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Mörkl S, Narrath M, Schlotmann D, Sallmutter MT, Putz J, Lang J, Brandstätter A, Pilz R, Karl Lackner H, Goswami N, Steuber B, Tatzer J, Lackner S, Holasek S, Painold A, Jauk E, Wenninger J, Horvath A, Spicher N, Barth A, Butler MI, Wagner-Skacel J. Multi-species probiotic supplement enhances vagal nerve function - results of a randomized controlled trial in patients with depression and healthy controls. Gut Microbes 2025; 17:2492377. [PMID: 40298641 PMCID: PMC12045568 DOI: 10.1080/19490976.2025.2492377] [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: 10/03/2024] [Revised: 03/04/2025] [Accepted: 04/07/2025] [Indexed: 04/30/2025] Open
Abstract
Major depression (MD) significantly impacts individual well-being and society. The vagus nerve plays a pivotal role in the gut-brain axis, facilitating bidirectional communication between these systems. Recent meta-analyses suggest potential antidepressant effects of probiotics, although their mechanisms remain unclear. This study aimed to assess the impact of a multi-species probiotic (OMNi-BiOTiC® STRESS Repair) on vagus nerve function in 43 MD patients and 43 healthy controls (HC). Participants received either probiotics or placebo twice daily. Serum and stool samples were collected at baseline, 7 days, 28 days, and 3 months. Vagus nerve (VN) function was evaluated using 24-hour electrocardiography (ECG) for heart rate variability (HRV), alongside stool microbiome analysis via 16S rRNA sequencing. After 3 months, MD patients receiving probiotics demonstrated significantly improved morning VN function compared to HC. MD participants who were in the probiotic group showed a significant increase in Christensellales, particularly Akkermansia muciniphila along with improved sleep parameters (use of sleep medication, sleep latency) as measured by the Pittsburgh Sleep Quality Inventory (PSI). This study highlights potential physiological benefits of probiotics in MD, potentially mediated through VN stimulation. Understanding these mechanisms could lead to novel therapeutic approaches for MD management.
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Affiliation(s)
- Sabrina Mörkl
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Martin Narrath
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Daria Schlotmann
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Marie-Therese Sallmutter
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Julia Putz
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Julia Lang
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Andreas Brandstätter
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Rene Pilz
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Helmut Karl Lackner
- Division of Physiology und Pathophysiology, Medical University of Graz, Graz, Austria
| | - Nandu Goswami
- Division of Physiology und Pathophysiology, Medical University of Graz, Graz, Austria
- Gravitational Physiology and Medicine Research Unit, Division of Physiology und Pathophysiology, Medical University of Graz, Graz, Austria
- Center for Space and Aviation Health, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Bianca Steuber
- Division of Physiology und Pathophysiology, Medical University of Graz, Graz, Austria
- Gravitational Physiology and Medicine Research Unit, Division of Physiology und Pathophysiology, Medical University of Graz, Graz, Austria
| | - Jasmin Tatzer
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Sonja Lackner
- Division of Immunology, Medical University of Graz, Graz, Austria
| | - Sandra Holasek
- Division of Immunology, Medical University of Graz, Graz, Austria
| | - Annamaria Painold
- Division of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Emanuel Jauk
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Julian Wenninger
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Angela Horvath
- Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Nicolai Spicher
- Department of Medical Informatics, University Medical Center Göttingen, Göttingen, Germany
| | - Asmus Barth
- Department of Medical Informatics, University Medical Center Göttingen, Göttingen, Germany
| | - Mary I Butler
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Jolana Wagner-Skacel
- Division of Medical Psychology, Psychosomatics and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
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Mehta P, Saha D, Das A, Das BK. Gut microbiota in diabetic-linked polycystic ovarian syndrome: Mechanisms and therapeutic insights. Tissue Cell 2025; 95:102870. [PMID: 40154106 DOI: 10.1016/j.tice.2025.102870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 01/16/2025] [Accepted: 03/15/2025] [Indexed: 04/01/2025]
Abstract
Polycystic ovarian syndrome (PCOS) is a complex multisystem disorder prevalent among women of reproductive age, commonly marked by insulin resistance, hyperinsulinemia, and metabolic disruptions such as hypertension and dyslipidemia, which elevate risks of cardiovascular disease and hepatic steatosis. Recent advances underscore the gut microbiome's critical role in modulating insulin resistance and metabolic homeostasis in PCOS. This review highlights novel insights into gut dysbiosis-driven inflammation, gut-brain hormonal signaling, and immune modulation as underlying mechanisms connecting PCOS with metabolic dysfunction and diabetes. We comprehensively analyzed studies up to September 2024 on gut microbiota, diabetes, PCOS, and metformin, exploring emerging perspectives on the microbiome's therapeutic potential in managing PCOS. Metformin's dual role in insulin sensitivity improvement and gut microbiome modulation is emphasized, including its indirect effects on weight management. This review also identifies gaps in current research, urging a shift toward precision therapies targeting microbiome-related pathways in PCOS. Further exploration of the gut-brain axis, pathogen-associated molecular patterns, and the need for controlled clinical trials are discussed to enhance therapeutic approaches.
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Affiliation(s)
- Prachi Mehta
- Department of Pharmacology, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Azara, Guwahati, Assam 781017, India
| | - Dipankar Saha
- Department of Pharmacology, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Azara, Guwahati, Assam 781017, India
| | - Abinash Das
- Department of Pharmacology, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Azara, Guwahati, Assam 781017, India
| | - Bhrigu Kumar Das
- Department of Pharmacology, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Azara, Guwahati, Assam 781017, India.
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Horn JA, Delgadillo DR, Mayer EA. Understanding Microbial Mediation of the Brain-Gut Axis. Gastroenterol Clin North Am 2025; 54:367-381. [PMID: 40348493 DOI: 10.1016/j.gtc.2024.12.004] [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] [Indexed: 05/14/2025]
Abstract
Bidirectional communications between the gut and the brain play an important role in the regulation of food intake, pain perception, mood, and cognitive function. The involved communication pathways are modulated by signals generated by the gut microbiome. Alterations in these communications have been implicated in several chronic brain and gut disorders, including food addiction, mood disorders, neurodevelopmental and neurodegenerative disorders, and functional and inflammatory bowel disorders. The gut microbiome holds great promise for the development of novel therapies normalizing altered brain-gut interactions.
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Affiliation(s)
- Jill A Horn
- Department of Population and Public Health Sciences, Keck School of Medicine at USC, 1845 N Soto Street, Los Angeles, CA 90032, USA
| | - Desiree R Delgadillo
- Goodman-Luskin Microbiome Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, CHS 42-210, MC737818, Los Angeles, CA 90095-73787, USA
| | - Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress & Resilience; UCLA Vatche & Tamar Manoukian Division of Digestive Diseases, Goodman Luskin Microbiome Center, UCLA.
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Işık M, Köse F, Budak Ö, Özbayer C, Kaya RK, Aydın S, Küçük AC, Demirci MA, Doğanay S, Bağcı C. Probiotic Bactolac alleviates depression-like behaviors by modulating BDNF, NLRP3 and MC4R levels, reducing neuroinflammation and promoting neural repair in rat model. Pflugers Arch 2025; 477:797-814. [PMID: 40281288 DOI: 10.1007/s00424-025-03084-6] [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: 12/20/2024] [Revised: 03/16/2025] [Accepted: 03/30/2025] [Indexed: 04/29/2025]
Abstract
Depression, a prevalent psychiatric disorder, exerts severe and debilitating impacts on an individual's mental and physical well-being, and it is considered a chronic mental illness. Chronic stress plays an important role in the pathophysiology of depression. Lactobacillus plantarum and Streptococcus thermophilus are psychobiotic bacteria and synthesize some neurotransmitters that play a role in the pathogenesis of depression. In this study, we aimed to investigate the therapeutic effects of Bactolac (Lactobacillus plantarum NBIMCC 8767 + Streptococcus thermophilus NBIMCC 8258) on chronic stress-induced depression in rats. Behavioral tests, including the sucrose preference test, elevated plus maze test, forced swim test, and three-chamber sociability test, were employed to assess depressive and anxiety-like behaviors. The expression level of the 5-HT1A, DRD1, ADRA-2A, GABA-A α1, CNR1, NR3C2, NOD1, NLRP3 and MC4R; BDNF levels, glial activity and intestinal permeability were determined in chronic stress-induced depression in rats. In conclusions, chronic stress decreased the expression levels of 5-HT1A, DRD1, ADRA-2A, GABA-A α1, CNR1, NR3C2, NOD1 and BDNF level; increased the expression levels of NLRP3 and MC4R, caused neurodegeneration and glial activity, ultimately led to depressive effects. Bactolac was effective in reducing depressive-like behaviors according to the results of behavioral tests. Bactolac treatment provided high neuronal survival rate increasing BDNF level, prevented the excessive release of pro-inflammatory cytokines by reducing the expression levels of NLRP3 and MC4R, therefore, prevented the excessive activation of the hypothalamus-pituitary-adrenal (HPA) axis and accordingly, reduced neurodegeneration and glial cell activation in depressed rats. We can suggest that Bactolac supplementation may be beneficial in coping with stress, alleviate the effects of chronic stress and help to protect mental health.
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Affiliation(s)
- Musab Işık
- Department of Physiology, İstanbul Aydın University Medical Faculty, Istanbul, Turkey.
| | - Fadime Köse
- Department of Physiology, Sakarya University Medical Faculty, Sakarya, Turkey
| | - Özcan Budak
- Department of Hıstology-Embryology, Sakarya University Medical Faculty, Sakarya, Turkey
| | - Cansu Özbayer
- Department of Medical Biology, Medical Faculty, Kütahya Health Sciences University, Kutahya, Turkey
| | - Rumeysa Keleş Kaya
- Department of Medical Pharmacology, University of Health Sciences Hamidiye International School of Medicine, Istanbul, Turkey.
| | - Sevda Aydın
- Department of Hıstology-Embryology, Sakarya University Medical Faculty, Sakarya, Turkey
| | - Aleyna Ceren Küçük
- Department of Hıstology-Embryology, Sakarya University Medical Faculty, Sakarya, Turkey
| | - Mehmet Arif Demirci
- Department of Health Systems Management, Muş Alparslan University, Faculty of Health Sciences, Muş, Turkey
| | - Songül Doğanay
- Department of Physiology, Sakarya University Medical Faculty, Sakarya, Turkey
| | - Cahit Bağcı
- Department of Physiology, Sakarya University Medical Faculty, Sakarya, Turkey
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Shawky E, Surendran S, El-Khair RMA. Fermented Vegetables as a Source of Psychobiotics: A Review of the Evidence for Mental Health Benefits. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10592-5. [PMID: 40402417 DOI: 10.1007/s12602-025-10592-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/11/2025] [Indexed: 05/23/2025]
Abstract
The human gut microbiome, comprised of trillions of microorganisms, plays a pivotal role in both physical and mental health. Recent research underscores the intriguing connection between gut bacteria and mental well-being, leading to the emergence of psychobiotics-microbes with mental health benefits. This review aims to explore fermented vegetables, a traditional dietary staple experiencing renewed interest, as a potential source of psychobiotics. Fermentation alters the microbial composition of vegetables, enriching them with beneficial bacteria such as Lactobacillus and Bifidobacterium. Various fermented vegetables, including kimchi, sauerkraut, and tempeh, host distinct bacterial communities. The review investigates how these psychobiotics may impact mental health through the gut-brain axis, a communication network between the gut and the central nervous system. Possible mechanisms encompass neurotransmitter modulation (e.g., serotonin, GABA), inflammation reduction and immunity modulation, and stress response enhancement through the hypothalamic-pituitary adrenal (HPA) axis. Clinical studies exploring the influence of fermented vegetables on mental health outcomes, including anxiety, depression, and cognitive function, are critically evaluated. The review assesses the efficacy of different fermented vegetables and probiotic strains while recognizing limitations in existing research and the necessity for further investigation.
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Affiliation(s)
- Eman Shawky
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alkhartoom Square, Alexandria, 21521, Egypt.
| | - Shelini Surendran
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Rasha M Abu El-Khair
- Pharmacognosy Department, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alexandria, Egypt
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Schiavone N, Isoldi G, Calcagno S, Rovida E, Antiga E, De Almeida CV, Lulli M. Exploring the Gut Microbiota-Retina Axis: Implications for Health and Disease. Microorganisms 2025; 13:1101. [PMID: 40431274 DOI: 10.3390/microorganisms13051101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2025] [Revised: 05/07/2025] [Accepted: 05/08/2025] [Indexed: 05/29/2025] Open
Abstract
The gut microbiota represents a rich and adaptive microbial network inhabiting the gastrointestinal tract, performing key functions in nutrient processing, immune response modulation, intestinal wall protection, and microbial defense. Its composition remains highly personalized and responsive to external influences, including lifestyle patterns, physical activity, body composition, and nutritional intake. The interactions of the gut microbiota with bodily systems are conventionally interpreted as broad systemic impacts on organ balance. Yet, emerging research-exemplified by the gut microbiota-brain axis-suggests the potential existence of more targeted and direct communication mechanisms. Dysbiosis, characterized by microbial ecosystem disturbance, generates multiple metabolic compounds capable of entering systemic circulation and reaching distant tissues, notably including ocular structures. This microbial imbalance has been associated with both systemic and localized conditions linked to eye disorders. Accumulating scientific evidence now supports the concept of a gut-retina axis, underscoring the significant role of microbiota disruption in generating various retinal pathologies. This review comprehensively investigates gut microbiota composition, functional dynamics, and dysbiosis-induced alterations, with specific focus on retinal interactions in age-related macular degeneration, diabetic retinopathy, glaucoma, and retinal artery occlusion. Moreover, the review explores microbiota-targeted therapeutic strategies, including precision nutritional interventions and microbial transplantation, as potential modulators of retinal disease progression.
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Affiliation(s)
- Nicola Schiavone
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, University of Florence, 50134 Florence, Italy
| | - Giulia Isoldi
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, University of Florence, 50134 Florence, Italy
| | - Sara Calcagno
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, University of Florence, 50134 Florence, Italy
| | - Elisabetta Rovida
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, University of Florence, 50134 Florence, Italy
| | - Emiliano Antiga
- Department of Health Sciences, Section of Dermatology, University of Florence, 50139 Florence, Italy
| | - Carolina Vieira De Almeida
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, University of Florence, 50134 Florence, Italy
- Press Start SRL Società Benefit, 50134 Florence, Italy
| | - Matteo Lulli
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, University of Florence, 50134 Florence, Italy
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Ruciński J, Kurowska-Rucińska E, Myślińska D, Grembecka B, Piekarczyk N, Necel A, Kosznik-Kwaśnicka K, Majkutewicz I. Galactooligosaccharides Attenuate Behavioural, Haematological and Immunological Abnormalities and Influence Gut Microbiota in Rats with Amygdala Hyperactivation Induced by Electrical Stimulation. Int J Mol Sci 2025; 26:4353. [PMID: 40362590 PMCID: PMC12073049 DOI: 10.3390/ijms26094353] [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: 04/10/2025] [Revised: 04/30/2025] [Accepted: 05/01/2025] [Indexed: 05/15/2025] Open
Abstract
The amygdala, especially its central nucleus (CeA), is one of the key brain structures regulating fear, anxiety and stress responses and is also involved in gut microbiota signal processing. Amygdala hyperactivity, as well as microbiota alterations, plays an important role in the pathophysiology of anxiety disorders, depression or post-traumatic stress disorder (PTSD). The present study determines whether 3 weeks of galactooligosaccharide (GOS) supplementation alleviates behavioural, haematological, immunological and gut microbiota disturbances induced by long-term electrical stimulation of the CeA in rats (Stim). The unsupplemented Stim group showed locomotor hyperactivity and higher anxiety (measured with an actometer and the elevated plus maze, respectively), as well as a decrease in white blood cells (WBCs), lymphocytes (LYMs), red blood cells (RBCs) and platelets (PLTs); an elevation of TNFα; a reduction in IL-10 concentration in plasma; and microbiota alterations as compared to the control (Sham) group. GOS supplementation alleviated all these Stim-induced adverse effects or even normalised them to the sham group level. The effect of GOS was comparable to citalopram and even more effective in WBC and PLT normalisation and IL-10 induction. The obtained results indicate the high therapeutic potential of GOS in anxiety and stress-related disorders. GOS supplementation may support conventional therapy or the prevention of PTSD, depression and anxiety disorders.
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Affiliation(s)
- Jan Ruciński
- Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59 St., 80-308 Gdańsk, Poland; (J.R.); (E.K.-R.); (D.M.); (B.G.); (N.P.)
| | - Ewelina Kurowska-Rucińska
- Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59 St., 80-308 Gdańsk, Poland; (J.R.); (E.K.-R.); (D.M.); (B.G.); (N.P.)
| | - Dorota Myślińska
- Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59 St., 80-308 Gdańsk, Poland; (J.R.); (E.K.-R.); (D.M.); (B.G.); (N.P.)
| | - Beata Grembecka
- Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59 St., 80-308 Gdańsk, Poland; (J.R.); (E.K.-R.); (D.M.); (B.G.); (N.P.)
| | - Natalia Piekarczyk
- Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59 St., 80-308 Gdańsk, Poland; (J.R.); (E.K.-R.); (D.M.); (B.G.); (N.P.)
| | - Agnieszka Necel
- Division of Medical Microbiology, Department of Microbiology, Faculty of Medicine, Medical University of Gdańsk, M. Skłodowskiej-Curie 3a St., 80-210 Gdańsk, Poland; (A.N.); (K.K.-K.)
| | - Katarzyna Kosznik-Kwaśnicka
- Division of Medical Microbiology, Department of Microbiology, Faculty of Medicine, Medical University of Gdańsk, M. Skłodowskiej-Curie 3a St., 80-210 Gdańsk, Poland; (A.N.); (K.K.-K.)
| | - Irena Majkutewicz
- Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59 St., 80-308 Gdańsk, Poland; (J.R.); (E.K.-R.); (D.M.); (B.G.); (N.P.)
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Ma M, Li B, Qu Z, Liu S, Li S. Efficacy of probiotics in patients with cognitive impairment: A systematic review and meta-analysis. PLoS One 2025; 20:e0321567. [PMID: 40315198 PMCID: PMC12047807 DOI: 10.1371/journal.pone.0321567] [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: 11/06/2024] [Accepted: 03/09/2025] [Indexed: 05/04/2025] Open
Abstract
OBJECTIVE To conduct an in-depth exploration of the specific impacts of probiotics and prebiotic supplements on cognitive impairment, it is imperative to also investigate pertinent factors, including the optimal dosage of probiotics for enhancing cognitive function. This investigation is essential for optimizing probiotic interventions to prevent and treat cognitive decline, aimed at preventing and aiding in the treatment of cognitive decline among patients with cognitive impairment. METHODS A comprehensive computerized search was conducted across the Embase, PubMed, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang and WeiPu Data. Studies targeting randomized controlled trials (RCTs) were included. This search covered a timeframe extending from the inception of each database to September 2024. Following an independent process of literature screening, data extraction, and rigorous quality assessment conducted by two investigators, a meta-analysis was performed using Stata 15.0 software. RESULTS A total of ten studies, involving 778 patients, were included in the analysis. The meta-analysis revealed that probiotics were effective in enhancing cognitive function among patients with cognitive impairment, with a standardized mean difference (SMD) of 0.52 (95% CI: 0.07, 0.98; P < 0.001). Subgroup analysis further demonstrated that the largest effect size was observed for studies utilizing the Mini-Mental State Examination (MMSE) scale as the outcome measure (SMD = 0.88). Additionally, the greatest efficacy was associated with single-strain probiotics (SMD = 0.81), and interventions lasting ≤12 weeks exhibited the most pronounced effect (SMD = 0.61). CONCLUSION Probiotics have been shown to enhance cognitive function, with a probiotic intervention program featuring a single probiotic strain and a duration of ≤12 weeks demonstrating particularly robust efficacy in improving cognitive function, as assessed by the MMSE scale.
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Affiliation(s)
- Miaomiao Ma
- College of Nursing and Health, Henan University, Kaifeng, Henan, China
- Department of Chronic Disease Risk Assessment, Henan University, Kaifeng, Henan, China
| | - Bo Li
- College of Nursing and Health, Henan University, Kaifeng, Henan, China
- Department of Chronic Disease Risk Assessment, Henan University, Kaifeng, Henan, China
| | - Zhi Qu
- College of Nursing and Health, Henan University, Kaifeng, Henan, China
- Department of Chronic Disease Risk Assessment, Henan University, Kaifeng, Henan, China
| | - Shejuan Liu
- College of Nursing and Health, Henan University, Kaifeng, Henan, China
- Department of Chronic Disease Risk Assessment, Henan University, Kaifeng, Henan, China
| | - Sisi Li
- College of Nursing and Health, Henan University, Kaifeng, Henan, China
- Department of Chronic Disease Risk Assessment, Henan University, Kaifeng, Henan, China
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9
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Li Q, Zhang Y, Wang X, Dai L, Zhao W. Gut microbiota of patients with post-stroke depression in Chinese population: a systematic review and meta-analysis. Front Cell Infect Microbiol 2025; 15:1444793. [PMID: 40375894 PMCID: PMC12078233 DOI: 10.3389/fcimb.2025.1444793] [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: 06/07/2024] [Accepted: 03/17/2025] [Indexed: 05/18/2025] Open
Abstract
Background Evidence of changes in the composition and function of the gut microbiota (GM) in post-stroke depression (PSD) patients is gradually accumulating. This study aimed to systematically evaluate the relationship between PSD and GM. Methods We searched in PubMed, Web of Science, Embase, Cochrane databases, Wangfang, VIP, CBM, and CNKI from the establishment of the database to April 17, 2024, and systematic review and meta-analysis were performed to investigate the differences of GM between patients with PSD spectrum and healthy controls (HC) or stroke spectrum. Result There were 14 studies consisting a total of 1,556 individuals included in the meta-analysis. The pooled results showed that PSD spectrum demonstrated significantly increased α diversity as indexed by Chao1 index, ACE indexes, Shannon index, and Simpson index as compared to HC. Additionally, stroke spectrum significantly increased α diversity as indexed by Simpson index compared to PSD. Furthermore, the pooled estimation of relative abundance showed that Bacteroidota, Fusobacteriota, and Pseudomonadota in PSD patients were significantly higher than those in the HC group, while the abundance of Bacillota was higher in the HC group. Moreover, significant differences in GM were observed between PSD patients and HC at the family and genus levels. Conclusion This study found that the α diversity of PSD patients was higher than that of HC. Moreover, there were also differences in the distribution of GM at the phylum, family, and genus levels, respectively. At the same time, the level of Lachnospira in PSD patients was lower than that in the stroke group. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024582708.
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Affiliation(s)
- Qiaoling Li
- Graduate School, Hunan University of Chinese Medicine, Changsha, China
| | - Yuejuan Zhang
- Department of Nursing, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Xiaoqian Wang
- Department of Nursing, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Lin Dai
- Graduate School, Hunan University of Chinese Medicine, Changsha, China
| | - Wenli Zhao
- Graduate School, Hunan University of Chinese Medicine, Changsha, China
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10
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BharathwajChetty B, Kumar A, Deevi P, Abbas M, Alqahtani A, Liang L, Sethi G, Liu L, Kunnumakkara AB. Gut microbiota and their influence in brain cancer milieu. J Neuroinflammation 2025; 22:129. [PMID: 40312370 PMCID: PMC12046817 DOI: 10.1186/s12974-025-03434-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 04/01/2025] [Indexed: 05/03/2025] Open
Abstract
Microbial communities are not simply remnants of the past but dynamic entities that continuously evolve under the selective pressures of nature, reflecting the intricate and adaptive processes of evolution. The microbiota residing in the various regions of the human body has numerous roles in different physiological processes such as nutrition, metabolism, immune regulation, etc. In the zeal of achieving empirical insights into the ambit of the gut microbiome, the research over the years led to the revelation of reciprocal interaction between the gut microbiome and the cognitive functioning of the human body. Dysbiosis in the gut microbial composition disturbs the homeostatic cognitive functioning of the human body. This dysbiosis has been associated with various chronic diseases, including brain cancer, such as glioma, glioblastoma, etc. This review explores the mechanistic role of dysbiosis-mediated progression of brain cancers and their subtypes. Moreover, it demonstrates the regulatory role of microbial metabolites produced by the gut microbiota, such as short-chain fatty acids, amino acids, lipids, etc., in the tumour progression. Further, we also provide valuable insights into the microbiota mediating the efficiency of therapeutic regimens, thereby leveraging gut microbiota as potential biomarkers and targets for improved treatment outcomes.
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Affiliation(s)
- Bandari BharathwajChetty
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, 781039, Assam, India
| | - Aviral Kumar
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, 781039, Assam, India
| | - Pranav Deevi
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, 781039, Assam, India
- International Joint M. Tech Degree in Food Science and Technology, Department of Chemical Engineering, Indian Institute of Technology Guwahati (IITG), Guwahati, 781039, Assam, India
| | - Mohamed Abbas
- Electrical Engineering Department, College of Engineering, King Khalid University, Abha, 61421, Saudi Arabia
| | - Athba Alqahtani
- Research Centre, King Fahad Medical City, Riyadh, 11525, Saudi Arabia
| | - Liping Liang
- Guangzhou Key Laboratory of Digestive Diseases, Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
- NUS Centre for Cancer Research, Yong Loo Lin Scool of Medicine, National University of Singapore, Singapore, 117699, Singapore.
| | - Le Liu
- Integrated Clinical Microecology Center, Shenzhen Hospital, Southern Medical University, Shenzhen, 518000, China.
- Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, 781039, Assam, India.
- International Joint M. Tech Degree in Food Science and Technology, Department of Chemical Engineering, Indian Institute of Technology Guwahati (IITG), Guwahati, 781039, Assam, India.
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11
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Zhang X, Liu S, Xin R, Hu W, Zhang Q, Lu Q, Han L. Reactive oxygen species-responsive prodrug nanomicelle-functionalized Lactobacillus rhamnosus probiotics for amplified therapy of ulcerative colitis. MATERIALS HORIZONS 2025. [PMID: 40296848 DOI: 10.1039/d5mh00114e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
Characterized by elevated reactive oxygen species (ROS) and disrupted gut flora, ulcerative colitis (UC) affects millions of patients worldwide. Probiotic therapy is commonly utilized in clinical practice to modulate intestinal flora and ameliorate colitis symptoms. Nonetheless, oral probiotics encounter challenges such as limited bioactivity, brief retention time, intricate pathological conditions, and singular efficacy. Here we designed plant-derived 18β-glycyrrhetinic acid (18β-GA) prodrug nanomicelles with ROS and inflammation-resolving capabilities, as well as anti-depressant effects, to protect probiotics and amplify their therapeutic effects in alleviating UC and UC-associated depression-like behaviors. Upon oral administration to UC lesion sites, prodrug nanomicelles can be dissociated by excessive ROS and release 18β-GA to attenuate colonic inflammatory responses and oxidative stress, which in turn provided a favorable microenvironment for LGG to repair intestinal barrier integrity and restore the gut microbiota. The synergistic therapeutic effects of STG nanomicelles and LGG alleviated UC-associated depression-like behavior by suppressing the activation of microglia and reducing neuroinflammation. This study introduces a promising strategy for oral nanomedicine with satisfactory therapeutic outcomes for the treatment of inflammatory diseases by integrating naturally derived small-molecule drugs with probiotics.
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Affiliation(s)
- Xinyue Zhang
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, China.
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266071, Shandong, China
| | - Shuyun Liu
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, China.
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266071, Shandong, China
| | - Rui Xin
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, China.
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266071, Shandong, China
| | - Wenxiu Hu
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, China.
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266071, Shandong, China
| | - Qiqi Zhang
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, China.
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266071, Shandong, China
| | - Qian Lu
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, China.
- Marine Traditional Chinese Medicine R&D Laboratory, Marine Biomedical Research Institute of Qingdao, Qingdao 266071, Shandong, China
| | - Lu Han
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, China.
- Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266071, Shandong, China
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12
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Agarwal V, Chaudhary R, Gupta A. Probiotics as a Treatment of Chronic Stress Associated Abnormalities. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10553-y. [PMID: 40285929 DOI: 10.1007/s12602-025-10553-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/17/2025] [Indexed: 04/29/2025]
Abstract
Chronic stress is a widespread problem that significantly affects both physical and mental health, leading to numerous complications such as mood disorders, cognitive impairments, gastrointestinal issues, and chronic diseases. The dysregulation of the hypothalamic pituitary adrenal (HPA) axis and the gut-brain axis underlies several stress related disorders, leading to systemic inflammation, neuroinflammation, dysbiosis, and impaired gut barrier integrity. This review emphasizes the growing significance of probiotics as a potential treatment strategy for addressing chronic stress. Probiotics are living bacteria that provide health benefits when consumed in sufficient quantities, acting via several processes including restoration of gut microbial composition, augmentation of gut barrier integrity, and synthesis bioactive compounds such as neurotransmitters and short-chain fatty acids. These effects lead to reduced systemic and neuroinflammation, enhanced neuroplasticity, and the regulation of stress responsive pathways, including the HPA axis. Moreover, probiotics enhance parasympathetic nervous system activity by modulating vagus signaling. Current review indicates the promise of probiotics in alleviating chronic stress; nonetheless, substantial gaps exist regarding strain specific benefits, appropriate doses, and long-term safety. It is essential to address these constraints by comprehensive, large scale clinical studies and tailored therapies. This review highlights the significance of probiotics as a natural, non-invasive approach to chronic stress management, providing an innovative solution for the worldwide issue of stress related health problems.
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Affiliation(s)
- Vipul Agarwal
- MIT College of Pharmacy, Ram Ganga Vihar Phase-II, Moradabad, 244001, U.P, India.
| | - Rishabh Chaudhary
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, 226 025, U.P, India
| | - Anugya Gupta
- Faculty of Medical and Paramedical Sciences, Madhyanchal Professional University, Bhopal, 462044, M.P, India.
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13
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Zhao H, Qiu X, Wang S, Wang Y, Xie L, Xia X, Li W. Multiple pathways through which the gut microbiota regulates neuronal mitochondria constitute another possible direction for depression. Front Microbiol 2025; 16:1578155. [PMID: 40313405 PMCID: PMC12043685 DOI: 10.3389/fmicb.2025.1578155] [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: 02/17/2025] [Accepted: 03/31/2025] [Indexed: 05/03/2025] Open
Abstract
As a significant mental health disorder worldwide, the treatment of depression has long faced the challenges of a low treatment rate, significant drug side effects and a high relapse rate. Recent studies have revealed that the gut microbiota and neuronal mitochondrial dysfunction play central roles in the pathogenesis of depression: the gut microbiota influences the course of depression through multiple pathways, including immune regulation, HPA axis modulation and neurotransmitter metabolism. Mitochondrial function serves as a key hub that mediates mood disorders through mechanisms such as defective energy metabolism, impaired neuroplasticity and amplified neuroinflammation. Notably, a bidirectional regulatory network exists between the gut microbiota and mitochondria: the flora metabolite butyrate enhances mitochondrial biosynthesis through activation of the AMPK-PGC1α pathway, whereas reactive oxygen species produced by mitochondria counteract the flora composition by altering the intestinal epithelial microenvironment. In this study, we systematically revealed the potential pathways by which the gut microbiota improves neuronal mitochondrial function by regulating neurotransmitter synthesis, mitochondrial autophagy, and oxidative stress homeostasis and proposed the integration of probiotic supplementation, dietary fiber intervention, and fecal microbial transplantation to remodel the flora-mitochondrial axis, which provides a theoretical basis for the development of novel antidepressant therapies targeting gut-brain interactions.
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Affiliation(s)
- Hongyi Zhao
- School of Basic Medical Science, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiongfeng Qiu
- School of Basic Medical Science, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shuyu Wang
- School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yi Wang
- School of Basic Medical Science, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Li Xie
- School of Basic Medical Science, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiuwen Xia
- School of Basic Medical Science, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Weihong Li
- School of Basic Medical Science, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Sichuan College of Traditional Chinese Medicine, Mianyang, China
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14
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Liu X, Mao B, Tang X, Zhang Q, Zhao J, Chen W, Cui S. Bacterial viability retention in probiotic foods: a review. Crit Rev Food Sci Nutr 2025:1-23. [PMID: 40215221 DOI: 10.1080/10408398.2025.2488228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2025]
Abstract
Probiotics offer substantial health benefits, leading to their increased consumption in various food products. The viability of probiotics is a critical factor that influences the nutritional and therapeutic efficacy of these foods. However, as probiotics often lose viability during production and oral administration, effective preservation and encapsulation technologies are needed to overcome this challenge. This review elucidates the diverse sources and incorporation strategies of probiotics, while systematically analyzing the effects of water transformation (ice front velocity, glass transition temperature, and collapse temperature), processing conditions (food matrix, temperature, and dissolved oxygen), and gastrointestinal challenges (gastric fluid, digestive enzymes, and bile salts) on probiotic viability. Effective strategies to strengthen probiotic viability encompass three primary domains: fermentation processes, production techniques, and encapsulation methods. Specifically, these include meticulous fermentation control (nitrogen sources, lipids, and carbon sources), pre-stress treatments (pre-cooling, heat shock, NaCl stress, and acid stress), optimized lyoprotectant selection (carbohydrates, proteins, and polyols), synergistic freeze-drying technologies (infrared technology, spray drying, and microwave), bulk encapsulation approaches (polysaccharide or protein-based microencapsulation), and single-cell encapsulation methods (self-assembly and surface functionalization). Despite these advancements, targeting specific probiotics and food matrices remains challenging, necessitating further research to enhance probiotic viability.
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Affiliation(s)
- Xuewu Liu
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Bingyong Mao
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Xin Tang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Qiuxiang Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- International Joint Research Laboratory for Maternal-Infant Microbiota and Health, Jiangnan University, Wuxi, China
| | - Wei Chen
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China
| | - Shumao Cui
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, China
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- International Joint Research Laboratory for Maternal-Infant Microbiota and Health, Jiangnan University, Wuxi, China
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15
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Rai AK, Yadav M, Duary RK, Shukla P. Gut Microbiota Modulation Through Dietary Approaches Targeting Better Health During Metabolic Disorders. Mol Nutr Food Res 2025:e70033. [PMID: 40195821 DOI: 10.1002/mnfr.70033] [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: 10/05/2024] [Revised: 02/26/2025] [Accepted: 03/07/2025] [Indexed: 04/09/2025]
Abstract
The impact of gut microbiota is known to play a significant role in an individual's metabolism and health. Many harmful food products or dietary imbalance adversely affect human health and changing lifestyle, environmental factors, and food habits may have their effect on gut microbiota. It has emerged that gut microbiota is regarded as an emerging metabolic organ, which is dependent on individual's diet and its composition. This review discusses the significance of lactic acid bacteria as a prominent inhabitant in the gut microbiota and the role of probiotics, prebiotics, and polyphenols to improve human health and metabolism. The role of fermented foods as an important source of probiotics and bioactive molecules is also discussed along with the role of gut microbiota in metabolic disorders like dyslipidemia, obesity, hypercholesterolemia, cancer, and hypertension. Finally, the review gives insights into the effective therapeutic prospects through gut microbiota alterations to tackle these metabolic disorders.
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Affiliation(s)
- Amit Kumar Rai
- BRIC-National Agri-Food and Biomanufacturing Institute (BRIC-NABI), SAS Nagar, Mohali, India
| | | | - Raj Kumar Duary
- Department of Dairy Science and Food Technology, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, India
| | - Pratyoosh Shukla
- Enzyme Technology and Protein Bioinformatics Laboratory, School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, India
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16
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Noor S, Ali S, Summer M, Riaz A, Nazakat L, Aqsa. Therapeutic Role of Probiotics Against Environmental-Induced Hepatotoxicity: Mechanisms, Clinical Perspectives, Limitations, and Future. Probiotics Antimicrob Proteins 2025; 17:516-540. [PMID: 39316257 DOI: 10.1007/s12602-024-10365-6] [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] [Accepted: 09/10/2024] [Indexed: 09/25/2024]
Abstract
Hepatotoxicity is one of the biggest health challenges, particularly in the context of liver diseases, often aggravated by gut microbiota dysbiosis. The gut-liver axis has been regarded as a key idea in liver health. It indicates that changes in gut flora caused by various hepatotoxicants, including alcoholism, acetaminophen, carbon tetrachloride, and thioacetamide, can affect the balance of the gut's microflora, which may lead to increased dysbiosis and intestinal permeability. As a result, bacterial endotoxins would eventually enter the bloodstream and liver, causing hepatotoxicity and inducing inflammatory reactions. Many treatments, including liver transplantation and modern drugs, can be used to address these issues. However, because of the many side effects of these approaches, scientists and medical experts are still hoping for a therapeutic approach with fewer side effects and more positive results. Thus, probiotics have become well-known as an adjunctive strategy for managing, preventing, or reducing hepatotoxicity in treating liver injury. By altering the gut microbiota, probiotics offer a secure, non-invasive, and economical way to improve liver health in the treatment of hepatotoxicity. Through various mechanisms such as regulation of gut microbiota, reduction of pathogenic overgrowth, suppression of inflammatory mediators, modification of hepatic lipid metabolism, improvement in the performance of the epithelial barrier of the gut, antioxidative effects, and modulation of mucosal immunity, probiotics play their role in the treatment and prevention of hepatotoxicity. This review highlights the mechanistic effects of probiotics in environmental toxicants-induced hepatotoxicity and current findings on this therapeutic approach's experimental and clinical trials.
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Affiliation(s)
- Shehzeen Noor
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Shaukat Ali
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan.
| | - Muhammad Summer
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Anfah Riaz
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Laiba Nazakat
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Aqsa
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
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17
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O'Riordan KJ, Moloney GM, Keane L, Clarke G, Cryan JF. The gut microbiota-immune-brain axis: Therapeutic implications. Cell Rep Med 2025; 6:101982. [PMID: 40054458 PMCID: PMC11970326 DOI: 10.1016/j.xcrm.2025.101982] [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: 05/24/2024] [Revised: 10/15/2024] [Accepted: 01/29/2025] [Indexed: 03/21/2025]
Abstract
The microbiota-gut-brain axis has major implications for human health including gastrointestinal physiology, brain function, and behavior. The immune system represents a key pathway of communication along this axis with the microbiome implicated in neuroinflammation in health and disease. In this review, we discuss the mechanisms as to how the gut microbiota interacts with the brain, focusing on innate and adaptive immunity that are often disrupted in gut-brain axis disorders. We also consider the implications of these observations and how they can be advanced by interdisciplinary research. Leveraging an increased understanding of how these interactions regulate immunity has the potential to usher in a new era of precision neuropsychiatric clinical interventions for psychiatric, neurodevelopmental, and neurological disorders.
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Affiliation(s)
| | - Gerard M Moloney
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Lily Keane
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
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18
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Lin D, Howard A, Raihane AS, Di Napoli M, Cáceres E, Ortiz M, Davis J, Abdelrahman AN, Divani AA. Traumatic Brain Injury and Gut Microbiome: The Role of the Gut-Brain Axis in Neurodegenerative Processes. Curr Neurol Neurosci Rep 2025; 25:23. [PMID: 40087204 DOI: 10.1007/s11910-025-01410-0] [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] [Accepted: 02/20/2025] [Indexed: 03/17/2025]
Abstract
PURPOSE OF REVIEW A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI). RECENT FINDINGS The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., "leaky gut"), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.
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Affiliation(s)
- Derek Lin
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Andrea Howard
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Ahmed S Raihane
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Mario Di Napoli
- Neurological Service, dell'Annunziata Hospital, Sulmona, L'Aquila, Italy
| | - Eder Cáceres
- Bioscience, School of Engineering, Universidad de La Sabana, Chía, Colombia
- Department of Critical Care, Clínica Universidad de La Sabana, Chía, Colombia
- Unisabana Center for Translational Science, School of Medicine, Universidad de La Sabana, Chía, Colombia
| | - Michael Ortiz
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Justin Davis
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Allae N Abdelrahman
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Afshin A Divani
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA.
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19
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Huang H, Zhao T, Ma W. Omega-3 polyunsaturated fatty acids attenuates cognitive impairment via the gut-brain axis in diabetes-associated cognitive dysfunction rats. Brain Behav Immun 2025; 127:147-169. [PMID: 40068791 DOI: 10.1016/j.bbi.2025.03.015] [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: 07/09/2024] [Revised: 02/11/2025] [Accepted: 03/06/2025] [Indexed: 03/17/2025] Open
Abstract
Diabetes-related cognitive dysfunction (DACD) is a comorbidity of type 2 diabetes that has a negative effect on patients' quality of life. Research has indicated that disruption of the gut microbiota (GM) may be linked to dementia with altered cognitive performance. Conversely, omega-3 polyunsaturated fatty acids (n-3 PUFAs) may reverse DACD. The present study aimed to assess the effects of an n-3 PUFA intervention and fecal microbiota transplantation (FMT) on high-fat and streptozotocin-induced DACD model rats. In DACD rats, n-3 PUFA treatment restored fasting blood glucose (FBG) levels and cognitive function, increased the expression of anti-inflammatory cytokines and downregulated the expression of proinflammatory cytokines in the cortex and colon. Additionally, the expression of the postsynaptic density protein-95 mRNA and protein varied with n-3 PUFA treatment. Treatment with n-3 PUFAs also increased the expression of tight junction proteins. Beneficial and short-chain fatty acid-producing bacteria were more abundant when rats were exposed to n-3 PUFAs. After FMT from the rats with DACD symptoms that were improved by the n-3 PUFA dietary intervention into another batch of DACD rats, we observed recovery in recipient DACD rats. These results indicated that the alleviation of DACD symptoms by n-3 PUFAs was attributed to gut microbiota remodeling.
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Affiliation(s)
- Hongying Huang
- School of Public Health, Capital Medical University, Beijing 100069, People's Republic of China; Nanchang Institute of Disease Control and Prevention, China Railway Nanchang Bureau Group Co., Ltd., Nanchang, 330003, People's Republic of China
| | - Tong Zhao
- School of Public Health, Capital Medical University, Beijing 100069, People's Republic of China
| | - Weiwei Ma
- School of Public Health, Capital Medical University, Beijing 100069, People's Republic of China.
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20
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Valderrama B, Daly I, Gunnigle E, O'Riordan KJ, Chichlowski M, Banerjee S, Skowronski AA, Pandey N, Cryan JF, Clarke G, Nagpal J. From in silico screening to in vivo validation in zebrafish - a framework for reeling in the right psychobiotics. Food Funct 2025; 16:2018-2030. [PMID: 39962981 DOI: 10.1039/d4fo03932g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2025]
Abstract
The potential of gut bacteria to interact with the nervous system is now well known. Therefore, the characterization of bacterial strains that can modulate signalling pathways of the nervous system is a topic of growing interest, as it represents a potential alternative therapeutic target to treat central nervous system disorders. However, a streamlined screening framework is required to guide the rational identification and selection of such bacteria, known as psychobiotics. In this work, we introduce a framework that integrates in silico, in vitro and in vivo approaches to identify psychobiotic candidates capable of both metabolising prebiotics of interest and producing neuroactive molecules. To prove the effectiveness of the approach, we characterized a bacterial strain, Lactiplantibacillus plantarum APC2688, for its capacity to modulate the GABAergic system and alter the stress-related behaviour of zebrafish larvae. In brief, in silico analyses of the genomic content of APC2688 identified it as capable of degrading different prebiotics and producing neuroactive compounds known to modulate the stress response in animal models. Then, in vitro results confirmed the ability of this strain to produce GABA, tryptophan and acetate, while growing with the candidate prebiotics of interest, fructooligosaccharides (FOS), galactooligosaccharides (GOS) and inositol. In vivo experiments demonstrated that the administration of bacterial supernatants induced changes in the expression of gad1 and gabra1 in zebrafish larvae, two essential genes in the GABAergic signalling pathway, and altered the anxiety-like behaviour of the larvae. These results highlight the efficiency of our framework in integrating orthogonal approaches to discover and characterise bacteria capable of modulating the microbiome-gut-brain axis.
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Affiliation(s)
- Benjamin Valderrama
- APC Microbiome Ireland, University College Cork, T12 YT20, Cork, Ireland.
- Department of Anatomy and Neuroscience, University College Cork, T12 YT20, Cork, Ireland
| | - Isabelle Daly
- APC Microbiome Ireland, University College Cork, T12 YT20, Cork, Ireland.
| | - Eoin Gunnigle
- APC Microbiome Ireland, University College Cork, T12 YT20, Cork, Ireland.
| | | | - Maciej Chichlowski
- Nutrition Science Platform, Reckitt|Mead Johnson Nutrition, Evansville, IN, USA
| | | | - Alicja A Skowronski
- Nutrition Science Platform, Reckitt|Mead Johnson Nutrition, Parsippany, NJ, USA
| | - Neeraj Pandey
- Nutrition Science Platform, Reckitt|Mead Johnson Nutrition, Slough, UK
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, T12 YT20, Cork, Ireland.
- Department of Anatomy and Neuroscience, University College Cork, T12 YT20, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, T12 YT20, Cork, Ireland.
- Department of Psychiatry & Neurobehavioural Sciences, University College Cork, T12 YT20, Cork, Ireland
| | - Jatin Nagpal
- APC Microbiome Ireland, University College Cork, T12 YT20, Cork, Ireland.
- Department of Pharmacology & Therapeutics, School of Medicine, and School of Pharmacy, University College Cork, T12 YT20, Cork, Ireland
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21
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Mehta I, Juneja K, Nimmakayala T, Bansal L, Pulekar S, Duggineni D, Ghori HK, Modi N, Younas S. Gut Microbiota and Mental Health: A Comprehensive Review of Gut-Brain Interactions in Mood Disorders. Cureus 2025; 17:e81447. [PMID: 40303511 PMCID: PMC12038870 DOI: 10.7759/cureus.81447] [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] [Accepted: 03/30/2025] [Indexed: 05/02/2025] Open
Abstract
The human gut flora of trillions of bacteria is vital for general health and greatly influences digestion, immune system function, and brain development. Through neuronal, hormonal, and immunological channels, the gut-brain axis (GBA), a bidirectional communication network, links the gut microbiota to the central nervous system (CNS). This relationship has been linked to affective diseases, including depression and anxiety, as well as mental health issues. This review explores the intricate relationship between gut bacteria and mood disorders, focusing on how gut microbiota-host interactions, immune system modulation, and neurotransmitter control support mental health. The function of important microbial metabolites, including short-chain fatty acids (SCFAs), in preserving blood-brain barrier integrity and modulating neuroinflammation is covered in this review. It also examines the bidirectional impact between gut health and mental health, including how dysbiosis could aggravate mood disorders and how depressed states might change the composition of gut bacteria. Furthermore, we discuss how psychotropic drugs affect gut flora and consider other elements such as nutrition and lifestyle that affect gut microbiome composition. Potential paths for treating mood disorders through gut microbiota modification are presented as emerging treatment techniques, including probiotics, nutritional therapies, and precision medicine. The development of new therapeutic approaches for mood disorders depends on the awareness of the GBA. Gut bacteria significantly affect mental health through immune modulation, neurotransmitter generation, and other intricate processes. Future studies should concentrate on large, varied populations to better understand these interactions and to create customized treatments that combine gut microbiota modulation with conventional mental health therapies.
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Affiliation(s)
- Ishani Mehta
- Psychiatry and Behavioral Sciences, Maharaja Agrasen Institute of Medical Research and Education, Hisar, IND
| | | | - Tharun Nimmakayala
- Medicine and Surgery, Apollo Institute of Medical Sciences and Research, Chittoor, IND
| | - Lajpat Bansal
- Psychiatry and Behavioral Sciences, Maharaja Agrasen Institute of Medical Research and Education, Hisar, IND
| | - Shivani Pulekar
- General Practice, Davao Medical School Foundation, Davao, PHL
| | | | | | - Nishi Modi
- Medicine, Government Medical College, Surat, Surat, IND
| | - Salma Younas
- Pharmacy, Punjab University College of Pharmacy, Lahore, PAK
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22
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Serretti A. Anhedonia: Current and future treatments. PCN REPORTS : PSYCHIATRY AND CLINICAL NEUROSCIENCES 2025; 4:e70088. [PMID: 40129874 PMCID: PMC11930767 DOI: 10.1002/pcn5.70088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 02/22/2025] [Accepted: 03/08/2025] [Indexed: 03/26/2025]
Abstract
Anhedonia is a transdiagnostic domain that leads to poor disorder outcome and low remission rates. This narrative review describes a broad range of interventions targeting anhedonia, including pharmacological, neuromodulatory, behavioral, and lifestyle-based approaches. Drugs such as vortioxetine, agomelatine, bupropion, ketamine, and brexpiprazole show promising anti-anhedonic effects, while traditional antidepressants, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and, even more so, selective serotonin reuptake inhibitors (SSRIs), are less effective. Neuromodulation techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous auricular vagus nerve stimulation, proved effective at improving anhedonia, particularly when used in targeted areas. Psychotherapeutic interventions, including behavioral activation, mindfulness-based strategies, and savoring techniques, also help re-engage patients with pleasurable activities and enhance positive affect. Innovative treatments, such as aticaprant and psilocybin, showed promising results. Substantial evidence suggests that improving anhedonia leads to better psychosocial functioning, quality of life, and sustained remission. Although most data come from short-term studies, several long-term analyses suggest that maintaining hedonic improvements is feasible and beneficial. The reviewed evidence underscores the importance of routine assessment of anhedonia and the integration of symptom-specific strategies. Tailoring interventions to address individual patterns of reward disruption may optimize outcomes for patients with anhedonia.
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Affiliation(s)
- Alessandro Serretti
- Department of Medicine and SurgeryKore University of EnnaEnnaItaly
- Oasi Research Institute‐IRCCSTroinaItaly
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23
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Johnstone N, Cohen Kadosh K. Indicators of improved emotion behavior in 6-14-year-old children following a 4-week placebo controlled prebiotic supplement intervention at home with a parent. Nutr J 2025; 24:34. [PMID: 40025494 PMCID: PMC11871729 DOI: 10.1186/s12937-025-01098-5] [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: 11/04/2024] [Accepted: 02/14/2025] [Indexed: 03/04/2025] Open
Abstract
BACKGROUND In this double-blind placebo-controlled randomised intervention we investigated the potential benefits of a prebiotic supplement on children's well-being in a home setting. The primary aim was to determine if this supplement could effectively reduce anxiety, improve mood, and enhance cognitive function, similar to findings in young adults. METHODS Fifty-three healthy children, aged 6 to 14, participated in an 8-week trial. The trial consisted of three testing time points; day zero marked the baseline measurement (T1) followed by a 28-day supplement intervention period during which they consumed 5.5 g of the prebiotic galactooligosaccharides (GOS) daily under parental guidance. Endline measures (T2) were conducted on the last day of supplement consumption, with a final follow-up testing session (T3) on day 56. Primary outcomes were trait anxiety using a questionnaire and emotional behavior in a dot-probe task on responses to positive and negative images. Secondary outcomes encompassed depression levels, cognitive function tests, and dietary intake recorded in a 4-day food diary. Additionally, we explored whether parents' emotional behavior had an impact on children's responses. RESULTS While our statistical analysis did not reveal significant effects of GOS, there were noteworthy trends. Trait anxiety levels decreased over time in both groups, with a more pronounced decrease in the GOS group (after intervention, p =.090; after follow-up, p =.031). The GOS group exhibited reduced negative emotional responses compared to the placebo group (p =.105), and post-trial depression levels decreased in the GOS group over time (p =.015). Although parental emotional responses correlated with various emotional outcomes in children, they did not influence the intervention effects. CONCLUSIONS These findings suggest positive trends in line with our hypotheses, however further investigation with greater statistical power would be beneficial. TRIAL REGISTRATION Retrospectively registered on https://clinicaltrials.gov/ [NCT06258135] on February 6, 2024.
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Affiliation(s)
- Nicola Johnstone
- School of Psychology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK.
| | - Kathrin Cohen Kadosh
- School of Psychology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK.
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24
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Tzikos G, Chamalidou E, Christopoulou D, Apostolopoulou A, Gkarmiri S, Pertsikapa M, Menni AE, Theodorou IM, Stavrou G, Doutsini ND, Shrewsbury AD, Papavramidis T, Tsetis JK, Theodorou H, Konsta A, Kotzampassi K. Psychobiotics Ameliorate Depression and Anxiety Status in Surgical Oncology Patients: Results from the ProDeCa Study. Nutrients 2025; 17:857. [PMID: 40077722 PMCID: PMC11901992 DOI: 10.3390/nu17050857] [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: 01/22/2025] [Revised: 02/25/2025] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
Background: Psychological disorders are prevalent in patients having undergone gastrointestinal cancer surgery, and their emotional status may further deteriorate during subsequent chemotherapy. Psychobiotics are specific probiotics that have the unique characteristics of producing neuroactive substances that are thought to act on the brain-gut axis. The aim of the present study was to evaluate the benefits of a psychobiotic formula on depression and anxiety status, as well as on perceived stress, versus a placebo in patients on a chemotherapy course following gastrointestinal surgery for cancer. Patients: The enrolled patients, allocated to the psychobiotic and placebo groups, were assessed by means of these psychometric tests: Beck's Depression Inventory and the Hamilton Depression Rating 17-item Scale for depression; the General Anxiety Disorder-7 for anxiety; and the Perceived Stress Scale-14 Item for perceived stress at three time-points: upon allocation [T1], after one month of treatment [T2], and two months thereafter [T3]. Results: In total, 266 patients were included. One month of psychobiotic treatment improved [i] depression status by 60.4% [48 depressed patients at T1, reduced to 16 at T3]; [ii] anxiety by 57.0% [72 patients at T1, 26 at T3]; and [iii] stress by 60.4% [42 at T1, 14 at T3]. The placebo-treated patients experienced a deterioration in all parameters studied, i.e., depression increased by 62.9%, anxiety by 39.7%, and stress by 142.5%. Conclusions: Based on these findings, it can be recognized that psychobiotic treatment has great potential for every patient at risk of suffering from depression, anxiety, or stress during the course of surgery/chemotherapy for gastrointestinal cancer.
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Affiliation(s)
- Georgios Tzikos
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (G.T.); (D.C.); (A.-E.M.); (N.-D.D.); (A.D.S.); (T.P.)
| | - Eleni Chamalidou
- Outpatient Surgical Oncology Unit, Chemotherapy Department, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece;
| | - Dimitra Christopoulou
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (G.T.); (D.C.); (A.-E.M.); (N.-D.D.); (A.D.S.); (T.P.)
| | - Aikaterini Apostolopoulou
- Department of Emergency Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.A.); (S.G.); (M.P.)
| | - Sofia Gkarmiri
- Department of Emergency Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.A.); (S.G.); (M.P.)
| | - Marianthi Pertsikapa
- Department of Emergency Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.A.); (S.G.); (M.P.)
| | - Alexandra-Eleftheria Menni
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (G.T.); (D.C.); (A.-E.M.); (N.-D.D.); (A.D.S.); (T.P.)
| | | | - George Stavrou
- Department of Surgery, 417 NIMTS (Army Share Fund Hospital), 11521 Athens, Greece;
| | - Nektaria-Dimitra Doutsini
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (G.T.); (D.C.); (A.-E.M.); (N.-D.D.); (A.D.S.); (T.P.)
| | - Anne D. Shrewsbury
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (G.T.); (D.C.); (A.-E.M.); (N.-D.D.); (A.D.S.); (T.P.)
| | - Theodosios Papavramidis
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (G.T.); (D.C.); (A.-E.M.); (N.-D.D.); (A.D.S.); (T.P.)
| | | | - Helen Theodorou
- Department of Sociology, School of Social Sciences, University of Crete, 74100 Rethymno, Greece;
| | - Anastasia Konsta
- First Department of Psychiatry, “Papageorgiou” General Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Katerina Kotzampassi
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (G.T.); (D.C.); (A.-E.M.); (N.-D.D.); (A.D.S.); (T.P.)
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25
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García G, Carlin M, Cano RDJ. Holobiome Harmony: Linking Environmental Sustainability, Agriculture, and Human Health for a Thriving Planet and One Health. Microorganisms 2025; 13:514. [PMID: 40142407 PMCID: PMC11945859 DOI: 10.3390/microorganisms13030514] [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: 01/30/2025] [Revised: 02/14/2025] [Accepted: 02/21/2025] [Indexed: 03/28/2025] Open
Abstract
The holobiome is an interconnected network of microbial ecosystems spanning soil, plants, animals, humans, and the environment. Microbial interactions drive nutrient cycling, pathogen suppression, and climate regulation. Soil microbiomes facilitate carbon sequestration and enhance soil fertility, while marine microbiomes contribute to carbon capture and climate stability. However, industrial agriculture, extensive herbicide use, antibiotic overuse, and climate change threaten microbial diversity, leading to ecosystem and health disruptions. Probiotic interventions help to restore microbial balance. In human health, probiotics support gut microbiota diversity, reduce inflammation, and regulate metabolism. In agriculture, soil probiotics enhance microbial diversity, improve nutrient cycling, and degrade contaminants, increasing crop yields and soil health. Case studies show that microbial inoculants effectively remediate degraded soils and enhance nutrient uptake. Artificial intelligence is transforming microbiome research by enabling predictive modeling, precision probiotic design, and microbial consortia optimization. Interdisciplinary collaboration and supportive policies are essential for restoring microbial equilibria, ensuring ecosystem resilience, and promoting long-term sustainability. The integration of artificial intelligence, clinical research, and sustainable practices is crucial for advancing holobiome science. The holobiome framework underscores the need for interdisciplinary collaboration to address global challenges, bridging environmental sustainability, agriculture, and public health for a resilient future.
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Affiliation(s)
- Gissel García
- Pathology Department, Hospital Hermanos Ameijeiras, La Habana 10400, Cuba;
| | | | - Raul de Jesus Cano
- Biological Sciences Department, California Polytechnic State University, San Luis Obispo, CA 93407, USA
- Chauvell, LLC, San Luis Obispo, CA 93401, USA
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26
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Garzone S, Charitos IA, Mandorino M, Maggiore ME, Capozzi L, Cakani B, Dias Lopes GC, Bocchio-Chiavetto L, Colella M. Can We Modulate Our Second Brain and Its Metabolites to Change Our Mood? A Systematic Review on Efficacy, Mechanisms, and Future Directions of "Psychobiotics". Int J Mol Sci 2025; 26:1972. [PMID: 40076598 PMCID: PMC11899754 DOI: 10.3390/ijms26051972] [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: 12/17/2024] [Revised: 02/18/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Psychobiotics, live microorganisms that provide mental health by interacting with the gut microbiota, are emerging as a promising therapeutic option for psychiatric and neurodevelopmental disorders. Their effectiveness in addressing conditions such as depression, anxiety, insomnia, stress, autism spectrum disorder (ASD), and eating disorders were examined through a comprehensive analysis of existing studies up to the first half of 2024, based on data from reliable electronic databases. We found that psychobiotics can significantly reduce symptoms of various psychiatric disorders by influencing neurotransmitter levels, regulating the hypothalamic-pituitary-adrenal (HPA) axis, and improving gut barrier function through short-chain fatty acids (SCFAs) and other metabolites. However, several limitations were identified, including inconsistent study methodologies, small sample sizes, and a lack of data on long-term safety. Addressing these limitations through rigorous research is essential for establishing standardized protocols and fully confirming the therapeutic potential of psychobiotics. In conclusion, psychobiotics show great promise as complementary treatments for mental health conditions, but continued research is necessary to refine their application and integrate them into clinical practice effectively.
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Affiliation(s)
- Stefania Garzone
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari, 70124 Bari, Italy; (S.G.); (M.M.); (M.E.M.); (L.C.)
| | - Ioannis Alexandros Charitos
- Istituti Clinici Scientifici Maugeri IRCCS, Pneumology and Respiratory Rehabilitation Unit, “Institute” of Bari, 70124 Bari, Italy
| | - Manuela Mandorino
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari, 70124 Bari, Italy; (S.G.); (M.M.); (M.E.M.); (L.C.)
| | - Maria Elena Maggiore
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari, 70124 Bari, Italy; (S.G.); (M.M.); (M.E.M.); (L.C.)
| | - Loredana Capozzi
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari, 70124 Bari, Italy; (S.G.); (M.M.); (M.E.M.); (L.C.)
- Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, 71121 Foggia, Italy
| | - Bujar Cakani
- Department of Clinical Disciplines, “Alexander Xhuvani” University of Elbasan, 3001 Elbasan, Albania;
| | - Gabriel César Dias Lopes
- Department of Neuroscience and Mental Health, School of Science of Health, Logos University International (UNILOGOS), Miami, FL 33137, USA;
- Department of Neuroscience and Mental Health, School of Science of Health, European International University, 75018 Paris, France
| | - Luisella Bocchio-Chiavetto
- IRCCS Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy;
- Department of Theoretical and Applied Sciences (DiSTA), eCampus University, 22060 Novedrate, Italy
| | - Marica Colella
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari, 70124 Bari, Italy; (S.G.); (M.M.); (M.E.M.); (L.C.)
- Department of Theoretical and Applied Sciences (DiSTA), eCampus University, 22060 Novedrate, Italy
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27
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Nayak U, Manikkath J, Arora D, Mudgal J. Impact of neuroinflammation on brain glutamate and dopamine signalling in schizophrenia: an update. Metab Brain Dis 2025; 40:119. [PMID: 39907868 PMCID: PMC11799129 DOI: 10.1007/s11011-025-01548-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 01/30/2025] [Indexed: 02/06/2025]
Abstract
Schizophrenia is one of the most severe and chronic psychiatric disorders. Over the years, numerous treatment options have been introduced for schizophrenia. Although they are relatively successful in managing the positive symptoms of schizophrenia, most of the current treatments have a negligible effect on the negative and cognitive symptoms. Thus, none of them could prevent the relapse of psychotic episodes. Among the numerous hypotheses explaining the development and progression of schizophrenia, the cytokine hypothesis explains the role of inflammatory markers as a significant culprit in the development of schizophrenia. Elevated cytokines are reported in animal models and schizophrenic patients. The cytokine hypothesis is based on how increased inflammatory markers can cause changes in the dopaminergic, glutamate, and tryptophan metabolism pathways, like that observed in schizophrenic patients. Reasons, such as autoimmune disease, maternal immune activation, infection, etc., can pave the way for the development of schizophrenia and are associated with the negative, positive and cognitive symptoms of schizophrenia. Thus, there is a need to focus on the significance of anti-inflammatory drugs against these symptoms. The development of new treatment strategies in the management of schizophrenia can provide better therapeutic outcomes in terms of the severity of symptoms and treatment of drug-resistant schizophrenia. This review attempts to explain the association between elevated inflammatory markers and various neurotransmitters, and the possible use of medications like nonsteroidal anti-inflammatory drugs, monoclonal antibodies, statins, and estrogens as adjuvant therapy. Over the years, these hypotheses have been the basis for drug discovery for the treatment of schizophrenia.
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Affiliation(s)
- Usha Nayak
- Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Jyothsna Manikkath
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Devinder Arora
- School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, 4222, Australia
| | - Jayesh Mudgal
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
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28
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Mottawea W, Yousuf B, Sultan S, Ahmed T, Yeo J, Hüttmann N, Li Y, Bouhlel NE, Hassan H, Zhang X, Minic Z, Hammami R. Multi-level analysis of gut microbiome extracellular vesicles-host interaction reveals a connection to gut-brain axis signaling. Microbiol Spectr 2025; 13:e0136824. [PMID: 39699251 PMCID: PMC11792502 DOI: 10.1128/spectrum.01368-24] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 09/12/2024] [Indexed: 12/20/2024] Open
Abstract
Microbiota-released extracellular vesicles (MEVs) have emerged as a key player in intercellular signaling. However, their involvement in the gut-brain axis has been poorly investigated. We hypothesize that MEVs cross host cellular barriers and deliver their cargoes of bioactive compounds to the brain. In this study, we aimed to investigate the cargo capacity of MEVs for bioactive metabolites and their interactions with the host cellular barriers. First, we conducted a multi-omics profiling of MEVs' contents from ex vivo and stool samples. Metabolomics analysis identified various neuro-related compounds encapsulated within MEVs, such as arachidonyl-dopamine, gabapentin, glutamate, and N-acylethanolamines. Metaproteomics unveiled an enrichment of enzymes involved in neuronal metabolism, primarily in the glutamine/glutamate/gamma-aminobutyric acid (GABA) pathway. These neuro-related proteins and metabolites were correlated with Bacteroides spp. We isolated 18 Bacteroides strains and assessed their GABA production capacity in extracellular vesicles (EVs) and culture supernatant. A GABA-producing Bacteroides finegoldii, released EVs with a high GABA content (4 µM) compared to Phocaeicola massiliensis. Upon testing the capacity of MEVs to cross host barriers, MEVs exhibited a dose-dependent paracellular transport and were endocytosed by Caco-2 and hCMEC/D3 cells. Exposure of Caco-2 cells to MEVs did not alter expression of genes related to intestinal barrier integrity, while affected immune pathways and cell apoptosis process as revealed by RNA-seq analyses. In vivo, MEVs biodistributed across mice organs, including the brain, liver, stomach, and spleen. Our results highlight the ability of MEVs to cross the intestinal and blood-brain barriers to deliver their cargoes to distant organs, with potential implication for the gut-brain axis. IMPORTANCE Microbiota-released extracellular vesicles (MEVs) have emerged as a key player in intercellular signaling. In this study, a multi-level analysis revealed presence of a diverse array of biologically active molecules encapsulated within MEVs, including neuroactive metabolites, such as arachidonyl-dopamine, gabapentin, glutamate, and N-acylethanolamines, and gamma-aminobutyric acid (GABA). Metaproteomics also unveiled an enrichment of neural-related proteins, mainly the glutamine/glutamate/GABA pathway. MEVs were able to cross epithelial and blood-brain barriers in vitro. RNA-seq analyses showed that MEVs stimulate several immune pathways while suppressing cell apoptosis process. Furthermore, MEVs were able to traverse the intestinal barriers and reach distal organs, including the brain, thereby potentially influencing brain functionality and contributing to mental and behavior.
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Affiliation(s)
- Walid Mottawea
- NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Basit Yousuf
- NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada
| | - Salma Sultan
- NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada
| | - Tamer Ahmed
- NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada
| | - JuDong Yeo
- NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada
| | - Nico Hüttmann
- John L. Holmes Mass Spectrometry Facility, Faculty of Science, University of Ottawa, Ottawa, Canada
| | - Yingxi Li
- John L. Holmes Mass Spectrometry Facility, Faculty of Science, University of Ottawa, Ottawa, Canada
| | - Nour Elhouda Bouhlel
- NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada
| | - Hebatoallah Hassan
- NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada
| | - Xu Zhang
- Regulatory Research Division, Centre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, Canada
| | - Zoran Minic
- John L. Holmes Mass Spectrometry Facility, Faculty of Science, University of Ottawa, Ottawa, Canada
| | - Riadh Hammami
- NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
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29
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Chakravarty K, Gaur S, Kumar R, Jha NK, Gupta PK. Exploring the Multifaceted Therapeutic Potential of Probiotics: A Review of Current Insights and Applications. Probiotics Antimicrob Proteins 2025; 17:341-363. [PMID: 39069588 DOI: 10.1007/s12602-024-10328-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] [Accepted: 07/13/2024] [Indexed: 07/30/2024]
Abstract
The interplay between human health and the microbiome has gained extensive attention, with probiotics emerging as pivotal therapeutic agents due to their vast potential in treating various health issues. As significant modulators of the gut microbiota, probiotics are crucial in maintaining intestinal homeostasis and enhancing the synthesis of short-chain fatty acids. Despite extensive research over the past decades, there remains an urgent need for a comprehensive and detailed review that encapsulates probiotics' latest insights and applications. This review focusses on the multifaceted roles of probiotics in promoting health and preventing disease, highlighting the complex mechanisms through which these beneficial bacteria influence both gut flora and the human body at large. This paper also explores probiotics' neurological and gastrointestinal applications, focussing on their significant impact on the gut-brain axis and their therapeutic potential in a broad spectrum of pathological conditions. Current innovations in probiotic formulations, mainly focusing on integrating genomics and biotechnological advancements, have also been comprehensively discussed herein. This paper also critically examines the regulatory landscape that governs probiotic use, ensuring safety and efficacy in clinical and dietary settings. By presenting a comprehensive overview of recent studies and emerging trends, this review aims to illuminate probiotics' extensive therapeutic capabilities, leading to future research and clinical applications. However, besides extensive research, further advanced explorations into probiotic interactions and mechanisms will be essential for developing more targeted and effective therapeutic strategies, potentially revolutionizing health care practices for consumers.
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Affiliation(s)
- Kashyapi Chakravarty
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, Uttar Pradesh, 201309, India
| | - Smriti Gaur
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, Uttar Pradesh, 201309, India.
| | - Rohit Kumar
- Centre for Development of Biomaterials and Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, 201310, India
| | - Niraj Kumar Jha
- Department of Biotechnology, Sharda School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh, 201310, India
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, 602105, India
- School of Bioengineering & Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
- Centre of Research Impact and Outcome, Chitkara University, Rajpura, Punjab, 140401, India
| | - Piyush Kumar Gupta
- Centre for Development of Biomaterials and Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, 201310, India.
- Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun, Uttarakhand, 248002, India.
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30
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Wu H, Huang C, Xiong S. Gut microbiota as a potential therapeutic target for children with cerebral palsy and epilepsy. Brain Dev 2025; 47:104286. [PMID: 39426843 DOI: 10.1016/j.braindev.2024.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 08/28/2024] [Accepted: 09/04/2024] [Indexed: 10/21/2024]
Abstract
Gut microbiota (GM), the "second genome," exerts influence on human health by impacting brain function through the gut-brain axis. This interaction involves various mechanisms, including immune regulation, metabolites, and neuronal pathways. The application of the next-generation sequencing technology provides a revolutionary tool for the study of GM, which contributes to a deeper comprehension of the GM-host relationship. Children with cerebral palsy (CP), a common neurological disorder in children, are more likely to develop epilepsy, which can exacerbate CP symptoms, particularly those related to cognitive impairment and gastrointestinal tract, such as constipation. The current study identified specific changes in the GM of children with CP accompanied by epilepsy. Furthermore, both diet and oral microbiota have the potential to influence the composition of the GM. Interventions with probiotics and dietary fiber based on GM can improve constipation and cognition, and this approach may be a potential therapeutic strategy.
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Affiliation(s)
- Hui Wu
- Child Healthcare Department, Maternal and Child Health Hospital of PanYu District, Guangzhou, China
| | - Congfu Huang
- Department of Pediatrics, Longgang District Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Shenghua Xiong
- Department of Pediatrics, Longgang District Maternity & Child Healthcare Hospital, Shenzhen, China.
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31
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Li B, Zhang X, Zhang Q, Zheng T, Li Q, Yang S, Shao J, Guan W, Zhang S. Nutritional strategies to reduce intestinal cell apoptosis by alleviating oxidative stress. Nutr Rev 2025; 83:e518-e532. [PMID: 38626282 DOI: 10.1093/nutrit/nuae023] [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] [Indexed: 04/18/2024] Open
Abstract
The gut barrier is the first line of defense against harmful substances and pathogens in the intestinal tract. The balance of proliferation and apoptosis of intestinal epithelial cells (IECs) is crucial for maintaining the integrity of the intestinal mucosa and its function. However, oxidative stress and inflammation can cause DNA damage and abnormal apoptosis of the IECs, leading to the disruption of the intestinal epithelial barrier. This, in turn, can directly or indirectly cause various acute and chronic intestinal diseases. In recent years, there has been a growing understanding of the vital role of dietary ingredients in gut health. Studies have shown that certain amino acids, fibers, vitamins, and polyphenols in the diet can protect IECs from excessive apoptosis caused by oxidative stress, and limit intestinal inflammation. This review aims to describe the molecular mechanism of apoptosis and its relationship with intestinal function, and to discuss the modulation of IECs' physiological function, the intestinal epithelial barrier, and gut health by various nutrients. The findings of this review may provide a theoretical basis for the use of nutritional interventions in clinical intestinal disease research and animal production, ultimately leading to improved human and animal intestinal health.
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Affiliation(s)
- Baofeng Li
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Xiaoli Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Qianzi Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Tenghui Zheng
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Qihui Li
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Siwang Yang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Jiayuan Shao
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Wutai Guan
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Shihai Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, China
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32
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Wankhede NL, Kale MB, Kyada A, M RM, Chaudhary K, Naidu KS, Rahangdale S, Shende PV, Taksande BG, Khalid M, Gulati M, Umekar MJ, Fareed M, Kopalli SR, Koppula S. Sleep deprivation-induced shifts in gut microbiota: Implications for neurological disorders. Neuroscience 2025; 565:99-116. [PMID: 39622383 DOI: 10.1016/j.neuroscience.2024.11.070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 11/26/2024] [Accepted: 11/27/2024] [Indexed: 12/07/2024]
Abstract
Sleep deprivation is a prevalent issue in contemporary society, with significant ramifications for both physical and mental well-being. Emerging scientific evidence illuminates its intricate interplay with the gut-brain axis, a vital determinant of neurological function. Disruptions in sleep patterns disturb the delicate equilibrium of the gut microbiota, resulting in dysbiosis characterized by alterations in microbial composition and function. This dysbiosis contributes to the exacerbation of neurological disorders such as depression, anxiety, and cognitive decline through multifaceted mechanisms, including heightened neuroinflammation, disturbances in neurotransmitter signalling, and compromised integrity of the gut barrier. In response to these challenges, there is a burgeoning interest in therapeutic interventions aimed at restoring gut microbial balance and alleviating neurological symptoms precipitated by sleep deprivation. Probiotics, dietary modifications, and behavioural strategies represent promising avenues for modulating the gut microbiota and mitigating the adverse effects of sleep disturbances on neurological health. Moreover, the advent of personalized interventions guided by advanced omics technologies holds considerable potential for tailoring treatments to individualized needs and optimizing therapeutic outcomes. Interdisciplinary collaboration and concerted research efforts are imperative for elucidating the underlying mechanisms linking sleep, gut microbiota, and neurological function. Longitudinal studies, translational research endeavours, and advancements in technology are pivotal for unravelling the complex interplay between these intricate systems.
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Affiliation(s)
- Nitu L Wankhede
- Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra 441002, India
| | - Mayur B Kale
- Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra 441002, India
| | - Ashishkumar Kyada
- Marwadi University Research Center, Department of Pharmacy, Faculty of Health Sciences Marwadi University, Rajkot 360003, Gujarat, India
| | - Rekha M M
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Kamlesh Chaudhary
- Department of Neurology, National Institute of Medical Sciences, NIMS University Rajasthan, Jaipur, India
| | - K Satyam Naidu
- Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh, India
| | - Sandip Rahangdale
- Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra 441002, India
| | - Prajwali V Shende
- Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra 441002, India
| | - Brijesh G Taksande
- Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra 441002, India
| | - Mohammad Khalid
- Department of Pharmacognosy, College of Pharmacy Prince Sattam Bin Abdulaziz University Alkharj, Saudi Arabia
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 1444411, India; ARCCIM, Faculty of Health, University of Technology Sydney, Ultimo, NSW 20227, Australia
| | - Milind J Umekar
- Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra 441002, India
| | - Mohammad Fareed
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia
| | - Spandana Rajendra Kopalli
- Department of Bioscience and Biotechnology, Sejong University, Gwangjin-gu, Seoul 05006, Republic of Korea
| | - Sushruta Koppula
- College of Biomedical and Health Sciences, Konkuk University, Chungju-Si, Chungcheongbuk Do 27478, Republic of Korea.
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Casado A, Fernández E, Sánchez-Llana E, Fernández M, Ladero V, Alvarez MA. The development of a whole-cell biosensor enabled the identification of agmatine-producing Hafnia spp. in cheese. Int J Food Microbiol 2025; 427:110970. [PMID: 39546898 DOI: 10.1016/j.ijfoodmicro.2024.110970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 11/05/2024] [Accepted: 11/06/2024] [Indexed: 11/17/2024]
Abstract
Agmatine, the decarboxylation product of arginine, is the precursor of putrescine - a harmful biogenic amine (BA) - that can accumulate in dairy products via bacterial metabolism involving the agmatine deiminase (AGDI) pathway. This first requires agmatine be produced via the decarboxylation of arginine and it remains unknown which microorganisms are responsible for this prior decarboxylation step. In addition, agmatine, as other BA, plays different physiological roles including those of co-transmitter and neuromodulator. Preclinical and clinical studies have shown agmatine to have a neuroprotective effect, rendering it of therapeutic interest being agmatine-producing bacteria proposed as psychobiotics. The identification of BA-producing microorganisms is based on the rise in pH due to the consumption of H+ during such decarboxylation reactions. However, in the detection of agmatine-producing microorganisms in cheese, this would lead to false positives since many bacteria possess arginine deiminase activity; this produces ornithine and ammonium from arginine, which also increases the pH. To overcome this problem, a whole-cell biosensor based on a previously developed agmatine-inducible transcription system was designed, and a protocol optimized for the successful identification of agmatine-producing microorganisms in cheese. The application of this protocol in cheese samples allowed for the isolation of agmatine-producing microorganisms identified as Hafnia spp. and unravels, for first time, the capacity of Hafnia paralvei to produce agmatine. This finding evidence the potential role of Hafnia spp. in putrescine accumulation in dairy products.
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Affiliation(s)
- Angel Casado
- Dairy Research Institute, IPLA, CSIC, C/ Francisco Pintado Fé, 26. 33011, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario s/n, 33011 Oviedo, Asturias, Spain
| | - Eva Fernández
- Dairy Research Institute, IPLA, CSIC, C/ Francisco Pintado Fé, 26. 33011, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario s/n, 33011 Oviedo, Asturias, Spain
| | - Esther Sánchez-Llana
- Dairy Research Institute, IPLA, CSIC, C/ Francisco Pintado Fé, 26. 33011, Oviedo, Spain
| | - María Fernández
- Dairy Research Institute, IPLA, CSIC, C/ Francisco Pintado Fé, 26. 33011, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario s/n, 33011 Oviedo, Asturias, Spain
| | - Victor Ladero
- Dairy Research Institute, IPLA, CSIC, C/ Francisco Pintado Fé, 26. 33011, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario s/n, 33011 Oviedo, Asturias, Spain.
| | - Miguel A Alvarez
- Dairy Research Institute, IPLA, CSIC, C/ Francisco Pintado Fé, 26. 33011, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario s/n, 33011 Oviedo, Asturias, Spain
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Tyagi A, Choi YY, Shan L, Vinothkanna A, Lee ES, Chelliah R, Barathikannan K, Raman ST, Park SJ, Jia AQ, Choi GP, Oh DH. Limosilactobacillus reuteri fermented brown rice alleviates anxiety improves cognition and modulates gut microbiota in stressed mice. NPJ Sci Food 2025; 9:5. [PMID: 39799113 PMCID: PMC11724862 DOI: 10.1038/s41538-025-00369-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 01/01/2025] [Indexed: 01/15/2025] Open
Abstract
Chronic stress disrupts gut microbiota homeostasis, contributing to anxiety and depression. This study explored the effects of Limosilactobacillus reuteri fermented brown rice (FBR) on anxiety using an ICR mouse chronic mild stress (CMS) model. Anxiety was assessed through body weight, corticosterone levels, neurotransmitter profiles, and behavioral tests. A four-week FBR regimen reduced corticosterone, restored neurotransmitters like gamma-aminobutyric acid (GABA) and serotonin, and improved anxiety-related behaviors. Metagenomic (16S rRNA) and metabolomic analyses revealed enhanced amino acid metabolism, energy metabolism, and short-chain fatty acid (SCFA) production in FBR-treated mice. FBR-enriched beneficial gut bacteria, aligning the microbiota profile with that of non-stressed mice. FBR also modulated GABA receptor-related gene expression, promoting relaxation. Network pharmacology identified quercetin, GABA, glutamic acid, phenylalanine, and ferulic acid as bioactive compounds with neuroprotective potential. These findings highlight FBR's potential as a gut-brain axis-targeted therapeutic for anxiety and stress-related disorders.
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Affiliation(s)
- Akanksha Tyagi
- Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, Purdue, IN, USA
- Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Yu-Yeong Choi
- Department of Natural Resources and Environmental Science, Kangwon National University, Chuncheon, South Korea
| | - Lingyue Shan
- Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Annadurai Vinothkanna
- School of Chemistry and Chemical Engineering and Key Laboratory of Ministry of Education for Advanced Materials in Tropical Island Resources, Hainan University, Haikou, China
| | - Eun-Seok Lee
- Department of Natural Resources and Environmental Science, Kangwon National University, Chuncheon, South Korea
| | - Ramachandran Chelliah
- Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
- Saveetha School of Engineering, Saveetha University, Chennai, Tamil Nadu, India
| | | | - Sivakumar Thasma Raman
- School of Food and Biological Engineering, Jiangsu University, Jiangsu, Zhenjiang, PR China
| | - Se Jin Park
- Department of Natural Resources and Environmental Science, Kangwon National University, Chuncheon, South Korea
| | - Ai-Qun Jia
- Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Geun Pyo Choi
- Department of Barista and Bakery, Gangwon State University, Gangneung, South Korea
| | - Deog Hwan Oh
- Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea.
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35
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González-Parra JA, Barrera-Conde M, Kossatz E, Veza E, de la Torre R, Busquets-Garcia A, Robledo P, Pizarro N. Microbiota and social behavior alterations in a mouse model of down syndrome: Modulation by a synbiotic treatment. Prog Neuropsychopharmacol Biol Psychiatry 2025; 136:111200. [PMID: 39571716 DOI: 10.1016/j.pnpbp.2024.111200] [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: 07/08/2024] [Revised: 11/16/2024] [Accepted: 11/18/2024] [Indexed: 11/26/2024]
Abstract
Sex differences in the composition and functionality of gut microbiota are an emerging field of interest in neurodevelopmental disorders, as they may help in understanding the phenotypic disparities between males and females. This study aimed to characterize sex-related specific alterations in gut microbiota composition in a mouse model of Down syndrome (Ts65Dn mice, TS mice) through the sequencing of the PCR-amplified 16S ribosomal DNA fraction. Moreover, it intended to examine whether the modulation of gut microbiota by the administration of a synbiotic (SYN) treatment would be beneficial for the behavioral alterations observed in male and female TS mice. Our results show that male, but not female, TS mice exhibit alterations in beta diversity compared to their wild-type (WT) littermates. Sex-dependent differences are also observed in the relative abundance of the classes Bacilli and Clostridia. Administering the SYN effectively counteracts hypersociability in females, and normalizes the overall abundance of Bacilli, specifically by increasing Lactobacillaceae. On the contrary, it rescues emotional recognition deficits in male TS mice and increases the relative abundance of the families Lactobacillaceae, Streptococcaceae and Atopobiaceae. In addition, a metagenome KEGG analysis of differentially enriched pathways shows relevant changes in the cofactor biosynthesis and the amino acid synthesis categories. Finally, following SYN treatment, both male and female TS mice exhibit a robust increase in propionic acid levels compared to WT littermates. These findings suggest sex-specific mechanisms that could link gut microbiota composition with behavior in TS mice, and underscore the potential of targeted gut microbiota interventions to modulate social abnormalities in neurodevelopmental disorders.
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Affiliation(s)
- Jose Antonio González-Parra
- Cell-Type Mechanisms in Normal and Pathological Behavior Research Group, Neuroscience Programme, Hospital del Mar Research Institute, Barcelona, Spain
| | - Marta Barrera-Conde
- Integrative Pharmacology and Systems Neuroscience, Neuroscience Research Program, Hospital del Mar Research Institute, Barcelona, Spain
| | - Elk Kossatz
- Integrative Pharmacology and Systems Neuroscience, Neuroscience Research Program, Hospital del Mar Research Institute, Barcelona, Spain
| | - Emma Veza
- Integrative Pharmacology and Systems Neuroscience, Neuroscience Research Program, Hospital del Mar Research Institute, Barcelona, Spain
| | - Rafael de la Torre
- Integrative Pharmacology and Systems Neuroscience, Neuroscience Research Program, Hospital del Mar Research Institute, Barcelona, Spain; Department of Medicine and Life Sciences, University Pompeu Fabra, Barcelona, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERON), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Arnau Busquets-Garcia
- Cell-Type Mechanisms in Normal and Pathological Behavior Research Group, Neuroscience Programme, Hospital del Mar Research Institute, Barcelona, Spain.
| | - Patricia Robledo
- Integrative Pharmacology and Systems Neuroscience, Neuroscience Research Program, Hospital del Mar Research Institute, Barcelona, Spain; Department of Medicine and Life Sciences, University Pompeu Fabra, Barcelona, Spain.
| | - Nieves Pizarro
- Integrative Pharmacology and Systems Neuroscience, Neuroscience Research Program, Hospital del Mar Research Institute, Barcelona, Spain.
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Gajewska A, Wysokiński A, Strzelecki D, Gawlik-Kotelnicka O. Limited Changes in Red Blood Cell Parameters After Probiotic Supplementation in Depressive Individuals: Insights from a Secondary Analysis of the PRO-DEMET Randomized Controlled Trial. J Clin Med 2025; 14:265. [PMID: 39797347 PMCID: PMC11721667 DOI: 10.3390/jcm14010265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 12/29/2024] [Accepted: 01/02/2025] [Indexed: 01/13/2025] Open
Abstract
Background: Depression often coexists with anemia, potentially sharing common pathways, highlighting the need for treatments addressing both conditions simultaneously. This study evaluated the effect of probiotics on red blood cell (RBC) parameters in adults with depressive disorder. We hypothesized that probiotics would positively influence RBC parameters, potentially modulated by baseline inflammation or dietary intake, with improved RBC function correlating with better antidepressant outcomes. Methods: This secondary analysis of a two-arm, randomized, double-blind, controlled trial involved 116 adults with depressive disorder. Participants received a probiotic formulation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 or a placebo for 60 days. Data from 97 subjects were analyzed for RBC parameters, including hemoglobin (HGB), RBC count, hematocrit (HCT), mean corpuscular volume (MCV), mean hemoglobin concentration (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC distribution width (RDW). Results: Probiotic supplementation did not result in significant changes in RBC parameters compared to the placebo. However, probiotics may help stabilize HGB, HCT, MCH, and MCHC levels, potentially preventing fluctuations observed in the placebo group. Conclusions: While probiotics showed potential benefits for depressive symptoms, significant changes in RBC parameters were not observed. Larger studies are needed to clarify the mechanisms and clinical implications.
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Affiliation(s)
| | - Adam Wysokiński
- Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, 92-216 Lodz, Poland;
| | - Dominik Strzelecki
- Department of Affective and Psychotic Disorders, Medical University of Lodz, 92-216 Lodz, Poland;
| | - Oliwia Gawlik-Kotelnicka
- Department of Affective and Psychotic Disorders, Medical University of Lodz, 92-216 Lodz, Poland;
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Slykerman RF, Davies N, Vlckova K, O'Riordan KJ, Bassett SA, Dekker J, Schellekens H, Hyland NP, Clarke G, Patterson E. Precision Psychobiotics for Gut-Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy. Microb Biotechnol 2025; 18:e70079. [PMID: 39815671 PMCID: PMC11735468 DOI: 10.1111/1751-7915.70079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/19/2024] [Accepted: 12/26/2024] [Indexed: 01/18/2025] Open
Abstract
Advancing microbiome-gut-brain axis science requires systematic, rational and translational approaches to bridge the critical knowledge gaps currently preventing full exploitation of the gut microbiome as a tractable therapeutic target for gastrointestinal, mental and brain health. Current research is still marked by many open questions that undermine widespread application to humans. For example, the lack of mechanistic understanding of probiotic effects means it remains unclear why even apparently closely related strains exhibit different effects in vivo. For the therapeutic application of live microbial psychobiotics, consensus on their application as adjunct treatments to conventional neuromodulators, use in unmedicated populations or in at-risk cohorts with sub-clinical symptomatology is warranted. This missing information on both sides of the therapeutic equation when treating central nervous system (CNS) conditions makes psychobiotic research challenging, especially when compared to other pharmaceutical or functional food approaches. Expediting the transition from positive preclinical data to proven benefits in humans includes interpreting the promises and pitfalls of animal behavioural assays, as well as navigating mechanism-informed decision making to select the right microbe(s) for the job. In this review, we consider how these decisions can be supported in light of information accrued from a range of clinical studies across healthy, at-risk and pathological study populations, where specific strains have been evaluated in the context of gastrointestinal physiology, brain function and behaviour. Examples of successful, partial and unsuccessful translation from bench to bedside are considered. We also discuss the developments in in silico analyses that have enhanced our understanding of the gut microbiome and that have moved research towards pinpointing the host-microbe interactions most important for optimal gut-brain axis function. Combining this information with knowledge from functional assays across in vitro and ex vivo domains and incorporating model organisms can prime the discovery pipelines with the most promising and rationally selected psychobiotic candidates.
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Affiliation(s)
| | - Naomi Davies
- Department of Psychological MedicineUniversity of AucklandAucklandNew Zealand
| | - Klara Vlckova
- Fonterra Microbiome Research CentreUniversity College CorkCorkIreland
| | | | - Shalome A. Bassett
- Fonterra Research and Development CentrePalmerston NorthNew Zealand
- Riddet InstituteMassey UniversityPalmerston NorthNew Zealand
| | - James Dekker
- Fonterra Research and Development CentrePalmerston NorthNew Zealand
| | - Harriët Schellekens
- APC Microbiome IrelandUniversity College CorkCorkIreland
- Department of Anatomy and NeuroscienceUniversity College CorkCorkIreland
| | - Niall P. Hyland
- APC Microbiome IrelandUniversity College CorkCorkIreland
- Department of PhysiologyUniversity College CorkCorkIreland
| | - Gerard Clarke
- APC Microbiome IrelandUniversity College CorkCorkIreland
- Department of Psychiatry and Neurobehavioural ScienceUniversity College CorkCorkIreland
| | - Elaine Patterson
- Fonterra Microbiome Research CentreUniversity College CorkCorkIreland
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38
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Serretti A. Understanding mood disorder treatments. Int Clin Psychopharmacol 2025; 40:1-2. [PMID: 39611714 DOI: 10.1097/yic.0000000000000573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2024]
Affiliation(s)
- Alessandro Serretti
- Department of Medicine and Surgery, Kore University of Enna, Enna
- Oasi Research Institute-IRCCS, Troina, Italy
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39
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Timmis K, Karahan ZC, Ramos JL, Koren O, Pérez‐Cobas AE, Steward K, de Lorenzo V, Caselli E, Douglas M, Schwab C, Rivero V, Giraldo R, Garmendia J, Turner RJ, Perlmutter J, Borrero de Acuña JM, Nikel PI, Bonnet J, Sessitsch A, Timmis JK, Pruzzo C, Prieto MA, Isazadeh S, Huang WE, Clarke G, Ercolini D, Häggblom M. Microbes Saving Lives and Reducing Suffering. Microb Biotechnol 2025; 18:e70068. [PMID: 39844583 PMCID: PMC11754571 DOI: 10.1111/1751-7915.70068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 11/25/2024] [Indexed: 01/24/2025] Open
Affiliation(s)
- Kenneth Timmis
- Institute of MicrobiologyTechnical University BraunschweigBraunschweigGermany
| | - Zeynep Ceren Karahan
- Department of Medical Microbiology and Ibn‐i Sina Hospital Central Microbiology LaboratoryAnkara University School of MedicineAnkaraTurkey
| | - Juan Luis Ramos
- Consejo Superior de Investigaciones Científicas, Estación Experimental del ZaidínGranadaSpain
| | - Omry Koren
- Azrieli Faculty of MedicineBar‐Ilan UniversitySafedIsrael
| | - Ana Elena Pérez‐Cobas
- Department of Microbiology, Ramón y Cajal Institute for Health Research (IRYCIS)Ramón y Cajal University HospitalMadridSpain
- CIBER in Infectious Diseases (CIBERINFEC)MadridSpain
| | | | - Victor de Lorenzo
- Department of Systems BiologyNational Centre of Biotechnology CSICMadridSpain
| | - Elisabetta Caselli
- Section of Microbiology, Department of Environmental and Prevention SciencesUniversity of FerraraFerraraItaly
| | - Margaret Douglas
- Usher InstituteUniversity of Edinburgh Medical School, and Public Health ScotlandEdinburghUK
| | - Clarissa Schwab
- Department of Biological and Chemical EngineeringAarhus UniversityAarhusDenmark
| | - Virginia Rivero
- Polymer Biotechnology Lab, Biological Research Center Margarita SalasSpanish National Research Council (CIB‐CSIC)MadridSpain
| | - Rafael Giraldo
- Department of Microbial BiotechnologyNational Centre for Biotechnology (CNB‐CSIC)MadridSpain
| | - Junkal Garmendia
- Instituto de AgrobiotecnologíaConsejo Superior de Investigaciones Científicas (IdAB‐CSIC)‐Gobierno de Navarra, MutilvaMadridSpain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES)MadridSpain
| | - Raymond J. Turner
- Department of Biological SciencesUniversity of CalgaryCalgaryAlbertaCanada
| | | | | | - Pablo Ivan Nikel
- The Novo Nordisk Foundation Center for BiosustainabilityTechnical University of DenmarkLyngbyDenmark
| | - Jerome Bonnet
- Centre de Biochimie Structurale, INSERM/CNRSUniversity of MontpellierMontpellierFrance
| | - Angela Sessitsch
- Bioresources UnitAIT Austrian Institute of TechnologyViennaAustria
| | - James K. Timmis
- Department of Political ScienceUniversity of FreiburgFreiburgGermany
- Athena Institute for Research on Innovation and Communication in Health and Life SciencesVrije UniversiteitAmsterdamThe Netherlands
| | - Carla Pruzzo
- Department of Earth, Environmental and Life Sciences (DISTAV)University of GenoaGenovaItaly
| | - M. Auxiliadora Prieto
- Polymer Biotechnology Lab, Biological Research Center Margarita SalasSpanish National Research Council (CIB‐CSIC)MadridSpain
| | - Siavash Isazadeh
- Corporate Technical & PerformanceVeolia North AmericaParamusNew JerseyUSA
| | - Wei E. Huang
- Department of Engineering ScienceUniversity of OxfordOxfordUK
| | - Gerard Clarke
- APC Microbiome IrelandUniversity College CorkCorkIreland
- Department of Psychiatry & Neurobehavioral SciencesUniversity College CorkCorkIreland
| | - Danilo Ercolini
- Department of Agricultural SciencesUniversity of Naples Federico IINaplesItaly
| | - Max Häggblom
- Department of Biochemistry and Microbiology, RutgersThe State University of New JerseyNew BrunswickNew JerseyUSA
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Berding K, Bastiaanssen TFS, Moloney GM, Clarke G, Dinan TG, Cryan JF. Adherence to a psychobiotic diet stabilizes the microbiome and reduces perceived stress: plenty of food for thought. Mol Psychiatry 2025; 30:349-350. [PMID: 39020105 DOI: 10.1038/s41380-024-02674-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 07/08/2024] [Accepted: 07/11/2024] [Indexed: 07/19/2024]
Affiliation(s)
- Kirsten Berding
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Thomaz F S Bastiaanssen
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Gerard M Moloney
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Timothy G Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
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Leon-Derecho CMPD. Microbiome-based therapeutics. HUMAN MICROBIOME DRUG TARGETS 2025:233-244. [DOI: 10.1016/b978-0-443-15435-5.00017-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Castro EM, Lotfipour S, Leslie FM. Neuroglia in substance use disorders. HANDBOOK OF CLINICAL NEUROLOGY 2025; 210:347-369. [PMID: 40148055 DOI: 10.1016/b978-0-443-19102-2.00014-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Abstract
Substance use disorders (SUD) remain a major public health concern in which individuals are unable to control their use of substances despite significant harm and negative consequences. Drugs of abuse dysregulate major brain and behavioral functions. Glial cells, primarily microglia and astrocytes, play a crucial role in these drug-induced molecular and behavioral changes. This review explores preclinical and clinical studies of how neuroglia and their associated neuroinflammatory responses contribute to SUD and reward-related properties. We evaluate preclinical and clinical evidence for targeting neuroglia as therapeutic interventions. In addition, we evaluate the literature on the gut microbiome and its role in SUD. Clinical treatments are most effective for reducing drug cravings, and some have yielded promising results in other measures of drug use. N-Acetylcysteine, through modulation of cysteine-glutamate antiporter of glial cells, shows encouraging results across a variety of drug classes. Neuroglia and gut microbiome interactions are important factors to consider with regard to SUD and could lead to novel therapeutic avenues. Age- and sex-dependent properties of neuroglia, gut microbiome, and drug use behaviors are important areas in need of further investigation.
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Affiliation(s)
- Emily M Castro
- Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, United States
| | - Shahrdad Lotfipour
- Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, United States; Department of Emergency Medicine, School of Medicine, University of California, Irvine, Irvine, CA, United States; Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Irvine, Irvine, CA, United States
| | - Frances M Leslie
- Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, United States.
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Zhao S, Liang S, Tao J, Peng Y, Chen S, Wai HKF, Chung FY, Sin ZY, Wong MKL, Haqq AM, Chang WC, Ni MY, Chan FKL, Ng SC, Tun HM. Probiotics for adults with major depressive disorder compared with antidepressants: a systematic review and network meta-analysis. Nutr Rev 2025; 83:72-82. [PMID: 38219239 DOI: 10.1093/nutrit/nuad171] [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] [Indexed: 01/16/2024] Open
Abstract
CONTEXT Despite recent advances in antidepressants in treating major depression (MDD), their usage is marred by adverse effects and social stigmas. Probiotics may be an efficacious adjunct or standalone treatment, potentially circumventing the aforementioned issues with antidepressants. However, there is a lack of head-to-head clinical trials between these 2 interventions. OBJECTIVE A systematic review and network meta-analysis was conducted to compare the efficacy and acceptability of these 2 interventions in treating MDD. DATA SOURCES Six databases and registry platforms for the clinical trial were systematically searched to identify the eligible double-blinded, randomized controlled trials published between 2015 and 2022. DATA EXACTION Two authors selected independently the placebo-controlled trials of antidepressants and microbiota-targeted interventions (prebiotics, probiotics, and synbiotics) used for the treatment of MDD in adults (≥18 years old). Standardized mean differences (SMDs) of depressive symptom scores from individual trials were pooled for network meta-analysis (PROSPERO no. CRD42020222305). RESULTS Forty-two eligible trials covering 22 interventions were identified, of which 16 were found to be effective in MDD treatment and the certainty of evidence was moderate to very low. When all trials were considered, compared with placebo, SMDs of interventions ranged from -0.16 (95% credible interval: -0.30, -0.04) for venlafaxine to -0.81 (-1.06, -0.52) for escitalopram. Probiotics were superior to brexpiprazole (SMD [95% credible interval]: -0.42 [-0.68, -0.17]), cariprazine (-0.44 [-0.69, -0.24]), citalopram (-0.37 [-0.66, -0.07]), duloxetine (-0.26, [-0.51, -0.04]), desvenlafaxine (-0.38 [-0.63, -0.14]), ketamine (-0.32 [-0.66, -0.01]), venlafaxine (-0.47 [-0.73, -0.23]), vilazodone (-0.37 [-0.61, -0.12]), vortioxetine (-0.39 [-0.63, -0.15]), and placebo (-0.62 [-0.86, -0.42]), and were noninferior to other antidepressants. In addition, probiotics ranked the second highest in the treatment hierarchy after escitalopram. Long-term treatment (≥8 weeks) using probiotics showed the same tolerability as antidepressants. CONCLUSION Probiotics, compared with antidepressants and placebo, may be efficacious as an adjunct or standalone therapy for treating MDD. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42020222305.
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Affiliation(s)
- Shilin Zhao
- Microbiota I-Center (MagIC), Hong Kong Special Administrative Region (SAR), China
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- System Microbiology and Antimicrobial Resistance (SMART) Lab, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Suisha Liang
- Microbiota I-Center (MagIC), Hong Kong Special Administrative Region (SAR), China
- System Microbiology and Antimicrobial Resistance (SMART) Lab, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jun Tao
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Ye Peng
- Microbiota I-Center (MagIC), Hong Kong Special Administrative Region (SAR), China
- System Microbiology and Antimicrobial Resistance (SMART) Lab, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Siqi Chen
- Maternal and Child Medicine Research Institute, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, China
| | - Hogan K F Wai
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Feng-Ying Chung
- Department of Internal Medicine, Taipei Municipal Wanfang Hospital, Taipei, Taiwan
| | - Zhen Y Sin
- System Microbiology and Antimicrobial Resistance (SMART) Lab, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Matthew K L Wong
- Microbiota I-Center (MagIC), Hong Kong Special Administrative Region (SAR), China
- System Microbiology and Antimicrobial Resistance (SMART) Lab, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Andrea M Haqq
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
- Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, Canada
| | - Wing C Chang
- Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Michael Y Ni
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Francis K L Chan
- Microbiota I-Center (MagIC), Hong Kong Special Administrative Region (SAR), China
- Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Siew C Ng
- Microbiota I-Center (MagIC), Hong Kong Special Administrative Region (SAR), China
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Hein M Tun
- Microbiota I-Center (MagIC), Hong Kong Special Administrative Region (SAR), China
- System Microbiology and Antimicrobial Resistance (SMART) Lab, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Ortega MA, Fraile-Martinez O, García-Montero C, Diaz-Pedrero R, Lopez-Gonzalez L, Monserrat J, Barrena-Blázquez S, Alvarez-Mon MA, Lahera G, Alvarez-Mon M. Understanding immune system dysfunction and its context in mood disorders: psychoneuroimmunoendocrinology and clinical interventions. Mil Med Res 2024; 11:80. [PMID: 39681901 DOI: 10.1186/s40779-024-00577-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 11/01/2024] [Indexed: 12/18/2024] Open
Abstract
Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society, being mainly represented by major depressive disorder (MDD) and bipolar disorder (BD). The etiopathogenesis of mood disorders is extremely complex, with a wide spectrum of biological, psychological, and sociocultural factors being responsible for their appearance and development. In this sense, immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders, worsening mainly the central nervous system (neuroinflammation) and the periphery of the body (systemic inflammation). However, these alterations cannot be understood separately, but as part of a complex picture in which different factors and systems interact with each other. Psychoneuroimmunoendocrinology (PNIE) is the area responsible for studying the relationship between these elements and the impact of mind-body integration, placing the immune system as part of a whole. Thus, the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche, damage to the nervous system, alterations to the endocrine and metabolic systems, and disruption of the microbiota and intestinal ecosystem, as well as of other organs and, in turn, all these mechanisms are responsible for inducing and enhancing the immune dysfunction. Similarly, the clinical approach to these patients is usually multidisciplinary, and the therapeutic arsenal includes different pharmacological (for example, antidepressants, antipsychotics, and lithium) and non-pharmacological (i.e., psychotherapy, lifestyle, and electroconvulsive therapy) treatments. These interventions also modulate the immune system and other elements of the PNIE in these patients, which may be interesting to understand the therapeutic success or failure of these approaches. In this sense, this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE. Likewise, an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients, in order to identify the mechanisms described and their possible uses as biomarkers.
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Affiliation(s)
- Miguel A Ortega
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain.
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain.
| | - Oscar Fraile-Martinez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain.
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain.
| | - Raul Diaz-Pedrero
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain
| | - Laura Lopez-Gonzalez
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcala de Henares, Spain
| | - Jorge Monserrat
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
| | - Silvestra Barrena-Blázquez
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Department of Nursing and Physiotherapy, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
| | - Miguel Angel Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, 28031, Madrid, Spain
| | - Guillermo Lahera
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Psychiatry Service, Center for Biomedical Research in the Mental Health Network, University Hospital Príncipe de Asturias, 28806, Alcalá de Henares, Spain
| | - Melchor Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research IRYCIS, 28034, Madrid, Spain
- Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Príncipe de Asturias, CIBEREHD, 28806, Alcalá de Henares, Spain
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Ngah WZW, Ahmad HF, Ankasha SJ, Makpol S, Tooyama I. Dietary Strategies to Mitigate Alzheimer's Disease: Insights into Antioxidant Vitamin Intake and Supplementation with Microbiota-Gut-Brain Axis Cross-Talk. Antioxidants (Basel) 2024; 13:1504. [PMID: 39765832 PMCID: PMC11673287 DOI: 10.3390/antiox13121504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/03/2024] [Accepted: 12/08/2024] [Indexed: 01/11/2025] Open
Abstract
Alzheimer's disease (AD), which is characterized by deterioration in cognitive function and neuronal death, is the most prevalent age-related progressive neurodegenerative disease. Clinical and experimental research has revealed that gut microbiota dysbiosis may be present in AD patients. The changed gut microbiota affects brain function and behavior through several mechanisms, including tau phosphorylation and increased amyloid deposits, neuroinflammation, metabolic abnormalities, and persistent oxidative stress. The lack of effective treatments to halt or reverse the progression of this disease has prompted a search for non-pharmaceutical tools. Modulation of the gut microbiota may be a promising strategy in this regard. This review aims to determine whether specific dietary interventions, particularly antioxidant vitamins, either obtained from the diet or as supplements, may support the formation of beneficial microbiota in order to prevent AD development by contributing to the systemic reduction of chronic inflammation or by acting locally in the gut. Understanding their roles would be beneficial as it may have the potential to be used as a future therapy option for AD patients.
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Affiliation(s)
- Wan Zurinah Wan Ngah
- Medical Innovation Research Center, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan;
| | - Hajar Fauzan Ahmad
- Department of Industrial Biotechnology, Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Gambang 26300, Pahang, Malaysia;
| | - Sheril June Ankasha
- Unisza Science and Medicine Foundation Centre, Universiti Sultan Zainal Abidin, Gong Badak Campus, Kuala Nerus 21300, Terengganu, Malaysia;
| | - Suzana Makpol
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia;
| | - Ikuo Tooyama
- Medical Innovation Research Center, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan;
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46
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Li C, Chen S, Wang Y, Su Q. Microbiome-Based Therapeutics for Insomnia. Int J Mol Sci 2024; 25:13208. [PMID: 39684918 DOI: 10.3390/ijms252313208] [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: 10/25/2024] [Revised: 11/25/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
Insomnia poses considerable risks to both physical and mental health, leading to cognitive impairment, weakened immune function, metabolic dysfunction, cardiovascular issues, and reduced quality of life. Given the significant global increase in insomnia and the growing scientific evidence connecting gut microbiota to this disorder, targeting gut microbiota as an intervention for insomnia has gained popularity. In this review, we summarize current microbiome-based therapeutics for insomnia, including dietary modifications; probiotic, prebiotic, postbiotic, and synbiotic interventions; and fecal microbiota transplantation. Moreover, we assess the capabilities and weaknesses of these technologies to offer valuable insights for future studies.
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Affiliation(s)
- Chenyu Li
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Sizhe Chen
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yun Wang
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Qi Su
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
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47
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Parkar N, Young W, Olson T, Hurst C, Janssen P, Spencer NJ, McNabb WC, Dalziel JE. Peripherally Restricted Activation of Opioid Receptors Influences Anxiety-Related Behaviour and Alters Brain Gene Expression in a Sex-Specific Manner. Int J Mol Sci 2024; 25:13183. [PMID: 39684893 DOI: 10.3390/ijms252313183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 11/26/2024] [Accepted: 12/04/2024] [Indexed: 12/18/2024] Open
Abstract
Although effects of stress-induced anxiety on the gastrointestinal tract and enteric nervous system (ENS) are well studied, how ENS dysfunction impacts behaviour is not well understood. We investigated whether ENS modulation alters anxiety-related behaviour in rats. We used loperamide, a potent μ-opioid receptor agonist that does not cross the blood-brain barrier, to manipulate ENS function and assess changes in behaviour, gut and brain gene expression, and microbiota profile. Sprague Dawley (male/female) rats were acutely dosed with loperamide (subcutaneous) or control solution, and their behavioural phenotype was examined using open field and elevated plus maze tests. Gene expression in the proximal colon, prefrontal cortex, hippocampus, and amygdala was assessed by RNA-seq and caecal microbiota composition determined by shotgun metagenome sequencing. In female rats, loperamide treatment decreased distance moved and frequency of supported rearing, indicating decreased exploratory behaviour and increased anxiety, which was associated with altered hippocampal gene expression. Loperamide altered proximal colon gene expression and microbiome composition in both male and female rats. Our results demonstrate the importance of the ENS for communication between gut and brain for normo-anxious states in female rats and implicate corticotropin-releasing hormone and gamma-aminobutyric acid gene signalling pathways in the hippocampus. This study also sheds light on sexually dimorphic communication between the gut and the brain. Microbiome and colonic gene expression changes likely reflect localised effects of loperamide related to gut dysmotility. These results suggest possible ENS pharmacological targets to alter gut to brain signalling for modulating mood.
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Affiliation(s)
- Nabil Parkar
- AgResearch, Palmerston North 4410, New Zealand
- Riddet Institute, Massey University, Palmerston North 4410, New Zealand
- School of Food and Advanced Technology, Massey University, Palmerston North 4410, New Zealand
| | - Wayne Young
- AgResearch, Palmerston North 4410, New Zealand
- Riddet Institute, Massey University, Palmerston North 4410, New Zealand
| | - Trent Olson
- AgResearch, Palmerston North 4410, New Zealand
| | | | - Patrick Janssen
- School of Food and Advanced Technology, Massey University, Palmerston North 4410, New Zealand
| | - Nick J Spencer
- College of Medicine and Public Health, Flinders Health & Medical Research Institute, Bedford Park, Adelaide, SA 5042, Australia
| | - Warren C McNabb
- Riddet Institute, Massey University, Palmerston North 4410, New Zealand
| | - Julie E Dalziel
- AgResearch, Palmerston North 4410, New Zealand
- Riddet Institute, Massey University, Palmerston North 4410, New Zealand
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Pan I, Issac PK, Rahman MM, Guru A, Arockiaraj J. Gut-Brain Axis a Key Player to Control Gut Dysbiosis in Neurological Diseases. Mol Neurobiol 2024; 61:9873-9891. [PMID: 37851313 DOI: 10.1007/s12035-023-03691-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/02/2023] [Indexed: 10/19/2023]
Abstract
Parkinson's disease is a chronic neuropathy characterised by the formation of Lewy bodies (misfolded alpha-synuclein) in dopaminergic neurons of the substantia nigra and other parts of the brain. Dopaminergic neurons play a vital role in generating both motor and non-motor symptoms. Finding therapeutic targets for Parkinson's disease (PD) is hindered due to an incomplete understanding of the disease's pathophysiology. Existing evidence suggests that the gut microbiota participates in the pathogenesis of PD via immunological, neuroendocrine, and direct neural mechanisms. Gut microbial dysbiosis triggers the loss of dopaminergic neurons via mitochondrial dysfunction. Gut dysbiosis triggers bacterial overgrowth in the small intestine, which increases the permeability barrier and induces systemic inflammation. It results in excessive stimulation of the innate immune system. In addition to that, activation of enteric neurons and enteric glial cells initiates the aggregation of alpha-synuclein. This alpha-synucleinopathy thus affects all levels of the brain-gut axis, including the central, autonomic, and enteric nervous systems. Though the neurobiological signaling cascade between the gut microbiome and the central nervous system is poorly understood, gut microbial metabolites may serve as a promising therapeutic strategy for PD. This article summarises all the known possible ways of bidirectional signal communication, i.e., the "gut-brain axis," where microbes from the middle gut interact with the brain and vice versa, and highlights a unique way to treat neurodegenerative diseases by maintaining homeostasis. The tenth cranial nerve (vagus nerve) plays a significant part in this signal communication. However, the leading regulatory factor for this axis is a diet that helps with microbial colonisation and brain function. Short-chain fatty acids (SCFAs), derived from microbially fermented dietary fibres, link host nutrition to maintain intestinal homeostasis. In addition to that, probiotics modulate cognitive function and the metabolic and behavioural conditions of the body. As technology advances, new techniques will emerge to study the tie-up between gut microbes and neuronal diseases.
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Affiliation(s)
- Ieshita Pan
- Institute of Biotechnology, Department of Medical Biotechnology and Integrative Physiology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, Tamil Nadu, 602105, India.
| | - Praveen Kumar Issac
- Institute of Biotechnology, Department of Medical Biotechnology and Integrative Physiology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, Tamil Nadu, 602105, India
| | - Md Mostafizur Rahman
- Laboratory of Environmental Health and Ecotoxicology, Department of Environmental Sciences, Jahangirnagar University, Dhaka, 1342, Bangladesh
| | - Ajay Guru
- Department of Cariology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
| | - Jesu Arockiaraj
- Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulatur, Chengalpattu District, Tamil Nadu, 603203, India.
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49
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Zhang JX, Li QL, Wang XY, Zhang CC, Chen ST, Liu XH, Dong XY, Zhao H, Huang DH. Causal Link between Gut Microbiota and Infertility: A Two-sample Bidirectional Mendelian Randomization Study. Curr Med Sci 2024; 44:1312-1324. [PMID: 39551855 DOI: 10.1007/s11596-024-2931-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: 01/30/2024] [Accepted: 06/12/2024] [Indexed: 11/19/2024]
Abstract
OBJECTIVE To investigate the associations of the gut microbiota with reproductive system diseases, including female infertility, male infertility, polycystic ovary syndrome (PCOS), primary ovarian failure, endometriosis, uterine fibroids, uterine polyps, sexual dysfunction, orchitis, and epididymitis. METHODS A two-sample bidirectional Mendelian randomization (MR) analysis was performed to evaluate the potential causal relationship between the composition of gut microbiota and infertility, along with associated diseases. RESULTS Sixteen strong causal associations between gut microbes and reproductive system diseases were identified. Sixty-one causal associations between gut microbes and reproductive system diseases were determined. The genus Eubacterium hallii was a protective factor against premature ovarian failure and a pathogenic factor of endometriosis. The genus Erysipelatoclostridium was the pathogenic factor of many diseases, such as PCOS, endometriosis, epididymitis, and orchitis. The genus Intestinibacter is a pathogenic factor of male infertility and sexual dysfunction. The family Clostridiaceae 1 was a protective factor against uterine polyps and a pathogenic factor of orchitis and epididymitis. The results of reverse causal association analysis revealed that endometriosis, orchitis, and epididymitis all led to a decrease in the abundance of bifidobacteria and that female infertility-related diseases had a greater impact on gut microbes than male infertility-related diseases did. CONCLUSIONS The findings from the MR analysis indicate that there is a bidirectional causal relationship between the gut microbiota and infertility as well as associated ailments. Compared with ovarian diseases, uterine diseases are more likely to lead to changes in women's gut microbiota. The findings of this research offer valuable perspectives on the mechanism and clinical investigation of reproductive system diseases caused by microorganisms.
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Affiliation(s)
- Jia-Xin Zhang
- Institute of Reproduction Health Research, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Qin-Lan Li
- Institute of Reproduction Health Research, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xiao-Yan Wang
- Reproductive Center, Qingdao Women and Children's Hospital Affiliated to Qingdao University, Qingdao, 266034, China
| | - Cheng-Chang Zhang
- Institute of Reproduction Health Research, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Shu-Ting Chen
- Institute of Reproduction Health Research, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xiao-Hang Liu
- Institute of Reproduction Health Research, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xin-Yi Dong
- Institute of Reproduction Health Research, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Hu Zhao
- Department of Human Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- National Demonstration Center for Experimental Basic Medical Education, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Dong-Hui Huang
- Institute of Reproduction Health Research, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518109, China.
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Cheng H, Liu J, Zhang D, Wu J, Wu J, Zhou Y, Tan Y, Feng W, Peng C. Natural products: Harnessing the power of gut microbiota for neurological health. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156019. [PMID: 39305747 DOI: 10.1016/j.phymed.2024.156019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 05/19/2024] [Accepted: 09/01/2024] [Indexed: 12/01/2024]
Abstract
BACKGROUND Neurological diseases are the primary cause of disability and death and impose substantial financial burdens. However, existing treatments only relieve symptoms and may cause many adverse effects. Natural products are a promising source of neurological therapeutic agents due to their excellent neuroprotective effect and safety. The gut microbiota has an essential impact on maintaining brain homeostasis via the gut-brain axis. Multiple investigations show that natural products offer neuroprotective effects by regulating gut microbiota-driven signaling networks. OBJECTIVES This review aims to provide a systematic review of how natural products promote neurological health by harnessing the power of gut microbiota. METHODS The pre-January 1, 2024 literature was gathered from several databases, including Scopus, PubMed, Google Scholar, and Web of Science, utilizing appropriate keywords. The gathered publications underwent a review process and were classified based on their study content, specifically focusing on the impact of natural products on gut microbiota and neurological health. RESULTS Here, we review how natural products promote neurological health by regulating the gut microbiota-brain axis. Specifically, we focus on the following areas. (1) Altering microorganism community structure, including increasing α-diversity and altering β-diversity. (2) Regulating the population of certain bacteria, including enriching beneficial microorganisms Akkermansia and Bifidobacterium, and inhibiting potentially hazardous microorganisms Bilophila, Klebsiella, and Helicobacter. (3) Regulating microbial neuroactive metabolites levels, including short-chain fatty acids, tryptophan and its derivatives, trimethylamine N-oxide, dopa/dopamine, γ-aminobutyric acid, and lipopolysaccharide. Furthermore, we review how natural products promote neurological health by regulating intestinal barrier homeostasis. CONCLUSION Natural products promote neurological health by harnessing the power of gut microbiota. This review will contribute to understanding how natural products promote neurological health by orchestrating the gut microbiota-brain axis.
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Affiliation(s)
- Hao Cheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Juan Liu
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Dandan Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jing Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinlu Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yaochuan Zhou
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yuzhu Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wuwen Feng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
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