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Deng F, Yang D, Qing L, Chen Y, Zou J, Jia M, Wang Q, Jiang R, Huang L. Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway: a potential therapeutic approach for neurodegenerative diseases. Neural Regen Res 2025; 20:3095-3112. [PMID: 39589173 PMCID: PMC11881707 DOI: 10.4103/nrr.nrr-d-24-00607] [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: 06/01/2024] [Revised: 08/07/2024] [Accepted: 09/10/2024] [Indexed: 11/27/2024] Open
Abstract
The interaction between the gut microbiota and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut-brain axis. The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites, which activates the vagus nerve and modulates the immune and neuroendocrine systems. Conversely, alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota, creating a dynamic network of microbial-host interactions. This reciprocal regulation affects neurodevelopment, neurotransmitter control, and behavioral traits, thus playing a role in the modulation of neurological diseases. The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation, mitochondrial dysfunction, abnormal energy metabolism, microglial activation, oxidative stress, and neurotransmitter release, which collectively influence the onset and progression of neurological diseases. This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway, along with its implications for potential therapeutic interventions in neurological diseases. Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders. This can be achieved through various methods such as dietary modifications, probiotic supplements, Chinese herbal extracts, combinations of Chinese herbs, and innovative dosage forms. These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.
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Affiliation(s)
- Fengcheng Deng
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Dan Yang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Lingxi Qing
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Yifei Chen
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Jilian Zou
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Meiling Jia
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Qian Wang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Runda Jiang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Lihua Huang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
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Tiwari S, Paramanik V. Role of Probiotics in Depression: Connecting Dots of Gut-Brain-Axis Through Hypothalamic-Pituitary Adrenal Axis and Tryptophan/Kynurenic Pathway involving Indoleamine-2,3-dioxygenase. Mol Neurobiol 2025; 62:7230-7241. [PMID: 39875781 DOI: 10.1007/s12035-025-04708-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 01/14/2025] [Indexed: 01/30/2025]
Abstract
Depression is one of the most disabling mental disorders worldwide and characterized by symptoms including worthlessness, anhedonia, sleep, and appetite disturbances. Recently, studies have suggested that tryptophan (Trp) metabolism plays a key role in depressed mood through serotonin and kynurenine pathway involving enzyme tryptophan 5-monooxygenase (TPH) and indoleamine-2,3-dioxygenase (IDO) respectively. Moreover, during neuroinflammation, IDO is activated by proinflammatory cytokines and affects neurogenesis, cognition, disturbed hypothalamic-pituitary-adrenal (HPA) axis, and gut homeostasis by altering the gut bacteria and its metabolites like Trp derivatives. Furthermore, over the decades, researchers have focused on understanding communication between the human microbiome, especially gut microbiota, and mental health, called gut-brain-axis (GBA), particularly through Trp metabolism. Supplementation of probiotics in depression has gained attention from researchers and clinicians. However, there is limited information about probiotics supplementation on depression involving enzyme IDO and kynurenine pathway metabolites. This review discussed the potential role of probiotics in depression through the tryptophan/kynurenine pathway.
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Affiliation(s)
- Sneha Tiwari
- Cellular and Molecular Neurobiology and Drug Targeting Laboratory, Department of Zoology, Indira Gandhi National Tribal University, Amarkantak-484 887, MP, India
| | - Vijay Paramanik
- Cellular and Molecular Neurobiology and Drug Targeting Laboratory, Department of Zoology, Indira Gandhi National Tribal University, Amarkantak-484 887, MP, India.
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Tiwari S, Paramanik V. Lactobacillus fermentum ATCC 9338 Supplementation Prevents Depressive-Like Behaviors Through Glucocorticoid Receptor and N-Methyl-D-aspartate2b in Chronic Unpredictable Mild Stress Mouse Model. Mol Neurobiol 2025; 62:7927-7944. [PMID: 39956887 DOI: 10.1007/s12035-025-04738-3] [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: 07/09/2024] [Accepted: 01/31/2025] [Indexed: 02/18/2025]
Abstract
Depression is a long-term, related to stress neuropsychiatric disorder, leading to psychological health issues including worthlessness, anhedonia, sleep and appetite disturbances, dysregulated HPA axis, neuronal cell death, and alterations in the gut microbiota (GM). Dysregulated HPA axis increases level of glucocorticoids that induce proinflammatory response with activation of abnormal kynurenine pathway via metabolizing indoleamine-2,3-dioxygenase (IDO). Kynurenine pathway leads to excitotoxicity of N-methyl-D-aspartate (NMDA) receptor responsible for neuronal cell death. Further, probiotics supplementation gained attention from researchers and clinicians to treat neuropsychiatric diseases. GM alteration remains a key reason for depression; however, there is limited information about the role of probiotics on depression involving glucocorticoid receptor and NMDA excitotoxicity through IDO. Chronic unpredictable mild stress (CUMS) model was prepared to check the role of Lactobacillus fermentum ATCC 9338 (LF) and 1-methyl-D-tryptophan (1-MT) in depression. Herein, mice were placed into experimental groups: control, CUMS stressed, CUMS vehicle, CUMS LF, CUMS 1-MT, and CUMS UT (untreated). Results showed that peroral administration of 1 × 108 CFU/day/mouse LF and intraperitoneal dose of 1-MT (15 mg/kg BW/day) alleviate depressive-like behavior and improve motor coordination and walking patterns. Mice supplemented with LF and 1-MT exhibited a decreased expression of GR and NMDAR2b in the cortex, hippocampus, and medulla. Acetylcholinesterase, SOD, and CAT activities were improved in CUMS mice with supplementation of LF and 1-MT. The GM abundance in LF mice was similar to that in control mice. Such study suggests the roles of LF and 1-MT in depression and oxidative stress, and helpful to understand their therapeutic potential through the HPA axis and IDO.
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Affiliation(s)
- Sneha Tiwari
- Cellular and Molecular Neurobiology and Drug Targeting Laboratory, Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh-484 887, India
| | - Vijay Paramanik
- Cellular and Molecular Neurobiology and Drug Targeting Laboratory, Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh-484 887, India.
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Petrut SM, Bragaru AM, Munteanu AE, Moldovan AD, Moldovan CA, Rusu E. Gut over Mind: Exploring the Powerful Gut-Brain Axis. Nutrients 2025; 17:842. [PMID: 40077713 PMCID: PMC11901622 DOI: 10.3390/nu17050842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 02/18/2025] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
Background: The human gastrointestinal tract is home to a wide variety of microorganisms. For some decades now, bacteria known as probiotics have been added to various foods because of their beneficial effects for human health. Evidence indicates that probiotics significantly regulate gut microbiota, which is vital for digestion, metabolism, immune function, and mental health. Methods: We conducted a narrative review of available original research published in PubMed for the past ten years focusing on recent advancements that provide a thorough understanding of the relationship between the gastrointestinal system and the brain. Results: Recent advances in research have focused on the importance of gut microbiota in influencing mental health. The microbiota-gut-brain axis is a complex, bidirectional communication network linking the central nervous system and the gastrointestinal tract, which highlights how the gut and brain are deeply interconnected and influence each other in ways that affect our overall health, emotions, and behavior. This powerful link is a major area of research as scientists discover more about how gut health can impact mental well-being. Conclusions: A comprehensive understanding of microbiota composition and mechanisms involved in these interactions between the gut and the brain could shape future medical and therapeutic approaches. It would balance scientific explanation with clinical relevance, offering insights into how understanding the brain-gut axis can revolutionize our approach to treating mental health and gastrointestinal disorders.
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Affiliation(s)
- Stefana-Maria Petrut
- Department of Preclinical Sciences, Faculty of Medicine, Titu Maiorescu University, 031593 Bucharest, Romania; (S.-M.P.); (E.R.)
| | - Alexandra Maria Bragaru
- Doctoral School of Medicine, Titu Maiorescu University of Bucharest, 040317 Bucharest, Romania; (A.M.B.); (A.-D.M.)
| | - Alice Elena Munteanu
- Department of Medico-Surgical and Prophylactic Sciences, Faculty of Medicine, Titu Maiorescu University, 031593 Bucharest, Romania;
- Department of Cardiology, “Dr. Carol Davila” Central Military Emergency University Hospital, 010825 Bucharest, Romania
| | - Adina-Diana Moldovan
- Doctoral School of Medicine, Titu Maiorescu University of Bucharest, 040317 Bucharest, Romania; (A.M.B.); (A.-D.M.)
- MedLife SA, 010719 Bucharest, Romania
| | - Cosmin-Alec Moldovan
- Department of Medico-Surgical and Prophylactic Sciences, Faculty of Medicine, Titu Maiorescu University, 031593 Bucharest, Romania;
- Department of General Surgery, Witting Clinical Hospital, 010243 Bucharest, Romania
| | - Elena Rusu
- Department of Preclinical Sciences, Faculty of Medicine, Titu Maiorescu University, 031593 Bucharest, Romania; (S.-M.P.); (E.R.)
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Xu Q, Xiang Q, Tan Z, Yang Q. Global research trends in the intestinal microflora and depression: bibliometrics and visual analysis. Front Cell Infect Microbiol 2025; 15:1507667. [PMID: 40070374 PMCID: PMC11893873 DOI: 10.3389/fcimb.2025.1507667] [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: 10/08/2024] [Accepted: 02/07/2025] [Indexed: 03/14/2025] Open
Abstract
Background In recent years, the relationship between gut microbiota and human health has garnered significant attention. Notably, the potential connection between gut microbiota and mental health issues, such as depression and anxiety, has emerged as a new focal point for research. While some studies suggest a possible link between these factors, the field remains in its early stages of development, and there are notable methodological and sample size limitations. Purpose This study aims to systematically summarize the knowledge systems, research hotspots, and development trends related to intestinal microflora within the context of depression research. Methods This study conducted a search for publications related to intestinal microflora and depression in the Web of Science Core Collection (WOSCC) prior to August 6, 2024. The selected literature was subsequently analyzed using VOSviewer (v.1.6.20), SCImago Graphica (v.1.0.39), and CiteSpace (v.6.3.1). Results The study encompassed a total of 1,046 publications, demonstrating a consistent increase in annual publication volume. The primary research countries identified are China and the United States, with notable contributions from institutions such as the University of California and University College Cork, among others. Keywords analysis highlighted high-frequency terms including "gut microbiota," "depression," and "anxiety," and revealed 10 keyword clusters along with 20 strongest citation bursts keywords. The focus of research has shifted from compositional analysis of gut microbiota to its role in the pathogenesis of depression. Conclusions Research on gut microbiota and depression is growing, but there is still a need for greater collaboration between authors and institutions across regions, more ongoing interaction and communication to further explore the mechanisms of action of gut microbiota, to develop microbiota-based interventions, and to facilitate translation of research findings into clinical practice.
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Affiliation(s)
- Qian Xu
- School of Clinical Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Qingwei Xiang
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Zihu Tan
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Qiong Yang
- School of Clinical Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
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Wu Z, Luo X, Dou P, Liu T, Zhou J. Asthma, social isolation and loneliness, and risk of incident osteoarthritis. Arthritis Res Ther 2025; 27:29. [PMID: 39930511 PMCID: PMC11808944 DOI: 10.1186/s13075-025-03496-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 01/31/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Incidence of osteoarthritis (OA) was increased in patients with asthma, while no prospective cohort study has tested the association of asthma with OA, and the modified effect of social isolation and loneliness remains unclear. METHODS This prospective cohort study included 448,920 participants without OA at baseline from UK Biobank cohort. The evaluation of asthma was based on diagnosis and self-reported history. The outcome was OA including knee OA, hip OA and hand OA by referring to hospital admission records. Two Cox regression models were constructed to assess the relationship of asthma and risk of OA. RESULTS With a median of 12.5 years of follow up, a total of 57,573 incident OA were recorded. Compared with participants without asthma, the hazard ratios (HRs) were 1.32 (95% CI: 1.29-1.35) for all OA, 1.21 (95% CI: 1.16-1.25) for knee OA, 1.12 (95% CI: 1.07-1.18) for hip OA and 1.62 (95% CI:1.42-1.85) for hand OA in participants with asthma. In addition, we found that social isolation and loneliness significantly modified the associations of asthma with OA (P-interaction < 0.001). Asthma was a stronger predictor of OA than lifestyle risk factors including smoking, alcohol and healthy diet. CONCLUSIONS In this cohort study of UK Biobank participants, asthma was related to increased risk of OA; such association was more pronounced among those with higher social isolation or loneliness score.
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Affiliation(s)
- Ziyi Wu
- Department of Orthopedics, The Second Xiangya Hospital of Central South University, Renmin Middle Road, No. 139, Changsha, China
| | - Xukun Luo
- Clinical Medicine Eight-year Program, 2302 Class, 2023 Grade, Central South University, Changsha, Hunan, 410013, China
| | - Pengcheng Dou
- Department of Orthopedics, The Second Xiangya Hospital of Central South University, Renmin Middle Road, No. 139, Changsha, China
| | - Tang Liu
- Department of Orthopedics, The Second Xiangya Hospital of Central South University, Renmin Middle Road, No. 139, Changsha, China
| | - Jian Zhou
- Department of Orthopedics, The Second Xiangya Hospital of Central South University, Renmin Middle Road, No. 139, Changsha, China.
- Postdoctoral Mobile Station of Clinical Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
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Bertollo AG, Santos CF, Bagatini MD, Ignácio ZM. Hypothalamus-pituitary-adrenal and gut-brain axes in biological interaction pathway of the depression. Front Neurosci 2025; 19:1541075. [PMID: 39981404 PMCID: PMC11839829 DOI: 10.3389/fnins.2025.1541075] [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: 12/06/2024] [Accepted: 01/16/2025] [Indexed: 02/22/2025] Open
Abstract
The hypothalamus-pituitary-adrenal (HPA) and gut-brain axes are vital biological pathways in depression. The HPA axis regulates the body's stress response, and chronic stress can lead to overactivation of the HPA axis, resulting in elevated cortisol levels that contribute to neuronal damage, particularly in regions such as the hippocampus and prefrontal cortex, both of which are involved in mood regulation and mental disorders. In parallel, the gut-brain axis, a bidirectional communication network between the gut microbiota and the central nervous system, influences emotional and cognitive functions. Imbalances in gut microbiota can affect the HPA axis, promoting inflammation and increasing gut permeability. This allows endotoxins to enter the bloodstream, contributing to neuroinflammation and altering neurotransmitter production, including serotonin. Since the majority of serotonin is produced in the gut, disruptions in this pathway may be linked to depressive symptoms. This review explores the interplay between the HPA axis and the gut-brain axis in the context of depression.
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Liu M, Fan G, Meng L, Yang K, Liu H. New perspectives on microbiome-dependent gut-brain pathways for the treatment of depression with gastrointestinal symptoms: from bench to bedside. J Zhejiang Univ Sci B 2025; 26:1-25. [PMID: 39428337 PMCID: PMC11735910 DOI: 10.1631/jzus.b2300343] [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: 08/29/2023] [Indexed: 10/22/2024]
Abstract
Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.
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Affiliation(s)
- Menglin Liu
- The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Brain Disease Regional Diagnosis and Treatment Center, Zhengzhou 450000, China
- Tianjin University of Traditional Chinese Medicine, Tianjin 301600, China
| | - Genhao Fan
- Tianjin University of Traditional Chinese Medicine, Tianjin 301600, China
- The First Affiliated Hospital of Zhengzhou University, Department of Geriatrics, Zhengzhou 450052, China
| | - Lingkai Meng
- Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300131, China
| | - Kuo Yang
- Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300131, China
| | - Huayi Liu
- Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300131, China.
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Văcărean-Trandafir IC, Amărandi RM, Ivanov IC, Dragoș LM, Mențel M, Iacob Ş, Muşină AM, Bărgăoanu ER, Roată CE, Morărașu Ș, Țuțuianu V, Ciobanu M, Dimofte MG. Impact of antibiotic prophylaxis on gut microbiota in colorectal surgery: insights from an Eastern European stewardship study. Front Cell Infect Microbiol 2025; 14:1468645. [PMID: 39872941 PMCID: PMC11770057 DOI: 10.3389/fcimb.2024.1468645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/18/2024] [Indexed: 01/30/2025] Open
Abstract
Introduction Antibiotic overuse is driving a global rise in antibiotic resistance, highlighting the need for robust antimicrobial stewardship (AMS) initiatives to improve prescription practices. While antimicrobials are essential for treating sepsis and preventing surgical site infections (SSIs), they can inadvertently disrupt the gut microbiota, leading to postoperative complications. Treatment methods vary widely across nations due to differences in drug choice, dosage, and therapy duration, affecting antibiotic resistance rates, which can reach up to 51% in some countries. In Romania and the Republic of Moldova, healthcare practices for surgical antibiotic prophylaxis differ significantly despite similarities in genetics, culture, and diet. Romania's stricter healthcare regulations result in more standardized antibiotic protocols, whereas Moldova's limited healthcare funding leads to less consistent practices and greater variability in treatment outcomes. Methods This study presents the results of a prospective cross-border investigation involving 86 colorectal cancer patients from major oncological hospitals in Romania and Moldova. We analyzed fecal samples collected from patients before and 7 days post-antibiotic treatment, focusing on the V3-V4 region of the 16S rRNA gene. Results Our findings indicate that inconsistent antibiotic prophylaxis policies-varying in type, dosage, or therapy duration-significantly impacted the gut microbiota and led to more frequent dysbiosis compared to stricter prophylactic antibiotic practices (single dose, single product, limited time). Discussion We emphasize the need for standardized antibiotic prophylaxis protocols to minimize dysbiosis and its associated risks, promoting more effective antimicrobial use, particularly in low- and middle-income countries (LMICs).
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Affiliation(s)
| | | | | | | | - Mihaela Mențel
- TRANSCEND Research Centre, Regional Institute of Oncology, Iasi, Romania
| | - Ştefan Iacob
- Second Surgical Oncology Department, Regional Institute of Oncology, Iasi, Romania
- Surgery Department, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Ana-Maria Muşină
- Second Surgical Oncology Department, Regional Institute of Oncology, Iasi, Romania
- Surgery Department, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | | | - Cristian Ene Roată
- Second Surgical Oncology Department, Regional Institute of Oncology, Iasi, Romania
- Surgery Department, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Ștefan Morărașu
- Second Surgical Oncology Department, Regional Institute of Oncology, Iasi, Romania
- Surgery Department, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Valeri Țuțuianu
- Scientific Laboratory of Cancer Biology, Institute of Oncology, Chișinău, Moldova
| | - Marcel Ciobanu
- Surgical Oncology Department, Proctology, Institute of Oncology, Chișinău, Moldova
| | - Mihail-Gabriel Dimofte
- Second Surgical Oncology Department, Regional Institute of Oncology, Iasi, Romania
- Surgery Department, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
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McGrew K, de Oca NM, Kosten TA. Effect of Relocation, Social Housing Changes, and Diarrhea Status on Microbiome Composition of Juvenile Cynomolgus Macaques ( Macaca fascicularis). Microorganisms 2025; 13:98. [PMID: 39858866 PMCID: PMC11767897 DOI: 10.3390/microorganisms13010098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 12/16/2024] [Accepted: 12/23/2024] [Indexed: 01/27/2025] Open
Abstract
Social housing changes are likely stressful and can be associated with diarrhea, the most common health problem noted in captive macaque populations. Diarrhea may reflect a negative shift in the gut flora ("gut dysbiosis"). This study reported on changes in the gut microbiome composition of juvenile primates (Macaca fascicularis) that experienced a change in social housing and exhibited diarrhea. A matched-case-control design was utilized to compare fecal samples from gut-unhealthy animals to healthy counterparts (n = 61). Baseline samples from recently imported animals were collected during routine sedation events. When an animal experienced a housing change, the entire cohort was monitored for diarrhea. Post-relocation samples were collected from animals that exhibited diarrhea and from their matched controls. Samples were assessed via 16S rRNA next-generation sequencing for a microbiome analysis and by ELISA for cortisol levels. Fecal cortisol levels did not differ between groups or across time points. Alpha diversity increased after relocation and differed by sex with males demonstrating a greater change in alpha diversity (p < 0.01). Although exhibiting diarrhea did not affect alpha diversity levels, it was associated with increased beta diversity (p < 0.05). Understanding how the microbiome may be affected by relocation will help guide prevention strategies such as the use of specific probiotics to reduce the incidence of diarrhea.
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Affiliation(s)
- Keely McGrew
- Charles River Laboratories, Inc., Houston, TX 77047, USA; (K.M.); (N.M.d.O.)
- Department of Psychology, University of Houston, Houston, TX 77004, USA
| | - Nicole Monts de Oca
- Charles River Laboratories, Inc., Houston, TX 77047, USA; (K.M.); (N.M.d.O.)
| | - Therese A. Kosten
- Department of Psychology, University of Houston, Houston, TX 77004, USA
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11
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Nami Y, Barghi A, Shahgolzari M, Salehian M, Haghshenas B. Mechanism of Action and Beneficial Effects of Probiotics in Amateur and Professional Athletes. Food Sci Nutr 2025; 13:e4658. [PMID: 39803224 PMCID: PMC11717059 DOI: 10.1002/fsn3.4658] [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: 05/25/2024] [Revised: 11/09/2024] [Accepted: 11/25/2024] [Indexed: 01/16/2025] Open
Abstract
Probiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. According to the International Society of Sports Nutrition (ISSN), probiotic supplementation can optimize the health, performance, and recovery of athletes at all stages of their careers. Recent research suggests that probiotics can improve immune system functions, reduce gastrointestinal distress, and increase gut permeability in athletes. Additionally, probiotics may provide athletes with secondary health benefits that could positively affect athletic performance through enhanced recovery from fatigue, improved immune function, and maintenance of healthy gastrointestinal tract function. The integration of some probiotic strains into athletes' diets and the consumption of multi-strain compounds may lead to an improvement in performance and can positively affect performance-related aspects such as fatigue, muscle pain, body composition, and cardiorespiratory fitness. In summary, probiotics can be beneficial for athletes at all stages of their careers, from amateur to professional. This paper reviews the progress of research on the role of probiotic supplementation in improving energy metabolism and immune system functions, reducing gastrointestinal distress, and enhancing recovery from fatigue in athletes at different levels.
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Affiliation(s)
- Yousef Nami
- Department of Food Biotechnology, Branch for Northwest and West RegionAgricultural Biotechnology Research Institute of Iran, Agricultural Research, Education and Extension Organization (AREEO)TabrizIran
| | - Anahita Barghi
- Institute of Agricultural Life ScienceDong‐A UniversityBusanSouth Korea
| | - Mehdi Shahgolzari
- Department of Medical Nanotechnology, Faculty of Advanced Medical SciencesTabriz University of Medical SciencesTabrizIran
- Biotechnology Research CenterTabriz University of Medical SciencesTabrizIran
| | - Melika Salehian
- Student Research CommitteeKermanshah University of Medical SciencesKermanshahIran
| | - Babak Haghshenas
- Regenerative Medicine Research Center (RMRC), Health Technology InstituteKermanshah University of Medical SciencesKermanshahIran
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Varghese SM, Patel S, Nandan A, Jose A, Ghosh S, Sah RK, Menon B, K V A, Chakravarty S. Unraveling the Role of the Blood-Brain Barrier in the Pathophysiology of Depression: Recent Advances and Future Perspectives. Mol Neurobiol 2024; 61:10398-10447. [PMID: 38730081 DOI: 10.1007/s12035-024-04205-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 04/19/2024] [Indexed: 05/12/2024]
Abstract
Depression is a highly prevalent psychological disorder characterized by persistent dysphoria, psychomotor retardation, insomnia, anhedonia, suicidal ideation, and a remarkable decrease in overall well-being. Despite the prevalence of accessible antidepressant therapies, many individuals do not achieve substantial improvement. Understanding the multifactorial pathophysiology and the heterogeneous nature of the disorder could lead the way toward better outcomes. Recent findings have elucidated the substantial impact of compromised blood-brain barrier (BBB) integrity on the manifestation of depression. BBB functions as an indispensable defense mechanism, tightly overseeing the transport of molecules from the periphery to preserve the integrity of the brain parenchyma. The dysfunction of the BBB has been implicated in a multitude of neurological disorders, and its disruption and consequent brain alterations could potentially serve as important factors in the pathogenesis and progression of depression. In this review, we extensively examine the pathophysiological relevance of the BBB and delve into the specific modifications of its components that underlie the complexities of depression. A particular focus has been placed on examining the effects of peripheral inflammation on the BBB in depression and elucidating the intricate interactions between the gut, BBB, and brain. Furthermore, this review encompasses significant updates on the assessment of BBB integrity and permeability, providing a comprehensive overview of the topic. Finally, we outline the therapeutic relevance and strategies based on BBB in depression, including COVID-19-associated BBB disruption and neuropsychiatric implications. Understanding the comprehensive pathogenic cascade of depression is crucial for shaping the trajectory of future research endeavors.
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Affiliation(s)
- Shamili Mariya Varghese
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India
| | - Shashikant Patel
- Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, Telangana, 500007, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Amritasree Nandan
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India
| | - Anju Jose
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India
| | - Soumya Ghosh
- Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, Telangana, 500007, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Ranjay Kumar Sah
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India
| | - Bindu Menon
- Department of Psychiatry, Amrita School of Medicine, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India
| | - Athira K V
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India.
| | - Sumana Chakravarty
- Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, Telangana, 500007, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
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Abildinova GZ, Benberin VV, Vochshenkova TA, Afshar A, Mussin NM, Kaliyev AA, Zhussupova Z, Tamadon A. The gut-brain-metabolic axis: exploring the role of microbiota in insulin resistance and cognitive function. Front Microbiol 2024; 15:1463958. [PMID: 39659426 PMCID: PMC11628546 DOI: 10.3389/fmicb.2024.1463958] [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: 07/12/2024] [Accepted: 11/13/2024] [Indexed: 12/12/2024] Open
Abstract
The gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic-pituitary-adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.
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Affiliation(s)
- Gulshara Zh Abildinova
- Gerontology Center, Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
- Corporate Fund “Institute for Innovational and Profilaxy Medicine”, Astana, Kazakhstan
| | - Valeriy V. Benberin
- Gerontology Center, Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
- Corporate Fund “Institute for Innovational and Profilaxy Medicine”, Astana, Kazakhstan
| | - Tamara A. Vochshenkova
- Gerontology Center, Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
- Corporate Fund “Institute for Innovational and Profilaxy Medicine”, Astana, Kazakhstan
| | - Alireza Afshar
- Gerontology Center, Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
- Corporate Fund “Institute for Innovational and Profilaxy Medicine”, Astana, Kazakhstan
| | - Nadiar M. Mussin
- Department of Surgery No. 2, West Kazakhstan Medical University, Aktobe, Kazakhstan
| | - Asset A. Kaliyev
- Department of Surgery No. 2, West Kazakhstan Medical University, Aktobe, Kazakhstan
| | - Zhanna Zhussupova
- Department of Neurology, Psychiatry and Narcology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Amin Tamadon
- Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- PerciaVista R&D Co., Shiraz, Iran
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14
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Lee M, Ahn KS, Kim M. Effects of Artemisia asiatica ex on Akkermansia muciniphila dominance for modulation of Alzheimer's disease in mice. PLoS One 2024; 19:e0312670. [PMID: 39466764 PMCID: PMC11516174 DOI: 10.1371/journal.pone.0312670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 10/07/2024] [Indexed: 10/30/2024] Open
Abstract
The gut microbiome influences neurological disorders through bidirectional communication between the gut and the brain, i.e., the gut-brain axis. Artemisia asiatica ex, an extract of Artemisia asiatica Nakai (Stillen®, DA-9601) has been reported to improve depression by increasing brain-derived neurotropic factor. Therefore, we hypothesized that DA-9601 can be a potential therapeutic candidate for Alzheimer's disease (AD) acting through the gut-brain axis. Four groups of Tg2576 mice were used as the animal model for AD: wild type mice (n = 6), AD mice (n = 6), and DA-9601-administered AD mice given dosages of 30mg/kg/day (DA_30mg; n = 6) or 100mg/kg/day (DA_100mg; n = 6). Microglial activation, blood‒brain barrier integrity, amyloid beta accumulation, cognitive behavior, and changes in the gut microbiome were analyzed. DA-9601 improved the cognitive behavior of mice (DA_30mg **p<0.01; DA_100mg **p<0.01) and reduced amyloid beta accumulation (DA_30mg ***p<0.001; DA_100mg **p<0.01). Increased Iba-1 and upregulation of claudin-5 (DA_30mg *p<0.05) and occludin (DA_30mg **p<0.01; DA_100mg ***p<0.001) indicated altered microglial activation and improved blood‒brain barrier integrity. Akkermansia muciniphila was dramatically increased by DA-9601 administration (DA_30mg 47%; DA_100mg 61%). DA-9601 improved AD pathology with Akkermansia muciniphila dominance in the gut microbiome in a mouse model of AD, inferring that DA-9601 can affect AD through the gut-brain axis.
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Affiliation(s)
- Mijung Lee
- Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea
| | - Kwang-Sung Ahn
- Functional Genome Institute, PDXen. Biosystem Co., Gyeongi-do, South Korea
| | - Manho Kim
- Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea
- Neuroscience Dementia Research Institute, Seoul National University College of Medicine, Seoul, South Korea
- Protein Metabolism Medical Research Center, College of Medicine, Seoul National University Hospital, Seoul, South Korea
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Zhang J, Xin H, Wang W, Li Y, Wu R, Wei L, Su S, Wang X, Wang X, Wang X, Li L, Hu R. Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC-MS metabolomics analysis. Sci Rep 2024; 14:22111. [PMID: 39333605 PMCID: PMC11437287 DOI: 10.1038/s41598-024-72793-2] [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: 06/12/2024] [Accepted: 09/10/2024] [Indexed: 09/29/2024] Open
Abstract
Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC-MS metabolomics analysis to investigate the regulatory effects and mechanisms of lactoferrin in a rat model of depression. After one week of acclimatization, twenty-four 7-week-old male Sprague-Dawley rats were randomly and equally assigned into three groups: the control group, the model group, and the lactoferrin intervention group. The control group rats were housed under standard conditions, while the rats in the model and lactoferrin intervention groups were individually housed and exposed to chronic unpredictable mild stress for 44 days simultaneously. The lactoferrin intervention group was provided with water containing 2% lactoferrin (2 g/100 ml). Behavioural tests were conducted at week 7. Upon completion of the behavioral tests, the rats were anesthetized with isoflurane, humanely euthanized using a rat guillotine, and tissue samples were collected for further experiments. The results indicated that lactoferrin intervention led to an increase in sucrose solution consumption, horizontal movement distance, number of cross platforms, and residence time in the target quadrant. Additionally, it resulted in an increase in jejunal tight junction protein ZO-1 expression and a suppression of serum expression of inflammatory factors, Lipopolysaccharide and Diamine oxidase. In summary, lactoferrin can regulate the metabolic disorder of intestinal flora, reduce intestinal permeability, and further regulate the metabolic balance of hippocampal tissues through the microbiota-gut-brain axis. This process ultimately alleviates the depression-like behavior in rats.
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Affiliation(s)
- Jing Zhang
- Basic Medical College, Inner Mongolia Medical University, Hohhot, 010110, China
| | - Hongmei Xin
- College of Humanities Education , Inner Mongolia Medical University, Hohhot, 010110, China
| | - Wuji Wang
- Wuhan Pulmonary Hospital/Wuhan Institute for Tuberculosis Control, Wuhan, 430030, China
| | - Yanyi Li
- School of Nursing,Inner Mongolia Medical University, Hohhot, 010110, China
| | - Riga Wu
- Mongolian Medicine College , Inner Mongolia Medical University, Hohhot, 010110, China
| | - Lisi Wei
- Mongolian Medicine College , Inner Mongolia Medical University, Hohhot, 010110, China
| | - Si Su
- Mongolian Medicine College , Inner Mongolia Medical University, Hohhot, 010110, China
| | - Xiaohong Wang
- Laboratory Animal Center, Inner Mongolia Medical University, Hohhot, 010110, China
| | - Xiujuan Wang
- Basic Medical College, Inner Mongolia Medical University, Hohhot, 010110, China
| | - Xiaojuan Wang
- Basic Medical College, Inner Mongolia Medical University, Hohhot, 010110, China
| | - Li Li
- Basic Medical College, Inner Mongolia Medical University, Hohhot, 010110, China.
| | - Rilebagen Hu
- Mongolian Medicine College , Inner Mongolia Medical University, Hohhot, 010110, China.
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16
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Zhao J, Yuan J, Zhang Y, Deng L, Pan Y, Bai X, Jia L, Wang Y, Geng W. Bifidobacterium pseudonumeratum W112 alleviated depressive and liver injury symptoms induced by chronic unpredictable mild stress via gut-liver-brain axis. Front Nutr 2024; 11:1421007. [PMID: 39224184 PMCID: PMC11366711 DOI: 10.3389/fnut.2024.1421007] [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: 04/21/2024] [Accepted: 07/29/2024] [Indexed: 09/04/2024] Open
Abstract
Introduction Several studies indicated that depression is associated with liver injury. The role of probiotics in alleviating depression is focused on improving the abnormalities of the central nervous system through the gut-brain axis, while the effect on liver injury is still unclear. The aim of this study was to elucidate the potential link between the antidepressant effect of a potential probiotic strain Bifidobacterium pseudocatenulatum W112 and its effect on alleviating liver injury. Methods The 4-week-old Kunming mice were exposed to chronic stress for 4 weeks to establish a depression model. Results The depression-like behavior and related biomakers in chronic unpredictable mild stress (CUMS) mice were altered by supplemented with W112 for 2 weeks. Meanwhile, the modulation effect of W112 the gut microbiota in CUMS mice also result in an increase in the abundance of beneficial bacteria and a decrease in the abundance of harmful bacteria. Significantly, liver injury was observed in CUMS model mice. W112 improved liver injury by reducing AST/ALT in serum. Quantitative PCR results indicated that the mechanism of action of W112 in ameliorating liver injury was that the altered gut microbiota affected hepatic phospholipid metabolism and bile acid metabolism. Discussion In short, W112 could significantly improve the depressive and liver injury symptoms caused by CUMS. The gut-liver-brain axis is a potential connecting pathway between the antidepressant effects of W112 and its alleviation of liver injury.
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Affiliation(s)
- Jingqi Zhao
- Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China
- Key Laboratory of Traditional Chinese Medicine Lifeomics and Innovative Drug Research and Development, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Jiahu Yuan
- Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China
| | - Yihua Zhang
- Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China
| | - Langni Deng
- Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China
| | - Yajing Pan
- Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China
| | - Xiaojia Bai
- Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China
| | - Longgang Jia
- Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China
| | - Yanping Wang
- Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China
| | - Weitao Geng
- Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China
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Liu S, Xi H, Xue X, Sun X, Huang H, Fu D, Mi Y, He Y, Yang P, Tang Y, Zheng P. Clostridium butyricum regulates intestinal barrier function via trek1 to improve behavioral abnormalities in mice with autism spectrum disorder. Cell Biosci 2024; 14:95. [PMID: 39034406 PMCID: PMC11265103 DOI: 10.1186/s13578-024-01278-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 07/16/2024] [Indexed: 07/23/2024] Open
Abstract
BACKGROUND Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that has been found to be associated with dysregulation of gastrointestinal functions and gut microbial homeostasis (the so-called "gut-brain axis"). ASD is often accompanied by poor performances in social interaction and repetitive behaviors. Studies on the gut-brain axis provide novel insights and candidate targets for ASD therapeutics and diagnosis. Based on the ASD mice model, this work aims to reveal the mechanisms behind the interaction of intestinal barrier function and probiotics in ASD mouse models. RESULTS We found an altered intestinal barrier in both BTBR T+ Itpr3tf/J (BTBR) and valproic acid (VPA) mice, including increased intestinal permeability, decreased expression of intestinal tight junction proteins (claudin1, claudin3, and occludin), and increased levels of IL-6, TNF-α, and IFN-γ. Based on intestinal microbial alternation, C. butyricum can drive reduced expression of histone deacetylases 1 (HDAC1) and enhanced intestinal barrier function, significantly promoting behavioral abnormalities of ASD in BTBR mice. In parallel, we confirmed that C. butyricum was involved in the regulation of intestinal function by the Trek1 channel, indicating that it is a target of C. butyricum/butyric acid to improve intestinal barrier function in ASD mice. CONCLUSIONS Our finding provides solid evidence for the gut microbiota involved in ASD through the brain-gut axis. In addition, the probiotics C. butyricum hold promise to improve gut health and ameliorate behavioral abnormalities associated with ASD.
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Affiliation(s)
- Simeng Liu
- Marshall B. J. Medical Research Center, Zhengzhou University, Zhengzhou, 450052, Henan, China.
- Xiangyu Medical CO., LTD, Anyang, 456300, Henan, China.
| | - Huayuan Xi
- Marshall B. J. Medical Research Center, Zhengzhou University, Zhengzhou, 450052, Henan, China
- Department of Gastroenterology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Xia Xue
- Marshall B. J. Medical Research Center, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Xiangdong Sun
- Marshall B. J. Medical Research Center, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Huang Huang
- Department of Gastroenterology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Dongjun Fu
- Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yang Mi
- Marshall B. J. Medical Research Center, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Yongzheng He
- Xiangyu Medical CO., LTD, Anyang, 456300, Henan, China
| | - Pingchang Yang
- Brain Body Institute, McMaster University, Hamilton, ON, Canada
| | - Youcai Tang
- Department of Pediatrics, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
| | - Pengyuan Zheng
- Marshall B. J. Medical Research Center, Zhengzhou University, Zhengzhou, 450052, Henan, China.
- Department of Gastroenterology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
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18
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Xu D, Ren L, Zhang W, Wu S, Yu M, He X, Wei Z. Therapeutic effects and mechanisms of fecal microbiota transplantation on EAE partly through HPA axis-mediated neuroendocrine regulation. Heliyon 2024; 10:e33214. [PMID: 39021924 PMCID: PMC11252752 DOI: 10.1016/j.heliyon.2024.e33214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 06/16/2024] [Accepted: 06/17/2024] [Indexed: 07/20/2024] Open
Abstract
Background The pathogenesis of multiple sclerosis (MS) may be closely related to immune regulation and inflammatory cytokines induced by specific flora. Repairing the intestinal flora may alter the immune response in MS patients, thus opening up novel approaches for the treatment of MS. Objective We aimed to test the therapeutic effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and the characteristics of intestinal microbiota composition changes, explore the potential mechanisms of FMT treatment. Methods EAE animals were treated with FMT, with the therapeutic effects were evaluated by observing neurological scores and measuring serum levels of cortisol, IL-17, and TLR-2. Fecal microbiome 16S rRNA sequencing was used to profile changes in microbiota composition, and adrenalectomy pretreatment was used to test whether FMT effects were dependent on HPA axis function. Results FMT improved neurological function and reduced serum IL-17 to levels that were close to the control group. FMT reestablished intestinal homeostasis by altering the structure of the intestinal flora, increasing the abundance of beneficial flora, and regulating intestinal metabolites. We found that the therapeutic effects of FMT depended partly on the efferent function of the HPA axis; surgical disruption of the HPA axis altered the abundance and diversity of the intestinal flora. Conclusion FMT showed a neuroprotective effect on EAE by increasing the abundance of the beneficial flora, rebuilding intestinal homeostasis, reducing IL-17 and cortisol serum levels, and promoting serum TLR-2; the therapeutic effect of FMT on EAE is partly dependent on the HPA axis.
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Affiliation(s)
- Danhong Xu
- Department of Critical Care Medicine, First School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Linxiang Ren
- Department of Neurology, Neurological Research Institute of Integrated Traditional Chinese and Western Medicine, First School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Wenbin Zhang
- Department of Neurology, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, 518106, China
| | - Shaohua Wu
- Department of Neurology, Neurological Research Institute of Integrated Traditional Chinese and Western Medicine, First School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Minling Yu
- Department of Neurology, Neurological Research Institute of Integrated Traditional Chinese and Western Medicine, First School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Xingxiang He
- Department of Gastroenterology, First School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Zhisheng Wei
- Department of Neurology, Neurological Research Institute of Integrated Traditional Chinese and Western Medicine, First School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
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Li X, Cheng X, Shi Y, Jian C, Zhu W, Bao H, Jiang M, Peng Z, Hu Y, Chen J, Shu X. Mixed probiotics reduce the severity of stress-induced depressive-like behaviors. J Affect Disord 2024; 355:450-458. [PMID: 38537751 DOI: 10.1016/j.jad.2024.03.117] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 03/01/2024] [Accepted: 03/23/2024] [Indexed: 04/09/2024]
Abstract
In recent years, the gut microbiome has gained significant attention in the spheres of research and public health. As a result, studies have increasingly explored the potential of probiotic dietary supplements as treatment interventions for conditions such as anxiety and depression. The present study examined the effect of mixed probiotics (Lacticaseibacillus rhamnosus and Enterococcus faecium) on inflammation, microbiome composition, and depressive-like behaviors in a macaque monkey model. The mixed probiotics effectively reduced the severity of depressive-like behaviors in macaque monkeys. Further, treatment with mixed probiotics gradually increased the abundance of beneficial bacteria in the gut, improving the balance of the gut microbiota. Additionally, macaques treated with the mixed probiotics showed decreased serum levels of inflammatory factors (P < 0.05), an increased rate of L-tryptophan metabolism (P < 0.05), and the restoration of 5-HT and 5-HTP levels (P < 0.05). Correlation analysis confirmed that Lacticaseibacillus and other beneficial bacteria exhibited a negative correlation with inflammation in the body (P < 0.05), and a positive correlation with tryptophan metabolism (P < 0.05). In conclusion, the mixed probiotics effectively restored intestinal homeostasis in macaques and enhanced tryptophan metabolism, ultimately alleviating inflammation and depressive-like behaviors.
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Affiliation(s)
- Xianguo Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Xukai Cheng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yongping Shi
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Chenxing Jian
- College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou 350004, Fujian, China
| | - Wenzhong Zhu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Haijun Bao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Mi Jiang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Zuojie Peng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yuan Hu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Jinhuang Chen
- Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Xiaogang Shu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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20
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Stolfi F, Abreu H, Sinella R, Nembrini S, Centonze S, Landra V, Brasso C, Cappellano G, Rocca P, Chiocchetti A. Omics approaches open new horizons in major depressive disorder: from biomarkers to precision medicine. Front Psychiatry 2024; 15:1422939. [PMID: 38938457 PMCID: PMC11210496 DOI: 10.3389/fpsyt.2024.1422939] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 05/28/2024] [Indexed: 06/29/2024] Open
Abstract
Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can simultaneously contribute to its development, which complicates its diagnosis. According to practical guidelines, antidepressants are the first-line treatment for moderate to severe major depressive episodes. Traditional treatment strategies often follow a one-size-fits-all approach, resulting in suboptimal outcomes for many patients who fail to experience a response or recovery and develop the so-called "therapy-resistant depression". The high biological and clinical inter-variability within patients and the lack of robust biomarkers hinder the finding of specific therapeutic targets, contributing to the high treatment failure rates. In this frame, precision medicine, a paradigm that tailors medical interventions to individual characteristics, would help allocate the most adequate and effective treatment for each patient while minimizing its side effects. In particular, multi-omic studies may unveil the intricate interplays between genetic predispositions and exposure to environmental factors through the study of epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and immunomics. The integration of the flow of multi-omic information into molecular pathways may produce better outcomes than the current psychopharmacological approach, which targets singular molecular factors mainly related to the monoamine systems, disregarding the complex network of our organism. The concept of system biomedicine involves the integration and analysis of enormous datasets generated with different technologies, creating a "patient fingerprint", which defines the underlying biological mechanisms of every patient. This review, centered on precision medicine, explores the integration of multi-omic approaches as clinical tools for prediction in MDD at a single-patient level. It investigates how combining the existing technologies used for diagnostic, stratification, prognostic, and treatment-response biomarkers discovery with artificial intelligence can improve the assessment and treatment of MDD.
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Affiliation(s)
- Fabiola Stolfi
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Hugo Abreu
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Riccardo Sinella
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Sara Nembrini
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Sara Centonze
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Virginia Landra
- Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy
| | - Claudio Brasso
- Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy
| | - Giuseppe Cappellano
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
| | - Paola Rocca
- Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy
| | - Annalisa Chiocchetti
- Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy
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Kono H, Furuya S, Akaike H, Shoda K, Kawaguchi Y, Amemiya H, Kawaida H, Ichikawa D. Rikkunshito increases peripheral incretin-hormone levels in humans and rats. World J Methodol 2024; 14:88518. [PMID: 38577198 PMCID: PMC10989408 DOI: 10.5662/wjm.v14.i1.88518] [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: 09/29/2023] [Revised: 12/27/2023] [Accepted: 02/03/2024] [Indexed: 03/07/2024] Open
Abstract
BACKGROUND It was reported that rikkunshito (TJ-43) improved the cisplatin-induced decreases in the active form of ghrelin in plasma; however, other effects on gastrointestinal hormones have not been investigated. AIM To investigate the effects of TJ-43 on peripheral levels of incretin hormones, including gastric inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1), in humans and rats. METHODS Patients were divided into two groups, namely patients who received TJ-43 immediately following surgery [TJ-43(+) group] and those who received TJ-43 on postoperative day 21 [TJ-43(-) group], and the plasma levels of active GIP and active GLP-1 were assessed. In animal experiments, rats were treated with TJ-43 [rat (r)TJ-43(+) group] or without [rTJ-43(-) group] by gavage for 4 wk, and the plasma active GIP and active GLP-1 levels were measured. The expression of incretin hormones in the gastrointestinal tract and insulin in the pancreas were investigated by immunohistochemistry. Furthermore, the cyclic adenosine monophosphate activities were assessed in pancreatic tissues from rats treated with or without TJ-43 in vivo, and the blood glucose levels and plasma insulin levels were measured in rats treated with or without TJ-43 in oral glucose tolerance tests. RESULTS In humans, the active incretin hormone levels increased, and values were significantly greater in the TJ-43(+) group compared those in the TJ-43(-) group. In rats, the plasma active incretin levels significantly increased in the rTJ-43(+) group compared with those in the rTJ-43(-) group. GIP and GLP-1 expressions were enhanced by TJ-43 treatment. Moreover, plasma insulin levels increased and blood glucose levels were blunted in the rTJ-43(+) group. CONCLUSION The results show that TJ-43 may be beneficial for patients who undergo pancreatic surgery.
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Affiliation(s)
- Hiroshi Kono
- The First Department of Surgery, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan
| | - Shinji Furuya
- The First Department of Surgery, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan
| | - Hidenori Akaike
- The First Department of Surgery, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan
| | - Katsutoshi Shoda
- The First Department of Surgery, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan
| | - Yoshihiko Kawaguchi
- The First Department of Surgery, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan
| | - Hidetake Amemiya
- The First Department of Surgery, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan
| | - Hiromichi Kawaida
- The First Department of Surgery, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan
| | - Daisuke Ichikawa
- The First Department of Surgery, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan
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22
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K I, Y M, A N, D S, G G, R S, D G, V SN, O S, M F, S R, S O, J MG, A M. Cognitive behavioral and mindfulness with daily exercise intervention is associated with changes in intestinal microbial taxa and systemic inflammation in patients with Crohn's disease. Gut Microbes 2024; 16:2337269. [PMID: 38591914 PMCID: PMC11005811 DOI: 10.1080/19490976.2024.2337269] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 03/27/2024] [Indexed: 04/10/2024] Open
Abstract
Crohn's disease (CD) is a chronic inflammatory bowel disease associated with psychological distress and intestinal microbial changes. Here, we examined whether a 3-month period of Cognitive Behavioral and Mindfulness with Daily Exercise (COBMINDEX) intervention, which improves the wellbeing and inflammatory state of CD patients, may also affect their gut microbiome. Gut microbiota, circulating inflammatory markers and hormones were analyzed in 24 CD patients before (T1) and after 3 months of COBMINDEX (T2), and in 25 age- and sex-matched wait-list control patients at the corresponding time-points. Microbiota analysis examined relative taxonomical abundance, alpha and beta diversity, and microbiome correlations with inflammatory and psychological parameters. At T1, CD patients exhibited a characteristic microbial profile mainly constituted of Proteobacteria (17.71%), Firmicutes (65.56%), Actinobacteria (8.46%) and Bacteroidetes (6.24%). Baseline bacterial abundances showed significant correlations with psychological markers of distress and with IFNγ . Following COBMINDEX, no significant changes in alpha and beta diversity were observed between both study groups, though a trend change in beta diversity was noted. Significant changes occurred in the abundance of phyla, families and genera only among the COBMINDEX group. Furthermore, abundance of phyla, families and genera that were altered following COBMNIDEX, significantly correlated with levels of cytokines and psychological parameters. Our results demonstrated that a short-term intervention of COBMINDEX was associated with changes in microbial indices, some of which are linked to psychological manifestations and systemic inflammation in CD patients. Psychological interventions to reduce chronic stress, such as COBMINDEX, appear to be beneficial in mitigating the pathobiology of CD patients, and may thus provide a useful adjunct to pharmacological therapy.
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Affiliation(s)
- Ilan K
- The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
- The National Institute of Biotechnology in the Negev, School of Brain Sciences and Cognition, and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Motro Y
- MAGICAL Group, Department of Health Policy and Management, School of Public Health, Faculty of Health Sciences, Ben‐Gurion University of the Negev, Beer‐Sheva, Israel
| | - Nemirovsky A
- The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
- The National Institute of Biotechnology in the Negev, School of Brain Sciences and Cognition, and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Schwartz D
- Department of Gastroenterology and Hepatology, Soroka Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Goren G
- Spitzer Department of Social Work, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Sergienko R
- Department of Health Policy and Management, School of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Greenberg D
- Department of Health Policy and Management, School of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Slonim-Nevo V
- Spitzer Department of Social Work, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Sarid O
- Spitzer Department of Social Work, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Friger M
- Department of Epidemiology, Biostatistics and Community Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Regev S
- Spitzer Department of Social Work, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Odes S
- Department of Gastroenterology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Moran-Gilad J
- MAGICAL Group, Department of Health Policy and Management, School of Public Health, Faculty of Health Sciences, Ben‐Gurion University of the Negev, Beer‐Sheva, Israel
| | - Monsonego A
- The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
- The National Institute of Biotechnology in the Negev, School of Brain Sciences and Cognition, and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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Sah RK, Nandan A, Kv A, S P, S S, Jose A, Venkidasamy B, Nile SH. Decoding the role of the gut microbiome in gut-brain axis, stress-resilience, or stress-susceptibility: A review. Asian J Psychiatr 2024; 91:103861. [PMID: 38134565 DOI: 10.1016/j.ajp.2023.103861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 12/01/2023] [Accepted: 12/08/2023] [Indexed: 12/24/2023]
Abstract
Increased exposure to stress is associated with stress-related disorders, including depression, anxiety, and neurodegenerative conditions. However, susceptibility to stress is not seen in every individual exposed to stress, and many of them exhibit resilience. Thus, developing resilience to stress could be a big breakthrough in stress-related disorders, with the potential to replace or act as an alternative to the available therapies. In this article, we have focused on the recent advancements in gut microbiome research and the potential role of the gut-brain axis (GBA) in developing resilience or susceptibility to stress. There might be a complex interaction between the autonomic nervous system (ANS), immune system, endocrine system, microbial metabolites, and bioactive lipids like short-chain fatty acids (SCFAs), neurotransmitters, and their metabolites that regulates the communication between the gut microbiota and the brain. High fiber intake, prebiotics, probiotics, plant supplements, and fecal microbiome transplant (FMT) could be beneficial against gut dysbiosis-associated brain disorders. These could promote the growth of SCFA-producing bacteria, thereby enhancing the gut barrier and reducing the gut inflammatory response, increase the expression of the claudin-2 protein associated with the gut barrier, and maintain the blood-brain barrier integrity by promoting the expression of tight junction proteins such as claudin-5. Their neuroprotective effects might also be related to enhancing the expression of brain-derived neurotrophic factor (BDNF) and glucagon-like peptide (GLP-1). Further investigations are needed in the field of the gut microbiome for the elucidation of the mechanisms by which gut dysbiosis contributes to the pathophysiology of neuropsychiatric disorders.
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Affiliation(s)
- Ranjay Kumar Sah
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, Kerala, India
| | - Amritasree Nandan
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, Kerala, India
| | - Athira Kv
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, Kerala, India.
| | - Prashant S
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, Kerala, India
| | - Sathianarayanan S
- NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Mangalore, India
| | - Asha Jose
- JSS College of Pharmacy, JSS Academy of Higher Education and research, Ooty 643001, Tamil Nadu, India
| | - Baskar Venkidasamy
- Department of Oral & Maxillofacial Surgery, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600 077, Tamil Nadu, India.
| | - Shivraj Hariram Nile
- Division of Food and Nutritional Biotechnology, National Agri-Food Biotechnology Institute (NABI), Sector-81, Mohali 140306, Punjab, India.
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Nikrad N, Farhangi MA, Fard Tabrizi FP, Vaezi M, Mahmoudpour A, Mesgari-Abbasi M. The effect of calorie-restriction along with thylakoid membranes of spinach on the gut-brain Axis Pathway and oxidative stress biomarkers in obese women with polycystic ovary syndrome: a Randomized, Double-blind, placebo-controlled clinical trial. J Ovarian Res 2023; 16:216. [PMID: 37968684 PMCID: PMC10652637 DOI: 10.1186/s13048-023-01288-x] [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: 03/07/2023] [Accepted: 09/28/2023] [Indexed: 11/17/2023] Open
Abstract
BACKGROUND Women with polycystic ovary syndrome (PCOS) have higher intestinal mucosal permeability, leading to the lipopolysaccharide (LPS) leakage and endotoxemia. This, in turn, leads to oxidative stress (OS) and neuro-inflammation caused by the gut-brain axis, affecting the neurotrophic factors levels such as brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100 B) levels. In this study, it was hypothesized that the thylakoid membranes of spinach supplementation along with a hypocaloric diet may have improved the LPS levels, neurotrophic factors, and OS in PCOS patients. METHODS In this double-blind, randomized, placebo-controlled, and clinical trial, 48 women with obesity and diagnosed with PCOS based on Rotterdam criteria were randomly assigned to thylakoid (N = 21) and placebo groups (N = 23). A personalized hypocaloric diet with 500 calories less than the total energy expenditure was prescribed to all patients. The participants were daily supplemented with either a 5 g/day thylakoid-rich spinach extract or a placebo (5 g cornstarch) for 12 weeks along with a prescribed low-calorie diet. Anthropometric measurements and biochemical parameters were assessed at baseline and after the 12-week intervention. RESULTS A statistically significant decrease in the LPS levels (P < 0.001) and an increase in the BDNF levels (P < 0.001) were recorded for the participants receiving the oral thylakoid supplements and a low-calorie diet. Furthermore, significant decreases were observed in fasting blood glucose, insulin, homeostatic model of assessment for insulin resistance, free testosterone index, and follicle-stimulating hormone / luteinizing hormone ratio in both groups (P < 0.05). No significant differences were detected between the two groups regarding the changes in malondialdehyde, catalase, total antioxidant capacity, and S100B levels (P > 0.05). CONCLUSIONS In sum, the thylakoid membranes of spinach supplemented with a hypocaloric diet reduced the LPS levels, increased the BDNF levels, and improved the glycemic profile and sex-hormone levels; however, they had no effects on the OS markers levels after 12 weeks of intervention.
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Affiliation(s)
- Negin Nikrad
- Department of Community Nutrition, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahdieh Abbasalizad Farhangi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Attar Neyshabouri, Daneshgah Blv, Tabriz, Iran.
| | | | - Maryam Vaezi
- Fellowship Gynecology-Oncology, Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Obstetrics and Gynecology, Alzahra Teaching Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ata Mahmoudpour
- Department of Anesthesiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehran Mesgari-Abbasi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Attar Neyshabouri, Daneshgah Blv, Tabriz, Iran
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Nie D, Li C, Zhang Y. PitNETs and the gut microbiota: potential connections, future directions. Front Endocrinol (Lausanne) 2023; 14:1255911. [PMID: 38027221 PMCID: PMC10657991 DOI: 10.3389/fendo.2023.1255911] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 10/20/2023] [Indexed: 12/01/2023] Open
Abstract
The role of the gut microbiome has been widely discussed in numerous works of literature. The biggest concern is the association of the gut microbiome with the central nervous system through the microbiome-brain-gut axis in the past ten years. As more and more research has been done on the relationship between the disease of the central nervous system and gut microbes. This fact is being revealed that gut microbes seem to play an important role from the onset and progression of the disease to clinical symptoms, and new treatments. As a special tumor of the central nervous system, pituitary neuroendocrine tumors (PitNETs)are closely related to metabolism, endocrinology, and immunity. These factors are the vectors through which intestinal microbes interact with the central nervous system. However, little is known about the effects of gut microbes on the PitNET. In this review, the relationship of gut microbiota in PitNETs is introduced, the potential effects of the gut-brain axis in this relationship are analyzed, and future research directions are presented.
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Affiliation(s)
| | | | - Yazhuo Zhang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
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26
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Hao W, Gan H, Wang L, Huang J, Chen J. Polyphenols in edible herbal medicine: targeting gut-brain interactions in depression-associated neuroinflammation. Crit Rev Food Sci Nutr 2023; 63:12207-12223. [PMID: 35838146 DOI: 10.1080/10408398.2022.2099808] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Supplementing with edible herbal medicine is an important strategy because of its role in nutrition. Many polyphenols, which are universal components in edible herbal medicines, have low bioavailability. Therefore, gut microbiota is a key determinant of polyphenol bioactivity. Polyphenols can alter the abundance of flora associated with neuroinflammation by reversing intestinal microbiota dysbiosis. Intestinal flora-mediated chemical modification of polyphenols can result in their conversion into active secondary metabolites. The current review summarizes the main edible medicines used in anti-depression and details the interactions between polyphenols and gut microbiota; in addition, it provides insights into the mechanisms underlying the possible suppression of neuroinflammation associated with depression, by polyphenols in edible herbal medicine. A better understanding of polyphenols with bioactivities that are crucial in edible herbal medicine may facilitate their use in the prevention and treatment of neuroinflammation associated with depression.
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Affiliation(s)
- Wenzhi Hao
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Hua Gan
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Lu Wang
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Junqing Huang
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Jiaxu Chen
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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27
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Wolniczak E, Meyer F, Albrecht A. [The abdominal brain: neuroanatomic perspectives for the abdominal surgeon]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1037-1045. [PMID: 37142237 DOI: 10.1055/a-2013-7633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
The "abdominal brain" does not only consist of a separate enteric nervous system but also of bidirectional connections to the autonomous nerve system with parasympathicus und sympathicus as well as brain and spinal cord. Novel studies have shown that these connections can quickly transfer information on the ingested nutrients to the brain to conduct the feeling of hunger and more complex behaviour, such as "reward-related learning". However, even emotional experience, in particular, stress, has a strong impact onto the gastrointestinal system. The immune system, motility and barrier function of the gastrointestinal tract are modulated by the intestinal microbiota. Local bacteria may directly influence neuronal communication by released metabolic products and neuropeptides as well as may control inflammatory factors. Intensive research over the last 10 years was able to provide evidence that intestinal microbiota may affect emotional and cognitive aspects of our behaviour and, thus, it might be in the focus of numerous neuropsychiatric diseases, such as depressions and anxiety disorders.The presented review is to provide a short summary of the I): anatomic basics of the so-called gut-brain axis and II): modi of the bidirectional regulation. Through indirect connections to the limbic system, gut-brain axis can substantially influence stress and anxiety but also the pain processing. In addition, the role of microbiota is outlined and future paths are shown, e.g., how the (microbiota-)gut-brain axis may alter emotional experience, pain processing and intestinal function. Such associations are relevant for further development of visceral medicine, and, thus, also for the abdominal surgeon to derive future treatment concepts with interdisciplinary orientation.
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Affiliation(s)
- Erik Wolniczak
- Institut für Anatomie, Otto-von-Guericke-Universität zu Magdeburg, Magdeburg, Deutschland
| | - Frank Meyer
- Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie, Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Deutschland
| | - Anne Albrecht
- Institut für Anatomie, Otto-von-Guericke-Universität zu Magdeburg, Magdeburg, Deutschland
- Center for Behavioral Brain Science (CBBS), Magdeburg, Germany
- Center for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (C-I-R-C), Jena-Magdeburg-Halle, Germany
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Homer B, Judd J, Mohammadi Dehcheshmeh M, Ebrahimie E, Trott DJ. Gut Microbiota and Behavioural Issues in Production, Performance, and Companion Animals: A Systematic Review. Animals (Basel) 2023; 13:ani13091458. [PMID: 37174495 PMCID: PMC10177538 DOI: 10.3390/ani13091458] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 04/12/2023] [Accepted: 04/17/2023] [Indexed: 05/15/2023] Open
Abstract
The literature has identified poor nutrition as the leading factor in the manifestation of many behavioural issues in animals, including aggression, hyperalertness, and stereotypies. Literature focused on all species of interest consistently reported that although there were no significant differences in the richness of specific bacterial taxa in the microbiota of individual subjects with abnormal behaviour (termed alpha diversity), there was variability in species diversity between these subjects compared to controls (termed beta diversity). As seen in humans with mental disorders, animals exhibiting abnormal behaviour often have an enrichment of pro-inflammatory and lactic acid-producing bacteria and a reduction in butyrate-producing bacteria. It is evident from the literature that an association exists between gut microbiota diversity (and by extension, the concurrent production of microbial metabolites) and abnormal behavioural phenotypes across various species, including pigs, dogs, and horses. Similar microbiota population changes are also evident in human mental health patients. However, there are insufficient data to identify this association as a cause or effect. This review provides testable hypotheses for future research to establish causal relationships between gut microbiota and behavioural issues in animals, offering promising potential for the development of novel therapeutic and/or preventative interventions aimed at restoring a healthy gut-brain-immune axis to mitigate behavioural issues and, in turn, improve health, performance, and production in animals.
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Affiliation(s)
- Bonnie Homer
- School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, SA 5371, Australia
| | - Jackson Judd
- School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, SA 5371, Australia
| | | | - Esmaeil Ebrahimie
- School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, SA 5371, Australia
- Genomics Research Platform, School of Life Sciences, College of Science, Health and Engineering, La Trobe University, Melbourne, VIC 3086, Australia
- School of BioSciences, The University of Melbourne, Melbourne, VIC 3010, Australia
| | - Darren J Trott
- School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, SA 5371, Australia
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Liu H, Zhang X, Shi P, Yuan J, Jia Q, Pi C, Chen T, Xiong L, Chen J, Tang J, Yue R, Liu Z, Shen H, Zuo Y, Wei Y, Zhao L. α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect. J Neuroinflammation 2023; 20:84. [PMID: 36973813 PMCID: PMC10041767 DOI: 10.1186/s12974-023-02768-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 03/17/2023] [Indexed: 03/28/2023] Open
Abstract
Depression is a common mental illness, which is related to monoamine neurotransmitters and the dysfunction of the cholinergic, immune, glutamatergic, and neuroendocrine systems. The hypothesis of monoamine neurotransmitters is one of the commonly recognized pathogenic mechanisms of depression; however, the drugs designed based on this hypothesis have not achieved good clinical results. A recent study demonstrated that depression and inflammation were strongly correlated, and the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR)-mediated cholinergic anti-inflammatory pathway (CAP) in the cholinergic system exhibited good therapeutic effects against depression. Therefore, anti-inflammation might be a potential direction for the treatment of depression. Moreover, it is also necessary to further reveal the key role of inflammation and α7 nAChR in the pathogenesis of depression. This review focused on the correlations between inflammation and depression as well-discussed the crucial role of α7 nAChR in the CAP.
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Affiliation(s)
- Huiyang Liu
- grid.410578.f0000 0001 1114 4286Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000 People’s Republic of China
- grid.488387.8Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, 646000 Sichuan People’s Republic of China
- grid.410578.f0000 0001 1114 4286Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
- grid.488387.8Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
| | - Xiaomei Zhang
- grid.469520.c0000 0004 1757 8917Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, Institute of Medicinal Chemistry of Chinese Medicine, Chongqing Academy of Chinese Materia Medica, Chongqing, 400065 People’s Republic of China
| | - Peng Shi
- grid.410578.f0000 0001 1114 4286Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000 People’s Republic of China
- grid.488387.8Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, 646000 Sichuan People’s Republic of China
- grid.410578.f0000 0001 1114 4286Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
- grid.488387.8Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
| | - Jiyuan Yuan
- grid.488387.8Clinical Trial Center, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
| | - Qiang Jia
- grid.488387.8Ethics Committee Office, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan China
| | - Chao Pi
- grid.410578.f0000 0001 1114 4286Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000 People’s Republic of China
| | - Tao Chen
- grid.410578.f0000 0001 1114 4286Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000 People’s Republic of China
- grid.488387.8Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, 646000 Sichuan People’s Republic of China
- grid.410578.f0000 0001 1114 4286Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
- grid.488387.8Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
| | - Linjin Xiong
- grid.410578.f0000 0001 1114 4286Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000 People’s Republic of China
- grid.488387.8Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, 646000 Sichuan People’s Republic of China
- grid.410578.f0000 0001 1114 4286Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
- grid.488387.8Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
| | - Jinglin Chen
- grid.410578.f0000 0001 1114 4286Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000 People’s Republic of China
- grid.488387.8Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, 646000 Sichuan People’s Republic of China
- grid.410578.f0000 0001 1114 4286Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
- grid.488387.8Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
| | - Jia Tang
- grid.410578.f0000 0001 1114 4286Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000 People’s Republic of China
- grid.488387.8Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, 646000 Sichuan People’s Republic of China
- grid.410578.f0000 0001 1114 4286Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
- grid.488387.8Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
| | - Ruxu Yue
- grid.410578.f0000 0001 1114 4286Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000 People’s Republic of China
- grid.488387.8Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, 646000 Sichuan People’s Republic of China
- grid.410578.f0000 0001 1114 4286Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
- grid.488387.8Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
| | - Zerong Liu
- Central Nervous System Drug Key Laboratory of Sichuan Province, Sichuan Credit Pharmaceutical CO., Ltd., Luzhou, 646000 Sichuan China
- grid.190737.b0000 0001 0154 0904Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030 China
| | - Hongping Shen
- grid.488387.8Clinical Trial Center, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
| | - Ying Zuo
- grid.488387.8Department of Comprehensive Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, 646000 Sichuan China
| | - Yumeng Wei
- grid.410578.f0000 0001 1114 4286Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
| | - Ling Zhao
- grid.488387.8Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, 646000 Sichuan People’s Republic of China
- grid.410578.f0000 0001 1114 4286Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
- grid.488387.8Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000 Sichuan People’s Republic of China
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Paramanik V, Kurrey K, Singh P, Tiwari S. Roles of genistein in learning and memory during aging and neurological disorders. Biogerontology 2023; 24:329-346. [PMID: 36828983 DOI: 10.1007/s10522-023-10020-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 01/23/2023] [Indexed: 02/26/2023]
Abstract
Genistein (GEN) is a non-steroidal phytoestrogen that belongs to the isoflavone class. It is abundantly found in soy. Soy and its products are used as food components in many countries including India. The present review is focused to address roles of GEN in brain functions in the context of learning and memory as a function of aging and neurological disorders. Memory decline is one of the most disabling features observed during normal aging and age-associated neurodegenerative disorders namely Alzheimer's disease (AD) and Parkinson's disease (PD), etc. Anatomical, physiological, biochemical and molecular changes in the brain with advancement of age and pathological conditions lead to decline of cognitive functions. GEN is chemically comparable to estradiol and binds to estrogen receptors (ERs). GEN acts through ERs and mimics estrogen action. After binding to ERs, GEN regulates a plethora of brain functions including learning and memory; however detailed study still remains elusive. Due to the neuroprotective, anti-oxidative and anti-inflammatory properties, GEN is used to restore or improve memory functions in different animal models and humans. The present review may be helpful to understand roles of GEN in learning and memory during aging and neurological disorders, its direction of research and therapeutic perspectives.
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Affiliation(s)
- Vijay Paramanik
- Cellular and Molecular Neurobiology & Drug Targeting Laboratory, Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, 484 887, MP, India.
| | - Khuleshwari Kurrey
- Department of Psychiatry and Behavioral Sciences, Neurobiology Division, John Hopkins University, School of Medicine, Baltimore, MD, 21287, USA
| | - Padmanabh Singh
- Cellular and Molecular Neurobiology & Drug Targeting Laboratory, Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, 484 887, MP, India
| | - Sneha Tiwari
- Cellular and Molecular Neurobiology & Drug Targeting Laboratory, Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, 484 887, MP, India
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Fermented Wheat Germ Alleviates Depression-like Behavior in Rats with Chronic and Unpredictable Mild Stress. Foods 2023; 12:foods12050920. [PMID: 36900437 PMCID: PMC10000856 DOI: 10.3390/foods12050920] [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: 01/11/2023] [Revised: 02/09/2023] [Accepted: 02/15/2023] [Indexed: 02/24/2023] Open
Abstract
Depression is a chronic mental illness with devastating effects on a person's physical and mental health. Studies have reported that food fermentation with probiotics can enrich the nutritional values of food and produce functional microorganisms that can alleviate depression and anxiety. Wheat germ is an inexpensive raw material that is rich in bioactive ingredients. For example, gamma-aminobutyric acid (GABA) is reported to have antidepressant effects. Several studies concluded that Lactobacillus plantarum is a GABA-producing bacteria and can alleviate depression. Herein, fermented wheat germs (FWGs) were used to treat stress-induced depression. FWG was prepared by fermenting wheat germs with Lactobacillus plantarum. The chronic unpredictable mild stress (CUMS) model was established in rats, and these rats were treated with FWG for four weeks to evaluate the effects of FWG in relieving depression. In addition, the study also analyzed the potential anti-depressive mechanism of FWG based on behavioral changes, physiological and biochemical index changes, and intestinal flora changes in depressed rats. The results demonstrated that FWG improved depression-like behaviors and increased neurotransmitter levels in the hippocampus of CUMS model rats. In addition, FWG effectively altered the gut microbiota structure and remodeled the gut microbiota in CUMS rats, restored neurotransmitter levels in depressed rats through the brain-gut axis, and restored amino acid metabolic functions. In conclusion, we suggest that FWG has antidepressant effects, and its potential mechanism may act by restoring the disordered brain-gut axis.
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Wang H, Bin Wang, Pan MB, Jiang ST, Wang YC, Zhu Y, Zhang QC, Dong YF. Disorders in the gut and liver are involved in depression contagion between isosexual post-stroke depression mice and the healthy cohabitors. Behav Brain Res 2023; 439:114246. [PMID: 36481213 DOI: 10.1016/j.bbr.2022.114246] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/21/2022] [Accepted: 11/29/2022] [Indexed: 12/12/2022]
Abstract
Despite the accumulated evidence that pair housing could attenuate post-stroke depression (PSD), but less attention has been paid to the healthy cohabitors, and the underlying mechanisms remain unclear. This study aimed to determine whether there is depressive contagion between PSD mice and their healthy cohabitors. PSD was induced by middle cerebral artery occlusion (MCAO) plus restraint stress for four weeks. Three days after MCAO, the mice were restrained two hours per day and isosexually pair-housed for four weeks. The results showed that, compared with the partners pair housed with normal control mice (Ctrl group), the partners pair housed with PSD mice (CH group) displayed depressive-like behaviors, including decreased sucrose preference rate, significantly shorter duration in the center arena and reduced total distance in the open-field test, and extended immobile time in forced swimming test and tail-suspension test without sex differences. Regarding the change in the body weight, only the males showed a significant reduction on days 17 and 24 after treatment. Furthermore, the CH group showed significantly increased corticosterone and decreased oxytocin (OXT) levels in serum, while the mRNA levels of OXT, vasopressin and oxytocin receptor were remarkably upregulated in the hypothalamus of the CH group. However, there was no significant change in the vasopressin receptor V1a. Interestingly, compared with the Ctrl group, there was a significant decrease in butyrate in serum of the CH group. Consistently, they had mild liver dysfunction with increased alanine transaminase, extended hepatic sinus surrounded by enhanced SLC22A9, and significantly increased Iba1-positive macrophages. Moreover, the expression of tight junction protein (Occludin and ZO-1) obviously decreased in the colon with increasing Iba1-positive cells. These results suggest that isosexual pair-housing with PSD mice causes the healthy partners to develop depressive-like behaviors with disturbances in the gut and liver.
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Affiliation(s)
- Hui Wang
- Department of Medical Care, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Bin Wang
- Department of Medical Care, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Mei-Bo Pan
- Department of Medical Care, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Su-Ting Jiang
- Department of Medical Care, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yi-Chen Wang
- Department of Medical Care, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Ying Zhu
- Department of Medical Care, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Qi-Chun Zhang
- Department of Clinical Pharmacy and Toxicity, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yin-Feng Dong
- Department of Medical Care, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Pathology and Pathophysiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
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Vallée A. Association between Social Isolation and Loneliness with Estimated Atherosclerotic Cardiovascular Disease Risk in a UK Biobank Population-Based Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:2869. [PMID: 36833566 PMCID: PMC9956863 DOI: 10.3390/ijerph20042869] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/02/2023] [Accepted: 02/04/2023] [Indexed: 06/18/2023]
Abstract
OBJECTIVE The association of cardiovascular (CV) risk with social isolation and loneliness remains poorly studied. The purpose of this cross-sectional study was to investigate the associations between social isolation and loneliness with estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk. METHODS Among 302,553 volunteers of the UK Biobank population, social isolation and loneliness were assessed with a questionnaire. Associations between social isolation and loneliness with ASCVD risk were estimated using multiple gender regressions. RESULTS Men presented a higher estimated 10-year ASCVD risk (8.63% vs. 2.65%, p < 0.001) and higher proportions of social isolation (9.13% vs. 8.45%, p < 0.001) and loneliness (6.16% vs. 5.57%, p < 0.001) than women. In all covariate-adjusted models, social isolation was associated with an increased ASCVD risk in men (B = 0.21 (0.16; 0.26), p < 0.001) and women (B = 0.12 (0.10; 0.14), p < 0.001). Loneliness was associated with an increased ASCVD risk in men (B = 0.08 (0.03; 0.14), p = 0.001) but not in women (p = 0.217). A significant interaction was observed between social isolation and loneliness with ASCVD risk in men (p = 0.009) and women (p = 0.016). After adjustment for all covariates, both social isolation and loneliness were significantly associated with ASCVD risk in men (B = 0.44 (0.28; 0.61), p < 0.001) and women (B = 0.20 (0.12; 0.29), p < 0.001). CONCLUSION Social isolation was associated with a higher estimated 10-year ASCVD risk in both genders but only loneliness among men. Social isolation and loneliness can be considered potential added risk factors for CV risk. Health policies should address these notions in prevention campaigns, in addition to traditional risk factors.
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Affiliation(s)
- Alexandre Vallée
- Department of Epidemiology-Data-Biostatistics, Delegation of Clinical Research and Innovation (DRCI), Foch Hospital, 92150 Suresnes, France
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Kasarello K, Cudnoch-Jedrzejewska A, Czarzasta K. Communication of gut microbiota and brain via immune and neuroendocrine signaling. Front Microbiol 2023; 14:1118529. [PMID: 36760508 PMCID: PMC9907780 DOI: 10.3389/fmicb.2023.1118529] [Citation(s) in RCA: 77] [Impact Index Per Article: 38.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 01/12/2023] [Indexed: 01/27/2023] Open
Abstract
The gastrointestinal tract of the human is inhabited by about 5 × 1013 bacteria (of about 1,000 species) as well as archaea, fungi, and viruses. Gut microbiota is known to influence the host organism, but the host may also affect the functioning of the microbiota. This bidirectional cooperation occurs in three main inter-organ signaling: immune, neural, and endocrine. Immune communication relies mostly on the cytokines released by the immune cells into circulation. Also, pathogen-associated or damage-associated molecular patterns (PAMPs or DAMPs) may enter circulation and affect the functioning of the internal organs and gut microbiota. Neural communication relies mostly on the direct anatomical connections made by the vagus nerve, or indirect connections via the enteric nervous system. The third pathway, endocrine communication, is the broadest one and includes the hypothalamic-pituitary-adrenal axis. This review focuses on presenting the latest data on the role of the gut microbiota in inter-organ communication with particular emphasis on the role of neurotransmitters (catecholamines, serotonin, gamma-aminobutyric acid), intestinal peptides (cholecystokinin, peptide YY, and glucagon-like peptide 1), and bacterial metabolites (short-chain fatty acids).
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Kheloui S, Smith A, Ismail N. Combined oral contraceptives and mental health: Are adolescence and the gut-brain axis the missing links? Front Neuroendocrinol 2023; 68:101041. [PMID: 36244525 DOI: 10.1016/j.yfrne.2022.101041] [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: 07/22/2022] [Revised: 09/16/2022] [Accepted: 10/07/2022] [Indexed: 11/05/2022]
Abstract
Combined oral contraceptives (containing synthetic forms of estradiol and progestins) are one of the most commonly used drugs among females. However, their effects on the gut-brain axis have not been investigated to a great extent despite clear evidence that suggest bi-directional interactions between the gut microbiome and endogenous sex hormones. Moreover, oral contraceptives are prescribed during adolescence, a critical period of development during which several brain structures and systems, such as hypothalamic-pituitary-gonadal axis, undergo maturation. Considering that oral contraceptives could impact the developing adolescent brain and that these effects may be mediated by the gut-brain axis, further research investigating the effects of oral contraceptives on the gut-brain axis is imperative. This article briefly reviews evidence from animal and human studies on the effects of combined oral contraceptives on the brain and the gut microbiota particularly during adolescence.
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Affiliation(s)
- Sarah Kheloui
- School of Psychology, Faculty of Social Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Andra Smith
- School of Psychology, Faculty of Social Sciences, University of Ottawa, Ottawa, ON, Canada; uOttawa Brain and Mind Research Institute, Ottawa, ON, Canada
| | - Nafissa Ismail
- School of Psychology, Faculty of Social Sciences, University of Ottawa, Ottawa, ON, Canada; uOttawa Brain and Mind Research Institute, Ottawa, ON, Canada; LIFE Research Institute, Ottawa, ON, Canada.
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Han W, Wang N, Han M, Ban M, Sun T, Xu J. Reviewing the role of gut microbiota in the pathogenesis of depression and exploring new therapeutic options. Front Neurosci 2022; 16:1029495. [PMID: 36570854 PMCID: PMC9772619 DOI: 10.3389/fnins.2022.1029495] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/24/2022] [Indexed: 12/14/2022] Open
Abstract
The relationship between gut microbiota (GM) and mental health is one of the focuses of psychobiology research. In recent years, the microbial-gut-brain axis (MGBA) concept has gradually formed about this bidirectional communication between gut and brain. But how the GM is involved in regulating brain function and how they affect emotional disorders these mechanisms are tenuous and limited to animal research, and often controversial. Therefore, in this review, we attempt to summarize and categorize the latest advances in current research on the mechanisms of GM and depression to provide valid information for future diagnoses and therapy of mental disorders. Finally, we introduced some antidepressant regimens that can help restore gut dysbiosis, including classic antidepressants, Chinese materia medica (CMM), diet, and exogenous strains. These studies provide further insight into GM's role and potential pathways in emotion-related diseases, which holds essential possible clinical outcomes for people with depression or related psychiatric disorders. Future research should focus on clarifying the causal role of GM in disease and developing microbial targets, applying these findings to the prevention and treatment of depression.
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Affiliation(s)
- Wenjie Han
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Pharmacology, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China
| | - Na Wang
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Pharmacology, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China
| | - Mengzhen Han
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Pharmacology, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China
| | - Meng Ban
- Liaoning Microhealth Biotechnology Co., Ltd., Shenyang, China
| | - Tao Sun
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Breast Medicine, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital, Shenyang, China
| | - Junnan Xu
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Pharmacology, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Breast Medicine, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital, Shenyang, China,*Correspondence: Junnan Xu,
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Park JC, Im SH. The gut-immune-brain axis in neurodevelopment and neurological disorders. MICROBIOME RESEARCH REPORTS 2022; 1:23. [PMID: 38046904 PMCID: PMC10688819 DOI: 10.20517/mrr.2022.11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
The gut-brain axis is gaining momentum as an interdisciplinary field addressing how intestinal microbes influence the central nervous system (CNS). Studies using powerful tools, including germ-free, antibiotic-fed, and fecal microbiota transplanted mice, demonstrate how gut microbiota perturbations alter the fate of neurodevelopment. Probiotics are also becoming more recognized as potentially effective therapeutic agents in alleviating symptoms of neurological disorders. While gut microbes may directly communicate with the CNS through their effector molecules, including metabolites, their influence on neuroimmune populations, including newly discovered brain-resident T cells, underscore the host immunity as a potent mediator of the gut-brain axis. In this review, we examine the unique immune populations within the brain, the effects of the gut microbiota on the CNS, and the efficacy of specific probiotic strains to propose the novel concept of the gut-immune-brain axis.
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Affiliation(s)
- John Chulhoon Park
- Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
| | - Sin-Hyeog Im
- Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
- Institute for Convergence Research and Education, Yonsei University, Seoul 03722, Republic of Korea
- ImmunoBiome Inc., POSTECH Biotech Center, Pohang 37673, Republic of Korea
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Zhao D, Zhang J, Zhu Y, He C, Fei W, Yue N, Wang C, Wang L. Study of Antidepressant-Like Effects of Albiflorin and Paeoniflorin Through Metabolomics From the Perspective of Cancer-Related Depression. Front Neurol 2022; 13:828612. [PMID: 35873784 PMCID: PMC9304767 DOI: 10.3389/fneur.2022.828612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Accepted: 06/13/2022] [Indexed: 11/13/2022] Open
Abstract
Mental health has become a new challenge in cancer treatment, with a high prevalence of depression in patients with cancer. Albiflorin (AF) and paeoniflorinn (PF) are isomers extracted from the root of Paeoniae Radix Alba (Baishao in Chinese), belonging to the monoterpene glycosides, and multiple studies have been conducted on their antidepression and anti-cancer effects. However, the effects of AF and PF on cancer-related depression are unclear. Therefore, the current study aims to investigate whether the two isomers are able to exert antidepressant-like effects and understand the underlying mechanisms in a rat model, established by combining irradiation with chronic restraint stress and solitary confinement. Our results demonstrate a significant regulation of AF and PF in the pharmacodynamic index, including the peripheral blood, organ index, behavioral traits, and HPA axis, relative to control rats. In serum and cerebral cortex metabonomics analysis, AF and PF showed a significantly restorative trend in abnormal biomarkers and regulating ether lipid metabolism, alanine, aspartate, glutamate metabolism, tryptophan metabolism, carnitine metabolism, arachidonic acid metabolism, arginine and proline metabolism pathway. Eight potential biomarkers were further screened by means of receiver operating characteristic (ROC) analysis. The data indicate that AF and PF could effectively ameliorate a depression-like state in the model rats, and the mechanism may be associated with the regulation of the neuroendocrine immune system and disrupted metabolic pathways. Further experiments are warranted to comprehensively evaluate the antidepressant effects of AF and PF in cancer-related depression. This study provides a better insight into the action mechanisms of antidepression of TCM, and provides a new perspective for the therapy of cancer-related depression.
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Affiliation(s)
- Danping Zhao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Jianjun Zhang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Jianjun Zhang
| | - Yingli Zhu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Cheng He
- Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Wenting Fei
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Na Yue
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Chenglong Wang
- Ethnic Medicine Characteristic Diagnosis and Treatment Center, Guangxi International Zhuang Medicine Hospital, Nanning, China
| | - Linyuan Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Linyuan Wang
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Amedei A. Editorial of Special Issue "The Interplay of Microbiome and Immune Response in Health and Diseases-2nd Edition". Int J Mol Sci 2022; 23:7169. [PMID: 35806172 PMCID: PMC9266988 DOI: 10.3390/ijms23137169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 06/26/2022] [Indexed: 02/04/2023] Open
Abstract
The microbiota refers to the great number of microorganisms (including bacteria, fungi, viruses and parasites) that live on and in humans and has sparked a surge of recent interest [...].
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Affiliation(s)
- Amedeo Amedei
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy;
- SOD of Interdisciplinary Internal Medicine, Azienda Ospedaliera Universitaria Careggi (AOUC), 50139 Florence, Italy
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40
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Dandekar MP, Palepu MSK, Satti S, Jaiswal Y, Singh AA, Dash SP, Gajula SNR, Sonti R. Multi-strain Probiotic Formulation Reverses Maternal Separation and Chronic Unpredictable Mild Stress-Generated Anxiety- and Depression-like Phenotypes by Modulating Gut Microbiome-Brain Activity in Rats. ACS Chem Neurosci 2022; 13:1948-1965. [PMID: 35735411 DOI: 10.1021/acschemneuro.2c00143] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Depression is a debilitating mental disorder that affects >322 million people worldwide. Despite the availability of several antidepressant agents, many patients remain treatment refractory. A growing literature study has indicated the role of gut microbiota in neuropsychiatric disorders. Herein, we examined the psychobiotic-like activity of multi-strain probiotic formulation in maternal separation (MS) and chronic unpredictable mild stress (CUMS) models of anxiety- and depression-like phenotypes in Sprague-Dawley rats. Early- and late-life stress was employed in both male and female rats by exposing them to MS and CUMS. The multi-strain probiotic formulation (Cognisol) containing Bacillus coagulans Unique IS-2, Lactobacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58, Bifidobacterium lactis UBBLa-70, Bifidobacterium breve UBBr-01, and Bifidobacterium infantis UBBI-01 at a total strength of 10 billion cfu along with l-glutamine was administered for 6 weeks via drinking water. Neurobehavioral assessment was done using the forced swim test (FST), sucrose preference test (SPT), elevated plus maze (EPM), and open field test (OFT). Animals were sacrificed after behavioral assessment, and blood, brain, and intestine samples were collected to analyze the levels of cytokines, metabolites, and neurotransmitters and histology. Animals exposed to stress showed increased passivity, consumed less sucrose solution, and minimally explored the open arms in the FST, SPT, and EPM, respectively. Administration of multi-strain probiotics along with l-glutamine for 6 weeks ameliorated the behavioral abnormalities. The locomotor activity of animals in the OFT and their body weight remained unchanged across the groups. Cognisol treatment reversed the decreased BDNF and serotonin levels and increased CRP, TNF-α, and dopamine levels in the hippocampus and/or frontal cortex. Administration of Cognisol also restored the plasma levels of l-tryptophan, l-kynurenine, kynurenic-acid, and 3-hydroxyanthranilic acid; the Firmicutes-to-Bacteroides ratio; the levels of acetate, propionate, and butyrate in fecal samples; the villi/crypt ratio; and the goblet cell count, which manifested in the restoration of intestinal functions. We suggest that the multi-strain probiotic and glutamine formulation (Cognisol) ameliorated the MS + UCMS-generated anxiety- and depression-like phenotypes by reshaping the gut microbiome-brain activity in both sexes.
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Affiliation(s)
- Manoj P Dandekar
- Department of Biological Sciences, Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India
| | - Mani Surya Kumar Palepu
- Department of Biological Sciences, Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India
| | - Srilakshmi Satti
- Department of Biological Sciences, Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India
| | - Yash Jaiswal
- Department of Biological Sciences, Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India
| | - Aditya A Singh
- Department of Biological Sciences, Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India
| | - Surya Prakash Dash
- Department of Biological Sciences, Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India
| | - Siva Nageswara Rao Gajula
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India
| | - Rajesh Sonti
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India
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Vetrani C, Di Nisio A, Paschou SA, Barrea L, Muscogiuri G, Graziadio C, Savastano S, Colao A, on behalf of the Obesity Programs of Nutrition, Education, Research and Assessment (OPERA) Group. From Gut Microbiota through Low-Grade Inflammation to Obesity: Key Players and Potential Targets. Nutrients 2022; 14:2103. [PMID: 35631244 PMCID: PMC9145366 DOI: 10.3390/nu14102103] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 05/13/2022] [Accepted: 05/16/2022] [Indexed: 02/01/2023] Open
Abstract
During the last decades, the gut microbiota has gained much interest in relation to human health. Mounting evidence has shown a strict association between gut microbiota and obesity and its related diseases. Inflammation has been appointed as the driving force behind this association. Therefore, a better understanding of the mechanisms by which gut microbiota might influence inflammation in the host could pave for the identification of effective strategies to reduce inflammation-related diseases, such as obesity and obesity-related diseases. For this purpose, we carried out an extensive literature search for studies published in the English language during the last 10 years. Most relevant studies were used to provide a comprehensive view of all aspects related to the association of gut microbiota and low-grade inflammation with obesity. Accordingly, this narrative review reports the evidence on the key players supporting the role of gut microbiota in the modulation of inflammation in relation to obesity and its complications. Moreover, therapeutic approaches to reduce microbiota-related inflammation are discussed to provide potential targets for future research.
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Affiliation(s)
- Claudia Vetrani
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University of Naples “Federico II”, 80131 Naples, Italy; (C.V.); (C.G.); (S.S.); (A.C.)
| | - Andrea Di Nisio
- Department of Medicine, Operative Unit of Andrology and Medicine of Human Reproduction, University of Padova, 35128 Padova, Italy;
| | - Stavroula A. Paschou
- Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Luigi Barrea
- Dipartimento di Scienze Umanistiche, Università Telematica Pegaso, 80143 Napoli, Italy;
- Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O), University of Naples “Federico II”, 80131 Naples, Italy
| | - Giovanna Muscogiuri
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University of Naples “Federico II”, 80131 Naples, Italy; (C.V.); (C.G.); (S.S.); (A.C.)
- Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O), University of Naples “Federico II”, 80131 Naples, Italy
- UNESCO Chair “Education for Health and Sustainable Development”, University of Naples “Federico II”, 80131 Naples, Italy
| | - Chiara Graziadio
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University of Naples “Federico II”, 80131 Naples, Italy; (C.V.); (C.G.); (S.S.); (A.C.)
- Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O), University of Naples “Federico II”, 80131 Naples, Italy
| | - Silvia Savastano
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University of Naples “Federico II”, 80131 Naples, Italy; (C.V.); (C.G.); (S.S.); (A.C.)
- Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O), University of Naples “Federico II”, 80131 Naples, Italy
| | - Annamaria Colao
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University of Naples “Federico II”, 80131 Naples, Italy; (C.V.); (C.G.); (S.S.); (A.C.)
- Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O), University of Naples “Federico II”, 80131 Naples, Italy
- UNESCO Chair “Education for Health and Sustainable Development”, University of Naples “Federico II”, 80131 Naples, Italy
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Firrman J, Liu L, Mahalak K, Tanes C, Bittinger K, Tu V, Bobokalonov J, Mattei L, Zhang H, Van den Abbeele P. The impact of environmental pH on the gut microbiota community structure and short chain fatty acid production. FEMS Microbiol Ecol 2022; 98:6564177. [PMID: 35383853 DOI: 10.1093/femsec/fiac038] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 02/17/2022] [Accepted: 04/01/2022] [Indexed: 11/12/2022] Open
Abstract
Environmental pH is a critical parameter for maintenance of the gut microbiota. Here, the impact of pH on the gut microbiota luminal and mucosal community structure and short chain fatty acid (SCFA) production was evaluated in vitro, and data compiled to reveal a donor-independent response to an increase or decrease in environmental pH. The results found that raising environmental pH significantly increased luminal community richness and decreased mucosal community evenness. This corresponded with an increased abundance of Ruminococcaceae Ruminococcus, and Erysipelotrichaceae Erysipelatoclostridium, and a decreased abundance of Coriobacteriaceae Collinsella, and Enterobacteriaceae Shigella for both the luminal and mucosal communities. Total SCFA levels were significantly higher, primarily due to an increase in acetic and 2-methylbutanoic acids. Lowering pH decreased luminal community evenness and decreased mucosal community evenness and richness. This corresponded with an increased abundance of Lachnospiraceae Enterocloster, Veillonellaceae Megasphaera, Veillonellaceae Sporomusa, Erysipelotrichaceae Eubacterium, and Alcaligenaceae Sutterella, and decreased abundance of Odoribacteraceae Butyricimonas, Fusobacteriaceae Fusobacterium, Veillonellaceae Phascolarctobacterium, and multiple Enterobacteriaceae species for both the luminal and mucosal communities. Total SCFA levels were significantly lower, with an observed drop in acetic and propionic acids, and increased butyric and valeric acids. Taken together, these results indicate that alterations to environmental pH can modulate the gut microbiota community structure and function, and some changes may occur in a donor-independent manner.
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Affiliation(s)
- Jenni Firrman
- Dairy and Functional Foods Research Unit, Eastern Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Wyndmoor, PA, United States of America
| | - LinShu Liu
- Dairy and Functional Foods Research Unit, Eastern Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Wyndmoor, PA, United States of America
| | - Karley Mahalak
- Dairy and Functional Foods Research Unit, Eastern Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Wyndmoor, PA, United States of America
| | - Ceylan Tanes
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America
| | - Kyle Bittinger
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America
| | - Vincent Tu
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America
| | - Jamshed Bobokalonov
- Dairy and Functional Foods Research Unit, Eastern Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Wyndmoor, PA, United States of America
| | - Lisa Mattei
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America
| | - Huanjia Zhang
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America
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Tayab MA, Islam MN, Chowdhury KAA, Tasnim FM. Targeting neuroinflammation by polyphenols: A promising therapeutic approach against inflammation-associated depression. Pharmacotherapy 2022; 147:112668. [DOI: 10.1016/j.biopha.2022.112668] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 01/12/2022] [Accepted: 01/24/2022] [Indexed: 02/06/2023]
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Seewoo BJ, Chua EG, Arena-Foster Y, Hennessy LA, Gorecki AM, Anderton R, Rodger J. Changes in the rodent gut microbiome following chronic restraint stress and low-intensity rTMS. Neurobiol Stress 2022; 17:100430. [PMID: 35146078 PMCID: PMC8819474 DOI: 10.1016/j.ynstr.2022.100430] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 01/11/2022] [Accepted: 01/17/2022] [Indexed: 12/19/2022] Open
Abstract
Gut microbiome composition is associated with mood-relating behaviours, including those reflecting depression-like phenotypes. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, is an effective treatment for depression, but its effects on the gut microbiome remain largely unknown. This study assessed microbial changes from rat faecal samples longitudinally following chronic restraint stress (CRS) and 10 Hz low-intensity rTMS treatment. CRS increased abundance within the Proteobacteria (Deltaproteobacteria, Desulfovibrionales) and Firmicutes (Anaerostipes, Frinsingococcus), with decreases in Firmicutes family (Acidaminococcaceae) and genera (Roseburia, Phascolarctobacterium and Fusicatenibacter) persisting for up to 4 weeks post CRS. The decrease in Firmicutes was not observed in the handling control and LI-rTMS groups, suggesting that handling alone may have sustained changes in gut microbiome associated with CRS. Nonetheless, LI-rTMS was specifically associated with an increase in Roseburia genus that developed 2 weeks after treatment, and the abundance of both Roseburia and Fusicatenibacter genera was significantly correlated with rTMS behavioural and MRI outcomes. In addition, LI-rTMS treated rats had a reduction in apoptosis pathways and several indicators of reduced inflammatory processes. These findings provide evidence that the brain can influence the gut microbiome in a "top-down" manner, presumably via stimulation of descending pathways, and/or indirectly via behavioural modification.
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Affiliation(s)
- Bhedita J. Seewoo
- School of Biological Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia
- Perron Institute for Neurological and Translational Science, 8 Verdun St, Nedlands, WA, 6009, Australia
- Centre for Microscopy, Characterisation & Analysis, Research Infrastructure Centres, The University of Western Australia, 6 Verdun St, Nedlands, WA, 6009, Australia
| | - Eng Guan Chua
- The Marshall Centre for Infectious Diseases Research and Training, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia
| | - Yasmin Arena-Foster
- School of Biological Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia
- Perron Institute for Neurological and Translational Science, 8 Verdun St, Nedlands, WA, 6009, Australia
| | - Lauren A. Hennessy
- School of Biological Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia
- Perron Institute for Neurological and Translational Science, 8 Verdun St, Nedlands, WA, 6009, Australia
| | - Anastazja M. Gorecki
- School of Biological Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia
- Perron Institute for Neurological and Translational Science, 8 Verdun St, Nedlands, WA, 6009, Australia
| | - Ryan Anderton
- Institute for Health Research and School of Health Sciences, University of Notre Dame Australia, 33 Phillimore Street, Fremantle, WA, Australia
| | - Jennifer Rodger
- School of Biological Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia
- Perron Institute for Neurological and Translational Science, 8 Verdun St, Nedlands, WA, 6009, Australia
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Lan H, Liu WH, Zheng H, Feng H, Zhao W, Hung WL, Li H. Bifidobacterium lactis BL-99 protects mice with osteoporosis caused by colitis via gut inflammation and gut microbiota regulation. Food Funct 2022; 13:1482-1494. [PMID: 35060590 DOI: 10.1039/d1fo02218k] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Patients diagnosed with inflammatory bowel disease or related conditions also frequently suffer from osteoporosis as a consequence of changes in the intestinal microenvironment and consequent dysbiosis. We hypothesized that anti-inflammatory probiotic treatment would be sufficient to alleviate intestinal inflammation and thereby prevent the development of osteoporosis. To that end, the ability of Bifidobacterium lactis BL-99 administration to protect against bone loss in an experimental model of dextran sodium sulfate-induced ulcerative colitis (UC) was analyzed, and the underlying molecular mechanisms were interrogated in detail. The results of these analyses revealed that BL-99 administration suppressed colitis-associated weight loss (P < 0.05), disease activity index scores, and the production of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17) (P < 0.05). Colon tissue pathological sections similarly revealed BL-99-mediated reductions in tissue injury severity. Micro-computed tomography (Micro-CT) analyses further exhibited significant improvements in percent bone volume (BV/TV) as well as trabecular number and thickness in BL-99-treated animals (P < 0.05). Such probiotic supplementation also resulted in pronounced changes in the composition of the gut microbiota. Moreover, BL-99 intervention markedly increased the expression of intestinal barrier-related proteins (Claudin-1, MUC2, ZO-1, and Occludin). Together, these results suggest that BL-99 can be utilized as a beneficial probiotic preparation to prevent the incidence of osteoporosis in UC patients owing to its ability to shape the intestinal microflora and to suppress inflammatory cytokine production.
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Affiliation(s)
- Hui Lan
- School of Public Health, Xiamen University, Xiamen 361102, Fujian, China.
| | - Wei-Hsien Liu
- Inner Mongolia Yili Industrial Group Co., Ltd., Hohhot 010110, Inner Mongolia, China.
| | - Hanying Zheng
- School of Public Health, Xiamen University, Xiamen 361102, Fujian, China.
| | - Haotian Feng
- Inner Mongolia Yili Industrial Group Co., Ltd., Hohhot 010110, Inner Mongolia, China.
| | - Wen Zhao
- Inner Mongolia Yili Industrial Group Co., Ltd., Hohhot 010110, Inner Mongolia, China.
| | - Wei-Lian Hung
- Inner Mongolia Yili Industrial Group Co., Ltd., Hohhot 010110, Inner Mongolia, China.
| | - Hongwei Li
- School of Public Health, Xiamen University, Xiamen 361102, Fujian, China.
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Nemirovsky A, Ilan K, Lerner L, Cohen-Lavi L, Schwartz D, Goren G, Sergienko R, Greenberg D, Slonim-Nevo V, Sarid O, Friger M, Regev S, Odes S, Hertz T, Monsonego A, on behalf of the Israeli IBD Research Nucleus (IIRN). Brain-immune axis regulation is responsive to cognitive behavioral therapy and mindfulness intervention: Observations from a randomized controlled trial in patients with Crohn's disease. Brain Behav Immun Health 2022; 19:100407. [PMID: 35024638 PMCID: PMC8728050 DOI: 10.1016/j.bbih.2021.100407] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 12/11/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND AND AIMS Crohn's disease (CD) is a chronic inflammatory bowel disease associated with psychological stress that is regulated primarily by the hypothalamus-pituitary-adrenal (HPA) axis. Here, we determined whether the psychological characteristics of CD patients associate with their inflammatory state, and whether a 3-month trial of cognitive-behavioral and mindfulness-based stress reduction (COBMINDEX) impacts their inflammatory process. METHODS Circulating inflammatory markers and a wide range of psychological parameters related to stress and well-being were measured in CD patients before and after COBMINDEX. Inflammatory markers in CD patients were also compared to age- and sex-matched healthy controls (HCs). RESULTS CD patients exhibited increased peripheral low-grade inflammation compared with HCs, demonstrated by interconnected inflammatory modules represented by IL-6, TNFα, IL-17, MCP-1 and IL-18. Notably, higher IL-18 levels correlated with higher score of stress and a lower score of wellbeing in CD patients. COBMINDEX was accompanied by changes in inflammatory markers that coincided with changes in cortisol: changes in serum levels of cortisol correlated positively with those of IL-10 and IFNα and negatively with those of MCP-1. Furthermore, inflammatory markers of CD patients at baseline predicted COBMINDEX efficacy, as higher levels of distinct cytokines and cortisol at baseline, correlated negatively with changes in disease activity (by Harvey-Bradshaw Index) and psychological distress (global severity index measure) following COBMINDEX. CONCLUSION CD patients have a characteristic immunological profile that correlates with psychological stress, and disease severity. We suggest that COBMINDEX induces stress resilience in CD patients, which impacts their well-being, and their disease-associated inflammatory process.
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Affiliation(s)
- Anna Nemirovsky
- The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
- The National Institute of Biotechnology in the Negev, Zlotowski Neuroscience Center, and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel
| | - Karny Ilan
- The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Livnat Lerner
- The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Liel Cohen-Lavi
- The National Institute of Biotechnology in the Negev, Zlotowski Neuroscience Center, and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel
- Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel
| | - Doron Schwartz
- Dept. of Gastroenterology and Hepatology, Soroka Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Ganit Goren
- Spitzer Department of Social Work Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Ruslan Sergienko
- Department of Public Health, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Dan Greenberg
- Department of Health Systems Management, School of Public Health, Guilford Glazer Faculty of Business and Management, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Vered Slonim-Nevo
- Spitzer Department of Social Work Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Orly Sarid
- Spitzer Department of Social Work Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Michael Friger
- Department of Public Health, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Shirley Regev
- Spitzer Department of Social Work Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Shmuel Odes
- Dept. of Gastroenterology and Hepatology, Soroka Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
| | - Tomer Hertz
- The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
- The National Institute of Biotechnology in the Negev, Zlotowski Neuroscience Center, and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel
- Vaccine and Infectious Disease Division, Fred Hutch Cancer Research Center, Seattle, WA, USA
| | - Alon Monsonego
- The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
- The National Institute of Biotechnology in the Negev, Zlotowski Neuroscience Center, and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel
| | - on behalf of the Israeli IBD Research Nucleus (IIRN)
- The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
- The National Institute of Biotechnology in the Negev, Zlotowski Neuroscience Center, and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel
- Spitzer Department of Social Work Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
- Department of Public Health, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
- Department of Health Systems Management, School of Public Health, Guilford Glazer Faculty of Business and Management, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
- Dept. of Gastroenterology and Hepatology, Soroka Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel
- Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel
- Vaccine and Infectious Disease Division, Fred Hutch Cancer Research Center, Seattle, WA, USA
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Xian J, Wang L, Sun M, Wang X, Zang XM, Yu HJ, Zhang X, Cheng B, Tan QW. Acupuncture for Subthreshold Depression: Study Protocol for a Randomized Controlled Trial. Front Psychiatry 2022; 12:772360. [PMID: 35153851 PMCID: PMC8828975 DOI: 10.3389/fpsyt.2021.772360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 12/13/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Subthreshold depression refers to a state of mental sub-health that has depressive symptoms but does not meet the diagnostic criteria for major depressive disorder. It is a strong risk factor for depression and is related to an increase in suicide and mortality. Studies suggest that acupuncture may be effective in the treatment of subthreshold depression, but no evidence has proven that the efficacy of acupuncture for subthreshold depression is a specific therapeutic effect or a placebo effect. METHODS This will be a prospective, randomized, controlled, and double-blind study of 64 patients with subthreshold depression. They will be randomly assigned as verum or minimal acupuncture group members. Patients in the verum acupuncture group will receive acupuncture at the acupoints, and those in the minimal acupuncture group will receive minimal acupuncture at non-acupoints. The interventions will be delivered over an 8-week period. The primary outcome measure will be the Hamilton Depression Scale-17 (HAMD-17). The secondary outcome measures will be the 9-item Patient Health Questionnaire (PHQ-9), 7-item Generalized Anxiety Disorder (GAD-7), and SF-12v2 Health Survey. The assessments will occur at baseline, 4 weeks, 8 weeks, and during a follow-up period. DISCUSSION The protocol uses a randomized controlled trial to examine the effectiveness of acupuncture for subthreshold depression and to further study the mechanisms of its effect.
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Affiliation(s)
- Jin Xian
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ling Wang
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Mi Sun
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xue Wang
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiao-Ming Zang
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Hui-Juan Yu
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xin Zhang
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Bin Cheng
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Qi-Wen Tan
- Shandong University of Traditional Chinese Medicine, Jinan, China
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Calpe-López C, Martínez-Caballero MA, García-Pardo MP, Aguilar MA. Resilience to the effects of social stress on vulnerability to developing drug addiction. World J Psychiatry 2022; 12:24-58. [PMID: 35111578 PMCID: PMC8783163 DOI: 10.5498/wjp.v12.i1.24] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/01/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
We review the still scarce but growing literature on resilience to the effects of social stress on the rewarding properties of drugs of abuse. We define the concept of resilience and how it is applied to the field of drug addiction research. We also describe the internal and external protective factors associated with resilience, such as individual behavioral traits and social support. We then explain the physiological response to stress and how it is modulated by resilience factors. In the subsequent section, we describe the animal models commonly used in the study of resilience to social stress, and we focus on the effects of chronic social defeat (SD), a kind of stress induced by repeated experience of defeat in an agonistic encounter, on different animal behaviors (depression- and anxiety-like behavior, cognitive impairment and addiction-like symptoms). We then summarize the current knowledge on the neurobiological substrates of resilience derived from studies of resilience to the effects of chronic SD stress on depression- and anxiety-related behaviors in rodents. Finally, we focus on the limited studies carried out to explore resilience to the effects of SD stress on the rewarding properties of drugs of abuse, describing the current state of knowledge and suggesting future research directions.
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Affiliation(s)
| | | | - Maria P García-Pardo
- Faculty of Social and Human Sciences, University of Zaragoza, Teruel 44003, Spain
| | - Maria A Aguilar
- Department of Psychobiology, University of Valencia, Valencia 46010, Spain
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Miaskowski C, Paul SM, Harris CS, Shin J, Oppegaard K, Conley YP, Hammer M, Kober KM, Levine JD. Determination of Cutpoints for Symptom Burden in Oncology Patients Receiving Chemotherapy. J Pain Symptom Manage 2022; 63:42-51. [PMID: 34333099 PMCID: PMC10791137 DOI: 10.1016/j.jpainsymman.2021.07.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/15/2021] [Accepted: 07/21/2021] [Indexed: 11/17/2022]
Abstract
CONTEXT Cutpoints can be used as a threshold for screening symptom(s) that warrant intervention(s) and for monitoring patients' responses to these interventions. OBJECTIVES In a sample of oncology patients undergoing chemotherapy, study purposes were to determine the optimal cutpoints for low, moderate, and high symptom burden and determine if these cutpoints distinguished among the symptom groups in any demographic, clinical, and stress characteristics, as well as QOL outcomes. METHODS Total of 1329 patients completed a modified version of the Memorial Symptom Assessment Scale (38 symptoms). Using the methodology of Serlin and colleagues, cutpoints were created using symptom occurrence rates and cancer-specific quality of life (QOL) scores. Cutpoints were validated using measures of stress and resilience and a generic measure of QOL (i.e., Medical Outcomes Study Short Form 12 (SF-12)). RESULTS Of the 25 possible cutpoints evaluated, the optimal cutpoint, with the largest between category F statistic, was CP8,15 (Low = 0-8, Moderate = 9-15, High = 16-38 symptoms). Percentage of patients in the Low, Moderate, and High cutpoint groups were 25.3%, 36.3%, and 38.4%, respectively. Significant differences were found among the symptom burden groups in global, cancer-specific, and cumulative life stress (i.e., Low < Moderate < High) and resilience and SF-12 (i.e., Low > Moderate > High) scores. CONCLUSION Our findings provide evidence for clinically meaningful cutpoints that can be used to guide symptom assessment and management. These cutpoints may be used to establish alert thresholds for electronic monitoring of symptoms in oncology patients.
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Affiliation(s)
- Christine Miaskowski
- School of Nursing (C.M., S.M.P., C.S.H., J.S., K.O., K.M.K.), University of California, San Francisco, California, USA; School of Medicine (C.M., J.D.L.), University of California, San Francisco, California, USA.
| | - Steven M Paul
- School of Nursing (C.M., S.M.P., C.S.H., J.S., K.O., K.M.K.), University of California, San Francisco, California, USA
| | - Carolyn S Harris
- School of Nursing (C.M., S.M.P., C.S.H., J.S., K.O., K.M.K.), University of California, San Francisco, California, USA
| | - Joosun Shin
- School of Nursing (C.M., S.M.P., C.S.H., J.S., K.O., K.M.K.), University of California, San Francisco, California, USA
| | - Kate Oppegaard
- School of Nursing (C.M., S.M.P., C.S.H., J.S., K.O., K.M.K.), University of California, San Francisco, California, USA
| | - Yvette P Conley
- School of Nursing (Y.P.C.), University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Marilyn Hammer
- Dana Farber Cancer Institute (M.H.), Boston, Massachusetts, USA
| | - Kord M Kober
- School of Nursing (C.M., S.M.P., C.S.H., J.S., K.O., K.M.K.), University of California, San Francisco, California, USA
| | - Jon D Levine
- School of Medicine (C.M., J.D.L.), University of California, San Francisco, California, USA
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Multi-Modal Regulation of Circadian Physiology by Interactive Features of Biological Clocks. BIOLOGY 2021; 11:biology11010021. [PMID: 35053019 PMCID: PMC8772734 DOI: 10.3390/biology11010021] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 12/21/2021] [Accepted: 12/23/2021] [Indexed: 12/26/2022]
Abstract
The circadian clock is a fundamental biological timing mechanism that generates nearly 24 h rhythms of physiology and behaviors, including sleep/wake cycles, hormone secretion, and metabolism. Evolutionarily, the endogenous clock is thought to confer living organisms, including humans, with survival benefits by adapting internal rhythms to the day and night cycles of the local environment. Mirroring the evolutionary fitness bestowed by the circadian clock, daily mismatches between the internal body clock and environmental cycles, such as irregular work (e.g., night shift work) and life schedules (e.g., jet lag, mistimed eating), have been recognized to increase the risk of cardiac, metabolic, and neurological diseases. Moreover, increasing numbers of studies with cellular and animal models have detected the presence of functional circadian oscillators at multiple levels, ranging from individual neurons and fibroblasts to brain and peripheral organs. These oscillators are tightly coupled to timely modulate cellular and bodily responses to physiological and metabolic cues. In this review, we will discuss the roles of central and peripheral clocks in physiology and diseases, highlighting the dynamic regulatory interactions between circadian timing systems and multiple metabolic factors.
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