1
|
Adıgüzel E, Yılmaz ŞG, Atabilen B, Şeref B. Microbiome modulation as a novel therapeutic modality for anxiety disorders: A review of clinical trials. Behav Brain Res 2025; 487:115595. [PMID: 40246176 DOI: 10.1016/j.bbr.2025.115595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 03/08/2025] [Accepted: 04/14/2025] [Indexed: 04/19/2025]
Abstract
Anxiety disorders are one of the major conditions in psychiatry characterized by symptoms such as worry, social and performance fears, unexpected and/or triggered panic attacks, anticipatory anxiety, and avoidance behaviors. Recent developments have drawn attention to the putative involvement of peripheral systems in the control of anxiety, and the gut microbiota has come to light as an emerging peripheral target for anxiety. The relationship between the gut-brain axis, a bidirectional communication network between the central nervous system (CNS) and enteric nervous system (ENS), and anxiety has been the subject of some recent studies. Therefore, this systematic review analyzed clinical trials evaluating the potential of microbiome modulation methods in mitigating and ameliorating anxiety disorders. Clinical studies on probiotic, prebiotic, synbiotic supplements, dietary interventions, and fecal microbiota transplantation in anxiety disorders were screened. All of the studies examined the effects of probiotic intervention. One of these studies compared a prebiotic-rich diet with probiotic supplementation. Longitudinal analyses showed that the probiotic intervention alleviated anxiety. However, most of the controlled studies reported that the probiotic intervention did not make a difference compared to placebo. Thus, the current findings suggest that it is too early to consider the promising role of microbiome modulation in the treatment of anxiety disorders. However, it is obvious that more clinical research is needed to clarify issues such as probiotic strains, prebiotic types, and their doses that may be effective on anxiety disorders.
Collapse
Affiliation(s)
- Emre Adıgüzel
- Karamanoğlu Mehmetbey University, Faculty of Health Sciences, Department of Nutrition and Dietetics, Karaman, Turkey.
| | - Şemsi Gül Yılmaz
- Karamanoğlu Mehmetbey University, Faculty of Health Sciences, Department of Nutrition and Dietetics, Karaman, Turkey.
| | - Büşra Atabilen
- Karamanoğlu Mehmetbey University, Faculty of Health Sciences, Department of Nutrition and Dietetics, Karaman, Turkey.
| | - Betül Şeref
- Karamanoğlu Mehmetbey University, Faculty of Health Sciences, Department of Nutrition and Dietetics, Karaman, Turkey.
| |
Collapse
|
2
|
Dai LY, Chen RR, Chen HR, Yin JH, Huang ZX, Yin BW, Liu XY. Potential clinical benefits of probiotics, prebiotics, synbiotics, and postbiotics for depression via the microbiota-gut-brain axis. World J Psychiatry 2025; 15:98436. [DOI: 10.5498/wjp.v15.i5.98436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 02/06/2025] [Accepted: 04/07/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND Depression is a common mental-health disorder worldwide. Several studies have demonstrated the effects of gut microbiota-targeting interventions, such as probiotics, prebiotics, synbiotics, and postbiotics (PPSP), on depression.
AIM To assess the potential benefits of PPSP on patients diagnosed with depressive disorder.
METHODS A literature search of the PubMed, Web of Science, and Elsevier Science Direct databases for relevant studies published from database inception to March 2024 was performed. Studies that used a randomized controlled trial design and evaluated differences in depression between PPSP and placebo were included. Depressive symptoms were assessed using a validated scale. Analysis was performed using Review Manager version 5.4 (The Cochrane Collaboration, 2020).
RESULTS Fourteen studies comprising 906 patients with depressive symptoms were included. PPSP improved depression compared with placebo [SMD: -0.39 (95%CI: -0.60 to -0.17); P < 0.001]. PPSP resulted in significant reductions in Hamilton Depression Rating Scale [MD: -1.72 (95%CI: -2.57 to -0.88); P < 0.001] and Beck Depression Inventory [MD: -2.69 (95%CI: -4.67 to -0.71); P < 0.001] scores. Sub-analysis confirmed the antidepressant effects of probiotics on depressive symptoms [SMD: -0.32 (95%CI: -0.48 to -0.16); P < 0.001], with prebiotics exerting no apparent effect [SMD: -0.08 (95%CI: -0.39 to -0.23); P = 0.62], and synbiotics exerting statistically significant benefits [SMD: -1.09 (95%CI: -1.45 to -0.73); P < 0.001].
CONCLUSION PPSP effectively alleviates depressive symptoms, and subgroup analysis supports the benefits of probiotics and synbiotics. Nevertheless, evidence supporting the use of PPSP for the treatment of depression remains insufficient.
Collapse
Affiliation(s)
- Ling-Yi Dai
- Department of General Psychiatry, Wenzhou Seventh People's Hospital, Wenzhou 325000, Zhejiang Province, China
| | - Ru-Ru Chen
- Department of General Psychiatry, Wenzhou Seventh People's Hospital, Wenzhou 325000, Zhejiang Province, China
| | - Hao-Ran Chen
- Department of General Psychiatry, Wenzhou Seventh People's Hospital, Wenzhou 325000, Zhejiang Province, China
| | - Jia-Hui Yin
- Department of General Psychiatry, Wenzhou Seventh People's Hospital, Wenzhou 325000, Zhejiang Province, China
| | - Zhen-Xing Huang
- Department of General Psychiatry, Wenzhou Seventh People's Hospital, Wenzhou 325000, Zhejiang Province, China
| | - Bo-Wen Yin
- Department of General Psychiatry, Wenzhou Seventh People's Hospital, Wenzhou 325000, Zhejiang Province, China
| | - Xing-Yan Liu
- Department of General Psychiatry, Wenzhou Seventh People's Hospital, Wenzhou 325000, Zhejiang Province, China
| |
Collapse
|
3
|
Cheng Q, Ran Y, Mo X, Xiao R, He D, Guo S, Wang H, Liu L, Xie P. The efficacy and acceptability of Lactobacillus reuteri for the treatment of depression: A systematic review and meta-analysis. Gen Hosp Psychiatry 2025; 95:122-132. [PMID: 40339531 DOI: 10.1016/j.genhosppsych.2025.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 04/22/2025] [Accepted: 05/02/2025] [Indexed: 05/10/2025]
Abstract
INTRODUCTION Some preclinical and clinical studies have demonstrated the positive effect of Lactobacillus reuteri (L. reuteri) supplementation on depressive symptoms. We conducted an updated systematic review on this topic. METHOD PubMed, EMBASE, Cochrane, Web of Science, and international trial registries were searched. We included randomized controlled trials (RCTs) and animal experiments on the use of mixed probiotics containing L. reuteri in the treatment of depression. Analyses were done using Review Manager version 5.4 and Stata 18.0. RESULTS In total, 12 RCTs including 1258 patients were included. The efficacy of the mixed probiotics containing L. reuteri in the treatment of depression was superior to the control group (SMD: -0.44, 95 %CI: -0.72 to -0.16). In terms of acceptability, there was no significant difference between the probiotic and control groups (OR: 1.04, 95 %CI: 0.75 to 1.45). In 9 animal experiments, mixed probiotics containing L. reuteri improved the symptoms of anxiety and depression. Subgroup analyses showed patients using multi-strain interventions (SMD: -0.56, 95 %CI: -0.97 to -0.15), having depressive symptoms (SMD: -0.39, 95 %CI: -0.74 to -0.03), and other clinical populations (SMD: -0.59, 95 %CI: -1.06 to -0.13), age < 60 years (SMD: -0.52, 95 %CI: -0.88 to -0.15), female patients (SMD: -0.45, 95 %CI: -0.78 to -0.13) may benefit more. CONCLUSION Mixed probiotics containing L. reuteri ameliorated depressive symptoms in patients and depression-like behaviors in animals. Combined microbiota seems to be more effective than single strain intervention in the treatment of depression. Patients with depressive symptoms, other clinical populations, age < 60 years, female patients may benefit more from probiotics. L. reuteri alone did not improve depressive symptoms.
Collapse
Affiliation(s)
- Qisheng Cheng
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yuxin Ran
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaolong Mo
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Rui Xiao
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Faculty of Basic Medicine, Department of Pathology, Chongqing Medical University, Chongqing, China
| | - Dian He
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Siyi Guo
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Haiyang Wang
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lanxiang Liu
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Xie
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China; Chongqing Institute for Brain and Intelligence, China.
| |
Collapse
|
4
|
Nikolova VL, Cleare AJ, Young AH, Stone JM. Exploring the mechanisms of action of probiotics in depression: Results from a randomized controlled pilot trial. J Affect Disord 2025; 376:241-250. [PMID: 39924003 DOI: 10.1016/j.jad.2025.01.153] [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: 02/28/2024] [Revised: 01/27/2025] [Accepted: 01/31/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND We previously reported greater reductions in depression and anxiety following probiotic supplementation in people with major depressive disorder (MDD) in a randomised double-blind placebo-controlled pilot trial (Nikolova et al., 2023). Here, we investigate the mechanisms underlying these effects. METHODS 49 people with MDD received a multi-strain probiotic (n = 24) or placebo (n = 25) for 8 weeks in addition to their antidepressant. Stool and blood samples were collected to analyse gut microbiota composition and inflammatory cytokines. Stool samples from 25 matched healthy volunteers (HVs) were also obtained. RESULTS Within the probiotic group, there was a significant increase in richness according to Chao1(bias-corrected) (w4 p = 0.04) and a trend for increased Total count (w4 p = 0.06, w8 p = 0.09) compared to baseline, but not to placebo. When compared to HVs post-treatment, only the placebo group had a significant decrease in Shannon' entropy (p = 0.03) and a trend for decreased Total count (p = 0.08) and Simpson's index (p = 0.09). Between-group differences in beta diversity were observed at week 4 (p = 0.04), but not week 8. Consistent between-group differences were seen in family Bacilleceae post-treatment (FDR p < 0.05), which correlated with decreases in anxiety (FDR p < 0.05). There were no differences in inflammatory markers. LIMITATIONS This study was limited by data loss during the COVID-19 Pandemic. CONCLUSION Probiotics may positively impact the microbiota by normalising diversity and increasing levels of health-related taxa, which may partially account for their benefits in MDD. Understanding how these changes relate to symptom improvement can inform their targeted use in clinical practice. Larger trials incorporating functional multi-omics are needed. TRIAL REGISTRATION NCT03893162.
Collapse
Affiliation(s)
- Viktoriya L Nikolova
- Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; ADM Health & Wellness, ADM Protexin Ltd., Somerset, UK.
| | - Anthony J Cleare
- Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, UK; South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, UK.
| | - Allan H Young
- Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, UK; South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, UK.
| | - James M Stone
- Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; Brighton and Sussex Medical School, Brighton BN1 9PX, UK.
| |
Collapse
|
5
|
Akerele CA, Koralnik LR, Lafont E, Gilman C, Walsh-Messinger J, Malaspina D. Nutrition and brain health: Implications of Mediterranean diet elements for psychiatric disorders. Schizophr Res 2025; 281:30-44. [PMID: 40315757 DOI: 10.1016/j.schres.2025.04.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 04/03/2025] [Accepted: 04/23/2025] [Indexed: 05/04/2025]
Abstract
The Mediterranean diet is an anti-inflammatory diet now recognized for prevention and intervention against cardiometabolic disorders, although emerging literature also shows its benefits for mental health. This paper surveys literature pertinent to the Mediterranean diet with respect to schizophrenia, bipolar and unipolar depression and cognition. The National Library of Medicine database of literature was searched for publications relating to our topic through June 2024. Our results highlight the Mediterranean diet's potential role in mediating inflammation, potentially through the gut-brain axis, and its neuroprotective role against cognitive decline. Moreover, individual components of the Mediterranean diet are potentially therapeutic as well as protective, particularly fruits, vegetables, fatty fish, and whole grains. These dietary components reduce systemic inflammation, modulate gut microbiota and influence critical pathways such as moderating oxidative stress. Overall, this survey of recent literature highlights the potential of the Mediterranean diet to promote mental health and reduce the risk or severity of psychiatric and neurodegenerative disorders. The analysis underscores broader implications for the Mediterranean diet in advancing mental health outcomes and emphasizes the need for further studies and increased public education to encourage healthier eating habits and dietary interventions.
Collapse
Affiliation(s)
| | | | - Ezequiel Lafont
- Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, NY 10029, USA
| | - Caitlin Gilman
- Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | | | - Dolores Malaspina
- Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, NY 10029, USA.
| |
Collapse
|
6
|
Hernández-Cacho A, García-Gavilán JF, Atzeni A, Konstanti P, Belzer C, Vioque J, Corella D, Fitó M, Vidal J, Mela V, Liang L, Torres-Collado L, Coltell O, Babio N, Clish C, Hernando-Redondo J, Martínez-González MÁ, Wang F, Moreno-Indias I, Ni J, Dennis C, Ruiz-Canela M, Tinahones FJ, Hu FB, Salas-Salvadó J. Multi-omics approach identifies gut microbiota variations associated with depression. NPJ Biofilms Microbiomes 2025; 11:68. [PMID: 40295565 PMCID: PMC12038053 DOI: 10.1038/s41522-025-00707-9] [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: 11/21/2024] [Accepted: 04/17/2025] [Indexed: 04/30/2025] Open
Abstract
The gut microbiota plays a potential role in the pathophysiology of depression through the gut-brain axis. This cross-sectional study in 400 participants from the PREDIMED-Plus study investigates the interplay between gut microbiota and depression using a multi-omics approach. Depression was defined as antidepressant use or high Beck Depression Inventory-II scores. Gut microbiota was characterized by 16S rRNA sequencing, and faecal metabolites were analysed via liquid chromatography-tandem mass spectrometry. Participants with depression exhibited significant differences in gut microbial composition and metabolic profiles. Differentially abundant taxa included Acidaminococcus, Christensenellaceae R-7 group, and Megasphaera, among others. Metabolomic analysis revealed 15 significantly altered metabolites, primarily lipids, organic acids, and benzenoids, some of which correlated with gut microbial features. This study highlights the interplay between the gut microbiota and depression, paving the way for future research to determine whether gut microbiota influences depression pathophysiology or reflects changes associated with depression.
Collapse
Affiliation(s)
- Adrián Hernández-Cacho
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental ANUT-DSM, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - Jesús F García-Gavilán
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental ANUT-DSM, Reus, Spain.
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain.
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
| | - Alessandro Atzeni
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental ANUT-DSM, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - Prokopis Konstanti
- Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands
| | - Jesús Vioque
- CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernández (ISABIAL-UMH), Alicante, Spain
| | - Dolores Corella
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Preventive Medicine, University of Valencia, Valencia, Spain
| | - Montserrat Fitó
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Unit of Cardiovascular Risk and Nutrition, Institut Hospital del Mar de Investigaciones Médicas Municipal d'Investigació Médica (IMIM), Barcelona, Spain
| | - Josep Vidal
- CIBER Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Endocrinology, Institut d'Investigacions Biomédiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Virginia Mela
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga - IBIMA, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Liming Liang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- The Broad Institute of Harvard and MIT, Boston, MA, USA
| | - Laura Torres-Collado
- CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernández (ISABIAL-UMH), Alicante, Spain
| | - Oscar Coltell
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Computer Languages and Systems, Jaume I University, Castellón, Spain
| | - Nancy Babio
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental ANUT-DSM, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - Clary Clish
- The Broad Institute of Harvard and MIT, Boston, MA, USA
| | - Javier Hernando-Redondo
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Unit of Cardiovascular Risk and Nutrition, Institut Hospital del Mar de Investigaciones Médicas Municipal d'Investigació Médica (IMIM), Barcelona, Spain
| | - Miguel Á Martínez-González
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Fenglei Wang
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Isabel Moreno-Indias
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga - IBIMA, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Jiaqi Ni
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental ANUT-DSM, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | | | - Miguel Ruiz-Canela
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Francisco J Tinahones
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga - IBIMA, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Frank B Hu
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Jordi Salas-Salvadó
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentació, Nutrició, Desenvolupament i Salut Mental ANUT-DSM, Reus, Spain.
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain.
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
| |
Collapse
|
7
|
Cho MY, Eom JH, Choi EM, Yang SJ, Lee D, Kim YY, Kim HS, Hwang I. Recent advances in therapeutic probiotics: insights from human trials. Clin Microbiol Rev 2025:e0024024. [PMID: 40261032 DOI: 10.1128/cmr.00240-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/24/2025] Open
Abstract
SUMMARYRecent advances in therapeutic probiotics have shown promising results across various health conditions, reflecting a growing understanding of the human microbiome's role in health and disease. However, comprehensive reviews integrating the diverse therapeutic effects of probiotics in human subjects have been limited. By analyzing randomized controlled trials (RCTs) and meta-analyses, this review provides a comprehensive overview of key developments in probiotic interventions targeting gut, liver, skin, vaginal, mental, and oral health. Emerging evidence supports the efficacy of specific probiotic strains and combinations in treating a wide range of disorders, from gastrointestinal (GI) and liver diseases to dermatological conditions, bacterial vaginosis, mental disorders, and oral diseases. We discuss the expanding understanding of microbiome-organ connections underlying probiotic mechanisms of action. While many clinical trials demonstrate significant benefits, we acknowledge areas requiring further large-scale studies to establish definitive efficacy and optimal treatment protocols. The review addresses challenges in standardizing probiotic research methodologies and emphasizes the importance of considering individual variations in microbiome composition and host genetics. Additionally, we explore emerging concepts such as the oral-gut-brain axis and future directions, including high-resolution microbiome profiling, host-microbe interaction studies, organoid models, and artificial intelligence applications in probiotic research. Overall, this review offers a comprehensive update on the current state of therapeutic probiotics across multiple domains of human health, providing insights into future directions and the potential for probiotics to revolutionize preventive and therapeutic medicine.
Collapse
Affiliation(s)
- Mu-Yeol Cho
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
| | - Je-Hyun Eom
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
| | - Eun-Mi Choi
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
| | | | - Dahye Lee
- Department of Orthodontics, Apple Tree Dental Hospital, Goyang-si, South Korea
| | - Young Youn Kim
- Department of Oral and Maxillofacial Surgery, Apple Tree Dental Hospital, Goyang-si, South Korea
| | - Hye-Sung Kim
- Department of Oral and Maxillofacial Surgery, Apple Tree Dental Hospital, Goyang-si, South Korea
| | - Inseong Hwang
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
| |
Collapse
|
8
|
Chang Z, Zhu Y, Wang P, Du L, Wu M, Wang X, Kong C, Huang D, Xie R, Ji G, Wang C, Cheng L, Yan X, Wei Q, Qin H. Multi-omic analyses of the development of obesity-related depression linked to the gut microbe Anaerotruncus colihominis and its metabolite glutamate. Sci Bull (Beijing) 2025:S2095-9273(25)00359-7. [PMID: 40274437 DOI: 10.1016/j.scib.2025.04.010] [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: 08/27/2024] [Revised: 02/06/2025] [Accepted: 03/24/2025] [Indexed: 04/26/2025]
Abstract
Emerging evidence implicates gut microbiota in the pathogenesis of obesity-related depression (OD); however, the underlying molecular mechanisms remain inadequately explored. This study compared the microbial and transcriptional profiles between patients with OD and healthy individuals. The results revealed an enrichment of Anaerotruncus colihominis (A. colihominis) and glutamate metabolism-related genes in the OD group. Fecal microbiota transplantation (FMT) from patients with OD induced weight gain, compromised barrier function, and intensified depression-like behaviors in high-fat diet (HFD) mice. Microbial analysis in the mice feces corroborated the clinical findings. Single-cell RNA sequencing highlighted the pivotal role of the Efnb2-Ephb2 interaction in cell communication among colon epithelial and hippocampal neuron subtypes in OD mice. Notably, A. colihominis correlated with glutamate levels in the OD mice and patients. It produced glutamate through a glutamic acid metabolism-related DNA sequence, verified in an engineered Escherichia coli MG1655 strain. Both A. colihominis and glutamate reduced barrier proteins in colon epithelial cells and modulated cognitive proteins in neurons. Finally, A. colihominis treatment induced the Efnb2-Ephb2 interaction, exacerbating depression-like behaviors in germ-free HFD mice. Collectively, these findings reveal that A. colihominis and glutamate are potential intervention targets for OD treatment.
Collapse
Affiliation(s)
- Zhengyan Chang
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Yefei Zhu
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225012, China
| | - Ping Wang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150001, China
| | - Lei Du
- Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Minkang Wu
- Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Xingchun Wang
- Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Cheng Kong
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Dengfeng Huang
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Ruting Xie
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Guo Ji
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Chao Wang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150001, China
| | - Liang Cheng
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150001, China.
| | - Xuebing Yan
- Jiangsu Provincial Innovation and Practice Base for Postdoctors, Suining First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Yangzhou University, Suining 221200, China.
| | - Qing Wei
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
| | - Huanlong Qin
- Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
| |
Collapse
|
9
|
Elahinejad V, Khorasanian AS, Tehrani‐Doost M, Khosravi‐Darani K, Mirsepasi Z, Effatpanah M, Askari‐Rabori R, Tajadod S, Jazayeri S. Effects of Probiotics as Adjunctive Therapy to Fluoxetine on Depression Severity and Serum Brain-Derived Neurotrophic Factor, Cortisol, and Adrenocorticotropic Hormone in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial. Food Sci Nutr 2025; 13:e4698. [PMID: 40177327 PMCID: PMC11961381 DOI: 10.1002/fsn3.4698] [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: 08/17/2024] [Revised: 11/22/2024] [Accepted: 12/03/2024] [Indexed: 04/05/2025] Open
Abstract
Probiotics may improve mood, but their role as adjunctive therapy for major depressive disorder (MDD) is not well understood. This study examines the effects of probiotics on depression severity, brain-derived neurotrophic factor (BDNF), adrenocorticotropic hormone (ACTH), and cortisol levels in MDD patients. Fifty medication-free MDD patients were randomized to receive probiotics with fluoxetine (n = 25) or placebo with fluoxetine (n = 25) for 8 weeks. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS-24), and fasting blood samples were collected at baseline and study conclusion. Forty-four patients completed the trial. The probiotic group showed a significant reduction in depression severity compared with the placebo group (p = 0.001). No significant differences were observed in serum cortisol (p = 0.46) and ACTH levels (p = 0.44). Plasma BDNF levels increased slightly in the probiotic group but were not statistically significant. Probiotic supplementation with fluoxetine significantly reduces depression severity in MDD patients.
Collapse
Affiliation(s)
- Vajihe Elahinejad
- Department of Nutrition, School of Public HealthIran University of Medical SciencesTehranIran
| | - Atie Sadat Khorasanian
- Department of Nutrition, School of Public HealthIran University of Medical SciencesTehranIran
- Endocrinology and Metabolism Research CenterEndocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical SciencesTehranIran
| | - Mehdi Tehrani‐Doost
- Department of PsychiatryRoozbeh Hospital, Tehran University of Medical SciencesTehranIran
| | - Kianoush Khosravi‐Darani
- Research Department of Food Technology ResearchNational Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical SciencesTehranIran
| | - Zahra Mirsepasi
- Department of PsychiatryRoozbeh Hospital, Tehran University of Medical SciencesTehranIran
| | - Mohammad Effatpanah
- School of MedicineZiaeian Hospital, International Campus, Tehran University of Medical SciencesTehranIran
| | | | - Shirin Tajadod
- Department of Nutrition, School of Public HealthIran University of Medical SciencesTehranIran
| | - Shima Jazayeri
- Department of Nutrition, School of Public HealthIran University of Medical SciencesTehranIran
- Research Center for Nutritional SciencesIran University of Medical SciencesTehranIran
| |
Collapse
|
10
|
Lutz M, Arancibia M, Moran-Kneer J, Manterola M. Ultraprocessed Foods and Neuropsychiatric Outcomes: Putative Mechanisms. Nutrients 2025; 17:1215. [PMID: 40218973 PMCID: PMC11990412 DOI: 10.3390/nu17071215] [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: 03/04/2025] [Revised: 03/21/2025] [Accepted: 03/26/2025] [Indexed: 04/14/2025] Open
Abstract
A body of evidence indicates an association between ultraprocessed foods (UPFs) and health outcomes. Most of it has been obtained through preclinical studies, although a number of observational studies substantiate how a high intake of these products increases the risk of neuropsychiatric disorders, and an increasing amount of dietary intervention studies confirm these findings. The aim of this narrative review is to describe some of the putative mechanisms involved in the deleterious effects of a high intake of UPFs on neuropsychiatric outcomes. A myriad of unhealthy actions may be associated with the consumption of UPFs, and some mechanisms are being discussed. They include UPFs' high caloric density; their high sugar, sodium, and additives content and low amounts of fiber; and a high palatability that induces overconsumption, acting as obesogens. Moreover, thermal treatment of these foods generates oxidative products such as glycotoxins, lipotoxins, and acrolein, all of which affect the brain. The chemical products act, directly or indirectly, on the gut microbiome and affect the gut-brain axis, causing neuroinflammation, oxidative stress, and neurodegeneration. UPFs also exert various epigenetic effects that affect mental health and might explain the intergenerational inheritance of neuropsychiatric disorders. A diet containing a high proportion of these foods has a low nutritional density, including bioactive protective agents such as antioxidant and anti-inflammatory compounds that promote eubiosis. The evidence shows that UPFs intake affects neuropsychiatric outcomes such as neurodegeneration, cognitive decline, dementia, and mood disorders and reinforces the need to promote a healthy dietary pattern throughout all life stages, thus interfering with the current commercial determinants of health.
Collapse
Affiliation(s)
- Mariane Lutz
- Center for Translational Studies in Stress and Mental Health (C-ESTRES), Universidad de Valparaíso, Valparaíso 2360102, Chile; (M.A.); (J.M.-K.); (M.M.)
- School of Medicine, Faculty of Medicine, Universidad de Valparaíso, Viña del Mar 2520000, Chile
| | - Marcelo Arancibia
- Center for Translational Studies in Stress and Mental Health (C-ESTRES), Universidad de Valparaíso, Valparaíso 2360102, Chile; (M.A.); (J.M.-K.); (M.M.)
- School of Medicine, Faculty of Medicine, Universidad de Valparaíso, Viña del Mar 2520000, Chile
| | - Javier Moran-Kneer
- Center for Translational Studies in Stress and Mental Health (C-ESTRES), Universidad de Valparaíso, Valparaíso 2360102, Chile; (M.A.); (J.M.-K.); (M.M.)
- School of Psychology, Faculty of Social Sciences, Universidad de Valparaíso, Valparaíso 2340000, Chile
| | - Marcia Manterola
- Center for Translational Studies in Stress and Mental Health (C-ESTRES), Universidad de Valparaíso, Valparaíso 2360102, Chile; (M.A.); (J.M.-K.); (M.M.)
- Human Genetics Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| |
Collapse
|
11
|
Mi J, Morys J, Nowacka-Chmielewska M, Burek M. The role of microbiome in gut-brain-axis dysbiosis causing depression: From mechanisms to treatment. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2025; 180:189-244. [PMID: 40414633 DOI: 10.1016/bs.irn.2025.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2025]
Abstract
Gut microbiota not only affects the function of the gastrointestinal tract but also the function of other organs, including the brain. The microbiota-gut-brain axis reflects the constant bidirectional communication between the central nervous system and the gastrointestinal tract. Gut microbiota metabolites can cross brain barriers, the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSF) and influence neuropsychiatric disorders, including depression. In recent years, the communication between the microbiome and brain in depression has been extensively studied in humans and animal models. In this chapter, we summarise the current literature on the role of gut microbiota in depression, focusing in particular on brain barriers and bidirectional gut-brain communication.
Collapse
Affiliation(s)
- Junqiao Mi
- University Hospital Würzburg, Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Würzburg, Germany
| | - Julia Morys
- Academy of Physical Education, Institute of Physiotherapy and Health Sciences, Laboratory of Molecular Biology, Katowice, Poland
| | - Marta Nowacka-Chmielewska
- Academy of Physical Education, Institute of Physiotherapy and Health Sciences, Laboratory of Molecular Biology, Katowice, Poland
| | - Malgorzata Burek
- University Hospital Würzburg, Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Würzburg, Germany.
| |
Collapse
|
12
|
Dekui J, Tian L, Chengying Z, Yi H. Joint association of dietary live microbe intake and depression with cancer survivor in US adults: evidence from NHANES. BMC Cancer 2025; 25:487. [PMID: 40098072 PMCID: PMC11912725 DOI: 10.1186/s12885-025-13699-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Accepted: 02/10/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND The mortality of cancer survivors is influenced by various factors. This study aims to investigate the relationship between dietary live microbe intake and depression with the mortality of cancer survivors among U.S. adults. METHODS This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2001 to 2018. Based on the classification by Sanders et al., foods were categorized by their levels of live microbes as follows: low (< 10^4 CFU/g), medium (10^4-10^7 CFU/g), and high (> 10^7 CFU/g). Using this classification and dietary questionnaire data, participants were divided into three groups: (1) low dietary live microbe intake (only low-level foods), (2) medium dietary live microbe intake (medium but not high-level foods), and (3) high dietary live microbe intake (any high-level foods). Additionally, foods classified as medium and high were combined into a "Medium-High" category. Cancer survivors were identified by their affirmative response to the question: "Have you ever been told by a doctor or other health professional that you had cancer or malignancy of any kind?" The Patient Health Questionnaire-9 (PHQ-9) was administered to assess depressive symptoms, with a score of ≥ 10 indicating depression. The study examined the independent and joint associations of dietary live microbe intake and depression with mortality outcomes in cancer survivors, employing Cox regression analysis adjusted for weights to calculate relative risk. Mediation analysis was conducted to evaluate the effect of PHQ-9 on the relationship between dietary live microbe intake and all-cause mortality in cancer patients. RESULTS During a median follow-up of 6.2 years, we identified a total of 605 all-cause mortality among participants, including 204 from cancer and 401 from non-cancer-related causes. The analysis showed that medium-high dietary live microbe intake was consistently associated with a lower risk of all-cause mortality (HR, 0.741; 95% CI, 0.602-0.912; P = 0.005) and non-CVD mortality (HR, 0.687; 95% CI, 0.545-0.866; P = 0.001) when compared to low dietary live microbe intake in adjusted models. Conversely, depression was linked to a higher risk of all-cause mortality (HR, 1.789; 95% CI, 1.281-2.473; P < 0.001) and non-CVD mortality (HR, 1.901; 95% CI, 1.249-2.793; P = 0.001) compared to individuals without depression. Notably, joint analyses revealed that low dietary live microbe intake was associated with the highest risk of all-cause mortality among cancer survivors who also experienced depression (HR, 3.122; 95% CI, 1.734-5.619; P < 0.001). Additionally, mediation analysis indicated that the PHQ-9 score mediated 18.4% of the association between dietary live microbe intake and all-cause mortality in cancer survivors mediation proportion 18.4%; 95% CI, 7.5-29.2%. CONCLUSIONS Our results indicated that low dietary live microbe intake and depression are associated with an increased risk of non-CVD and all-cause mortality among cancer survivors. Additionally, the PHQ-9 score demonstrated a mediating effect on the relationship between dietary live microbe intake and all-cause mortality in this population.
Collapse
Affiliation(s)
- Jin Dekui
- Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, 100853, China
- Department of General Practice, The Third Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
- Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, 100853, China
| | - Lv Tian
- Department of Neurology, Zhuji Affiliated Hospital of Wenzhou Medical University, Shaoxing, Zhejiang, China
| | - Zhang Chengying
- Department of General Practice, The Third Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Hu Yi
- Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, 100853, China.
| |
Collapse
|
13
|
Zhang J, He J, Hu J, Ji Y, Lou Z. Exploring the role of gut microbiota in depression: Pathogenesis and therapeutic insights. Asian J Psychiatr 2025; 105:104411. [PMID: 39999618 DOI: 10.1016/j.ajp.2025.104411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 02/19/2025] [Accepted: 02/20/2025] [Indexed: 02/27/2025]
Abstract
Depression is a common clinical mental disorder characterized by persistent low mood and anhedonia. It has become a major global public health issue due to its complex etiology and unclear mechanisms, resulting in limited diagnostic and therapeutic options. Recent studies indicate that dysbiosis of gut microbiota is closely related to the onset and progression of depression. This article systematically reviews the recent research on the 'microbiota-gut-brain axis' (MGBA), exploring the role and mechanisms of gut microbiota in preclinical and clinical studies. Additionally, it discusses the potential of modulating gut microbiota as a promising therapeutic approach for depression and suggests future research directions, aiming to provide a theoretical basis for research and clinical management of depression.
Collapse
Affiliation(s)
- Jiale Zhang
- Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China
| | - Jingkai He
- Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China
| | - Jieqiong Hu
- Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Ningbo Key Laboratory of Nervous System and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China
| | - Yunxin Ji
- Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Ningbo Key Laboratory of Nervous System and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China.
| | - Zhongze Lou
- Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Ningbo Key Laboratory of Nervous System and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Central Laboratory of the Medical Research Center, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China.
| |
Collapse
|
14
|
Hellwig K. The Tormented Soul: Caring for Older Adults with Depression in Home Healthcare. Home Healthc Now 2025; 43:78-85. [PMID: 40019259 DOI: 10.1097/nhh.0000000000001325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
This article explores depression in older adults, addressing types of depression, risk factors, signs and symptoms, prevention strategies, treatments, and the critical role of home care clinicians. It concludes with a discussion on the tragic issue of suicide among older adults, including its risk factors, prevention, and management.
Collapse
Affiliation(s)
- Karen Hellwig
- Karen Hellwig, MN, RN-BC, PHN , is the Psychiatric Case Manager, Physicians Choice Home Health, Torrance, California, and Professor Emerita of Nursing, El Camino College, Torrance, California
| |
Collapse
|
15
|
Wu D, Qu S, Sun H, Zhou S, Qu X, Chen Y, Hu H, Li X. Unveiling the brain mechanism underlying depression: 12 Years of insights from bibliometric and visualization analysis. Brain Res Bull 2025; 222:111246. [PMID: 39947302 DOI: 10.1016/j.brainresbull.2025.111246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 01/26/2025] [Accepted: 02/04/2025] [Indexed: 02/16/2025]
Abstract
Depression is a common but serious mental health illness affected human's physiology and psychology. In contemporary times, neurophysiological research on depression has emerged as a prominent area of investigation, yet there remains a paucity of review elucidating the central mechanisms of depression in the brain. Consequently, we undertook a bibliometric analysis and visualization assessment to underscore recent advancements in research pertaining to the neural underpinnings of depression. By employing these methods, we have collected articles spanning the period from 2013 to 2024, shedding light on the latest insights into the brain mechanisms associated with depression. Bibliometric analysis found 16327 research papers in the field of brain mechanism underlying depression, overall showing a sustained growth trend. Through meticulous analysis of collected data on institutions and countries, authors, co-cited literature, keywords, etc., this paper humbly aims to tentatively identify future research hotspots and frontiers, hoping to modestly contribute to and stimulate further scholarly progress in the field.
Collapse
Affiliation(s)
- Donghai Wu
- The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang 310053, China; Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China
| | - Siying Qu
- The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang 310053, China
| | - Haiju Sun
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang 310053, China
| | - Shuting Zhou
- The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang 310053, China; Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China
| | - Xinyuan Qu
- The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang 310053, China
| | - Yutian Chen
- The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang 310053, China
| | - Hantong Hu
- The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang 310053, China
| | - Xiaoyu Li
- The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang 310053, China; Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
| |
Collapse
|
16
|
Nikdasti A, Khodadadi ES, Ferdosi F, Dadgostar E, Yahyazadeh S, Heidari P, Ehtiati S, Vakili O, Khatami SH. Nutritional Strategies in Major Depression Disorder: From Ketogenic Diet to Modulation of the Microbiota-Gut-Brain Axis. Mol Neurobiol 2025; 62:2973-2994. [PMID: 39192045 DOI: 10.1007/s12035-024-04446-4] [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: 03/31/2024] [Accepted: 08/15/2024] [Indexed: 08/29/2024]
Abstract
Major depressive disorder (MDD) is a leading cause of disability worldwide. While traditional pharmacological treatments are effective for many cases, a significant proportion of patients do not achieve full remission or experience side effects. Nutritional interventions hold promise as an alternative or adjunctive approach, especially for treatment-resistant depression. This review examines the potential role of nutrition in managing MDD through addressing biological deficits and modulating pathways relevant to its pathophysiology. Specifically, it explores the ketogenic diet and gut microbiome modulation through various methods, including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Numerous studies link dietary inadequacies to increased MDD risk and deficiencies in nutrients like omega-3 s, vitamins D and B, magnesium, and zinc. These deficiencies impact neurotransmitters, inflammation, and other biological factors in MDD. The gut-brain axis also regulates mood, stress response, and immunity, and disruptions are implicated in MDD. While medications aid acute symptoms, nutritional strategies may improve long-term outcomes by preventing relapse and promoting sustained remission. This comprehensive review aims to provide insights into nutrition's multifaceted relationship with MDD and its potential for developing more effective integrated treatment approaches.
Collapse
Affiliation(s)
- Ali Nikdasti
- Department of Comparative Biomedicine and Food Science, University of Padova, Padova, Italy
| | - Elaheh Sadat Khodadadi
- Department of Comparative Biomedicine and Food Science, University of Padova, Padova, Italy
| | - Felora Ferdosi
- Department of Radiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ehsan Dadgostar
- Behavioral Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sheida Yahyazadeh
- Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Parasta Heidari
- School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Sajad Ehtiati
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Omid Vakili
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Seyyed Hossein Khatami
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
17
|
Zhang Y, Hu T, Wang X, Sun N, Cai Q, Kim HY, Fan Y, Liu D, Guan X. Profiles of gut microbiota and metabolites for high risk of transgenerational depression-like behavior by paternal methamphetamine exposure. FASEB J 2025; 39:e70386. [PMID: 39927989 DOI: 10.1096/fj.202402839r] [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: 11/13/2024] [Revised: 01/20/2025] [Accepted: 01/31/2025] [Indexed: 02/11/2025]
Abstract
Parental substance abuse increases the risk of neurological and psychiatric disorders in offsprings. However, its underlying mechanism remains elusive. Our previous study demonstrated that long-term exposure to methamphetamine (Meth), a psychostimulant drug with high addiction potential, remarkably alters the gut microbiome and metabolites in male mice, which contribute to Meth-induced anxiety-like behaviors. The current study aimed to investigate whether gut microbiota and metabolism serve as potential peripheral targets for transgenerational mental problems by paternal Meth exposure. We found that paternal Meth exposure induced depression-like behaviors both in the first (F1) and the second (F2) generations of male mice. Further, the depletion of gut bacteria through antibiotic treatments normalized the depression-like behaviors to normal levels in both F1 and F2 male mice. Then, alterations in gut bacterial composition were observed in both F1 and F2 male mice. Specifically, Eubacterium_ruminantium_group, Enterorhabdus, Alloprevotella, and Parabacteroides were the commonly affected bacterial taxa in F1 and F2 male mice. In addition, the results of alterations in gut metabolism showed that LPC 14:1-SN1 emerged as the consistently altered metabolite in the colons of F1 and F2 male mice. Taken together, our findings provide the first evidence that paternal Meth exposure enhances depression-like behaviors in F1 and F2 male mice, potentially mediated by the gut microbiome and metabolism.
Collapse
Affiliation(s)
- Yuanyuan Zhang
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, China
| | - Tao Hu
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xinyu Wang
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, China
| | - Nongyuan Sun
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, China
| | - Qinglong Cai
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hee Young Kim
- Department of Physiology, Yonsei University College of Medicine, Seoul, South Korea
| | - Yu Fan
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, China
| | - Dekang Liu
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaowei Guan
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, China
| |
Collapse
|
18
|
Pan B, Pan Y, Huang YS, Yi M, Hu Y, Lian X, Shi HZ, Wang M, Xiang G, Yang WY, Liu Z, Xia F. Efficacy and safety of gut microbiome-targeted treatment in patients with depression: a systematic review and meta-analysis. BMC Psychiatry 2025; 25:64. [PMID: 39838303 PMCID: PMC11753086 DOI: 10.1186/s12888-024-06438-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 12/23/2024] [Indexed: 01/23/2025] Open
Abstract
BACKGROUND The study aimed to comprehensively analyze and establish a framework for evaluating the efficacy of microbiome-targeted treatment (MTT) for depression. METHODS We searched PubMed, Embase, Cochrane Library, Web of Science, and the Chinese National Knowledge Infrastructure database for randomized controlled trials (RCTs) on MTT in treating depression until October 19, 2023. A meta-analysis was conducted to evaluate the efficacy and safety of MTT. Comprehensive subgroup analyses were undertaken to explore factors influencing MTT's efficacy in treating depression. This study was registered with PROSPERO (CRD42023483649). RESULTS The study selection process identified 51,570 studies, of which 34 met the inclusion criteria. The overall pooled estimates showed that MTT significantly improved depression symptoms (SMD -0.26, 95% CI [-0.32, -0.19], I2 = 54%) with acceptable safety. Subgroup analyses by geography showed that effectiveness was demonstrated in Asia (SMD -0.46, 95% CI [-0.56, -0.36], I2 = 36%), while no evidence of effectiveness was found in Europe (SMD -0.07, 95% CI [-0.19, 0.05], I2 = 55%), America (SMD -0.33, 95% CI [-0.67, 0.02], I2 = 60%), and Oceania (SMD 0.00, 95% CI [-0.18, 0.18], I2 = 0%). Besides, the efficacy was shown in depressed patients without comorbidities (SMD -0.31, 95% CI [-0.40, -0.22], I2 = 0%), whereas effectiveness was poor in those with digestive disorders, such as irritable bowel syndrome (SMD -0.37, 95% CI [-0.89, 0.16], I2 = 74%), chronic diarrhea (SMD -0.34, 95% CI [-0.73, 0.05]), and chronic constipation (SMD -0.23, 95% CI [-0.57, 0.11], I2 = 0%). In perinatal depressed patients, MTT was not effective (SMD 0.16, 95% CI [0.01, 0.31], I2 = 0%). It was found that < 8 weeks (SMD -0.33, 95% CI [-0.45, -0.22], I2 = 0%) and 8-12 weeks (SMD -0.34, 95% CI [-0.44, -0.23], I2 = 57%) MTT were effective, while > 12 weeks (SMD 0.02, 95% CI [-0.12, 0.17], I2 = 68%) MTT was ineffective. CONCLUSIONS Despite the overall effectiveness of MTT in treating depression and its acceptable safety profile, caution is warranted in drawing this conclusion due to limitations posed by the small sample size of included studies and heterogeneity. The efficacy of MTT for depression exhibits variation influenced by geography, patient comorbidities, and duration of administration.
Collapse
Affiliation(s)
- Bo Pan
- Institute of Blood Transfusion Institution, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu, Sichuan, China
- Key laboratory of transfusion adverse reactions, Chinese Academy of Medical Sciences, Chengdu, 610052, China
| | - Yiming Pan
- Institute of Blood Transfusion Institution, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu, Sichuan, China
- Key laboratory of transfusion adverse reactions, Chinese Academy of Medical Sciences, Chengdu, 610052, China
| | - Yu-Song Huang
- Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Haining Rd 100, Shanghai, 200080, China
| | - Meng Yi
- Institute of Blood Transfusion Institution, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu, Sichuan, China
| | - Yuwei Hu
- Institute of Blood Transfusion Institution, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu, Sichuan, China
- Key laboratory of transfusion adverse reactions, Chinese Academy of Medical Sciences, Chengdu, 610052, China
| | - Xiaoyu Lian
- Institute of Blood Transfusion Institution, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu, Sichuan, China
- Key laboratory of transfusion adverse reactions, Chinese Academy of Medical Sciences, Chengdu, 610052, China
| | - Hui-Zhong Shi
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China
| | - Mingwei Wang
- Institute of Blood Transfusion Institution, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu, Sichuan, China
- Key laboratory of transfusion adverse reactions, Chinese Academy of Medical Sciences, Chengdu, 610052, China
| | - Guifen Xiang
- Institute of Blood Transfusion Institution, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu, Sichuan, China
- Key laboratory of transfusion adverse reactions, Chinese Academy of Medical Sciences, Chengdu, 610052, China
- School of Public Health, Anhui Medical University, Hefei, 230032, China
| | - Wen-Yi Yang
- Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Haining Rd 100, Shanghai, 200080, China.
| | - Zhong Liu
- Institute of Blood Transfusion Institution, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu, Sichuan, China.
- Key laboratory of transfusion adverse reactions, Chinese Academy of Medical Sciences, Chengdu, 610052, China.
- School of Public Health, Anhui Medical University, Hefei, 230032, China.
| | - Fangfang Xia
- Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China.
| |
Collapse
|
19
|
Chen M, Huang H, Jiang Q, Wu Y. Effect of dietary live microbe intake on the prevalence and mortality risks of depression and suicidal ideation in adults: Evidence from a nationwide population-based study. J Affect Disord 2025; 368:847-856. [PMID: 39303884 DOI: 10.1016/j.jad.2024.09.127] [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: 06/03/2024] [Revised: 09/16/2024] [Accepted: 09/17/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Gut microbial dysbiosis has been implicated in the pathogenesis of depression. Dietary interventions offer promising microbial-targeted therapeutics for depression. However, limited evidence exists regarding the associations between dietary live microbe intake and the prevalence of depression, as well as its impact on mortality risks. METHODS This study included 28,133 participants from the U.S. National Health and Nutrition Examination Survey (2005-2018), and ascertained their underlying causes of death. Weighted logistic regression was utilized to assess the relationships between live microbe intake and risks of depression and suicidal ideation. Independent and joint associations between live microbe and mortality outcomes were evaluated using multivariable Cox regression and Kaplan-Meier survival curves to calculate relative risks. RESULTS In the fully adjusted model, participants with high dietary live microbe intake had a significantly lower prevalence of depression (OR = 0.727, 95%CI: 0.627,0.844) and suicidal ideation (OR = 0.778, 95%CI: 0.648,0.935) than those with low intake. The multivariable-adjusted HRs for individuals in the G1 were 1.217 (95%CI, 1.081, 1.370) for all-cause mortality and 1.307 (95%CI, 1.029,1.661) for cardiovascular disease mortality, compared to participants in the G3. Kaplan-Meier survival analysis revealed that cumulative hazard of cardiovascular mortality was progressively lower among participants with depression in the G3 than those without depression. CONCLUSIONS Higher live microbe intake was associated with a lower prevalence of depression and suicidal ideation, and was linked to significantly decreased risks of all-cause and cardiovascular mortality. Further larger prospective studies are essential to verify the health effects of live microbes, and personalized dietary recommendations are necessary.
Collapse
Affiliation(s)
- Man Chen
- Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Huilan Huang
- Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Qin Jiang
- Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Yigao Wu
- Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.
| |
Collapse
|
20
|
Slykerman RF, Davies N, Vlckova K, O'Riordan KJ, Bassett SA, Dekker J, Schellekens H, Hyland NP, Clarke G, Patterson E. Precision Psychobiotics for Gut-Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy. Microb Biotechnol 2025; 18:e70079. [PMID: 39815671 PMCID: PMC11735468 DOI: 10.1111/1751-7915.70079] [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: 10/16/2024] [Revised: 12/19/2024] [Accepted: 12/26/2024] [Indexed: 01/18/2025] Open
Abstract
Advancing microbiome-gut-brain axis science requires systematic, rational and translational approaches to bridge the critical knowledge gaps currently preventing full exploitation of the gut microbiome as a tractable therapeutic target for gastrointestinal, mental and brain health. Current research is still marked by many open questions that undermine widespread application to humans. For example, the lack of mechanistic understanding of probiotic effects means it remains unclear why even apparently closely related strains exhibit different effects in vivo. For the therapeutic application of live microbial psychobiotics, consensus on their application as adjunct treatments to conventional neuromodulators, use in unmedicated populations or in at-risk cohorts with sub-clinical symptomatology is warranted. This missing information on both sides of the therapeutic equation when treating central nervous system (CNS) conditions makes psychobiotic research challenging, especially when compared to other pharmaceutical or functional food approaches. Expediting the transition from positive preclinical data to proven benefits in humans includes interpreting the promises and pitfalls of animal behavioural assays, as well as navigating mechanism-informed decision making to select the right microbe(s) for the job. In this review, we consider how these decisions can be supported in light of information accrued from a range of clinical studies across healthy, at-risk and pathological study populations, where specific strains have been evaluated in the context of gastrointestinal physiology, brain function and behaviour. Examples of successful, partial and unsuccessful translation from bench to bedside are considered. We also discuss the developments in in silico analyses that have enhanced our understanding of the gut microbiome and that have moved research towards pinpointing the host-microbe interactions most important for optimal gut-brain axis function. Combining this information with knowledge from functional assays across in vitro and ex vivo domains and incorporating model organisms can prime the discovery pipelines with the most promising and rationally selected psychobiotic candidates.
Collapse
Affiliation(s)
| | - Naomi Davies
- Department of Psychological MedicineUniversity of AucklandAucklandNew Zealand
| | - Klara Vlckova
- Fonterra Microbiome Research CentreUniversity College CorkCorkIreland
| | | | - Shalome A. Bassett
- Fonterra Research and Development CentrePalmerston NorthNew Zealand
- Riddet InstituteMassey UniversityPalmerston NorthNew Zealand
| | - James Dekker
- Fonterra Research and Development CentrePalmerston NorthNew Zealand
| | - Harriët Schellekens
- APC Microbiome IrelandUniversity College CorkCorkIreland
- Department of Anatomy and NeuroscienceUniversity College CorkCorkIreland
| | - Niall P. Hyland
- APC Microbiome IrelandUniversity College CorkCorkIreland
- Department of PhysiologyUniversity College CorkCorkIreland
| | - Gerard Clarke
- APC Microbiome IrelandUniversity College CorkCorkIreland
- Department of Psychiatry and Neurobehavioural ScienceUniversity College CorkCorkIreland
| | - Elaine Patterson
- Fonterra Microbiome Research CentreUniversity College CorkCorkIreland
| |
Collapse
|
21
|
Xue L, Wang H, Wang X, Shao J, Sun Y, Zhu R, Yao Z, Lu Q. The relationship between demographic factors and brain hierarchical changes following antidepressant treatment in patients remitted from depression. J Psychiatr Res 2025; 181:425-432. [PMID: 39662329 DOI: 10.1016/j.jpsychires.2024.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 11/25/2024] [Accepted: 12/01/2024] [Indexed: 12/13/2024]
Abstract
To investigate the associations between demographic factors and brain hierarchical changes following successful selective serotonin reuptake inhibitor (SSRI) treatment, 57 major depressive disorder (MDD) patients who achieved remission after a 12-week SSRI treatment and 39 healthy controls (HCs) were recruited. MDD patients underwent diffusion tensor imaging (DTI) scans before treatment and after the 12-week SSRI treatment. Depression severity was evaluated with the Hamilton Rating Scale for Depression (HAMD) using the total score and the subscales: retardation, cognitive impairment, anxiety, and sleep disturbance. All HCs also underwent DTI scans after enrollment. Building on gradient mapping techniques, we developed a set of measures to quantify the dispersion within functional communities and also studied demographic-relevant differences in the three-dimensional gradient space of remitted MDD patients. We defined the Z-scores of the gradients in the pre-treatment group relative to the HC group as the disease pattern, post-treatment group relative to the HC group as the recovery pattern. The results showed that the disease pattern of depression is associated with age, as older age groups exhibit more severe impairments in depression. A significant difference was detected in the dispersion of the frontoparietal network (FPN) between pre-treatment and post-treatment patients. With the moderating effect of the age of onset, the dispersion of the FPN was related to the improvement in cognitive impairment, the dorsal attention network (DAN) was related to the improvement in retardation symptoms. Our findings help clinicians be alert to the role of demographic effects on clinical efficacy when treating depressed patients.
Collapse
Affiliation(s)
- Li Xue
- School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210096, China; Child Development and Learning Science, Key Laboratory of Ministry of Education, China
| | - Huan Wang
- School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210096, China; Child Development and Learning Science, Key Laboratory of Ministry of Education, China
| | - Xinyi Wang
- School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210096, China; Child Development and Learning Science, Key Laboratory of Ministry of Education, China
| | - Junneng Shao
- School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210096, China; Child Development and Learning Science, Key Laboratory of Ministry of Education, China
| | - Yurong Sun
- School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210096, China; Child Development and Learning Science, Key Laboratory of Ministry of Education, China
| | - Rongxin Zhu
- Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China; Nanjing Brain Hospital, Medical School of Nanjing University, Nanjing, 210093, China
| | - Zhijian Yao
- Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China; Nanjing Brain Hospital, Medical School of Nanjing University, Nanjing, 210093, China.
| | - Qing Lu
- School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210096, China; Child Development and Learning Science, Key Laboratory of Ministry of Education, China.
| |
Collapse
|
22
|
Ye Z, Yu S, Yang Y, Li S, Li S, Ma R, Fu W, Li X, Luo D. Association of probiotics, prebiotics, synbiotics or yogurt supplement with prevalence and all-cause mortality of depression: NHANES 2005-2016. J Affect Disord 2025; 368:547-554. [PMID: 39299595 DOI: 10.1016/j.jad.2024.09.034] [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: 05/27/2024] [Revised: 09/04/2024] [Accepted: 09/08/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND A growing body of studies revealed that enteric dysbacteriosis could result in depression via the "gut-microbiota-brain axis" (GMBA). Whether probiotics, prebiotics, and synbiotics supplements could lessen the risk of depression is a topic attracting attention. This research was conducted to evaluate the relationship between probiotics, prebiotics, synbiotics, or yogurt supplements and depression with large cross-sectional data. METHODS All data in our research was sourced from the National Health and Nutrition Examination Survey (NHANES) (2005-2016). Probiotics, prebiotics, synbiotics, and yogurt supplements were identified using Food Frequency Questionnaire (FFQ) and Dietary Supplement Use 30-Day (DSQ). We employed the Patient Health Questionnaire (PHQ-9) for evaluating depression. Logistic regression and the Kaplan-Meier curve were performed to examine the correlation between the supplements and depression, as well as mortality. RESULTS A total of 17,745 adult participants were selected. The participants who supplemented probiotics, prebiotics, synbiotics, or yogurt products in the last 30 days showed a significantly lower depression rate compared with those who didn't. Specifically, the supplements could alleviate depressive symptoms including sad, anhedonia, sleep problems, fatigue, appetite changes, and psychomotor changes. This association was more prominent in specific populations such as the population aged 40-60 years, male, whites. The supplements also show more significant effects on increasing survival rates in patients with mild depression. LIMITATION Cross-sectional analysis reveals correlative but not causative association. CONCLUSION Based on the analysis of NHANES data, our research highlights the positive effect the supplements have on preventing depression, relieving depressive symptoms and increasing survival rates. This effect varied across populations.
Collapse
Affiliation(s)
- Zhijun Ye
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Shiyao Yu
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Yunxiang Yang
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Shumin Li
- Liuzhou Workers' Hospital, the Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou 545000, China
| | - Sheng Li
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Rui Ma
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Wenbin Fu
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Xiangguang Li
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
| | - Ding Luo
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
| |
Collapse
|
23
|
Asad A, Kirk M, Zhu S, Dong X, Gao M. Effects of Prebiotics and Probiotics on Symptoms of Depression and Anxiety in Clinically Diagnosed Samples: Systematic Review and Meta-analysis of Randomized Controlled Trials. Nutr Rev 2024:nuae177. [PMID: 39731509 DOI: 10.1093/nutrit/nuae177] [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] [Indexed: 12/30/2024] Open
Abstract
CONTEXT The use of prebiotics and probiotics as a treatment for psychiatric conditions has gained interest due to their potential to modulate the gut-brain axis. This review aims to assess the effectiveness of these interventions in reducing symptoms of depression and anxiety in psychiatric populations. OBJECTIVE The aim was to comprehensively review and appraise the effectiveness of prebiotic, probiotic, and synbiotic interventions in reducing clinical depression and anxiety symptoms. DATA SOURCES Systematic searches were conducted across Embase, Medline, PsycINFO, CINAHL, Cochrane Library, and Science Citation Index from database inception to May 22, 2023. DATA EXTRACTION Randomized controlled trials investigating prebiotic, probiotic, or synbiotic interventions for treating clinical depression or anxiety symptoms in clinical samples were included. Data were extracted on study characteristics, intervention details, and outcome measures. The Cochrane Collaboration Tool was used to assess the risk of bias. DATA ANALYSIS The standardized mean difference (SMD) was calculated using Hedge's g as the metric of effect size. A random-effects model was applied to estimate pooled effect sizes with 95% CIs. Subgroup analyses were performed based on study characteristics, methodological factors, and intervention types. Sensitivity analyses excluded studies with a high risk of bias. RESULTS Twenty-three RCTs involving 1401 patients met the inclusion criteria, with 20 trials providing sufficient data for meta-analysis. Of these, 18 trials investigated probiotics for depression, 9 trials assessed probiotics for anxiety, and 3 trials examined prebiotics for depression. Probiotics demonstrated a significant reduction in depression symptoms (SMD: -0.96; 95% CI: -1.31, -0.61) and a moderate reduction in anxiety symptoms (SMD: -0.59; 95% CI: -0.98, -0.19). Prebiotics did not show a significant effect on depression (SMD: -0.28; 95% CI: -0.61, 0.04). High heterogeneity was observed across studies, and subgroup analyses indicated that study duration and probiotic formulations contributed to the variation in effect sizes. CONCLUSION Probiotics showed substantial reductions in depression symptoms and moderate reductions in anxiety symptoms. Prebiotics showed a nonsignificant trend toward reducing depression. An adjunctive mental health treatment approach that diagnoses, monitors, and treats the gut microbiome alongside traditional pharmacological treatment holds promise for clinical practice. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42023424136.
Collapse
Affiliation(s)
- Afrida Asad
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, United Kingdom
- Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, United Kingdom
| | - Megan Kirk
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, United Kingdom
- NIHR Oxford Health Biomedical Research Centre, Warneford Hospital, Oxford OX3 7JX, United Kingdom
| | - Sufen Zhu
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, United Kingdom
| | - Xue Dong
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, United Kingdom
| | - Min Gao
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, United Kingdom
- NIHR Oxford Health Biomedical Research Centre, Warneford Hospital, Oxford OX3 7JX, United Kingdom
| |
Collapse
|
24
|
Jia M, Fan Y, Ma Q, Yang D, Wang Y, He X, Zhao B, Zhan X, Qi Z, Ren Y, Dong Z, Zhu F, Wang W, Gao Y, Ma X. Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder. Transl Psychiatry 2024; 14:503. [PMID: 39719433 DOI: 10.1038/s41398-024-03211-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 12/05/2024] [Accepted: 12/16/2024] [Indexed: 12/26/2024] Open
Abstract
Evidence suggests that complex interactions among the gut microbiome, metabolic abnormalities, and brain have important etiological and therapeutic implications in major depressive disorder (MDD). However, the influence of microbiome-gut-brain cross-talk on cognitive impairment in MDD remains poorly characterized. We performed serum metabolomic profiling on 104 patients with MDD and 77 healthy controls (HCs), and also performed fecal metagenomic sequencing on a subset of these individuals, including 79 MDD patients and 60 HCs. The findings were validated in a separate cohort that included 40 patients with MDD and 40 HCs using serum-targeted metabolomics. Abnormal bile acid metabolism was observed in patients with MDD, which is related to cognitive dysfunction. The following gut microbiota corresponded to changes in bile acid metabolism and enzyme activities involved in the bile acid metabolic pathway, including Lachnospiraceae (Blautia_massiliensis, Anaerostipes_hadrus, Dorea_formicigenerans, and Fusicatenibacter_saccharivorans), Ruminococcaceae (Ruminococcus_bromii, Flavonifractor_plautii, and Ruthenibacterium_lactatiformans), and Escherichia_coli. Furthermore, a combinatorial marker classifier that robustly differentiated patients with MDD from HCs was identified. In conclusion, this study provides insights into the gut-brain interactions in the cognitive phenotype of MDD, indicating a potential therapeutic strategy for MDD-associated cognitive impairment by targeting the gut microbiota and bile acid metabolism.
Collapse
Affiliation(s)
- Min Jia
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yajuan Fan
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Qingyan Ma
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ding Yang
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yunpeng Wang
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaoyan He
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Binbin Zhao
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Med-X Institute, Center for Immunological and Metabolic Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xianyan Zhan
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhiyang Qi
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yifan Ren
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ziqing Dong
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Feng Zhu
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Med-X Institute, Center for Immunological and Metabolic Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Wei Wang
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yuan Gao
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
- Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
| | - Xiancang Ma
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
- Shaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
- Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
- Med-X Institute, Center for Immunological and Metabolic Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
- Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
| |
Collapse
|
25
|
Liu X, Liu H, Wu X, Zhao Z, Wang S, Wang H, Qin X. Xiaoyaosan against depression through suppressing LPS mediated TLR4/NLRP3 signaling pathway in "microbiota-gut-brain" axis. JOURNAL OF ETHNOPHARMACOLOGY 2024; 335:118683. [PMID: 39121928 DOI: 10.1016/j.jep.2024.118683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 08/06/2024] [Accepted: 08/07/2024] [Indexed: 08/12/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Depression impairs not only central nervous system, but also peripheral systems of the host. Gut microbiota have been proved to be involved in the pathogenesis of depression. Xiaoyaosan (XYS) has a history of over a thousand years in China for treating depression, dramatically alleviating anxiety, cognitive disorders, and especially gastrointestinal dysfunctions. Yet, it still just scratches the surface of the anti-depression mechanisms of XYS. AIM OF THE STUDY This study aims to elucidate the mechanism of actions of XYS from the perspective of "microbiota-gut-brain" axis. MATERIALS AND METHODS We firstly evaluated the effects of XYS on the macroscopic behaviors of depressed rats that induced by chronic unpredictable mild stress (CUMS). Secondly, the effects of XYS on intestinal homeostasis of depressed rats were revealed by using dysbacteriosis model. Subsequently, the underlying mechanisms were demonstrated by 16S rRNA gene sequencing technology and molecular biology methods. Finally, correlation analysis and visualization of the anti-depression effects of XYS were performed from the "microbiota - gut - brain" perspective. RESULTS Our data indicated that XYS ameliorated the depression-like symptoms of CUMS rats, partly depending on the presence of gut microbiota. Furthermore, we illustrated that XYS reversed CUMS-induced gut dysbiosis of depressed rats in terms of decreasing the Bacteroidetes/Firmicutes ratio and the abundances of Bacteroides, and Corynebacterium, while increasing the abundances of Lactobacillus and Adlercreutzia. The significant enrichment of Bacteroides and the level of lipopolysaccharides (LPS) suggested that depression damaged the immune responses and gut barrier. Mechanistically, XYS significantly down-regulated the expression levels of factors that involved in TLR4/NLRP3 signaling pathway in the colon and brain tissues of depressed rats. In addition, XYS significantly increased the levels of claudin 1 and ZO-1, showing that XYS positively maintained the integrity of gut and blood-brain barriers (BBB). CONCLUSION Our study offers insights into the anti-depression effects of XYS through a lens of "microbiota-TLR4/NLRP3 signaling pathway-barriers", providing a foundation for enhancing clinical efficiency and enriching drug selection, and contributing to our understanding of the mechanisms of traditional Chinese medicines (TCMs) in treating depression.
Collapse
Affiliation(s)
- Xiaojie Liu
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China.
| | - Huimin Liu
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China
| | - Xiaoling Wu
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China
| | - Ziyu Zhao
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China
| | - Senyan Wang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China
| | - Huimin Wang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China
| | - Xuemei Qin
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, 030006, Shanxi, China
| |
Collapse
|
26
|
Pacheco AP, Cedernaes J, Benedict C. Insomnia, OSA, and Mood Disorders: The Gut Connection. Curr Psychiatry Rep 2024; 26:703-711. [PMID: 39400694 PMCID: PMC11706850 DOI: 10.1007/s11920-024-01546-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/03/2024] [Indexed: 10/15/2024]
Abstract
PURPOSE OF REVIEW With the growing body of research examining the link between sleep disorders, including insomnia and obstructive sleep apnea (OSA), and the gut microbiome, this review seeks to offer a thorough overview of the most significant findings in this emerging field. RECENT FINDINGS Current evidence suggests a complex association between imbalances in the gut microbiome, insomnia, and OSA, with potential reciprocal interactions that may influence each other. Notably, specific gut microbiome species, whether over- or under-abundant, have been associated with variation in both sleep and mood in patients diagnosed with, e.g., major depressive disorder or bipolar disorder. Further studies are needed to explore the potential of targeting the gut microbiome as a therapeutic approach for insomnia and its possible effects on mood. The variability in current scientific literature highlights the importance of establishing standardized research methodologies.
Collapse
Affiliation(s)
- André P Pacheco
- Department of Research and Innovation, Division of Mental Health and Addiction, Oslo University Hospital, Sognsvannsveien 21, Oslo, 0372, Norway.
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Jonathan Cedernaes
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
- Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Christian Benedict
- Department of Pharmaceutical Biosciences, Uppsala University, Husargatan 3, Uppsala, 751 24, Sweden.
| |
Collapse
|
27
|
Yu H, Li R, Liang XJ, Yang WM, Guo L, Liu L, Tan QRR, Peng ZW. A cross-section study of the comparison of plasma inflammatory cytokines and short-chain fatty acid in patients with depression and schizophrenia. BMC Psychiatry 2024; 24:834. [PMID: 39567940 PMCID: PMC11577661 DOI: 10.1186/s12888-024-06277-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 11/08/2024] [Indexed: 11/22/2024] Open
Abstract
BACKGROUND Major depressive disorder (MDD) and schizophrenia (SCH) are common and severe mental disorders that are mainly diagnosed depending on the subjective identification by psychiatrists. Finding potential objective biomarkers that can distinguish these two diseases is still meaningful. METHODS In the present study, we investigate the differences in plasma inflammatory cytokines and short-chain fatty acids (SCFAs) among patients with MDD (n = 24) and SCH (n = 24), and gender- and age-matched healthy controls (HC, n = 27) and identify potential plasma biomarkers. RESULTS We found that the concentrations of pro-inflammatory cytokines were increased, whereas the anti-inflammatory cytokines were decreased in both MDD and SCH. Meanwhile, except for an increase in 4-Methylvaleric acid, other SCFAs with statistical differences were reduced in both MDD and SCH. Moreover, potential biomarker panels were developed that can effectively discriminate MDD from HC (AUC = 0.997), SCH from HC (AUC = 0.999), and from each other (MDD from SCH, AUC = 0.983). CONCLUSIONS These data suggest that alterations in plasma cytokines and SCFAs might be one of the potential features for distinguishing MDD and SCH. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2100051243, registration date: 2021/09/16.
Collapse
Affiliation(s)
- Huan Yu
- Department of Psychiatry, Chang'an Hospital, Xi'an, 710000, China
| | - Rui Li
- Department of Psychiatry, Chang'an Hospital, Xi'an, 710000, China
| | - Xue-Jun Liang
- Department of Psychiatry, Chang'an Hospital, Xi'an, 710000, China
- Mental Diseases Prevention and Treatment Institute of Chinese PLA,No.988, Hospital of Joint Logistic Support Force, Jiaozuo, Henan Province, Jiaozuo, Henan Province, 454003, China
| | - Wen-Mao Yang
- Department of Psychiatry, Chang'an Hospital, Xi'an, 710000, China
| | - Lin Guo
- Department of Psychiatry, Chang'an Hospital, Xi'an, 710000, China
| | - Ling Liu
- Military Medical Innovation Center, Air Force Medical University, Xi'an, 710032, China
| | - Qing-Rong R Tan
- Department of Psychiatry, Chang'an Hospital, Xi'an, 710000, China.
| | - Zheng-Wu Peng
- Department of Psychiatry, Chang'an Hospital, Xi'an, 710000, China.
- Military Medical Innovation Center, Air Force Medical University, Xi'an, 710032, China.
| |
Collapse
|
28
|
Xu C, Guo J, Chang B, Zhang Y, Tan Z, Tian Z, Duan X, Ma J, Jiang Z, Hou J. Design of probiotic delivery systems and their therapeutic effects on targeted tissues. J Control Release 2024; 375:20-46. [PMID: 39214316 DOI: 10.1016/j.jconrel.2024.08.037] [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: 03/05/2024] [Revised: 08/14/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024]
Abstract
The microbiota at different sites in the body is closely related to disease. The intake of probiotics is an effective strategy to alleviate diseases and be adjuvant in their treatment. However, probiotics may suffer from harsh environments and colonization resistance, making it difficult to maintain a sufficient number of live probiotics to reach the target sites and exert their original probiotic effects. Encapsulation of probiotics is an effective strategy. Therefore, probiotic delivery systems, as effective methods, have been continuously developed and innovated to ensure that probiotics are effectively delivered to the targeted site. In this review, initially, the design of probiotic delivery systems is reviewed from four aspects: probiotic characteristics, processing technologies, cell-derived wall materials, and interactions between wall materials. Subsequently, the review focuses on the effects of probiotic delivery systems that target four main microbial colonization sites: the oral cavity, skin, intestine, and vagina, as well as disease sites such as tumors. Finally, this review also discusses the safety concerns of probiotic delivery systems in the treatment of disease and the challenges and limitations of implementing this method in clinical studies. It is necessary to conduct more clinical studies to evaluate the effectiveness of different probiotic delivery systems in the treatment of diseases.
Collapse
Affiliation(s)
- Cong Xu
- College of Food Science and Engineering, Guiyang University, Guiyang 550005, China; Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China; Heilongjiang Green Food Science Research Institute, Harbin 150028, China
| | - Jiahui Guo
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China
| | - Baoyue Chang
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China
| | - Yiming Zhang
- Department of Psychiatry and Mental Health, Dalian Medical University, Dalian 116044, China
| | - Zhongmei Tan
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China
| | - Zihao Tian
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China
| | - Xiaolei Duan
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China
| | - Jiage Ma
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China; Heilongjiang Green Food Science Research Institute, Harbin 150028, China
| | - Zhanmei Jiang
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China.
| | - Juncai Hou
- College of Food Science and Engineering, Guiyang University, Guiyang 550005, China; Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China; Heilongjiang Green Food Science Research Institute, Harbin 150028, China.
| |
Collapse
|
29
|
Venable KE, Lee CC, Francis J. Addressing Mental Health in Rural Settings: A Narrative Review of Blueberry Supplementation as a Natural Intervention. Nutrients 2024; 16:3539. [PMID: 39458533 PMCID: PMC11510281 DOI: 10.3390/nu16203539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 09/23/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
Depression and anxiety are major public health issues; however, there is an unmet need for novel, effective, and accessible treatments, particularly in rural communities. Blueberries are an unexplored nutraceutical for these conditions due to their excellent nutritional profile, with particularly high levels of polyphenols and anthocyanins and benefits on mood, cognition, and health. Here, we present a narrative review of the literature concerning the etiology and treatments of major depressive disorder (MDD) and generalized anxiety disorder (GAD). In both animal and human studies, blueberry supplementation can ameliorate behavioral symptoms of both anxiety and depression. The mechanistic underpinnings of these behavioral improvements are not fully defined, but likely involve biochemical alterations in the gut-brain axis, including to inflammatory cytokines, reactive oxygen species, and growth factors. We also review the limitations of traditional therapies in rural settings. Finally, we assess the potential benefit of nutraceutical interventions, particularly blueberries, as novel therapeutics for these distinct, yet related mental health issues.
Collapse
Affiliation(s)
- Katy E. Venable
- Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA; (C.C.L.); (J.F.)
| | | | | |
Collapse
|
30
|
Xu J, Liu B, Shang G, Liu S, Feng Z, Zhang Y, Yang H, Liu D, Chang Q, Yuhan C, Yu X, Mao Z. Deep brain stimulation versus vagus nerve stimulation for the motor function of poststroke hemiplegia: study protocol for a multicentre randomised controlled trial. BMJ Open 2024; 14:e086098. [PMID: 39384245 PMCID: PMC11474896 DOI: 10.1136/bmjopen-2024-086098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 08/30/2024] [Indexed: 10/11/2024] Open
Abstract
INTRODUCTION Deep brain stimulation (DBS) and vagus nerve stimulation (VNS) can improve motor function in patients with poststroke hemiplegia. No comparison study exists. METHODS AND ANALYSIS This is a randomised, double-blind, controlled clinical trial involving 64 patients who had their first stroke at least 6 months ago and are experiencing poststroke limb dysfunction. These patients must receive necessary support at home and consent to participate. The aim is to evaluate the effectiveness and safety of DBS and VNS therapies. Patients are excluded if they have implantable devices that are sensitive to electrical currents, severe abnormalities in their lower limbs or are unable to comply with the trial procedures. The study has two parallel, distinct treatment arms: the Stimulation Group and the Sham Group. Initially, the Stimulation Group will undergo immediate electrical stimulation postsurgery, while the Sham Group will receive non-stimulation 1 month later. After 3 months, these groups will swap treatments, with the Stimulation Group discontinuing stimulation and the Sham Group initiating stimulation. Six months later, both groups will resume active stimulation. Our primary outcomes will meticulously assess motor function improvements, using the Fugl-Meyer Assessment, and safety, monitored by tracking adverse reaction rates. Furthermore, we will gain a comprehensive view of patient outcomes by evaluating secondary measures, including clinical improvement (National Institutes of Health Stroke Scale), surgical complications/side effects, quality of life (36-item Short Form Questionnaire) and mental health status (Hamilton Anxiety Rating Scale/Hamilton Depression Rating Scale). To ensure a thorough understanding of the long-term effects, we will conduct follow-ups at 9 and 12 months postsurgery, with additional long-term assessments at 15 and 18 months. These follow-ups will assess the sustained performance and durability of the treatment effects. The statistical analysis will uncover the optimal treatment strategy for poststroke hemiplegia, providing valuable insights for clinicians and patients alike. ETHICS AND DISSEMINATION This study was reviewed and approved by the Ethical Committee of Chinese PLA General Hospital (S2022-789-01). The findings will be submitted for publication in peer-reviewed journals with online accessibility, ensuring adherence to the conventional scientific publishing process while clarifying how the research outcomes will be disseminated and accessed. TRIAL REGISTRATION NUMBER NCT06121947.
Collapse
Affiliation(s)
- Junpeng Xu
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, Chinese PLA General Hospital First Medical Center, Beijing, China
| | - Bin Liu
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, Chinese PLA General Hospital First Medical Center, Beijing, China
| | - Guosong Shang
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, Chinese PLA General Hospital First Medical Center, Beijing, China
| | | | - Zhebin Feng
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, Chinese PLA General Hospital First Medical Center, Beijing, China
| | - Yanyang Zhang
- Department of Neurosurgery, Chinese PLA General Hospital First Medical Center, Beijing, China
| | - Haonan Yang
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, Chinese PLA General Hospital First Medical Center, Beijing, China
| | - Di Liu
- Department of Neurosurgery, Chinese PLA General Hospital First Medical Center, Beijing, China
| | - Qing Chang
- Department of Neurosurgery, Chinese PLA General Hospital First Medical Center, Beijing, China
| | - Chen Yuhan
- Hebei North University Basic Medical College, Zhangjiakou, China
| | - Xinguang Yu
- Department of Neurosurgery, Chinese PLA General Hospital First Medical Center, Beijing, China
| | - Zhiqi Mao
- Department of Neurosurgery, Chinese PLA General Hospital First Medical Center, Beijing, China
| |
Collapse
|
31
|
Huang R, Liu Y. Efficacy of bifidobacterium-related preparations on depression: the first meta-analysis. Front Psychiatry 2024; 15:1463848. [PMID: 39421068 PMCID: PMC11484414 DOI: 10.3389/fpsyt.2024.1463848] [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: 07/12/2024] [Accepted: 09/05/2024] [Indexed: 10/19/2024] Open
Abstract
Currently, depression-induced suicide has emerged as the primary contributor to the worldwide burden of disability. However, the prevailing drug treatment not only suffers from delayed effectiveness and limited efficacy, but also there are withdrawal symptoms and rebound phenomenon. Consequently, there is an imperative to investigate safer and more efficient treatments to ameliorate the clinical manifestations of depression. At present, there is increased evidence that probiotics can improve the symptoms of depression, but the existing studies use many and mixed types of probiotics, and it is impossible to determine the specific efficacy of bifidobacteria in the treatment of depression. This review will systematically review the effects of bifidobacteria on the treatment effect of depression, Meta-analysis showed that Bifidobacterium-related preparations effectively improved depressive symptoms in patients with depression. This study represents the initial meta-analysis conducted on the use of bifidobacteria-related agents for treating depression. The objective was to determine the effect of bifidobacteria-related preparations on improving depressive symptoms. We found that Bifidobacterium and its related agents can effectively reduce depression scale scores in patients with depression, suggesting the need for further research into this potential strategy for the prevention and treatment of depression.
Collapse
Affiliation(s)
- Ruihan Huang
- School of Public Health, Qilu Medical University, Zibo, Shandong, China
| | - Yongsheng Liu
- School of Clinical Medicine, Qilu Medical University, Zibo, Shandong, China
| |
Collapse
|
32
|
Dabboussi N, Debs E, Bouji M, Rafei R, Fares N. Balancing the mind: Toward a complete picture of the interplay between gut microbiota, inflammation and major depressive disorder. Brain Res Bull 2024; 216:111056. [PMID: 39182696 DOI: 10.1016/j.brainresbull.2024.111056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 08/07/2024] [Accepted: 08/22/2024] [Indexed: 08/27/2024]
Abstract
The intricate interplay existing between gut microbiota and homeostasis extends to the realm of the brain, where emerging research underscores the significant impact of the microbiota on mood regulation and overall neurological well-being and vice-versa, with inflammation playing a pivotal role in mediating these complex interactions. This comprehensive review explores the complex interplay between inflammation, alterations in gut microbiota, and their impact on major depressive disorder (MDD). It provides a cohesive framework for the puzzle pieces of this triad, emphasizing recent advancements in understanding the gut microbiota and inflammatory states' contribution to the depressive features. Two directions of communication between the gut and the brain in depression are discussed, with inflammation serving as a potential modulator. Therapeutic implications were discussed as well, drawing insights from interventional studies on the effects of probiotics on gut bacterial composition and depressive symptoms. Ultimately, this review will attempt to provide a complete and valuable framework for future research and therapeutic interventions in MDD.
Collapse
Affiliation(s)
- Nour Dabboussi
- Laboratory of Research in Physiology and pathophysiology, Faculty of Medicine, Saint Joseph University of Beirut, POBox. 17-5208 - Mar Mikhaël, Beirut 1104 2020, Lebanon; Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Science & Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon.
| | - Espérance Debs
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, P.O. Box 100, Tripoli, Lebanon.
| | - Marc Bouji
- Faculté des Sciences, Université Saint-Joseph de Beyrouth-Liban, Mar Roukos, Beirut, Lebanon.
| | - Rayane Rafei
- Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Science & Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon
| | - Nassim Fares
- Laboratory of Research in Physiology and pathophysiology, Faculty of Medicine, Saint Joseph University of Beirut, POBox. 17-5208 - Mar Mikhaël, Beirut 1104 2020, Lebanon.
| |
Collapse
|
33
|
Peng Y, Du Y, Zhang Y, Wang Z, Hu T, Mai Y, Song H, Pan W, Cai Q, Ge F, Fan Y, Kim HY, Liu D, Guan X. Gegen Qinlian decoction alleviates depression-like behavior by modulating the gut microenvironment in CUMS rats. BMC Complement Med Ther 2024; 24:339. [PMID: 39304871 DOI: 10.1186/s12906-024-04638-4] [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: 04/04/2024] [Accepted: 09/09/2024] [Indexed: 09/22/2024] Open
Abstract
BACKGROUND Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine (TCM) formula primarily utilized for treating gut disorders. GQD showed therapeutic effects on several diseases in clinical and animal studies by targeting gut microbes. Our recent studies also found that GQD efficiently alleviated anxiety in methamphetamine-withdrawn mice via regulating gut microbiome and metabolism. Given that various studies have indicated the link between the gut microbiome and the development of depression, here we endeavor to explore whether GQD can manage depression disorders by targeting the gut microbiome. METHODS AND MATERIALS The depression-like model was induced in rats through chronic unpredictable mild stress (CUMS) and the depression levels were determined using the sucrose preference test (SPT). To address the depression-like behavior in rats, oral administration of GQD was employed. The colon microbiome and metabolite patterns were determined by 16s rRNA sequencing and untargeted metabolomics, respectively. RESULTS We found 6 weeks of CUMS can induce depression-like behavior in rats and 4 weeks of GQD treatment can significantly alleviate the depression-like behavior. GQD treatment can also ameliorate the histological lesions in the colon of CUMS rats. Then, CUMS increased the abundance of gut microbes, while GQD treatment can restore it to a lower level. We further discovered that the abundances of 19 bacteria at the genus level were changed with CUMS treatment, among which the abundances of Ruminococcus, Lachnoclostridium, Pygmaiobacter, Bacteroides, Pseudomonas, and Pseudomonas Family_XIII_AD3011_group were stored by GQD treatment. Besides, we identified the levels of 36 colon metabolites were changed with CUMS treatment, among which the levels of Fasciculic acid B, Spermine, Fludrocortisone acetate, alpha-Ketoglutaric acid, 2-Oxoglutaric acid, N'-(benzoyloxy)-2-(2,2-dichlorocyclopropyl) ethanimidamide, N6-Succinyl Adenosine Oleanolic acid, KQH, Ergosta-5,7,9(11),22-Tetraen-3-beta-Ol, Gentisic acid, 4-Hydroxyretinoic Acid, FAHFA (3:0/16:0), Leucine-enkephalin and N-lactoyl-phenylalanine can be restored by GQD treatment. CONCLUSION Our findings provide evidence supporting the therapeutic efficacy of GQD in alleviating depression-like behavior in CUMS rats, potentially being targeted on colon bacteria (especially the abundance of Ruminococcus and Bacteroides) and metabolites (especially the level of Oleanolic acid).
Collapse
Affiliation(s)
- Yaqin Peng
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yao Du
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yuanyuan Zhang
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Ze Wang
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Tao Hu
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yuning Mai
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Hongxiu Song
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Weichao Pan
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Qinglong Cai
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Feifei Ge
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yu Fan
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Hee Young Kim
- Department of Physiology, Yonsei University College of Medicine, Seoul, South Korea
| | - Dekang Liu
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Xiaowei Guan
- Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| |
Collapse
|
34
|
Rahmannia M, Poudineh M, Mirzaei R, Aalipour MA, Shahidi Bonjar AH, Goudarzi M, Kheradmand A, Aslani HR, Sadeghian M, Nasiri MJ, Sechi LA. Strain-specific effects of probiotics on depression and anxiety: a meta-analysis. Gut Pathog 2024; 16:46. [PMID: 39245752 PMCID: PMC11382490 DOI: 10.1186/s13099-024-00634-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 07/17/2024] [Indexed: 09/10/2024] Open
Abstract
INTRODUCTION Depression and anxiety are pervasive mental health disorders with substantial global burdens. Probiotics, live microorganisms known for their health benefits, have emerged as a potential therapeutic intervention for these conditions. This systematic review and meta-analysis aim to evaluate the strain-specific effects of probiotics on relieving depressive and anxiety symptoms while elucidating underlying mechanisms. METHODS EMBASE, Cochrane CENTRAL and PubMed/Medline were systematically queried to identify studies released until May 15, 2024. Randomized Controlled Trials (RCTs) that employed standardized assessment tools for depression and anxiety namely Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Depression Anxiety Stress Scales (DASS), or Montgomery-Asberg Depression Rating Scale (MADRS) were included. RESULTS 12 RCTs involving 707 participants were included. Seven RCTs utilizing the BDI questionnaire demonstrated a significant decrease in depressive symptoms favoring probiotics containing strains such as Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium breve, and Bifidobacterium longum (MD: -2.69, CI95%: -4.22/-1.16, p value: 0.00). Conversely, RCTs using HAMD showed a non-significant reduction in depressive symptoms (MD: -1.40, CI95%: -3.29/0.48, p value: 0.14). RCTs employing DASS and MADRS scales also showed no significant differences. CONCLUSION This meta-analysis offers valuable insights into the strain-specific effects of probiotics containing Lactobacillus and Bifidobacterium species on depressive and anxiety symptoms. While our findings suggest a significant reduction in depressive symptoms based on the BDI scale favoring probiotics, the lack of significant effects observed on the HAMD, DASS, and MADRS scales underscores the complexity inherent in these conditions. It is imperative to acknowledge the mixed results across different measurement scales, indicating the need for cautious interpretation. Therefore, we advocate for a nuanced understanding of probiotics' impacts on various dimensions of mood, emphasizing the necessity for further research.
Collapse
Affiliation(s)
- Maryam Rahmannia
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohadeseh Poudineh
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Roya Mirzaei
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Amin Aalipour
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Hashem Shahidi Bonjar
- Scientist of Dental Materials and Restorative Dentistry, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Kheradmand
- Department of Psychiatry, Taleghani Hospital Clinical Research Development Unit, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Reza Aslani
- Department of Clinical Pharmacy, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
| | - Majid Sadeghian
- Department of Psychiatry, Taleghani Hospital Clinical Research Development Unit, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Javad Nasiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | | |
Collapse
|
35
|
Strodl E, Bambling M, Parnam S, Ritchie G, Cramb S, Vitetta L. Probiotics and magnesium orotate for the treatment of major depressive disorder: a randomised double blind controlled trial. Sci Rep 2024; 14:20841. [PMID: 39242786 PMCID: PMC11379959 DOI: 10.1038/s41598-024-71093-z] [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: 02/09/2024] [Accepted: 08/23/2024] [Indexed: 09/09/2024] Open
Abstract
Following on from our pilot studies, this study aimed to test the efficacy of a combination of probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus), magnesium orotate and coenzyme 10 for the treatment of major depressive disorder (MDD) through a double-blind placebo controlled clinical trial. The participants were 120 adults diagnosed with MDD randomised to daily oral administration, over 8 weeks, of either the intervention or placebo, with a 16-week follow-up period. Intent-to-treat analysis found a significantly lower frequency of the presence of a major depressive episode in the intervention group compared with placebo at the end of the 8-week treatment phase, with no difference between the two conditions at 8-week follow-up. Both the categorical and continuous measure of depressive symptoms showed a significant difference between the two conditions at 4 weeks, but not 8 and 16 weeks. The secondary end-point was demonstrated with an overall reduction in self-rated symptoms of anxiety and stress in the active treatment group compared with placebo. These findings suggest that the combination of probiotics, magnesium orotate and coenzyme 10 may be an effective treatment of MDD over an 8-week period.
Collapse
Affiliation(s)
- Esben Strodl
- School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia.
| | - Matthew Bambling
- Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - Sophie Parnam
- School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia
| | - Gabrielle Ritchie
- School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - Susanna Cramb
- Australian Centre for Health Services Innovation, School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia
| | - Luis Vitetta
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
| |
Collapse
|
36
|
Xu J, Liu B, Liu S, Feng Z, Zhang Y, Liu D, Chang Q, Yang H, Chen Y, Yu X, Mao Z. Efficacy and safety of deep brain stimulation in mesencephalic locomotor region for motor function in patients with post-stroke hemiplegia: a study protocol for a multi-center double-blind crossover randomized controlled trial. Front Neurol 2024; 15:1355104. [PMID: 39193146 PMCID: PMC11347412 DOI: 10.3389/fneur.2024.1355104] [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: 12/14/2023] [Accepted: 04/22/2024] [Indexed: 08/29/2024] Open
Abstract
Background Deep brain stimulation (DBS) is a potential treatment for improving movement disorder. However, few large-sample studies can reveal its efficacy and safety. This study aims to initially explore the efficacy and safety of DBS in the mesencephalic locomotor region (MLR) on motor function in patients with post-stroke hemiplegia. Methods/design This multicenter, prospective, double-blind, randomized crossover clinical trial aims to assess the safety and effectiveness of Deep Brain Stimulation (DBS) in the mesencephalic locomotor region (MLR) for patients with moderate to severe post-stroke hemiplegia. Sixty-two patients with stable disease after a year of conservative treatment will be enrolled and implanted with deep brain electrodes. Post-surgery, patients will be randomly assigned to either the DBS group or the control group, with 31 patients in each. The DBS group will receive electrical stimulation 1 month later, while the control group will undergo sham stimulation. Stimulation will be discontinued after 3 and 6 months, followed by a 2-week washout period. Subsequently, the control group will receive electrical stimulation, while the DBS group will undergo sham stimulation. Both groups will resume electrical stimulation at the 9th and 12th-month follow-ups. Post-12-month follow-up, motor-related scores will be collected for analysis, with the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE) as the primary metric. Secondary outcomes include balance function, neuropsychiatric behavior, fall risk, daily living activities, and quality of life. This study aims to provide insights into the therapeutic benefits of DBS for post-stroke hemiplegia patients. Result/conclusion We proposed this study for the first time to comprehensively explore the effectiveness and safety of DBS in improving motor function for post-stroke hemiplegia, and provide evidence for DBS in the treatment of post-stroke hemiplegia. Study limitations are related to the small sample size and short study period. Clinical Trial Registration Clinicaltrials.gov, identifier NCT05968248.
Collapse
Affiliation(s)
- Junpeng Xu
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Bin Liu
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shuzhen Liu
- Department of Chengde Medical University, Chengde, China
| | - Zhebin Feng
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yanyang Zhang
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Di Liu
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Qing Chang
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Haonan Yang
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yuhan Chen
- The First Clinical Medical College of Hebei North University, Zhangjiakou, China
| | - Xinguang Yu
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhiqi Mao
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| |
Collapse
|
37
|
Arteaga-Henríquez G, Ramos-Sayalero C, Ibañez-Jimenez P, Karina Rosales-Ortiz S, Kilencz T, Schiweck C, Schnorr I, Siegl A, Arias-Vasquez A, Bitter I, Fadeuilhe C, Ferrer M, Lavebratt C, Matura S, Reif A, Réthelyi JM, Richarte V, Rommelse N, Antoni Ramos-Quiroga J. Efficacy of a synbiotic in the management of adults with Attention-Deficit and Hyperactivity Disorder and/or Borderline Personality Disorder and high levels of irritability: Results from a multicenter, randomized, placebo-controlled, "basket" trial. Brain Behav Immun 2024; 120:360-371. [PMID: 38885746 DOI: 10.1016/j.bbi.2024.06.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 06/07/2024] [Accepted: 06/12/2024] [Indexed: 06/20/2024] Open
Abstract
Irritability worsens prognosis and increases mortality in individuals with Attention-Deficit and Hyperactivity Disorder (ADHD) and/or Borderline Personality Disorder (BPD). However, treatment options are still insufficient. The aim of this randomized, double blind, placebo-controlled study was to investigate the superiority of a synbiotic over placebo in the management of adults with ADHD and/or BPD and high levels of irritability. The study was conducted between February 2019 and October 2020 at three European clinical centers located in Hungary, Spain and Germany. Included were patients aged 18-65 years old diagnosed with ADHD and/or BPD and high levels of irritability (i.e., an Affectivity Reactivity Index (ARI-S) ≥ 5, plus a Clinical Global Impression-Severity Scale (CGI-S) score ≥ 4). Subjects were randomized 1(synbiotic):1(placebo); the agent was administered each day, for 10 consecutive weeks. The primary outcome measure was end-of-treatment response (i.e., a reduction ≥ 30 % in the ARI-S total score compared to baseline, plus a Clinical Global Impression-Improvement (CGI-I) total score of < 3 (very much, or much improved) at week 10). Between-treatment differences in secondary outcomes, as well as safety were also investigated. Of the 231 included participants, 180 (90:90) were randomized and included in the intention-to-treat-analyses. Of these, 117 (65 %) were females, the mean age was 38 years, ADHD was diagnosed in 113 (63 %), BPD in 44 (24 %), both in 23 (13 %). The synbiotic was well tolerated. At week 10, patients allocated to the synbiotic experienced a significantly higher response rate compared to those allocated to placebo (OR: 0.2, 95 % CI:0.1 to 0.7; P = 0.01). These findings suggest that that (add-on) treatment with a synbiotic may be associated with a clinically meaningful improvement in irritability in, at least, a subgroup of adults with ADHD and/or BPD. A superiority of the synbiotic over placebo in the management of emotional dysregulation (-3.6, 95 % CI:-6.8 to -0.3; P = 0.03), emotional symptoms (-0.6, 95 % CI:-1.2 to -0.05; P = 0.03), inattention (-1.8, 95 % CI: -3.2 to -0.4; P = 0.01), functioning (-2.7, 95 % CI: -5.2 to -0.2; P = 0.03) and perceived stress levels (-0.6, 95 % CI: -1.2 to -0.05; P = 0.03) was also suggested. Higher baseline RANK-L protein levels were associated with a significantly lower response rate, but only in the synbiotic group (OR: 0.1, 95 % CI: -4.3 to - 0.3, P = 0.02). In the placebo group, higher IL-17A levels at baseline were significantly associated with a higher improvement in in particular, emotional dysregulation (P = 0.04), opening a door for new (targeted) drug intervention. However, larger prospective studies are warranted to confirm the findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03495375.
Collapse
Affiliation(s)
- Gara Arteaga-Henríquez
- Department of Mental Health, Hospital Universitari Vall d́Hebron, Barcelona, Catalonia, Spain; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain; Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain; NCRR-The National Center for Register-Based Research, Aahrus University. Aahrus, Denmark.
| | - Carolina Ramos-Sayalero
- Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain
| | - Pol Ibañez-Jimenez
- Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain
| | - Silvia Karina Rosales-Ortiz
- Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain
| | - Tünde Kilencz
- Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary
| | - Carmen Schiweck
- Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany
| | - Isabel Schnorr
- Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany
| | - Anne Siegl
- Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany
| | - Alejandro Arias-Vasquez
- Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behavior, Nijmegen, the Netherlands; Department of Psychiatry, Radboudd University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen, the Netherlands
| | - István Bitter
- Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary
| | - Christian Fadeuilhe
- Department of Mental Health, Hospital Universitari Vall d́Hebron, Barcelona, Catalonia, Spain; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain; Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain
| | - Marc Ferrer
- Department of Mental Health, Hospital Universitari Vall d́Hebron, Barcelona, Catalonia, Spain; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain; Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autónoma de Barcelona, Barcelona, Catalonia, Spain
| | - Catharina Lavebratt
- Department of Molecular Medicine and Surgery, Karolinska Instituet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden
| | - Silke Matura
- Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany
| | - Andreas Reif
- Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany
| | - János M Réthelyi
- Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary
| | - Vanesa Richarte
- Department of Mental Health, Hospital Universitari Vall d́Hebron, Barcelona, Catalonia, Spain; Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autónoma de Barcelona, Barcelona, Catalonia, Spain
| | - Nanda Rommelse
- Karakter Child and Adolescent Psychiatry University Center, Stockholm, the Netherlands
| | - Josep Antoni Ramos-Quiroga
- Department of Mental Health, Hospital Universitari Vall d́Hebron, Barcelona, Catalonia, Spain; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain; Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autónoma de Barcelona, Barcelona, Catalonia, Spain
| |
Collapse
|
38
|
Sempach L, Doll JPK, Limbach V, Marzetta F, Schaub AC, Schneider E, Kettelhack C, Mählmann L, Schweinfurth-Keck N, Ibberson M, Lang UE, Schmidt A. Examining immune-inflammatory mechanisms of probiotic supplementation in depression: secondary findings from a randomized clinical trial. Transl Psychiatry 2024; 14:305. [PMID: 39048549 PMCID: PMC11269721 DOI: 10.1038/s41398-024-03030-7] [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: 03/21/2024] [Revised: 07/15/2024] [Accepted: 07/17/2024] [Indexed: 07/27/2024] Open
Abstract
We recently indicated that four-week probiotic supplementation significantly reduced depression along with microbial and neural changes in people with depression. Here we further elucidated the biological modes of action underlying the beneficial clinical effects of probiotics by focusing on immune-inflammatory processes. The analysis included a total of N = 43 participants with depression, from which N = 19 received the probiotic supplement and N = 24 received a placebo over four weeks, in addition to treatment as usual. Blood and saliva were collected at baseline, at post-intervention (week 4) and follow-up (week 8) to assess immune-inflammatory markers (IL-1β, IL-6, CRP, MIF), gut-related hormones (ghrelin, leptin), and a stress marker (cortisol). Furthermore, transcriptomic analyses were conducted to identify differentially expressed genes. Finally, we analyzed the associations between probiotic-induced clinical and immune-inflammatory changes. We observed a significant group x time interaction for the gut hormone ghrelin, indicative of an increase in the probiotics group. Additionally, the increase in ghrelin was correlated with the decrease in depressive symptoms in the probiotics group. Transcriptomic analyses identified 51 up- and 57 down-regulated genes, which were involved in functional pathways related to enhanced immune activity. We identified a probiotic-dependent upregulation of the genes ELANE, DEFA4 and OLFM4 associated to immune activation and ghrelin concentration. These results underscore the potential of probiotic supplementation to produce biological meaningful changes in immune activation in patients with depression. Further large-scale mechanistic trials are warranted to validate and extend our understanding of immune-inflammatory measures as potential biomarkers for stratification and treatment response in depression. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.
Collapse
Affiliation(s)
- Lukas Sempach
- Translational Neuroscience, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland.
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland.
| | - Jessica P K Doll
- Translational Neuroscience, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| | - Verena Limbach
- Translational Neuroscience, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| | - Flavia Marzetta
- Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
| | - Anna-Chiara Schaub
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
- Translational Psychiatry, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland
| | - Else Schneider
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
- Experimental Cognitive and Clinical Affective Neuroscience (ECAN) Laboratory, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland
| | - Cedric Kettelhack
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| | - Laura Mählmann
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| | | | - Mark Ibberson
- Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
| | - Undine E Lang
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| | - André Schmidt
- Translational Neuroscience, Department of Clinical Research (DKF), University of Basel, Basel, Switzerland
- University Psychiatric Clinics Basel (UPK), University of Basel, Basel, Switzerland
| |
Collapse
|
39
|
Grassi G, Pampaloni I. Gut Microbiota and Gastrointestinal Symptoms in the Global Assessment of Obsessive-Compulsive Disorder: A Narrative Review of Current Evidence and Practical Implications. Brain Sci 2024; 14:539. [PMID: 38928539 PMCID: PMC11201482 DOI: 10.3390/brainsci14060539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 05/19/2024] [Accepted: 05/22/2024] [Indexed: 06/28/2024] Open
Abstract
A growing body of literature suggests a link between bowel syndromes (e.g., irritable bowel syndrome and inflammatory bowel disease), gut microbiome alterations, and psychiatric disorders. This narrative review aims to explore the potential role of the gut microbiome in the pathogenesis and clinical presentation of obsessive-compulsive disorder (OCD) and to explore whether there is sufficient evidence to warrant considering gastrointestinal symptoms and their implication for the gut microbiome during the assessment and treatment of OCD. For this purpose, a PubMed search of studies focusing on OCD, gut microbiota, irritable bowel syndrome, and inflammatory bowel disease was conducted by two independent reviewers. While the current literature on gut microbiome and gastrointestinal issues in OCD remains limited, emerging evidence suggests gut microbiome alterations and high rates of bowel syndromes in this population. These findings emphasize the importance of incorporating comprehensive gastrointestinal assessments into the "global assessment of OCD". Such assessment should encompass various factors, including gastrointestinal physical comorbidities and symptoms, nutritional habits, bowel habits, fluid intake, exercise patterns, and potential microbiome dysfunctions and inflammation. Considering the treatment implications, interventions targeting gut health, such as probiotics and dietary modifications, may hold promise in improving symptoms in OCD patients with comorbid gastrointestinal problems. Further research in this area is warranted to better understand the interplay between gut health and OCD and to explore the effectiveness of targeted interventions in improving clinical outcomes.
Collapse
Affiliation(s)
| | - Ilenia Pampaloni
- National OCD and BDD Unit, South West London and St Georges NHS Trust, London SW17 7DJ, UK;
| |
Collapse
|
40
|
Costa CFFA, Ferreira-Gomes J, Barbosa F, Sampaio-Maia B, Burnet PWJ. Importance of good hosting: reviewing the bi-directionality of the microbiome-gut-brain-axis. Front Neurosci 2024; 18:1386866. [PMID: 38812976 PMCID: PMC11133738 DOI: 10.3389/fnins.2024.1386866] [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: 02/27/2024] [Accepted: 04/29/2024] [Indexed: 05/31/2024] Open
Abstract
Gut microorganisms have been shown to significantly impact on central function and studies that have associated brain disorders with specific bacterial genera have advocated an anomalous gut microbiome as the pathophysiological basis of several psychiatric and neurological conditions. Thus, our knowledge of brain-to-gut-to microbiome communication in this bidirectional axis seems to have been overlooked. This review examines the known mechanisms of the microbiome-to-gut-to-brain axis, highlighting how brain-to-gut-to-microbiome signaling may be key to understanding the cause of disrupted gut microbial communities. We show that brain disorders can alter the function of the brain-to-gut-to-microbiome axis, which will in turn contribute to disease progression, while the microbiome-to gut-to brain direction presents as a more versatile therapeutic axis, since current psychotropic/neurosurgical interventions may have unwanted side effects that further cause disruption to the gut microbiome. A consideration of the brain-to-gut-to-microbiome axis is imperative to better understand how the microbiome-gut-brain axis overall is involved in brain illnesses, and how it may be utilized as a preventive and therapeutic tool.
Collapse
Affiliation(s)
- Carolina F. F. A. Costa
- ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal
- NanoBiomaterials for Targeted Therapies, INEB-Institute of Biomedical Engineering, i3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
| | - Joana Ferreira-Gomes
- Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal
- IBMC-Institute for Molecular and Cell Biology, i3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
| | - Fernando Barbosa
- Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | - Benedita Sampaio-Maia
- NanoBiomaterials for Targeted Therapies, INEB-Institute of Biomedical Engineering, i3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
- Faculty of Dental Medicine, University of Porto, Porto, Portugal
| | | |
Collapse
|
41
|
Gawlik-Kotelnicka O, Margulska A, Płeska K, Skowrońska A, Strzelecki D. Metabolic Status Influences Probiotic Efficacy for Depression-PRO-DEMET Randomized Clinical Trial Results. Nutrients 2024; 16:1389. [PMID: 38732635 PMCID: PMC11085729 DOI: 10.3390/nu16091389] [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: 04/08/2024] [Revised: 04/29/2024] [Accepted: 04/30/2024] [Indexed: 05/13/2024] Open
Abstract
Probiotics may represent a safe and easy-to-use treatment option for depression or its metabolic comorbidities. However, it is not known whether metabolic features can influence the efficacy of probiotics treatments for depression. This trial involved a parallel-group, prospective, randomized, double-blind, controlled design. In total, 116 participants with depression received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 or placebo over 60 days. The psychometric data were assessed longitudinally at five time-points. Data for blood pressure, body weight, waist circumference, complete blood count, serum levels of C-reactive protein, cholesterol, triglycerides, and fasting glucose were measured at the beginning of the intervention period. There was no advantage of probiotics usage over placebo in the depression score overall (PRO vs. PLC: F(1.92) = 0.58; p = 0.45). However, we found a higher rate of minimum clinically important differences in patients supplemented with probiotics than those allocated to placebo generally (74.5 vs. 53.5%; X2(1,n = 94) = 4.53; p = 0.03; NNT = 4.03), as well as in the antidepressant-treated subgroup. Moreover, we found that the more advanced the pre-intervention metabolic abnormalities (such as overweight, excessive central adipose tissue, and liver steatosis), the lower the improvements in psychometric scores. A higher baseline stress level was correlated with better improvements. The current probiotic formulations may only be used as complementary treatments for depressive disorders. Metabolic abnormalities may require more complex treatments. ClinicalTrials.gov identifier: NCT04756544.
Collapse
Affiliation(s)
- Oliwia Gawlik-Kotelnicka
- Department of Affective and Psychotic Disorders, Medical University of Lodz, Czechoslowacka Street 251, 92-216 Lodz, Poland; (A.S.); (D.S.)
| | - Aleksandra Margulska
- Department of Adolescent Psychiatry, Medical University of Lodz, Czechoslowacka Street 8/10, 92-216 Lodz, Poland;
| | - Kacper Płeska
- Faculty of Medicine, Medical University of Lodz, Kosciuszki Avenue 4, 90-419 Lodz, Poland;
| | - Anna Skowrońska
- Department of Affective and Psychotic Disorders, Medical University of Lodz, Czechoslowacka Street 251, 92-216 Lodz, Poland; (A.S.); (D.S.)
| | - Dominik Strzelecki
- Department of Affective and Psychotic Disorders, Medical University of Lodz, Czechoslowacka Street 251, 92-216 Lodz, Poland; (A.S.); (D.S.)
| |
Collapse
|
42
|
Mosquera FEC, Lizcano Martinez S, Liscano Y. Effectiveness of Psychobiotics in the Treatment of Psychiatric and Cognitive Disorders: A Systematic Review of Randomized Clinical Trials. Nutrients 2024; 16:1352. [PMID: 38732599 PMCID: PMC11085935 DOI: 10.3390/nu16091352] [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: 03/17/2024] [Revised: 04/23/2024] [Accepted: 04/28/2024] [Indexed: 05/13/2024] Open
Abstract
In this study, a systematic review of randomized clinical trials conducted from January 2000 to December 2023 was performed to examine the efficacy of psychobiotics-probiotics beneficial to mental health via the gut-brain axis-in adults with psychiatric and cognitive disorders. Out of the 51 studies involving 3353 patients where half received psychobiotics, there was a notably high measurement of effectiveness specifically in the treatment of depression symptoms. Most participants were older and female, with treatments commonly utilizing strains of Lactobacillus and Bifidobacteria over periods ranging from 4 to 24 weeks. Although there was a general agreement on the effectiveness of psychobiotics, the variability in treatment approaches and clinical presentations limits the comparability and generalization of the findings. This underscores the need for more personalized treatment optimization and a deeper investigation into the mechanisms through which psychobiotics act. The research corroborates the therapeutic potential of psychobiotics and represents progress in the management of psychiatric and cognitive disorders.
Collapse
Affiliation(s)
- Freiser Eceomo Cruz Mosquera
- Grupo de Investigación en Salud Integral (GISI), Departamento Facultad de Salud, Universidad Santiago de Cali, Cali 760035, Colombia
| | - Santiago Lizcano Martinez
- Área Servicio de Alimentación, Área Nutrición Clínica Hospitalización UCI Urgencias Y Equipo de Soporte nutricional, Clínica Nuestra, Cali 760041, Colombia;
| | - Yamil Liscano
- Grupo de Investigación en Salud Integral (GISI), Departamento Facultad de Salud, Universidad Santiago de Cali, Cali 760035, Colombia
| |
Collapse
|
43
|
Bozzatello P, Novelli R, Montemagni C, Rocca P, Bellino S. Nutraceuticals in Psychiatric Disorders: A Systematic Review. Int J Mol Sci 2024; 25:4824. [PMID: 38732043 PMCID: PMC11084672 DOI: 10.3390/ijms25094824] [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: 04/04/2024] [Revised: 04/23/2024] [Accepted: 04/25/2024] [Indexed: 05/13/2024] Open
Abstract
Correct nutrition and diet are directly correlated with mental health, functions of the immune system, and gut microbiota composition. Diets with a high content of some nutrients, such as fibers, phytochemicals, and short-chain fatty acids (omega-3 fatty acids), seem to have an anti-inflammatory and protective action on the nervous system. Among nutraceuticals, supplementation of probiotics and omega-3 fatty acids plays a role in improving symptoms of several mental disorders. In this review, we collect data on the efficacy of nutraceuticals in patients with schizophrenia, autism spectrum disorders, major depression, bipolar disorder, and personality disorders. This narrative review aims to provide an overview of recent evidence obtained on this topic, pointing out the direction for future research.
Collapse
Affiliation(s)
- Paola Bozzatello
- Department of Neuroscience, University of Turin, Via Cherasco 15, 10126 Turin, Italy; (R.N.); (C.M.); (P.R.); (S.B.)
| | | | | | | | | |
Collapse
|
44
|
Liu P, Liu Z, Wang J, Wang J, Gao M, Zhang Y, Yang C, Zhang A, Li G, Li X, Liu S, Liu L, Sun N, Zhang K. Immunoregulatory role of the gut microbiota in inflammatory depression. Nat Commun 2024; 15:3003. [PMID: 38589368 PMCID: PMC11001948 DOI: 10.1038/s41467-024-47273-w] [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: 07/09/2023] [Accepted: 03/26/2024] [Indexed: 04/10/2024] Open
Abstract
Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.
Collapse
Affiliation(s)
- Penghong Liu
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
| | - Zhifen Liu
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Taiyuan, 030001, PR China
| | - Jizhi Wang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Medical University, Taiyuan, 030001, PR China
| | - Junyan Wang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Medical University, Taiyuan, 030001, PR China
| | - Mingxue Gao
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Medical University, Taiyuan, 030001, PR China
| | - Yanyan Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Medical University, Taiyuan, 030001, PR China
| | - Chunxia Yang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
| | - Aixia Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
| | - Gaizhi Li
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
| | - Xinrong Li
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
| | - Sha Liu
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Medical University, Taiyuan, 030001, PR China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
| | - Lixin Liu
- Experimental Center of Science and Research, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China
| | - Ning Sun
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China.
- Shanxi Medical University, Taiyuan, 030001, PR China.
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China.
| | - Kerang Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China.
- Shanxi Medical University, Taiyuan, 030001, PR China.
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, 030001, PR China.
| |
Collapse
|
45
|
Yang X, Lei L, Shi W, Li X, Huang X, Lan L, Lin J, Liang Q, Li W, Yang J. Probiotics are beneficial for liver cirrhosis: a systematic review and meta-analysis of randomized control trials. Front Med (Lausanne) 2024; 11:1379333. [PMID: 38618195 PMCID: PMC11010643 DOI: 10.3389/fmed.2024.1379333] [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: 02/02/2024] [Accepted: 03/19/2024] [Indexed: 04/16/2024] Open
Abstract
Introduction Gut dysbiosis may play a pivotal role in the pathogenesis of cirrhosis and the severity of complications. Numerous studies have investigated the probiotics as treatments for cirrhosis. However, there is still a lack of definitive evidence confirming the beneficial effects of probiotics on cirrhosis. Methods Databases including PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for randomized controlled trials that compared the effects of probiotic intervention and control treatments, including placebo, no treatment, and active control, on cirrhosis, published from inception to February 2024. Outcomes included hepatic encephalopathy (HE) reversal, safety and tolerability of probiotics, liver function, quality of life, and other cirrhotic-related outcomes. A meta-analysis was conducted to synthesize evidence. Results Thirty studies were included. The quantitative synthesis results showed that compared with the control group, probiotics significantly reverse minimal hepatic encephalopathy (MHE) (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.03 to 2.32) and improve HE (RR 1.94, 95% CI 1.24 to 3.06). Additionally, probiotics demonstrated higher safety and tolerability by causing a lower incidence of serious adverse events (RR 0.71, 95% CI 0.58 to 0.87). Probiotics could potentially improve liver function by reducing the Model for End-Stage Liver Disease (MELD) scores (standardized mean difference [SMD] -0.57, 95% CI -0.85 to -0.30), and displayed favorable changes in quality of life (SMD 0.51, 95% CI 0.27 to 0.75) and gut flora (SMD 1.67, 95% CI 1.28 to 2.06). Conclusion This systematic review and meta-analysis offers compelling evidence that probiotics are beneficial for cirrhosis by demonstrating reversal of HE, potential for liver function improvements, enhancements in quality of life, and regulation of gut dysbiosis. Furthermore, the apparent safety profile suggests that probiotics are a promising intervention for treating cirrhosis. Clinical trial registration number CRD42023478380.
Collapse
Affiliation(s)
- Xing Yang
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Langhuan Lei
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Wei Shi
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Xiaozhen Li
- Health Management Center, People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Xiaozhi Huang
- Health Management Center, People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Liuyan Lan
- Office of Hospital Quality and Safety Management Committee, People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Jiali Lin
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Qiuyu Liang
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Wei Li
- Health Management Center, People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Jianrong Yang
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| |
Collapse
|
46
|
Binda S, Tremblay A, Iqbal UH, Kassem O, Le Barz M, Thomas V, Bronner S, Perrot T, Ismail N, Parker J. Psychobiotics and the Microbiota-Gut-Brain Axis: Where Do We Go from Here? Microorganisms 2024; 12:634. [PMID: 38674579 PMCID: PMC11052108 DOI: 10.3390/microorganisms12040634] [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: 02/21/2024] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 04/28/2024] Open
Abstract
The bidirectional relationship between the gut microbiota and the nervous system is known as the microbiota-gut-brain axis (MGBA). The MGBA controls the complex interactions between the brain, the enteric nervous system, the gut-associated immune system, and the enteric neuroendocrine systems, regulating key physiological functions such as the immune response, sleep, emotions and mood, food intake, and intestinal functions. Psychobiotics are considered tools with the potential to modulate the MGBA through preventive, adjunctive, or curative approaches, but their specific mechanisms of action on many aspects of health are yet to be characterized. This narrative review and perspectives article highlights the key paradigms needing attention as the scope of potential probiotics applications in human health increases, with a growing body of evidence supporting their systemic beneficial effects. However, there are many limitations to overcome before establishing the extent to which we can incorporate probiotics in the management of neuropsychiatric disorders. Although this article uses the term probiotics in a general manner, it remains important to study probiotics at the strain level in most cases.
Collapse
Affiliation(s)
- Sylvie Binda
- Lallemand Health Solutions, 19 Rue des Briquetiers, BP 59, 31702 Blagnac, France; (M.L.B.); (V.T.)
- Rosell Institute for Microbiome and Probiotics, Lallemand Health Solutions, 6100 Royalmount Avenue, Montreal, QC H4P 2R2, Canada; (A.T.); (U.H.I.); (O.K.); (S.B.)
| | - Annie Tremblay
- Rosell Institute for Microbiome and Probiotics, Lallemand Health Solutions, 6100 Royalmount Avenue, Montreal, QC H4P 2R2, Canada; (A.T.); (U.H.I.); (O.K.); (S.B.)
| | - Umar Haris Iqbal
- Rosell Institute for Microbiome and Probiotics, Lallemand Health Solutions, 6100 Royalmount Avenue, Montreal, QC H4P 2R2, Canada; (A.T.); (U.H.I.); (O.K.); (S.B.)
| | - Ola Kassem
- Rosell Institute for Microbiome and Probiotics, Lallemand Health Solutions, 6100 Royalmount Avenue, Montreal, QC H4P 2R2, Canada; (A.T.); (U.H.I.); (O.K.); (S.B.)
| | - Mélanie Le Barz
- Lallemand Health Solutions, 19 Rue des Briquetiers, BP 59, 31702 Blagnac, France; (M.L.B.); (V.T.)
| | - Vincent Thomas
- Lallemand Health Solutions, 19 Rue des Briquetiers, BP 59, 31702 Blagnac, France; (M.L.B.); (V.T.)
| | - Stéphane Bronner
- Rosell Institute for Microbiome and Probiotics, Lallemand Health Solutions, 6100 Royalmount Avenue, Montreal, QC H4P 2R2, Canada; (A.T.); (U.H.I.); (O.K.); (S.B.)
| | - Tara Perrot
- Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS B3H 4R2, Canada;
| | - Nafissa Ismail
- Department of Psychology, University of Ottawa, Ottawa, ON K1N 6N5, Canada;
| | - J.Alex Parker
- Département de Neurosciences, Université de Montréal, Montreal, QC H3T 1J4, Canada;
| |
Collapse
|
47
|
Rajkumar RP. Resolving a paradox: antidepressants, neuroinflammation, and neurodegeneration. EXPLORATION OF NEUROPROTECTIVE THERAPY 2024:11-37. [DOI: 10.37349/ent.2024.00068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 12/12/2023] [Indexed: 01/03/2025]
Abstract
Depression is a known risk factor for dementia. Antidepressants are the most commonly used treatment for this condition, and are effective in at least half to two-thirds of cases. Extensive evidence from in vitro and animal models suggests that antidepressants have anti-inflammatory and neuroprotective properties. These effects have been shown to reduce the oxidative damage, amyloid aggregation, and expression of pro-inflammatory genes associated with animal models of neurodegenerative disorders. However, longitudinal research in humans has shown that antidepressants do not protect against dementia, and may even be associated with a risk of cognitive deterioration over time in older adults. The contrast between two sets of findings represents a paradox of significant clinical and public health significance, particularly when treating depression in late life. This review paper attempts to resolve this paradox by critically reviewing the medium- and long-term effects of antidepressants on peripheral immune-inflammatory responses, infection risk, gut microbiota, and neuroendocrine responses to stress, and how these effects may influence the risk of neurodegeneration. Briefly stated, it is possible that the peripheral actions of antidepressant medications may antagonize their beneficial effects against neuroinflammation. The implications of these findings are then explored with a particular focus on the development and testing of multimodal neuroprotective and anti-inflammatory treatments that could reduce the risk of Alzheimer’s and related dementias in patients suffering from depression.
Collapse
Affiliation(s)
- Ravi Philip Rajkumar
- Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, Pondicherry, India
| |
Collapse
|
48
|
Merkouris E, Mavroudi T, Miliotas D, Tsiptsios D, Serdari A, Christidi F, Doskas TK, Mueller C, Tsamakis K. Probiotics' Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014-2023 Clinical Trials. Microorganisms 2024; 12:411. [PMID: 38399815 PMCID: PMC10893170 DOI: 10.3390/microorganisms12020411] [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: 12/31/2023] [Revised: 02/11/2024] [Accepted: 02/17/2024] [Indexed: 02/25/2024] Open
Abstract
Changes in the gut microbiome can affect cognitive and psychological functions via the microbiota-gut-brain (MGB) axis. Probiotic supplements are thought to have largely positive effects on mental health when taken in sufficient amounts; however, despite extensive research having been conducted, there is a lack of consistent findings on the effects of probiotics on anxiety and depression and the associated microbiome alterations. The aim of our study is to systematically review the most recent literature of the last 10 years in order to clarify whether probiotics could actually improve depression and anxiety symptoms. Our results indicate that the majority of the most recent literature suggests a beneficial role of probiotics in the treatment of depression and anxiety, despite the existence of a substantial number of less positive findings. Given probiotics' potential to offer novel, personalized treatment options for mood disorders, further, better targeted research in psychiatric populations is needed to address concerns about the exact mechanisms of probiotics, dosing, timing of treatment, and possible differences in outcomes depending on the severity of anxiety and depression.
Collapse
Affiliation(s)
- Ermis Merkouris
- Neurology Department, Democritus University of Thrace, 68100 Alexandroupoli, Greece; (E.M.); (T.M.); (D.M.); (D.T.); (F.C.)
| | - Theodora Mavroudi
- Neurology Department, Democritus University of Thrace, 68100 Alexandroupoli, Greece; (E.M.); (T.M.); (D.M.); (D.T.); (F.C.)
| | - Daniil Miliotas
- Neurology Department, Democritus University of Thrace, 68100 Alexandroupoli, Greece; (E.M.); (T.M.); (D.M.); (D.T.); (F.C.)
| | - Dimitrios Tsiptsios
- Neurology Department, Democritus University of Thrace, 68100 Alexandroupoli, Greece; (E.M.); (T.M.); (D.M.); (D.T.); (F.C.)
- 3rd Neurology Department, Aristotle University, 54124 Thessaloniki, Greece
| | - Aspasia Serdari
- Department of Child and Adolescent Psychiatry, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
| | - Foteini Christidi
- Neurology Department, Democritus University of Thrace, 68100 Alexandroupoli, Greece; (E.M.); (T.M.); (D.M.); (D.T.); (F.C.)
| | | | - Christoph Mueller
- Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London SE5 8AB, UK;
- Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London SE5 8AF, UK
| | - Konstantinos Tsamakis
- Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London SE5 8AB, UK;
- Institute of Medical and Biomedical Education, St George’s, University of London, London SW17 0RE, UK
| |
Collapse
|
49
|
Kopera AF, Khiew YC, Amer Alsamman M, Mattar MC, Olsen RS, Doman DB. Depression and the Aberrant Intestinal Microbiome. Gastroenterol Hepatol (N Y) 2024; 20:30-40. [PMID: 38405047 PMCID: PMC10885418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2024]
Abstract
Depression is one of the most common mental health disorders affecting adults in the United States. The current treatment is the combination of pharmacotherapy and psychotherapy. Recently, the evidence linking gut microbiome dysregulation to the development of depression has grown. The pathophysiology is currently poorly understood, although leading hypotheses include involvement of the hypothalamic-pituitary-adrenal axis, a bidirectional relationship between the gut microbiome and the central nervous system, and production of signaling molecules by the gut microbiome. Available and emerging treatments of the aberrant microbiome include antidepressants, antibiotics, diet modification, probiotics, and fecal microbiota transplant. This article explores the interconnectivity of gut microbiota and depression and treatments targeted toward the gut, reviews the gastroenterologist's potential role in managing gut dysbiosis in patients with depression, and highlights research topics to be addressed to create evidence-based guidelines.
Collapse
Affiliation(s)
- Ann F. Kopera
- Department of Internal Medicine, MedStar Georgetown University Hospital, Washington, DC
| | - Yii Chun Khiew
- Department of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC
| | - Mohd Amer Alsamman
- Department of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC
| | - Mark C. Mattar
- Department of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC
| | - Raena S. Olsen
- Department of Gastroenterology, MedStar Health Gastroenterology at Silver Spring, Silver Spring, Maryland
| | - David B. Doman
- Department of Gastroenterology, MedStar Health Gastroenterology at Silver Spring, Silver Spring, Maryland
| |
Collapse
|
50
|
Trkulja V, Barić H. Combining Complementary and Alternative Medicine (CAM) with Conventional Treatments for Major Depressive Disorder. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1456:93-126. [PMID: 39261426 DOI: 10.1007/978-981-97-4402-2_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/13/2024]
Abstract
For many of the complementary and alternative (CAM) medicine methods, it is biologically plausible to expect that they could provide additional benefits in the treatment of major depressive disorder (e.g., enhanced initial response, augmentation, and tolerability) when combined with conventional treatments. Although most likely not comprehensively, herein we critically review current explicit clinical data pertaining to the most extensively evaluated CAMs in this setting: physical activity/exercise, mind and body methods, acupuncture, light therapy, diet, probiotics, various nutrients, and herbal preparations. While the absolute amount of data is enormous, the number of reliable primary studies (randomized controlled trials) and, particularly, meaningful meta-analyses of such studies are very limited. Consequently, the certainty of evidence about benefit or no benefit is very low for each of the addressed CAMs.
Collapse
Affiliation(s)
- Vladimir Trkulja
- Department of Pharmacology, Zagreb University School of Medicine, Zagreb, Croatia.
| | - Hrvoje Barić
- Department of Neurosurgery, University Hospital Center Zagreb, Zagreb, Croatia
| |
Collapse
|