptoms in 6 ethnic groups (Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, Moroccan; N = 3211), living in the same urban area. Diversity of the gut microbiota, both within (α-diversity) and between individuals (β-diversity), predicts depressive symptom levels, taking into account demographic, behavioural, and medical differences. These associations do not differ between ethnic groups. Further, β-diversity explains 29%-18% of the ethnic differences in depressive symptoms. Bacterial genera associated with depressive symptoms belong to mulitple families, prominently including the families Christensenellaceae, Lachnospiraceae, and Ruminococcaceae. In summary, the results show that the gut microbiota are linked to depressive symptom levels and that this association generalizes across ethnic groups. Moreover, the results suggest that ethnic differences in the gut microbiota may partly explain parallel disparities in depression.
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Affiliation(s)
- Jos A Bosch
- Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands.
- Department of Medical Psychology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Aeilko H Zwinderman
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Mélanie Deschasaux
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
- Paris 13 - Sorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center - University of Paris (CRESS), Bobigny, France
| | - Djawad Radjabzadeh
- Department of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Robert Kraaij
- Department of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Mark Davids
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Susanne R de Rooij
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Anja Lok
- Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
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27
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Freimer D, Yang TT, Ho TC, Tymofiyeva O, Leung C. The gut microbiota, HPA axis, and brain in adolescent-onset depression: Probiotics as a novel treatment. Brain Behav Immun Health 2022; 26:100541. [PMID: 36536630 PMCID: PMC9758412 DOI: 10.1016/j.bbih.2022.100541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 10/22/2022] [Indexed: 11/09/2022] Open
Abstract
Stress-associated disruptions in the development of frontolimbic regions may play a critical role in the emergence of adolescent-onset depression. These regions are particularly sensitive to Hypothalamic-Pituitary-Adrenal (HPA) axis signaling. The HPA axis is hyperactive in adolescent depression, and interventions that attenuate such hyperactivity hold promise as potential treatments. The Microbiome-Gut-Brain (MGB) axis is an important pathway through which stress dysregulates HPA-axis activity and thus exerts deleterious effects on the adolescent brain. Probiotic agents, which alter the gut microbiota composition by introducing bacterial strains with beneficial physiological effects, normalize aberrant HPA-axis activity and reduce depressive symptoms in both animal studies and adult clinical trials. While the potential utility of such agents in treating or preventing adolescent depression remains largely unexplored, recent data suggest the existence of an adolescent sensitive window during which probiotics may be especially efficacious in reducing depressive symptoms compared to effects observed in adult populations. In this review, we outline evidence that probiotic use may attenuate stress effects on frontolimbic development, providing a novel means of improving depressive symptoms among adolescent populations.
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Affiliation(s)
- Daniel Freimer
- University of California, San Francisco (UCSF), School of Medicine, USA
| | - Tony T. Yang
- University of California, San Francisco (UCSF), School of Medicine, USA
- Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, USA
- Division of Child and Adolescent Psychiatry, USA
- The Langley Porter Psychiatric Institute, USA
| | - Tiffany C. Ho
- University of California, San Francisco (UCSF), School of Medicine, USA
- Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, USA
| | - Olga Tymofiyeva
- University of California, San Francisco (UCSF), School of Medicine, USA
- Department of Radiology and Biomedical Imaging, USA
| | - Cherry Leung
- University of California, San Francisco (UCSF), School of Nursing, Department of Community Health Systems, USA
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28
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Antidepressive Effect of Natural Products and Their Derivatives Targeting BDNF-TrkB in Gut-Brain Axis. Int J Mol Sci 2022; 23:ijms232314968. [PMID: 36499295 PMCID: PMC9737781 DOI: 10.3390/ijms232314968] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/24/2022] [Accepted: 11/25/2022] [Indexed: 12/04/2022] Open
Abstract
Modern neurological approaches enable detailed studies on the pathophysiology and treatment of depression. An imbalance in the microbiota-gut-brain axis contributes to the pathogenesis of depression. This extensive review aimed to elucidate the antidepressive effects of brain-derived neurotrophic factor (BDNF)-targeting therapeutic natural products and their derivatives on the gut-brain axis. This information could facilitate the development of novel antidepressant drugs. BDNF is crucial for neuronal genesis, growth, differentiation, survival, plasticity, and synaptic transmission. Signaling via BDNF and its receptor tropomyosin receptor kinase B (TrkB) plays a vital role in the etiopathogenesis of depression and the therapeutic mechanism of antidepressants. This comprehensive review provides information to researchers and scientists for the identification of novel therapeutic approaches for neuropsychiatric disorders, especially depression and stress. Future research should aim to determine the possible causative role of BDNF-TrkB in the gut-brain axis in depression, which will require further animal and clinical research as well as the development of analytical approaches.
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29
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Anderson EM, Rozowsky JM, Fazzone BJ, Schmidt EA, Stevens BR, O’Malley KA, Scali ST, Berceli SA. Temporal Dynamics of the Intestinal Microbiome Following Short-Term Dietary Restriction. Nutrients 2022; 14:2785. [PMID: 35889742 PMCID: PMC9318361 DOI: 10.3390/nu14142785] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 06/28/2022] [Accepted: 07/02/2022] [Indexed: 12/04/2022] Open
Abstract
Short-term dietary restriction has been proposed as an intriguing pre-operative conditioning strategy designed to attenuate the surgical stress response and improve outcomes. However, it is unclear how this nutritional intervention influences the microbiome, which is known to modulate the systemic condition. Healthy individuals were recruited to participate in a four-day, 70% protein-restricted, 30% calorie-restricted diet, and stool samples were collected at baseline, after the restricted diet, and after resuming normal food intake. Taxonomy and functional pathway analysis was performed via shotgun metagenomic sequencing, prevalence filtering, and differential abundance analysis. High prevalence species were altered by the dietary intervention but quickly returned to baseline after restarting a regular diet. Composition and functional changes after the restricted diet included the decreased relative abundance of commensal bacteria and a catabolic phenotype. Notable species changes included Faecalibacterium prausnitzii and Roseburia intestinalis, which are major butyrate producers within the colon and are characteristically decreased in many disease states. The macronutrient components of the diet might have influenced these changes. We conclude that short-term dietary restriction modulates the ecology of the gut microbiome, with this modulation being characterized by a relative dysbiosis.
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Affiliation(s)
- Erik M. Anderson
- Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Rd., Gainesville, FL 32610, USA; (E.M.A.); (J.M.R.); (B.J.F.); (E.A.S.); (K.A.O.); (S.T.S.)
- Department of Surgery, Malcolm Randall Veteran Affairs Medical Center, 1601 SW Archer Rd., Gainesville, FL 32610, USA
| | - Jared M. Rozowsky
- Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Rd., Gainesville, FL 32610, USA; (E.M.A.); (J.M.R.); (B.J.F.); (E.A.S.); (K.A.O.); (S.T.S.)
- Department of Surgery, Malcolm Randall Veteran Affairs Medical Center, 1601 SW Archer Rd., Gainesville, FL 32610, USA
| | - Brian J. Fazzone
- Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Rd., Gainesville, FL 32610, USA; (E.M.A.); (J.M.R.); (B.J.F.); (E.A.S.); (K.A.O.); (S.T.S.)
- Department of Surgery, Malcolm Randall Veteran Affairs Medical Center, 1601 SW Archer Rd., Gainesville, FL 32610, USA
| | - Emilie A. Schmidt
- Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Rd., Gainesville, FL 32610, USA; (E.M.A.); (J.M.R.); (B.J.F.); (E.A.S.); (K.A.O.); (S.T.S.)
- Department of Surgery, Malcolm Randall Veteran Affairs Medical Center, 1601 SW Archer Rd., Gainesville, FL 32610, USA
| | - Bruce R. Stevens
- Department of Physiology and Functional Genomics, University of Florida College of Medicine, 1600 SW Archer Rd., Gainesville, FL 32610, USA;
| | - Kerri A. O’Malley
- Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Rd., Gainesville, FL 32610, USA; (E.M.A.); (J.M.R.); (B.J.F.); (E.A.S.); (K.A.O.); (S.T.S.)
- Department of Surgery, Malcolm Randall Veteran Affairs Medical Center, 1601 SW Archer Rd., Gainesville, FL 32610, USA
| | - Salvatore T. Scali
- Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Rd., Gainesville, FL 32610, USA; (E.M.A.); (J.M.R.); (B.J.F.); (E.A.S.); (K.A.O.); (S.T.S.)
- Department of Surgery, Malcolm Randall Veteran Affairs Medical Center, 1601 SW Archer Rd., Gainesville, FL 32610, USA
| | - Scott A. Berceli
- Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Rd., Gainesville, FL 32610, USA; (E.M.A.); (J.M.R.); (B.J.F.); (E.A.S.); (K.A.O.); (S.T.S.)
- Department of Surgery, Malcolm Randall Veteran Affairs Medical Center, 1601 SW Archer Rd., Gainesville, FL 32610, USA
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30
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Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, Martin M, de la Vega-Correa L, Zapata C, Burokas A, Blasco G, Coll C, Escrichs A, Biarnés C, Moreno-Navarrete JM, Puig J, Garre-Olmo J, Ramos R, Pedraza S, Brugada R, Vilanova JC, Serena J, Gich J, Ramió-Torrentà L, Pérez-Brocal V, Moya A, Pamplona R, Sol J, Jové M, Ricart W, Portero-Otin M, Deco G, Maldonado R, Fernández-Real JM. Microbiota alterations in proline metabolism impact depression. Cell Metab 2022; 34:681-701.e10. [PMID: 35508109 DOI: 10.1016/j.cmet.2022.04.001] [Citation(s) in RCA: 123] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 01/31/2022] [Accepted: 04/04/2022] [Indexed: 02/08/2023]
Abstract
The microbiota-gut-brain axis has emerged as a novel target in depression, a disorder with low treatment efficacy. However, the field is dominated by underpowered studies focusing on major depression not addressing microbiome functionality, compositional nature, or confounding factors. We applied a multi-omics approach combining pre-clinical models with three human cohorts including patients with mild depression. Microbial functions and metabolites converging onto glutamate/GABA metabolism, particularly proline, were linked to depression. High proline consumption was the dietary factor with the strongest impact on depression. Whole-brain dynamics revealed rich club network disruptions associated with depression and circulating proline. Proline supplementation in mice exacerbated depression along with microbial translocation. Human microbiota transplantation induced an emotionally impaired phenotype in mice and alterations in GABA-, proline-, and extracellular matrix-related prefrontal cortex genes. RNAi-mediated knockdown of proline and GABA transporters in Drosophila and mono-association with L. plantarum, a high GABA producer, conferred protection against depression-like states. Targeting the microbiome and dietary proline may open new windows for efficient depression treatment.
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Affiliation(s)
- Jordi Mayneris-Perxachs
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain; Girona Biomedical Research Institute (IDIBGI), Girona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Girona, Spain.
| | - Anna Castells-Nobau
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain; Girona Biomedical Research Institute (IDIBGI), Girona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Girona, Spain
| | - María Arnoriaga-Rodríguez
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain; Girona Biomedical Research Institute (IDIBGI), Girona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Girona, Spain; Department of Medical Sciences, School of Medicine, Girona, Spain
| | - Miquel Martin
- Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
| | - Lisset de la Vega-Correa
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain; Girona Biomedical Research Institute (IDIBGI), Girona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Girona, Spain
| | - Cristina Zapata
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain; Girona Biomedical Research Institute (IDIBGI), Girona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Girona, Spain
| | - Aurelijus Burokas
- Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain; Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Gerard Blasco
- Institute of Diagnostic Imaging (IDI)-Research Unit (IDIR), Parc Sanitari Pere Virgili, Barcelona, Spain; Medical Imaging, IDIBGI, Girona, Spain
| | - Clàudia Coll
- Girona Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Dr. Josep Trueta Hospital, Girona, Spain
| | - Anira Escrichs
- Computational Neuroscience Group, Center for Brain and Cognition, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain
| | - Carles Biarnés
- Institute of Diagnostic Imaging (IDI)-Research Unit (IDIR), Parc Sanitari Pere Virgili, Barcelona, Spain; Medical Imaging, IDIBGI, Girona, Spain; Department of Radiology (IDI), Dr. Josep Trueta Hospital, Girona, Spain
| | - José María Moreno-Navarrete
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain; Girona Biomedical Research Institute (IDIBGI), Girona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Girona, Spain; Department of Medical Sciences, School of Medicine, Girona, Spain
| | - Josep Puig
- Department of Medical Sciences, School of Medicine, Girona, Spain; Institute of Diagnostic Imaging (IDI)-Research Unit (IDIR), Parc Sanitari Pere Virgili, Barcelona, Spain; Medical Imaging, IDIBGI, Girona, Spain; Department of Radiology (IDI), Dr. Josep Trueta Hospital, Girona, Spain
| | - Josep Garre-Olmo
- Research Group on Aging, Disability, and Health, Girona Biomedical Research Institute (IdibGi), Girona, Spain; Serra-Hunter Fellow, Department of Nursing, University of Girona, Girona, Spain; Institut d'Assistència Sanitària, Girona, Spain
| | - Rafel Ramos
- Department of Medical Sciences, School of Medicine, Girona, Spain; Vascular Health Research Group of Girona (ISV-Girona), Jordi Gol Institute for Primary Care Research (Institut Universitari Recerca Atenció Primària Jordi Gol i Gorina-IDIAPJGol), Girona, Spain; IDIBGI, Dr. Josep Trueta Hospital, Girona, Spain
| | - Salvador Pedraza
- Department of Medical Sciences, School of Medicine, Girona, Spain; Medical Imaging, IDIBGI, Girona, Spain; Department of Radiology (IDI), Dr. Josep Trueta Hospital, Girona, Spain
| | - Ramón Brugada
- IDIBGI, Dr. Josep Trueta Hospital, Girona, Spain; Biomedical Research Networking Center for Cardiovascular Diseases (CIBER), Madrid, Spain
| | - Joan Carles Vilanova
- Department of Radiology (IDI), Dr. Josep Trueta Hospital, Girona, Spain; IDIBGI, Dr. Josep Trueta Hospital, Girona, Spain
| | - Joaquín Serena
- IDIBGI, Dr. Josep Trueta Hospital, Girona, Spain; Girona Neurodegeneration and Neuroinflammation Group, IDIBGI, Girona, Spain
| | - Jordi Gich
- Department of Medical Sciences, School of Medicine, Girona, Spain; Girona Neurodegeneration and Neuroinflammation Group, IDIBGI, Girona, Spain
| | - Lluís Ramió-Torrentà
- Department of Medical Sciences, School of Medicine, Girona, Spain; Girona Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Dr. Josep Trueta Hospital, Girona, Spain; Girona Neurodegeneration and Neuroinflammation Group, IDIBGI, Girona, Spain
| | - Vicente Pérez-Brocal
- Area of Genomics and Health, Foundation for the Promotion of Health and Biomedical Research of València Region (FISABIO-Public Health), València, Spain; Biomedical Research Networking Center for Epidemiology and Public Health (CIBEResp), Madrid, Spain
| | - Andrés Moya
- Area of Genomics and Health, Foundation for the Promotion of Health and Biomedical Research of València Region (FISABIO-Public Health), València, Spain; Biomedical Research Networking Center for Epidemiology and Public Health (CIBEResp), Madrid, Spain; Institute for Integrative Systems Biology (I2Sysbio), University of València and Spanish Research Council (CSIC), València, Spain
| | - Reinald Pamplona
- Metabolic Physiopathology Research Group, Experimental Medicine Department, Lleida University-Lleida Biochemical Research Institute (UdL-IRBLleida), Lleida, Spain
| | - Joaquim Sol
- Metabolic Physiopathology Research Group, Experimental Medicine Department, Lleida University-Lleida Biochemical Research Institute (UdL-IRBLleida), Lleida, Spain; Institut Català de la Salut, Atenció Primària, Lleida, Spain; Research Support Unit, Fundació Institut Universitari recerca l'Atenció Primària Salut Jordi Gol i Gorina (IDIAPJGol), Lleida, Spain
| | - Mariona Jové
- Metabolic Physiopathology Research Group, Experimental Medicine Department, Lleida University-Lleida Biochemical Research Institute (UdL-IRBLleida), Lleida, Spain
| | - Wifredo Ricart
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain; Girona Biomedical Research Institute (IDIBGI), Girona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Girona, Spain; Department of Medical Sciences, School of Medicine, Girona, Spain
| | - Manuel Portero-Otin
- Metabolic Physiopathology Research Group, Experimental Medicine Department, Lleida University-Lleida Biochemical Research Institute (UdL-IRBLleida), Lleida, Spain
| | - Gustavo Deco
- Computational Neuroscience Group, Center for Brain and Cognition, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain; Institucio Catalana de la Recerca i Estudis Avançats (ICREA), Barcelona, Spain; Department of Neuropsychology, Max Planck Institute for human Cognitive and Brain Sciences, Leipzig, Germany; Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia
| | - Rafael Maldonado
- Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
| | - José Manuel Fernández-Real
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain; Girona Biomedical Research Institute (IDIBGI), Girona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Girona, Spain; Department of Medical Sciences, School of Medicine, Girona, Spain.
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31
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Zhou R, Qian S, Cho WCS, Zhou J, Jin C, Zhong Y, Wang J, Zhang X, Xu Z, Tian M, Chan LWC, Zhang H. Microbiota-microglia connections in age-related cognition decline. Aging Cell 2022; 21:e13599. [PMID: 35349746 PMCID: PMC9124309 DOI: 10.1111/acel.13599] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 03/08/2022] [Accepted: 03/13/2022] [Indexed: 12/13/2022] Open
Abstract
Aging is an inevitable process that all individuals experience, of which the extent differs among individuals. It has been recognized as the risk factor of neurodegenerative diseases by affecting gut microbiota compositions, microglia, and cognition abilities. Aging-induced changes in gut microbiota compositions have a critical role in orchestrating the morphology and functions of microglia through the gut-brain axis. Gut microbiota communicates with microglia by its secreted metabolites and neurotransmitters. This is highly associated with age-related cognitive declines. Here, we review the main composition of microbiota in the aged individuals, outline the changes of the brain in age-related cognitive decline from a neuroinflammation perspective, especially the changes of morphology and functions of microglia, discuss the crosstalk between microbiota and microglia in the aged brain and further highlight the role of microbiota-microglia connections in neurodegenerative diseases (Alzheimer's disease and Parkinson's disease).
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Affiliation(s)
- Rui Zhou
- Department of Nuclear Medicine and Medical PET CenterThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
- Department of Health Technology and InformaticsThe Hong Kong Polytechnic UniversityHong Kong SARChina
| | - Shufang Qian
- Department of Nuclear Medicine and Medical PET CenterThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
| | - William C. S. Cho
- Department of Clinical OncologyQueen Elizabeth HospitalHong Kong SARChina
| | - Jinyun Zhou
- Department of Nuclear Medicine and Medical PET CenterThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
| | - Chentao Jin
- Department of Nuclear Medicine and Medical PET CenterThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
| | - Yan Zhong
- Department of Nuclear Medicine and Medical PET CenterThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
| | - Jing Wang
- Department of Nuclear Medicine and Medical PET CenterThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
| | - Xiaohui Zhang
- Department of Nuclear Medicine and Medical PET CenterThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
| | - Zhoujiao Xu
- Department of Nuclear Medicine and Medical PET CenterThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
| | - Mei Tian
- Department of Nuclear Medicine and Medical PET CenterThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
| | - Lawrence W. C. Chan
- Department of Health Technology and InformaticsThe Hong Kong Polytechnic UniversityHong Kong SARChina
| | - Hong Zhang
- Department of Nuclear Medicine and Medical PET CenterThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
- Key Laboratory for Biomedical Engineering of Ministry of EducationZhejiang UniversityHangzhouChina
- The College of Biomedical Engineering and Instrument Science of Zhejiang UniversityHangzhouChina
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32
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Gut–Skin Axis: Unravelling the Connection between the Gut Microbiome and Psoriasis. Biomedicines 2022; 10:biomedicines10051037. [PMID: 35625774 PMCID: PMC9138548 DOI: 10.3390/biomedicines10051037] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 04/23/2022] [Accepted: 04/27/2022] [Indexed: 12/11/2022] Open
Abstract
Evidence has shown that gut microbiome plays a role in modulating the development of diseases beyond the gastrointestinal tract, including skin disorders such as psoriasis. The gut–skin axis refers to the bidirectional relationship between the gut microbiome and skin health. This is regulated through several mechanisms such as inflammatory mediators and the immune system. Dysregulation of microbiota has been seen in numerous inflammatory skin conditions such as atopic dermatitis, rosacea, and psoriasis. Understanding how gut microbiome are involved in regulating skin health may lead to development of novel therapies for these skin disorders through microbiome modulation, in particularly psoriasis. In this review, we will compare the microbiota between psoriasis patients and healthy control, explain the concept of gut–skin axis and the effects of gut dysbiosis on skin physiology. We will also review the current evidence on modulating gut microbiome using probiotics in psoriasis.
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33
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Chang L, Wei Y, Hashimoto K. Brain Research Bulletin: Special Issue: Brain–body communication in health and diseases, Brain–gut–microbiota axis in depression: A historical overview and future directions. Brain Res Bull 2022; 182:44-56. [DOI: 10.1016/j.brainresbull.2022.02.004] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/03/2022] [Accepted: 02/04/2022] [Indexed: 12/14/2022]
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34
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Hillestad EMR, van der Meeren A, Nagaraja BH, Bjørsvik BR, Haleem N, Benitez-Paez A, Sanz Y, Hausken T, Lied GA, Lundervold A, Berentsen B. Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome. World J Gastroenterol 2022; 28:412-431. [PMID: 35125827 PMCID: PMC8790555 DOI: 10.3748/wjg.v28.i4.412] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 06/24/2021] [Accepted: 01/13/2022] [Indexed: 12/16/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal symptoms, recently described as a disturbance of the microbiota-gut-brain axis. Despite decades of research, the pathophysiology of this highly heterogeneous disorder remains elusive. However, a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture. Are we getting any closer to understanding IBS' etiology, or are we drowning in unspecific, conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing? In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota, clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation, neuroimaging and methods in microbiota analyses, and current and future challenges with big data analysis in IBS.
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Affiliation(s)
- Eline Margrete Randulff Hillestad
- Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
| | - Aina van der Meeren
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
| | - Bharat Halandur Nagaraja
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
| | - Ben René Bjørsvik
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
| | - Noman Haleem
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
| | - Alfonso Benitez-Paez
- Host-Microbe Interactions in Metabolic Health Laboratory, Principe Felipe Research Center, Valencia 46012, Spain
| | - Yolanda Sanz
- Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, National Research Council, Paterna-Valencia 46980, Spain
| | - Trygve Hausken
- Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
| | - Gülen Arslan Lied
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
| | - Arvid Lundervold
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
- Department of Biomedicine, University of Bergen, Bergen 5021, Norway
| | - Birgitte Berentsen
- Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
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McGuinness AJ, Davis JA, Dawson SL, Loughman A, Collier F, O’Hely M, Simpson CA, Green J, Marx W, Hair C, Guest G, Mohebbi M, Berk M, Stupart D, Watters D, Jacka FN. A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia. Mol Psychiatry 2022; 27:1920-1935. [PMID: 35194166 PMCID: PMC9126816 DOI: 10.1038/s41380-022-01456-3] [Citation(s) in RCA: 271] [Impact Index Per Article: 90.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 12/22/2021] [Accepted: 01/18/2022] [Indexed: 02/07/2023]
Abstract
The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.
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Affiliation(s)
- A. J. McGuinness
- grid.1021.20000 0001 0526 7079The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC Australia
| | - J. A. Davis
- grid.1021.20000 0001 0526 7079The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC Australia
| | - S. L. Dawson
- grid.1021.20000 0001 0526 7079The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC Australia ,grid.1058.c0000 0000 9442 535XMurdoch Children’s Research Institute, Parkville, VIC Australia
| | - A. Loughman
- grid.1021.20000 0001 0526 7079The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC Australia
| | - F. Collier
- grid.1021.20000 0001 0526 7079The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC Australia
| | - M. O’Hely
- grid.1021.20000 0001 0526 7079The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC Australia ,grid.1058.c0000 0000 9442 535XMurdoch Children’s Research Institute, Parkville, VIC Australia
| | - C. A. Simpson
- grid.1008.90000 0001 2179 088XMelbourne School of Psychological Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC Australia ,grid.1008.90000 0001 2179 088XMelbourne Neuropsychiatry Centre, Department of Medicine, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne and Melbourne Health, Melbourne, VIC Australia
| | - J. Green
- grid.1021.20000 0001 0526 7079The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC Australia ,grid.1002.30000 0004 1936 7857Monash Alfred Psychiatry Research Centre (MAPcr), Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Parkville, VIC Australia ,grid.466993.70000 0004 0436 2893Department of Psychiatry, Peninsula Health, Frankston, VIC Australia
| | - W. Marx
- grid.1021.20000 0001 0526 7079The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC Australia
| | - C. Hair
- grid.1021.20000 0001 0526 7079Deakin University, School of Medicine, Geelong, VIC Australia ,grid.414257.10000 0004 0540 0062Department of Gastroenterology, Barwon Health, Geelong, VIC Australia
| | - G. Guest
- grid.1021.20000 0001 0526 7079Deakin University, School of Medicine, Geelong, VIC Australia ,grid.415335.50000 0000 8560 4604Department of Surgery, University Hospital Geelong, Barwon Health, Geelong, VIC Australia
| | - M. Mohebbi
- grid.1021.20000 0001 0526 7079Biostatistics Unit, Faculty of Health, Deakin University, Melbourne, VIC Australia
| | - M. Berk
- grid.1021.20000 0001 0526 7079The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC Australia ,grid.1021.20000 0001 0526 7079Deakin University, School of Medicine, Geelong, VIC Australia ,grid.1008.90000 0001 2179 088XOrygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, The University of Melbourne, Melbourne, Australia
| | - D. Stupart
- grid.1021.20000 0001 0526 7079Deakin University, School of Medicine, Geelong, VIC Australia ,grid.415335.50000 0000 8560 4604Department of Surgery, University Hospital Geelong, Barwon Health, Geelong, VIC Australia
| | - D. Watters
- grid.1021.20000 0001 0526 7079Deakin University, School of Medicine, Geelong, VIC Australia ,grid.415335.50000 0000 8560 4604Department of Surgery, University Hospital Geelong, Barwon Health, Geelong, VIC Australia
| | - F. N. Jacka
- grid.1021.20000 0001 0526 7079The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Food & Mood Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC Australia ,grid.1058.c0000 0000 9442 535XCentre for Adolescent Health, Murdoch Children’s Research Institute, Melbourne, VIC Australia ,grid.418393.40000 0001 0640 7766Black Dog Institute, Sydney, NSW Australia ,grid.1011.10000 0004 0474 1797College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, QLD Australia
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The Role of the Gut Microbiota in the Development and Progression of Major Depressive and Bipolar Disorder. Nutrients 2021; 14:nu14010037. [PMID: 35010912 PMCID: PMC8746924 DOI: 10.3390/nu14010037] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/13/2021] [Accepted: 12/20/2021] [Indexed: 02/07/2023] Open
Abstract
A growing number of studies in rodents indicate a connection between the intestinal microbiota and the brain, but comprehensive human data is scarce. Here, we systematically reviewed human studies examining the connection between the intestinal microbiota and major depressive and bipolar disorder. In this review we discuss various changes in bacterial abundance, particularly on low taxonomic levels, in terms of a connection with the pathophysiology of major depressive and bipolar disorder, their use as a diagnostic and treatment response parameter, their health-promoting potential, as well as novel adjunctive treatment options. The diversity of the intestinal microbiota is mostly decreased in depressed subjects. A consistent elevation of phylum Actinobacteria, family Bifidobacteriaceae, and genus Bacteroides, and a reduction of family Ruminococcaceae, genus Faecalibacterium, and genus Roseburia was reported. Probiotics containing Bifidobacterium and/or Lactobacillus spp. seemed to improve depressive symptoms, and novel approaches with different probiotics and synbiotics showed promising results. Comparing twin studies, we report here that already with an elevated risk of developing depression, microbial changes towards a “depression-like” microbiota were found. Overall, these findings highlight the importance of the microbiota and the necessity for a better understanding of its changes contributing to depressive symptoms, potentially leading to new approaches to alleviate depressive symptoms via alterations of the gut microbiota.
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Hrbacek J, Morais D, Cermak P, Hanacek V, Zachoval R. Alpha-diversity and microbial community structure of the male urinary microbiota depend on urine sampling method. Sci Rep 2021; 11:23758. [PMID: 34887510 PMCID: PMC8660768 DOI: 10.1038/s41598-021-03292-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 11/30/2021] [Indexed: 02/06/2023] Open
Abstract
Considerable variation exists in the methodology of urinary microbiota studies published so far including the cornerstone of any biomedical analysis: sample collection. The aim of this study was to compare the urinary microbiota of first-catch voided urine (FCU), mid-stream voided urine (MSU) and aseptically catheterised urine in men and define the most suitable urine sampling method. Forty-nine men (mean age 71.3 years) undergoing endoscopic urological procedures were enrolled in the study. Each of them contributed three samples: first-catch urine (FCU), mid-stream urine (MSU) and a catheterised urine sample. The samples were subjected to next-generation sequencing (NGS, n = 35) and expanded quantitative urine culture (EQUC, n = 31). Using NGS, Bacteroidetes, Firmicutes, and Proteobacteria were the most abundant phyla in our population. The most abundant genera (in order of relative abundance) included: Prevotella, Veillonella, Streptococcus, Porphyromonas, Campylobacter, Pseudomonas, Staphylococcus, Ezakiella, Escherichia and Dialister. Eighty-two of 105 samples were dominated by a single genus. FCU, MSU and catheterised urine samples differed significantly in three of five alpha-diversity measures (ANOVA, p < 0.05): estimated number of operational taxonomic units, Chao1 and abundance-based coverage estimators. Beta-diversity comparisons using the PIME method (Prevalence Interval for Microbiome Evaluation) resulted in clustering of urine samples according to the mode of sampling. EQUC detected cultivable bacteria in 30/31 (97%) FCU and 27/31 (87%) MSU samples. Only 4/31 (13%) of catheterised urine samples showed bacterial growth. Urine samples obtained by transurethral catheterisation under aseptic conditions seem to differ from spontaneously voided urine samples. Whether the added value of a more exact reflection of the bladder microbiota free from urethral contamination outweighs the invasiveness of urethral catheterisation remains to be determined.
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Affiliation(s)
- Jan Hrbacek
- Department of Urology, 3rd Faculty of Medicine, Charles University, Thomayer University Hospital, Videnska 800, 14059, Prague, Czech Republic.
| | - Daniel Morais
- Laboratory of Environmental Microbiology, Institute of Microbiology, Czech Academy of Sciences, Videnska 1083, 14200, Prague, Czech Republic
| | - Pavel Cermak
- Department of Clinical Microbiology, Thomayer University Hospital, Videnska 800, 14059, Prague, Czech Republic
| | - Vitezslav Hanacek
- Department of Urology, 3rd Faculty of Medicine, Charles University, Thomayer University Hospital, Videnska 800, 14059, Prague, Czech Republic
| | - Roman Zachoval
- Department of Urology, 3rd Faculty of Medicine, Charles University, Thomayer University Hospital, Videnska 800, 14059, Prague, Czech Republic
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38
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Knudsen JK, Michaelsen TY, Bundgaard-Nielsen C, Nielsen RE, Hjerrild S, Leutscher P, Wegener G, Sørensen S. Faecal microbiota transplantation from patients with depression or healthy individuals into rats modulates mood-related behaviour. Sci Rep 2021; 11:21869. [PMID: 34750433 PMCID: PMC8575883 DOI: 10.1038/s41598-021-01248-9] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 10/26/2021] [Indexed: 02/02/2023] Open
Abstract
Differences in gut microbiota composition have been observed in patients with major depressive disorder (MDD) compared to healthy individuals. Here, we investigated if faecal microbiota transplantation (FMT) from patients with MDD into rats could induce a depressive-like phenotype. We performed FMT from patients with MDD (FMT-MDD) and healthy individuals (FMT-Healthy) into male Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats and assessed depressive-like behaviour. No behavioural differences were observed in the FSL rats. In FRL rats, the FMT-Healthy group displayed significantly less depressive-like behaviour than the FMT-MDD group. However, there was no difference in behaviour between FMT-MDD FRL rats and negative controls, indicating that FMT-Healthy FRL rats received beneficial bacteria. We additionally found different taxa between the FMT-MDD and the FMT-Healthy FRL rats, which could be traced to the donors. Four taxa, three belonging to the family Ruminococcaceae and the genus Lachnospira, were significantly elevated in relative abundance in FMT-MDD rats, while the genus Coprococcus was depleted. In this study, the FMT-MDD group was different from the FMT-Healthy group based on behaviour and intestinal taxa.
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Affiliation(s)
- Julie Kristine Knudsen
- Centre for Clinical Research, North Denmark Regional Hospital, Bispensgade 37, 9800, Hjørring, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | - Caspar Bundgaard-Nielsen
- Centre for Clinical Research, North Denmark Regional Hospital, Bispensgade 37, 9800, Hjørring, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - René Ernst Nielsen
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark
| | - Simon Hjerrild
- Psychosis Research Unit, Aarhus University Hospital, Aarhus, Denmark.,Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
| | - Peter Leutscher
- Centre for Clinical Research, North Denmark Regional Hospital, Bispensgade 37, 9800, Hjørring, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Gregers Wegener
- Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
| | - Suzette Sørensen
- Centre for Clinical Research, North Denmark Regional Hospital, Bispensgade 37, 9800, Hjørring, Denmark. .,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
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Chrisman BS, Paskov KM, Stockham N, Jung JY, Varma M, Washington PY, Tataru C, Iwai S, DeSantis TZ, David M, Wall DP. Improved detection of disease-associated gut microbes using 16S sequence-based biomarkers. BMC Bioinformatics 2021; 22:509. [PMID: 34666677 PMCID: PMC8527694 DOI: 10.1186/s12859-021-04427-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 10/06/2021] [Indexed: 12/31/2022] Open
Abstract
Background Sequencing partial 16S rRNA genes is a cost effective method for quantifying the microbial composition of an environment, such as the human gut. However, downstream analysis relies on binning reads into microbial groups by either considering each unique sequence as a different microbe, querying a database to get taxonomic labels from sequences, or clustering similar sequences together. However, these approaches do not fully capture evolutionary relationships between microbes, limiting the ability to identify differentially abundant groups of microbes between a diseased and control cohort. We present sequence-based biomarkers (SBBs), an aggregation method that groups and aggregates microbes using single variants and combinations of variants within their 16S sequences. We compare SBBs against other existing aggregation methods (OTU clustering and Microphenoor DiTaxa features) in several benchmarking tasks: biomarker discovery via permutation test, biomarker discovery via linear discriminant analysis, and phenotype prediction power. We demonstrate the SBBs perform on-par or better than the state-of-the-art methods in biomarker discovery and phenotype prediction. Results On two independent datasets, SBBs identify differentially abundant groups of microbes with similar or higher statistical significance than existing methods in both a permutation-test-based analysis and using linear discriminant analysis effect size. . By grouping microbes by SBB, we can identify several differentially abundant microbial groups (FDR <.1) between children with autism and neurotypical controls in a set of 115 discordant siblings. Porphyromonadaceae, Ruminococcaceae, and an unnamed species of Blastocystis were significantly enriched in autism, while Veillonellaceae was significantly depleted. Likewise, aggregating microbes by SBB on a dataset of obese and lean twins, we find several significantly differentially abundant microbial groups (FDR<.1). We observed Megasphaera andSutterellaceae highly enriched in obesity, and Phocaeicola significantly depleted. SBBs also perform on bar with or better than existing aggregation methods as features in a phenotype prediction model, predicting the autism phenotype with an ROC-AUC score of .64 and the obesity phenotype with an ROC-AUC score of .84. Conclusions SBBs provide a powerful method for aggregating microbes to perform differential abundance analysis as well as phenotype prediction. Our source code can be freely downloaded from http://github.com/briannachrisman/16s_biomarkers.
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Affiliation(s)
- Brianna S Chrisman
- Department of Bioengineering, Stanford University, Serra Mall, Stanford, USA.
| | - Kelley M Paskov
- Department of Biomedical Data Science, Stanford University, Serra Mall, Stanford, USA
| | - Nate Stockham
- Department of Neuroscience, Stanford University, Serra Mall, Stanford, USA
| | - Jae-Yoon Jung
- Department of Biomedical Data Science, Stanford University, Serra Mall, Stanford, USA
| | - Maya Varma
- Department of Computer Science, Stanford University, Serra Mall, Stanford, USA
| | - Peter Y Washington
- Department of Bioengineering, Stanford University, Serra Mall, Stanford, USA
| | - Christine Tataru
- Department of Computer Science, Oregon State University, SW Campus Way, Corvallis, USA
| | - Shoko Iwai
- Second Genome Inc, Allerton Ave, Brisbane, USA
| | | | - Maude David
- Department of Microbiology, Oregon State University, SW Campus Way, Corvallis, USA
| | - Dennis P Wall
- Department of Biomedical Data Science, Stanford University, Serra Mall, Stanford, USA.,Department of Pediatrics (Systems Medicine), Stanford University, 1265 Welch Road, Stanford, USA
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Hofmeister M, Clement F, Patten S, Li J, Dowsett LE, Farkas B, Mastikhina L, Egunsola O, Diaz R, Cooke NCA, Taylor VH. The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis. CMAJ Open 2021; 9:E1195-E1204. [PMID: 34933877 PMCID: PMC8695538 DOI: 10.9778/cmajo.20200283] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms. METHODS We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age ≥ 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect. RESULTS Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit. INTERPRETATION Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered. STUDY REGISTRATION PROSPERO no. 143178.
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Affiliation(s)
- Mark Hofmeister
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta
| | - Fiona Clement
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta
| | - Scott Patten
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta
| | - Joyce Li
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta
| | - Laura E Dowsett
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta
| | - Brenlea Farkas
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta
| | - Liza Mastikhina
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta
| | - Oluwaseun Egunsola
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta
| | - Ruth Diaz
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta
| | - Noah C A Cooke
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta
| | - Valerie H Taylor
- Department of Community Health Sciences (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and O'Brien Institute for Public Health (Hofmeister, Clement, Patten, Li, Dowsett, Farkas, Mastikhina, Egunsola, Diaz), and Departments of Psychiatry (Patten, Taylor) and Biochemistry and Molecular Biology (Cooke), Teaching Research and Wellness Building, University of Calgary, Calgary, Alta.
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Chen Y, Meng P, Cheng S, Jia Y, Wen Y, Yang X, Yao Y, Pan C, Li C, Zhang H, Zhang J, Zhang Z, Zhang F. Assessing the effect of interaction between C-reactive protein and gut microbiome on the risks of anxiety and depression. Mol Brain 2021; 14:133. [PMID: 34481527 PMCID: PMC8418706 DOI: 10.1186/s13041-021-00843-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 08/24/2021] [Indexed: 12/31/2022] Open
Abstract
Cumulative evidence shows that gut microbiome can influence brain function and behavior via the inflammatory processes. However, the role of interaction between gut dysbiosis and C-reactive protein (CRP) in the development of anxiety and depression remains to be elucidated. In this study, a total of 3321 independent single nucleotide polymorphism (SNP) loci associated with gut microbiome were driven from genome-wide association study (GWAS). Using individual level genotype data from UK Biobank, we then calculated the polygenetic risk scoring (PRS) of 114 gut microbiome related traits. Moreover, regression analysis was conducted to evaluate the possible effect of interaction between gut microbiome and CRP on the risks of Patient Health Questionnaire-9 (PHQ-9) (N = 113,693) and Generalized Anxiety Disorder-7 (GAD-7) (N = 114,219). At last, 11 candidate CRP × gut microbiome interaction with suggestive significance was detected for PHQ-9 score, such as F_Ruminococcaceae (β = - 0.009, P = 2.2 × 10-3), G_Akkermansia (β = - 0.008, P = 7.60 × 10-3), F_Acidaminococcaceae (β = 0.008, P = 1.22 × 10-2), G_Holdemanella (β = - 0.007, P = 1.39 × 10-2) and O_Lactobacillales (β = 0.006, P = 1.79× 10-2). 16 candidate CRP × gut microbiome interaction with suggestive significance was detected for GAD-7 score, such as O_Bacteroidales (β = 0.010, P = 4.00× 10-4), O_Selenomonadales (β = - 0.010, P = 1.20 × 10-3), O_Clostridiales (β = 0.009, P = 2.70 × 10-3) and G_Holdemanella (β = - 0.008, P = 4.20 × 10-3). Our results support the significant effect of interaction between CRP and gut microbiome on the risks of anxiety and depression, and identified several candidate gut microbiomes for them.
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Affiliation(s)
- Yujing Chen
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Peilin Meng
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Shiqiang Cheng
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Yumeng Jia
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Yan Wen
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Xuena Yang
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Yao Yao
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Chuyu Pan
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Chun'e Li
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Huijie Zhang
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Jingxi Zhang
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Zhen Zhang
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China
| | - Feng Zhang
- Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China.
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Stevens BR, Pepine CJ, Richards EM, Kim S, Raizada MK. Depressive hypertension: A proposed human endotype of brain/gut microbiome dysbiosis. Am Heart J 2021; 239:27-37. [PMID: 33984318 DOI: 10.1016/j.ahj.2021.05.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 05/04/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hypertension (HTN) is frequently linked with depression (DEP) in adults with cardiovascular disease (CVD), yet the underlying mechanism and successful management remain elusive. We approached this knowledge gap through the lens that humans are eukaryote-prokaryote "meta-organisms," such that cardiovascular disease dysregulation is a mosaic disorder involving dysbiosis of the gut. We hypothesized that patients diagnosed with hypertension plus depression harbor a unique gut microbial ecology with attending functional genomics engaged with their hosts' gut/brain axis physiology. METHODS Stool microbiome DNA was analyzed by whole metagenome shotgun sequencing in 54 subjects parsed into cohorts diagnosed with HTN only (N = 18), DEP only (N = 7), DEP plus HTN (DEP-HTN) (N = 8), or reference subjects with neither HTN nor DEP (N = 21). A novel battery of machine-learning multivariate analyses of de-noised data yielded effect sizes and permutational covariance-based dissimilarities that significantly differentiated the cohorts (false discovery rate (FDR)-adjusted P ≤ .05); data clustering within 95% confidence interval). RESULTS Metagenomic significant differences extricated the four cohorts. Data of the cohort exhibiting DEP-HTN were germane to the interplay of central control of blood pressure concomitant with the neuropathology of depressive disorders. DEP-HTN gut bacterial community ecology was defined by co-occurrence of Eubacterium siraeum, Alistipes obesi, Holdemania filiformis, and Lachnospiraceae bacterium 1.1.57FAA with Streptococcus salivariu. The corresponding microbial functional genomics of DEP-HTN engaged pathways degrading GABA and beneficial short chain fatty acids (SCFA), and are associated with enhanced sodium absorption and inflammasome induction. CONCLUSIONS These data suggest a new putative endotype of hypertension, which we denote "depressive-hypertension" (DEP-HTN), for which we posit a model that is distinctive from either HTN alone or DEP alone. An "endotype" is a subtype of a heterogeneous pathophysiological mechanism. The DEP-HTN model incorporates a unique signature of microbial taxa and functional genomics with crosstalk that putatively intertwines host pathophysiology involving the gastrointestinal tract with disruptions in central control of blood pressure and mood. The DEP-HTN endotype model engages cardiology with gastroenterology and psychiatry, providing a proof-of-concept foundation to explore future treatments, diagnosis, and prevention of HTN-coupled mood disorders.
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Exploring the Role of Nutraceuticals in Major Depressive Disorder (MDD): Rationale, State of the Art and Future Prospects. Pharmaceuticals (Basel) 2021; 14:ph14080821. [PMID: 34451918 PMCID: PMC8399392 DOI: 10.3390/ph14080821] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 08/17/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Major depressive disorder (MDD) is a complex and common disorder, with many factors involved in its onset and development. The clinical management of this condition is frequently based on the use of some pharmacological antidepressant agents, together with psychotherapy and other alternatives in most severe cases. However, an important percentage of depressed patients fail to respond to the use of conventional therapies. This has created the urgency of finding novel approaches to help in the clinical management of those individuals. Nutraceuticals are natural compounds contained in food with proven benefits either in health promotion or disease prevention and therapy. A growing interest and economical sources are being placed in the development and understanding of multiple nutraceutical products. Here, we summarize some of the most relevant nutraceutical agents evaluated in preclinical and clinical models of depression. In addition, we will also explore less frequent but interest nutraceutical products which are starting to be tested, also evaluating future roads to cover in order to maximize the benefits of nutraceuticals in MDD.
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Nakai M, Ribeiro RV, Stevens BR, Gill P, Muralitharan RR, Yiallourou S, Muir J, Carrington M, Head GA, Kaye DM, Marques FZ. Essential Hypertension Is Associated With Changes in Gut Microbial Metabolic Pathways: A Multisite Analysis of Ambulatory Blood Pressure. Hypertension 2021; 78:804-815. [PMID: 34333988 DOI: 10.1161/hypertensionaha.121.17288] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
[Figure: see text].
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Affiliation(s)
- Michael Nakai
- Hypertension Research Laboratory, School of Biological Sciences, Monash University, Melbourne, Australia (M.N., R.R.M., F.Z.M.)
| | - Rosilene V Ribeiro
- Charles Perkins Centre, University of Sydney, Australia (R.V.R.).,School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Australia (R.V.R.)
| | - Bruce R Stevens
- Department of Physiology and Functional Genomics, University of Florida, College of Medicine, Gainesville (B.R.S.)
| | - Paul Gill
- Department of Gastroenterology (P.G., J.M.), Monash University, Melbourne, Australia
| | - Rikeish R Muralitharan
- Hypertension Research Laboratory, School of Biological Sciences, Monash University, Melbourne, Australia (M.N., R.R.M., F.Z.M.).,Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur (R.R.M.)
| | - Stephanie Yiallourou
- Preclinical Disease and Prevention, Baker Heart and Diabetes Institute, Melbourne, Australia (S.Y., M.C.)
| | - Jane Muir
- Department of Gastroenterology (P.G., J.M.), Monash University, Melbourne, Australia
| | - Melinda Carrington
- Preclinical Disease and Prevention, Baker Heart and Diabetes Institute, Melbourne, Australia (S.Y., M.C.)
| | - Geoffrey A Head
- Department of Pharmacology, Faculty of Medicine Nursing and Health Sciences (G.A.H.), Monash University, Melbourne, Australia.,Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia (G.A.H.)
| | - David M Kaye
- Clinical School, Faculty of Medicine Nursing and Health Sciences (D.M.K.), Monash University, Melbourne, Australia.,Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Australia (D.M.K., F.Z.M.).,Department of Cardiology, Alfred Hospital, Melbourne, Australia (D.M.K.)
| | - Francine Z Marques
- Hypertension Research Laboratory, School of Biological Sciences, Monash University, Melbourne, Australia (M.N., R.R.M., F.Z.M.).,Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Australia (D.M.K., F.Z.M.)
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Knudsen JK, Bundgaard-Nielsen C, Hjerrild S, Nielsen RE, Leutscher P, Sørensen S. Gut microbiota variations in patients diagnosed with major depressive disorder-A systematic review. Brain Behav 2021; 11:e02177. [PMID: 34047485 PMCID: PMC8323045 DOI: 10.1002/brb3.2177] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 02/15/2021] [Accepted: 04/11/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE The etiology of major depressive disorder (MDD) is multi-factorial and has been associated with a perturbed gut microbiota. Thus, it is therefore of great importance to determine any variations in gut microbiota in patients with MDD. METHODS A systematic literature search was conducted including original research articles based on gut microbiota studies performed in patients with MDD. Demographic and clinical characteristics, applied methodology and observed gut microbiota composition were compared between included studies. RESULTS Seventeen studies were included with a total of 738 patients with MDD and 782 healthy controls using different DNA purification methods, sequencing platforms and data analysis models. Four studies found a reduced α-diversity in patients with MDD, while gut microbiota compositions clustered separately according to β-diversity between patients and controls in twelve studies. Additionally, there was an increase in relative abundance of Eggerthella, Atopobium, and Bifidobacterium and a decreased relative abundance of Faecalibacterium in patients with MDD compared with healthy controls. CONCLUSION Gut microbiota differs significantly when comparing patients with MDD and healthy controls, though inconsistently across studies. The heterogeneity in gut microbiota compositions between the studies may be explained by variations in study design.
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Affiliation(s)
- Julie Kristine Knudsen
- Centre for Clinical Research, North Denmark Regional Hospital, Hjoerring, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Caspar Bundgaard-Nielsen
- Centre for Clinical Research, North Denmark Regional Hospital, Hjoerring, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Simon Hjerrild
- Psychosis Research Unit, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aalborg, Denmark
| | - René Ernst Nielsen
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark
| | - Peter Leutscher
- Centre for Clinical Research, North Denmark Regional Hospital, Hjoerring, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Suzette Sørensen
- Centre for Clinical Research, North Denmark Regional Hospital, Hjoerring, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Young RB, Marcelino VR, Chonwerawong M, Gulliver EL, Forster SC. Key Technologies for Progressing Discovery of Microbiome-Based Medicines. Front Microbiol 2021; 12:685935. [PMID: 34239510 PMCID: PMC8258393 DOI: 10.3389/fmicb.2021.685935] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 05/25/2021] [Indexed: 12/22/2022] Open
Abstract
A growing number of experimental and computational approaches are illuminating the “microbial dark matter” and uncovering the integral role of commensal microbes in human health. Through this work, it is now clear that the human microbiome presents great potential as a therapeutic target for a plethora of diseases, including inflammatory bowel disease, diabetes and obesity. The development of more efficacious and targeted treatments relies on identification of causal links between the microbiome and disease; with future progress dependent on effective links between state-of-the-art sequencing approaches, computational analyses and experimental assays. We argue determining causation is essential, which can be attained by generating hypotheses using multi-omic functional analyses and validating these hypotheses in complex, biologically relevant experimental models. In this review we discuss existing analysis and validation methods, and propose best-practice approaches required to enable the next phase of microbiome research.
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Affiliation(s)
- Remy B Young
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.,Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia
| | - Vanessa R Marcelino
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.,Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia
| | - Michelle Chonwerawong
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.,Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia
| | - Emily L Gulliver
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.,Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.,Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia
| | - Samuel C Forster
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.,Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.,Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia
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Chen YH, Xue F, Yu SF, Li XS, Liu L, Jia YY, Yan WJ, Tan QR, Wang HN, Peng ZW. Gut microbiota dysbiosis in depressed women: The association of symptom severity and microbiota function. J Affect Disord 2021; 282:391-400. [PMID: 33421868 DOI: 10.1016/j.jad.2020.12.143] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 11/24/2020] [Accepted: 12/24/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The association between abnormal gut microbiome composition and depression is well established. However, the composition and functional capacity of the gut microbiota regarding depressed women has been poorly addressed. METHODS Stool samples from 62 female patients with major depressive disorder (MDD) and 46 healthy controls (Con) were analyzed by 16S rRNA gene sequencing; Twenty fecal samples from the patient group and 21 fecal samples from the Con group were further analyzed by shotgun metagenomic sequencing. Psychiatric symptoms and psychological, social, and professional functioning was also assessed. RESULTS Phylum Bacteroidetes, proteobaeteria, and Fusobacteria were greatly enriched in patients with MDD, while the Firmicutes and Actinobacteria phyla were consistently higher in Con. Notably, 18 microbial markers were identified on a random forest model and achieve an area under the curve of 0.92 between patients with MDD and the Con group. Forty-five species and their associated function were identified with statistically significant differences between patients with MDD and the Con group. LIMITATIONS The number of recruited samples, especially samples enrolled for shotgun metagenomic sequencing was relatively small, and the stool samples were collected only at baseline, making it difficult to establish a causal association between changes in gut microbiota compositions and disease remission. CONCLUSIONS This study characterizes the gut microbiota and their related function in female MDD. The gut microbiota-based biomarkers may be helpful in diagnosis and the altered gut microbial metabolites may contribute to the pathogenesis of MDD in women, representing potential microbial targets.
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Affiliation(s)
- Yi-Huan Chen
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Fen Xue
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China
| | - Shou-Fen Yu
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Xiao-Sa Li
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Ling Liu
- Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China
| | - Yan-Yan Jia
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Wen-Jun Yan
- Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, 730000, China
| | - Qing-Rong Tan
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Hua-Ning Wang
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
| | - Zheng-Wu Peng
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
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Gut-brain axis: A matter of concern in neuropsychiatric disorders…! Prog Neuropsychopharmacol Biol Psychiatry 2021; 104:110051. [PMID: 32758517 DOI: 10.1016/j.pnpbp.2020.110051] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 07/25/2020] [Accepted: 07/26/2020] [Indexed: 01/09/2023]
Abstract
The gut microbiota is composed of a large number of microbes, usually regarded as commensal bacteria. It has become gradually clear that gastrointestinal microbiota affects gut pathophysiology and the central nervous system (CNS) function by modulating the signaling pathways of the microbiota-gut-brain (MGB) axis. This bidirectional MGB axis communication primarily acts through neuroendocrine, neuroimmune, and autonomic nervous systems (ANS) mechanisms. Accumulating evidence reveals that gut microbiota interacts with the host brain, and its modulation may play a critical role in the pathology of neuropsychiatric disorders. Recently, neuroscience research has established the significance of gut microbiota in the development of brain systems that are essential to stress-related behaviors, including depression and anxiety. Application of modulators of the MGB, such as psychobiotics (e.g., probiotics), prebiotics, and specific diets, may be a promising therapeutic approach for neuropsychiatric disorders. The present review article primarily focuses on the relevant features of the disturbances of the MGB axis in the pathophysiology of neuropsychiatric disorders and its potential mechanisms.
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Hopper CP, De La Cruz LK, Lyles KV, Wareham LK, Gilbert JA, Eichenbaum Z, Magierowski M, Poole RK, Wollborn J, Wang B. Role of Carbon Monoxide in Host-Gut Microbiome Communication. Chem Rev 2020; 120:13273-13311. [PMID: 33089988 DOI: 10.1021/acs.chemrev.0c00586] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Nature is full of examples of symbiotic relationships. The critical symbiotic relation between host and mutualistic bacteria is attracting increasing attention to the degree that the gut microbiome is proposed by some as a new organ system. The microbiome exerts its systemic effect through a diverse range of metabolites, which include gaseous molecules such as H2, CO2, NH3, CH4, NO, H2S, and CO. In turn, the human host can influence the microbiome through these gaseous molecules as well in a reciprocal manner. Among these gaseous molecules, NO, H2S, and CO occupy a special place because of their widely known physiological functions in the host and their overlap and similarity in both targets and functions. The roles that NO and H2S play have been extensively examined by others. Herein, the roles of CO in host-gut microbiome communication are examined through a discussion of (1) host production and function of CO, (2) available CO donors as research tools, (3) CO production from diet and bacterial sources, (4) effect of CO on bacteria including CO sensing, and (5) gut microbiome production of CO. There is a large amount of literature suggesting the "messenger" role of CO in host-gut microbiome communication. However, much more work is needed to begin achieving a systematic understanding of this issue.
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Affiliation(s)
- Christopher P Hopper
- Institute for Experimental Biomedicine, University Hospital Wuerzburg, Wuerzburg, Bavaria DE 97080, Germany.,Department of Medicinal Chemistry, College of Pharmacy, The University of Florida, Gainesville, Florida 32611, United States
| | - Ladie Kimberly De La Cruz
- Department of Chemistry & Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30303, United States
| | - Kristin V Lyles
- Department of Biology, Georgia State University, Atlanta, Georgia 30303, United States
| | - Lauren K Wareham
- The Vanderbilt Eye Institute and Department of Ophthalmology & Visual Sciences, The Vanderbilt University Medical Center and School of Medicine, Nashville, Tennessee 37232, United States
| | - Jack A Gilbert
- Department of Pediatrics, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States
| | - Zehava Eichenbaum
- Department of Biology, Georgia State University, Atlanta, Georgia 30303, United States
| | - Marcin Magierowski
- Cellular Engineering and Isotope Diagnostics Laboratory, Department of Physiology, Jagiellonian University Medical College, Cracow PL 31-531, Poland
| | - Robert K Poole
- Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Sheffield S10 2TN, U.K
| | - Jakob Wollborn
- Department of Anesthesiology and Critical Care, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg DE 79085, Germany.,Department of Anesthesiology, Perioperative and Pain Management, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
| | - Binghe Wang
- Department of Chemistry & Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30303, United States
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Medina-Rodriguez EM, Madorma D, O’Connor G, Mason BL, Han D, Deo S, Oppenheimer M, Nemeroff CB, Trivedi MH, Daunert S, Beurel E. Identification of a Signaling Mechanism by Which the Microbiome Regulates Th17 Cell-Mediated Depressive-Like Behaviors in Mice. Am J Psychiatry 2020; 177:974-990. [PMID: 32731813 PMCID: PMC7647050 DOI: 10.1176/appi.ajp.2020.19090960] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Microbiota dysbiosis has been linked to major depressive disorder, but the mechanisms whereby the microbiota modulates mood remain poorly understood. The authors tested whether specific changes in the microbiome modulate depressive-like behaviors. METHODS Stools from learned helpless, non-learned helpless, and non-shocked mice were analyzed by V4 16S RNA sequencing to identify gut bacteria associated with learned helplessness and to quantify the level of the quorum-sensing molecule autoinducer-2 (AI-2). T cells were analyzed by flow cytometry, and serum amyloid proteins (SAA) were analyzed by quantitative real-time polymerase chain reaction. Fecal transfer approach and administration of oleic acid and AI-2 were used to determine the effects of the microbiome and quorum-sensing molecules on depressive-like behaviors. RESULTS Mice deficient in segmented filamentous bacteria (SFB) were resilient to the induction of depressive-like behavior, and were resensitized when SFB was reintroduced in the gut. SFB produces the quorum-sensing AI-2 and promotes the production of SAA1 and SAA2 by the host, which increases T helper 17 (Th17) cell production. Th17 cells were required to promote depressive-like behaviors by AI-2, as AI-2 administration did not promote susceptibility to depressive-like behaviors or SAA1 and SAA2 production in Th17-deficient mice after stress. Oleic acid, an AI-2 inhibitor, exhibited antidepressant properties, reducing depressive-like behavior, intestinal SAA1 and SAA2 production, and hippocampal Th17 cell accumulation. Stool samples from 10 people with current depressive symptoms and 10 matched healthy control subjects were analyzed as well. Patients with current major depressive disorder exhibited increased fecal interleukin 17A, SAA, and SFB levels. CONCLUSIONS The study results reveal a novel mechanism by which bacteria alter mood.
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Affiliation(s)
| | - Derik Madorma
- Department of Biochemistry and Molecular Biology,Dr. JT Macdonald Foundation Biomedical Nanotechnology Institute
| | - Gregory O’Connor
- Department of Biochemistry and Molecular Biology,Dr. JT Macdonald Foundation Biomedical Nanotechnology Institute
| | - Brittany L. Mason
- Department of Psychiatry, Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center, Dallas, TX 75390
| | - Dongmei Han
- Department of Psychiatry and Behavioral Sciences
| | - Sapna Deo
- Department of Biochemistry and Molecular Biology,Dr. JT Macdonald Foundation Biomedical Nanotechnology Institute
| | | | - Charles B. Nemeroff
- Department of Psychiatry, Mulva Clinic for Neurosciences, University of Texas Dell Medical School in Austin, TX 78712
| | - Madhukar H. Trivedi
- Department of Psychiatry, Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center, Dallas, TX 75390
| | - Sylvia Daunert
- Department of Biochemistry and Molecular Biology,Dr. JT Macdonald Foundation Biomedical Nanotechnology Institute,University of Miami Clinical and Translational Science Institute Miller School of Medicine, University of Miami, Miami, FL 33136
| | - Eléonore Beurel
- Department of Psychiatry and Behavioral Sciences,Department of Biochemistry and Molecular Biology,Corresponding author: Eléonore Beurel, Miller School of Medicine, University of Miami, 1011 NW 15th Street, Gautier Building room 415, Miami, Florida 33136, phone: 305-243-0263,
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