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Sall I, Foxall R, Felth L, Maret S, Rosa Z, Gaur A, Calawa J, Pavlik N, Whistler JL, Whistler CA. Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine. Gut Microbes 2025; 17:2446423. [PMID: 39800714 PMCID: PMC11730370 DOI: 10.1080/19490976.2024.2446423] [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: 04/16/2024] [Revised: 11/24/2024] [Accepted: 12/18/2024] [Indexed: 01/16/2025] Open
Abstract
The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.
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Affiliation(s)
- Izabella Sall
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
- Graduate program in Molecular and Evolutionary Systems Biology, University of New Hampshire, Durham, NH, USA
| | - Randi Foxall
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
| | - Lindsey Felth
- Center for Neuroscience, University of California–Davis, Davis, CA, USA
| | - Soren Maret
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
| | - Zachary Rosa
- Center for Neuroscience, University of California–Davis, Davis, CA, USA
| | - Anirudh Gaur
- Center for Neuroscience, University of California–Davis, Davis, CA, USA
| | - Jennifer Calawa
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
- Microbiology Graduate Program, University of New Hampshire, Durham, NH, USA
| | - Nadia Pavlik
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
| | - Jennifer L. Whistler
- Center for Neuroscience, University of California–Davis, Davis, CA, USA
- Department of Physiology and Membrane Biology, UC Davis School of Medicine, Davis, CA, USA
| | - Cheryl A. Whistler
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
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2
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Singh S, Abu Y, Antoine D, Gomez D, Tao J, Truitt B, Roy S. Probiotic supplementation mitigates sex-dependent nociceptive changes and gut dysbiosis induced by prenatal opioid exposure. Gut Microbes 2025; 17:2464942. [PMID: 39950489 PMCID: PMC11834462 DOI: 10.1080/19490976.2025.2464942] [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: 06/20/2024] [Revised: 11/21/2024] [Accepted: 02/04/2025] [Indexed: 02/20/2025] Open
Abstract
The gut microbiome has emerged as a promising target for modulating adverse effects of opioid exposure due to its significant role in health and disease. Opioid use disorder (OUD) has become increasingly prevalent, specifically in women of reproductive age, contributing to an increased incidence of offspring exposed to opioids in utero. Recent studies have shown that prenatal opioid exposure (POE) is associated with notable changes to the maternal gut microbiome, with subsequent implications for the offspring's microbiome and other adverse outcomes. However, the role of the gut microbiome in mediating sex-based differences in pain sensitivity has not yet been investigated. In this study, both male and female C57BL/6 offspring were used to determine sex-based differences in nociception and gut microbial composition as a result of POE. Our data reveals significant sex-based differences in offspring prenatally exposed to opioids. The gut microbiome of opioid-exposed females showed an enrichment of commensal bacteria including Lactobacillus compared to opioid-exposed males. Additionally, POE females demonstrated decreased nociceptive sensitivity, while males demonstrated increased nociceptive sensitivity. RNA sequencing of the prefrontal cortex showed sex-based differences in several canonical pathways, including an increase in the opioid signaling pathway of opioid-exposed females, which was not observed in males. Microbiome modification via maternal probiotic supplementation attenuated sex-based differences throughout the early stages of life. Together, our study provides further insight on sex-based differences arising from POE and highlights the pivotal role of the gut microbiome as a modifiable target for mitigating its negative effects.
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Affiliation(s)
- Salma Singh
- Department of Surgery, School of Medicine, University of Miami Miller, Miami, USA
| | - Yaa Abu
- Department of Surgery, School of Medicine, University of Miami Miller, Miami, USA
| | - Danielle Antoine
- Department of Surgery, School of Medicine, University of Miami Miller, Miami, USA
- Department of Neuroscience, School of Medicine, University of Miami Miller, Miami, USA
| | - Daniel Gomez
- Department of Surgery, School of Medicine, University of Miami Miller, Miami, USA
| | - Junyi Tao
- Department of Surgery, School of Medicine, University of Miami Miller, Miami, USA
| | - Bridget Truitt
- Department of Surgery, School of Medicine, University of Miami Miller, Miami, USA
- Department of Neuroscience, School of Medicine, University of Miami Miller, Miami, USA
| | - Sabita Roy
- Department of Surgery, School of Medicine, University of Miami Miller, Miami, USA
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Takyi E, Nirmalkar K, Adams J, Krajmalnik-Brown R. Interventions targeting the gut microbiota and their possible effect on gastrointestinal and neurobehavioral symptoms in autism spectrum disorder. Gut Microbes 2025; 17:2499580. [PMID: 40376856 PMCID: PMC12087657 DOI: 10.1080/19490976.2025.2499580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 04/22/2025] [Accepted: 04/24/2025] [Indexed: 05/18/2025] Open
Abstract
Autism spectrum disorder (ASD) is a developmental disorder that is characterized by deficits in social communication and restricted, repetitive, and stereotyped behaviors. In addition to neurobehavioral symptoms, children with ASD often have gastrointestinal symptoms (e.g. constipation, diarrhea, gas, abdominal pain, reflux). Several studies have proposed the role of gut microbiota and metabolic disorders in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients; these results offer promising avenues for novel treatments of this disorder. Interventions targeting the gut microbiota - such as fecal microbiota transplant (FMT), microbiota transplant therapy (MTT), probiotics, prebiotics, synbiotics, antibiotics, antifungals, and diet - promise to improve gut health and can potentially improve neurological symptoms. The modulation of the gut microbiota using MTT in ASD has shown beneficial and long-term effects on GI symptoms and core symptoms of autism. Also, the modulation of the gut microbiota to resemble that of typically developing individuals seems to be the most promising intervention. As most of the studies carried out with MTT are open-label studies, more extensive double-blinded randomized control trials are needed to confirm the efficacy of MTT as a therapeutic option for ASD. This review examines the current clinical research evidence for the use of interventions that target the microbiome - such as antibiotics, antifungals, probiotics/prebiotics, synbiotics, and MTT - and their effectiveness in changing the gut microbiota and improving gastrointestinal and neurobehavioral symptoms in ASD.
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Affiliation(s)
- Evelyn Takyi
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
| | - Khemlal Nirmalkar
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
| | - James Adams
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
- School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, USA
| | - Rosa Krajmalnik-Brown
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
- School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ, USA
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4
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Wang X, Hu M, Wu W, Lou X, Gao R, Ma T, Dheen ST, Cheng J, Xiong J, Chen X, Wang J. Indole derivatives ameliorated the methamphetamine-induced depression and anxiety via aryl hydrocarbon receptor along "microbiota-brain" axis. Gut Microbes 2025; 17:2470386. [PMID: 39996473 PMCID: PMC11864316 DOI: 10.1080/19490976.2025.2470386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 01/24/2025] [Accepted: 02/17/2025] [Indexed: 02/26/2025] Open
Abstract
In addition to the high neurotoxicity, depression, and anxiety are the most prominent characteristics of methamphetamine (Meth) withdrawal. Studies to date on the issue of Meth-associated depression and anxiety are focused on the brain, however, whether peripheral homeostasis, especially the "microbiota-gut" axis participates in these adverse outcomes, remains poorly understood. In the current study, with the fecal microbiota transplantation (FMT) assay, the mice received microbiota from Meth withdrawal mice displayed marked depression and anxiety behaviors. The 16S rRNA sequencing results showed that Meth withdrawal contributed to a striking reduction of Akkermansia, Bacteroides, Faecalibaculum, Desulfovibrio, and Anaerostipes, which are known to be associated with tryptophan (TRP) metabolism. Noteworthily, the substantial decreases of the indole derivatives from the TRP metabolic pathway, including IAA, IPA, ILA, IET, IArA, IAld, and TRM were observed in the serum of both Meth abusing humans and mice during Meth withdrawal with the UHPLC-MS/MS analysis. Combining the high and low TRP diet mouse model, the mice with high TRP diet obviously impeded Meth-associated depression and anxiety behaviors, and these results were further strengthened by the evidence that administration of IPA, IAA, and indole dramatically ameliorated the Meth induced aberrant behaviors. Importantly, these protective effects were remarkably counteracted in aryl hydrocarbon receptor knockout (AhR KO) mice, underlining the key roles of microbiota-indoles-AhR signaling in Meth-associated depression and anxiety. Collectively, the important contribution of the present work is that we provide the first evidence that peripheral gut homeostasis disturbance but not limited to the brain, plays a key role in driving the Meth-induced depression and anxiety in the periods of withdrawal, especially the microbiota and the indole metabolic disturbance. Therefore, targeting AhR may provide novel insight into the therapeutic strategies for Meth-associated psychological disorders.
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Affiliation(s)
- Xi Wang
- Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Miaoyang Hu
- Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Weilan Wu
- Department of Hygienic Analysis and Detection, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xinyu Lou
- Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Rong Gao
- Department of Hygienic Analysis and Detection, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Tengfei Ma
- Stem Cell and Neural Regeneration and Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China
| | - S Thameem Dheen
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jie Cheng
- Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Jianping Xiong
- Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xufeng Chen
- Department of Emergency Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jun Wang
- Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
- Department of Emergency Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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5
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Li P, Li M, Chen WH. Best practices for developing microbiome-based disease diagnostic classifiers through machine learning. Gut Microbes 2025; 17:2489074. [PMID: 40186338 PMCID: PMC11980492 DOI: 10.1080/19490976.2025.2489074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 03/13/2025] [Accepted: 03/28/2025] [Indexed: 04/07/2025] Open
Abstract
The human gut microbiome, crucial in various diseases, can be utilized to develop diagnostic models through machine learning (ML). The specific tools and parameters used in model construction such as data preprocessing, batch effect removal and modeling algorithms can impact model performance and generalizability. To establish an generally applicable workflow, we divided the ML process into three above-mentioned steps and optimized each sequentially using 83 gut microbiome cohorts across 20 diseases. We tested a total of 156 tool-parameter-algorithm combinations and benchmarked them according to internal- and external- AUCs. At the data preprocessing step, we identified four data preprocessing methods that performed well for regression-type algorithms and one method that excelled for non-regression-type algorithms. At the batch effect removal step, we identified the "ComBat" function from the sva R package as an effective batch effect removal method and compared the performance of various algorithms. Finally, at the ML algorithm selection step, we found that Ridge and Random Forest ranked the best. Our optimized work flow performed similarly comparing with previous exhaustive methods for disease-specific optimizations, thus is generally applicable and can provide a comprehensive guideline for constructing diagnostic models for a range of diseases, potentially serving as a powerful tool for future medical diagnostics.
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Affiliation(s)
- Peikun Li
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular Imaging, Center for Artificial Intelligence Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Min Li
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular Imaging, Center for Artificial Intelligence Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wei-Hua Chen
- Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular Imaging, Center for Artificial Intelligence Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China
- School of Biological Science, Jining Medical University, Rizhao, China
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6
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Rosell-Cardona C, Collins MK, O'Riordan KJ, Goodson MS, Kelley-Loughnane N, Cryan JF, Clarke G. Acute stress enhances synaptic plasticity in male mice via a microbiota-dependent mechanism. Neuropharmacology 2025; 273:110434. [PMID: 40154944 DOI: 10.1016/j.neuropharm.2025.110434] [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: 01/07/2025] [Revised: 03/25/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
Acute stress can enhance or impair synaptic plasticity depending on the nature, duration, and type of stress exposure as well as the brain region examined. The absence of a gut microbiome can also alter hippocampal plasticity. However, the possible interplay between synaptic plasticity, acute stress, and the gut microbiota remains unknown. Here, we examine this interaction and determine whether the gut microbiota impacts stress-induced alterations in hippocampal plasticity. Further, we explored whether exposure to the microbial metabolite butyrate is sufficient to counteract stress-induced alterations in synaptic plasticity. We used electrophysiological and molecular experiments in adult male C57/BL6 antibiotic-treated and acutely stressed mice. In electrophysiological experiments we treated hippocampal slices with 3 μM sodium butyrate to explore the effect of this microbial metabolite. We found the presence of the microbiota essential for the enhancement of both short- and long-term potentiation induced by 15 min of acute restraint stress. Furthermore, butyrate exposure effectively restored the stress-induced enhancement of potentiation in slices from microbiome-depleted animals while also enhancing long-term potentiation independent of stress. In addition, alterations of hippocampal synaptic plasticity markers were noted. Our findings highlight a critical new temporal role for gut-derived metabolites in defining the impact of acute stress on synaptic plasticity.
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Affiliation(s)
| | - Michael K Collins
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | | | - Michael S Goodson
- 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH, USA
| | - Nancy Kelley-Loughnane
- 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH, USA
| | - John F Cryan
- 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.
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7
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Haq SU, Ling W, Aqib AI, Danmei H, Aleem MT, Fatima M, Ahmad S, Gao F. Exploring the intricacies of antimicrobial resistance: Understanding mechanisms, overcoming challenges, and pioneering innovative solutions. Eur J Pharmacol 2025; 998:177511. [PMID: 40090539 DOI: 10.1016/j.ejphar.2025.177511] [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: 11/15/2024] [Revised: 03/07/2025] [Accepted: 03/14/2025] [Indexed: 03/18/2025]
Abstract
Antimicrobial resistance (AMR) poses a growing global threat. This review examines AMR from diverse angles, tracing the story of antibiotic resistance from its origins to today's crisis. It explores the rise of AMR, from its historical roots to the urgent need to counter this escalating menace. The review explores antibiotic classes, mechanisms, resistance profiles, and genetics. It details bacterial resistance mechanisms with illustrative examples. Multidrug-resistant bacteria spotlight AMR's resilience. Modern AMR control offers hope through precision medicine, stewardship, combination therapy, surveillance, and international cooperation. Converging traditional and innovative treatments presents an exciting frontier as novel compounds seek to enhance antibiotic efficacy. This review calls for global unity and proactive engagement to address AMR collectively, emphasizing the quest for innovative solutions and responsible antibiotic use. It underscores the interconnectedness of science, responsibility, and action in combatting AMR. Humanity faces a choice between antibiotic efficacy and obsolescence. The call is clear: unite, innovate, and prevail against AMR.
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Affiliation(s)
- Shahbaz Ul Haq
- Department of Pharmacology, Shantou University Medical College, Shantou, 515041, China.
| | - Wang Ling
- Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou, 730050, China
| | - Amjad Islam Aqib
- Department of Medicine, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 63100, Pakistan
| | - Huang Danmei
- Department of Pharmacology, Shantou University Medical College, Shantou, 515041, China
| | - Muhammad Tahir Aleem
- Department of Pharmacology, Shantou University Medical College, Shantou, 515041, China
| | - Mahreen Fatima
- Faculty of Biosciences, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 63100, Pakistan
| | - Saad Ahmad
- Engineering & Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Fenfei Gao
- Department of Pharmacology, Shantou University Medical College, Shantou, 515041, China.
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8
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Han Y, Zhou S, Yang Y, Hu S, Zhang W, Shen G, Peng C. Further negative effect of fibrous microplastics to the bioaccumulation and toxicity of decabromodiphenyl ethane on zebrafish. THE SCIENCE OF THE TOTAL ENVIRONMENT 2025; 980:179577. [PMID: 40319805 DOI: 10.1016/j.scitotenv.2025.179577] [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: 10/14/2024] [Revised: 04/06/2025] [Accepted: 04/28/2025] [Indexed: 05/07/2025]
Abstract
Co-pollution of microplastics (MPs) and novel brominated flame retardants (NBFRs) in aquatic environments is becoming increasingly common in aquatic environments, raising concerns about their comprehensive ecological impacts. This study investigated the effects of fibrous polyethylene terephthalate (PET) MPs on the bioaccumulation and toxicity of decabromodiphenyl ethane (DBDPE) in zebrafish (Danio rerio). In a 28-day water exposure experiment, co-exposure of fibrous MPs and DBDPE significantly increased the bioavailability of DBDPE in zebrafish and prolonged the half-life of DBDPE in vivo. The elimination rates of DBDPE concentration in muscles of single DBDPE exposure and co-exposure groups were 61.58 % and 56.63 %, respectively. Additionally, the co-exposure exacerbated intestinal damage, including structural deterioration and nutrients depletion, disrupted gut microbiota, promoted the enrichment of genes related to reproductive toxicity, and affected the gut-brain axis, indicating complex toxic interactions in zebrafish. Furthermore, genera of Aurantimicrobium, Cypionkella, and Gemmobacter were the gut microbes significantly associated with main differentially expressed genes(DEGs)in the brain. This study emphasized the exacerbating role of fibrous MPs in DBDPE toxicity, providing new insights into the ecological risks posed by the coexistence of MPs and NBFRs in aquatic ecosystems.
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Affiliation(s)
- Yanna Han
- School of Resource and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Shanqi Zhou
- School of Resource and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China; Xianghu Laboratory, Hangzhou 311231, China
| | - Yuhe Yang
- School of Resource and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Shuangqing Hu
- State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Academy of Environment Sciences, Shanghai 200233, China
| | - Wei Zhang
- School of Resource and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Genxiang Shen
- State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Academy of Environment Sciences, Shanghai 200233, China
| | - Cheng Peng
- School of Resource and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China; State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Academy of Environment Sciences, Shanghai 200233, China.
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9
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Li P, Wang S, Li J, Xiao Z, Zhu H, Sheng D, Liu W, Xiao B, Zhou L. Appraising the Effects of Gut Microbiota on Insomnia Risk Through Genetic Causal Analysis. Am J Med Genet B Neuropsychiatr Genet 2025; 198:e33021. [PMID: 39754389 DOI: 10.1002/ajmg.b.33021] [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: 01/09/2024] [Revised: 11/12/2024] [Accepted: 12/16/2024] [Indexed: 01/06/2025]
Abstract
BackgroundInsomnia is a common neurological disorder that exhibits connections with the gut microbiota; however, the exact causal relationship remains unclear. MethodsWe conducted a Mendelian randomization (MR) study to systematically evaluate the causal effects of genus-level gut microbiota on insomnia risk in individuals of European ancestry. Summary-level datasets on gut microbiota were sourced from the genome-wide association study (GWAS) of MiBioGen, while datasets on insomnia were obtained from the GWAS of Neale Lab and FinnGen. The primary analytical approach used was the inverse-variance weighted (IVW) method, supplemented by MR-Egger, maximum likelihood, MR-robust adjusted profile score, and weighted median. Sensitivity analyses were conducted to ensure robustness. ResultsThe microbial taxa Enterorhabdus, Family XIII AD3011 group, Paraprevotella, and Lachnospiraceae UCG004 were associated with an increased risk of insomnia, whereas Coprococcus1, Coprobacter, Desulfovibrio, Flavonifractor, Olsenella, Odoribacter, and Oscillibacter were linked to a decreased risk. Regarding the insomnia phenotype characterized by trouble falling asleep, the microbial taxon Eisenbergiella was correlated with an increased risk, while Haemophilus and the Eubacterium brachy group were associated with a reduced risk. Furthermore, for the insomnia phenotype characterized by waking too early, the microbial taxa Family XIII UCG001, Lachnospiraceae FCS020 group, and Olsenella were linked to an increased risk, whereas the Eubacterium brachy group and Victivallis were associated with a lower risk. The results remained robust across all sensitivity analyses. ConclusionOur MR study identified multiple genus-level gut microbial taxa that may exhibit potential causal effects on insomnia from a genetic perspective. These findings provide evidence supporting the theory of the microbiota-gut-brain axis and offer new insights into potential prevention and therapeutic targets for insomnia.
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Affiliation(s)
- Peihong Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
| | - Song Wang
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jiaxin Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zheng Xiao
- Department of Pathology, First Hospital of Changsha, Changsha, Hunan, China
| | - Haoyue Zhu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Dandan Sheng
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Weiping Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Bo Xiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Luo Zhou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
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10
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Younger DS. Pediatric early-onset neuropsychiatric obsessive compulsive disorders. J Psychiatr Res 2025; 186:84-97. [PMID: 40222306 DOI: 10.1016/j.jpsychires.2025.03.050] [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: 01/09/2025] [Revised: 03/06/2025] [Accepted: 03/25/2025] [Indexed: 04/15/2025]
Abstract
At the time of this writing, most pediatricians or child psychiatrists will probably have treated a child with early acute-onset obsessive compulsive disorder (OCD) behaviors due to the pediatric autoimmune neuropsychiatric disorder associated with Group A beta-hemolytic streptococcus, abbreviated PANDAS, described more than two decades ago; or Tourette syndrome, incorporating motor and vocal tics, described more than a century ago. One typically self-limited post-infectious OCD resulting from exposure to other putative microbial disease triggers defines PANS, abbreviating pediatric autoimmune neuropsychiatric syndrome. Tourette syndrome, PANDAS and PANS share overlapping neuroimaging features of hypometabolism of the medial temporal lobe and hippocampus on brain 18Fluorodeoxyglucose positron emission tomography fused to magnetic resonance imaging (PET/MRI) consistent with involvement of common central nervous system (CNS) pathways for the shared clinical expression of OCD. The field of pediatric neuropsychiatric disorders manifesting OCD behaviors is at a crossroads commensurate with recent advances in the neurobiology of the medial temporal area, with its wide-ranging connectivity and cortical cross-talk, and CNS immune responsiveness through resident microglia. This review advances the field of pediatric neuropsychiatric disorders and in particular PANS, by providing insights through clinical vignettes and descriptive clinical and neuroimaging correlations from the author's file. Neuroscience collaborations with child psychiatry and infectious disease practitioners are needed to design clinical trials with the necessary rigor to provide meaningful insights into the rational clinical management of PANS with the aim of developing evidence-based guidelines for the clinical management of early, abrupt-onset childhood OCD to avert potentially life-long neuropsychological struggles.
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Affiliation(s)
- David S Younger
- Department of Clinical Medicine and Neuroscience, CUNY School of Medicine, And the Department of Medicine, Section of Internal Medicine and Neurology, White Plains Hospital, White Plains, NY, USA.
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Tiwari S, Paramanik V. Lactobacillus fermentum ATCC 9338 Supplementation Prevents Depressive-Like Behaviors Through Glucocorticoid Receptor and N-Methyl-D-aspartate2b in Chronic Unpredictable Mild Stress Mouse Model. Mol Neurobiol 2025; 62:7927-7944. [PMID: 39956887 DOI: 10.1007/s12035-025-04738-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 01/31/2025] [Indexed: 02/18/2025]
Abstract
Depression is a long-term, related to stress neuropsychiatric disorder, leading to psychological health issues including worthlessness, anhedonia, sleep and appetite disturbances, dysregulated HPA axis, neuronal cell death, and alterations in the gut microbiota (GM). Dysregulated HPA axis increases level of glucocorticoids that induce proinflammatory response with activation of abnormal kynurenine pathway via metabolizing indoleamine-2,3-dioxygenase (IDO). Kynurenine pathway leads to excitotoxicity of N-methyl-D-aspartate (NMDA) receptor responsible for neuronal cell death. Further, probiotics supplementation gained attention from researchers and clinicians to treat neuropsychiatric diseases. GM alteration remains a key reason for depression; however, there is limited information about the role of probiotics on depression involving glucocorticoid receptor and NMDA excitotoxicity through IDO. Chronic unpredictable mild stress (CUMS) model was prepared to check the role of Lactobacillus fermentum ATCC 9338 (LF) and 1-methyl-D-tryptophan (1-MT) in depression. Herein, mice were placed into experimental groups: control, CUMS stressed, CUMS vehicle, CUMS LF, CUMS 1-MT, and CUMS UT (untreated). Results showed that peroral administration of 1 × 108 CFU/day/mouse LF and intraperitoneal dose of 1-MT (15 mg/kg BW/day) alleviate depressive-like behavior and improve motor coordination and walking patterns. Mice supplemented with LF and 1-MT exhibited a decreased expression of GR and NMDAR2b in the cortex, hippocampus, and medulla. Acetylcholinesterase, SOD, and CAT activities were improved in CUMS mice with supplementation of LF and 1-MT. The GM abundance in LF mice was similar to that in control mice. Such study suggests the roles of LF and 1-MT in depression and oxidative stress, and helpful to understand their therapeutic potential through the HPA axis and IDO.
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Affiliation(s)
- Sneha Tiwari
- Cellular and Molecular Neurobiology and Drug Targeting Laboratory, Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh-484 887, India
| | - Vijay Paramanik
- Cellular and Molecular Neurobiology and Drug Targeting Laboratory, Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh-484 887, India.
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12
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Cao Q, Shen M, Li R, Liu Y, Zeng Z, Zhou J, Niu D, Zhang Q, Wang R, Yao J, Zhang G. Elucidating the specific mechanisms of the gut-brain axis: the short-chain fatty acids-microglia pathway. J Neuroinflammation 2025; 22:133. [PMID: 40400035 PMCID: PMC12093714 DOI: 10.1186/s12974-025-03454-y] [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: 03/04/2025] [Accepted: 04/22/2025] [Indexed: 05/23/2025] Open
Abstract
In recent years, the gut microbiota has been increasingly recognized for its influence on various central nervous system diseases mediated by microglia, yet the underlying mechanisms remain unclear. As key metabolites of the gut microbiota, short-chain fatty acids (SCFAs) have emerged as a focal point in understanding microglia-related interactions. In this review, we further refine the connection between the gut microbiota and microglia by introducing the concept of the "SCFAs-microglia" pathway. We summarize current knowledge on this pathway, recent discoveries regarding its role in neurological diseases, and potential pharmacological strategies targeting it. Finally, we outlined the current challenges and limitations in this field of research. We hope this review provides new insights into the role of the gut microbiota in neuroimmune regulation.
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Affiliation(s)
- Qingyu Cao
- College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd, Linyi, 276005, China
| | - Mengmeng Shen
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd, Linyi, 276005, China
| | - Ruoqiu Li
- Key Laboratory of Marine Drugs, School of Medicine and Pharmacy, Ministry of Education, Ocean University of China, Qingdao, 266003, China
| | - Yan Liu
- School of Pharmacy, Qingdao University, Qingdao, 266071, China
| | - Zhen Zeng
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd, Linyi, 276005, China
| | - Jidong Zhou
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd, Linyi, 276005, China
| | - Dejun Niu
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd, Linyi, 276005, China
| | - Quancai Zhang
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd, Linyi, 276005, China
| | - Rongrong Wang
- Key Laboratory of Marine Drugs, School of Medicine and Pharmacy, Ministry of Education, Ocean University of China, Qingdao, 266003, China
| | - Jingchun Yao
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd, Linyi, 276005, China.
| | - Guimin Zhang
- College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China.
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd, Linyi, 276005, China.
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Yao J, Zhu CQ, Sun Y, Huang YW, Li QH, Liao HM, Deng XJ, Li WM. Insulin resistance: The role in comorbid type 2 diabetes mellitus and depression. Neurosci Biobehav Rev 2025; 175:106218. [PMID: 40403856 DOI: 10.1016/j.neubiorev.2025.106218] [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: 01/12/2025] [Revised: 04/04/2025] [Accepted: 05/16/2025] [Indexed: 05/24/2025]
Abstract
Insulin resistance (IR) plays a significant role in the pathophysiology of comorbid type 2 diabetes mellitus (T2DM) and depression (CDD) through multifaceted mechanisms, including dysregulation of insulin signaling (both central and peripheral), neuroendocrine disturbances (hypothalamic-pituitary-adrenal axis dysfunction and monoaminergic neurotransmission impairment), chronic inflammation, oxidative stress, disruption of the microbiota-gut-brain axis, reduced brain-derived neurotrophic factor levels, and altered synaptic plasticity. These IR-related pathways may predispose individuals to depressive symptoms or exacerbate existing mood disorders. A comprehensive understanding of these mechanisms is critical for developing integrated therapeutic strategies that concurrently target metabolic and psychiatric dysfunction. Antidepressant medications exhibit divergent effects on glucose metabolism. Tricyclic antidepressants, particularly amitriptyline and nortriptyline, worsen metabolic profiles by exacerbating IR, promoting weight gain, and inducing hyperglycemia, thereby increasing diabetes risk with prolonged use. Consequently, tricyclic antidepressants should be avoided in metabolically vulnerable populations unless alternatives are unavailable. Mirtazapine presents a paradoxical profile-while its appetite-stimulating effects often lead to weight gain (a known IR risk factor), some evidence suggests potential β-cell function preservation, necessitating cautious use of mirtazapine in individuals with metabolic syndrome. Among selective serotonin reuptake inhibitors, fluoxetine and escitalopram demonstrate favorable metabolic effects, including improved insulin sensitivity and glycemic control, though hypoglycemia risk (particularly with concomitant sulfonylureas) warrants monitoring. Bupropion, a norepinephrine-dopamine reuptake inhibitor, uniquely promotes weight loss and enhances glycemic control, making it a preferred option for depression comorbid with obesity or T2DM. Agomelatine, with its neutral metabolic profile and circadian rhythm-modulating properties, represents a safer alternative for patients with metabolic concerns. Concurrently, certain antidiabetic agents show promise in managing depression. Metformin and sodium-glucose cotransporter-2 inhibitors may be prioritized for diabetic patients at risk for depression, while glucagon-like peptide-1 receptor agonists appear particularly beneficial for obesity-related mood disturbances. Thiazolidinediones offer value in treatment-resistant cases, whereas insulin secretagogues should be used cautiously in psychiatrically vulnerable individuals. Future research should prioritize three key directions: (1) Mechanistic investigations using advanced neuroimaging to elucidate the contribution of IR to depressive phenotypes and evaluate novel interventions (such as intranasal insulin); (2) Precision medicine approaches incorporating biomarkers, including genetic polymorphisms, inflammatory markers, and gut microbiome signatures, to optimize antidepressant selection and develop personalized treatment algorithms; and (3) Therapeutic innovation, including dual GLP-1/GIP agonists and anti-inflammatory-antidepressant combinations, as well as integrating digital health technologies (e.g., continuous glucose monitoring coupled with mood tracking), will enable real-time, data-driven management. These advances will be instrumental in establishing integrated care paradigms for this comorbidity, which intertwines metabolic and psychiatric conditions.
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Affiliation(s)
- Jia Yao
- Department of Endocrinology, Guangzhou Twelfth People's Hospital, Guangzhou 510620, China; Department of Endocrinology, Guangzhou Occupational Disease Prevention and Treatment Hospital, Guangzhou 510620, China
| | - Chang-Qing Zhu
- Department of Endocrinology, Guangzhou Twelfth People's Hospital, Guangzhou 510620, China; Department of Endocrinology, Guangzhou Occupational Disease Prevention and Treatment Hospital, Guangzhou 510620, China
| | - Yan Sun
- Department of Endocrinology, Guangzhou Twelfth People's Hospital, Guangzhou 510620, China; Department of Endocrinology, Guangzhou Occupational Disease Prevention and Treatment Hospital, Guangzhou 510620, China
| | - Yi-Wen Huang
- Department of Endocrinology, Guangzhou Twelfth People's Hospital, Guangzhou 510620, China; Department of Endocrinology, Guangzhou Occupational Disease Prevention and Treatment Hospital, Guangzhou 510620, China
| | - Qing-Hua Li
- Department of Endocrinology, Guangzhou Twelfth People's Hospital, Guangzhou 510620, China; Department of Endocrinology, Guangzhou Occupational Disease Prevention and Treatment Hospital, Guangzhou 510620, China
| | - Hui-Min Liao
- Department of Endocrinology, Guangzhou Twelfth People's Hospital, Guangzhou 510620, China; Department of Endocrinology, Guangzhou Occupational Disease Prevention and Treatment Hospital, Guangzhou 510620, China
| | - Xue-Jian Deng
- Department of Endocrinology, Guangzhou Twelfth People's Hospital, Guangzhou 510620, China; Department of Endocrinology, Guangzhou Occupational Disease Prevention and Treatment Hospital, Guangzhou 510620, China
| | - Wan-Mei Li
- Department of Endocrinology, Guangzhou Twelfth People's Hospital, Guangzhou 510620, China; Department of Endocrinology, Guangzhou Occupational Disease Prevention and Treatment Hospital, Guangzhou 510620, China.
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Chang J, Zhang L, An Q, Ma Z, Xu P, Cernava T, Jin D. Novel insight into the mechanisms of neurotoxicity induced by type I and type II pyrethroids via disrupting the gut-brain axis in lizards. THE SCIENCE OF THE TOTAL ENVIRONMENT 2025; 983:179697. [PMID: 40398162 DOI: 10.1016/j.scitotenv.2025.179697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Revised: 05/13/2025] [Accepted: 05/15/2025] [Indexed: 05/23/2025]
Abstract
Type I and type II pyrethroids are widely used and frequently detected in agricultural environments. The neurotoxic effects and underlying mechanisms of pyrethroids in native animal populations, including lizards as common farmland inhabitants, remain unclear. This study exposed male lizards (Eremias argus) to type I bifenthrin (BF) and type II fluvalinate (FA) pyrethroids for 28 days, resulting in abnormal behaviors. Targeted analyses indicated that neurotransmitters, including dopamine, GABA, acetylcholine, and choline in lizard plasma, were significantly decreased with alterations in the cholinergic synapse, dopaminergic synapse, and cAMP signaling pathway in the brain after BF and FA treatment. Nervous system-related genes such as CACNA1A, CACNA1B, and CACNA1C were significantly down-regulated and highly correlated with arachidonic acid metabolism pathway-related metabolites in lizard gut. A notable decrease in metabolites within the arachidonic acid metabolism pathway and alterations in the gut microbiome were indicative for anti-inflammatory responses and neurotoxic effects. Interestingly, increased type I BF bioaccumulation in lizard intestines induced a higher abundance of Akkermansia, which resulted in reduced inflammation in the gut and lower neurotoxic effects compared to the low-dose BF exposure group. This study reveals contrasting dose-responses between pyrethroid types and suggests gut-brain axis-regulated neurotoxicity in lizards.
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Affiliation(s)
- Jing Chang
- Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
| | - Leisen Zhang
- Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Qiong An
- Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zheng Ma
- Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Peng Xu
- Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
| | - Tomislav Cernava
- Institute of Environmental Biotechnology, Graz University of Technology, Petersgasse 12, 8010 Graz, Austria; School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton SO17 1BJ, United Kingdom
| | - Decai Jin
- Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
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15
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Ruan YZ, Yang FC, Bai YM, Tsai CF, Liang CS, Su TP, Tsai SJ, Chen TJ, Tsai CK, Chen MH. Dose-dependent association between proton pump inhibitor use and the risk of migraine: a nationwide matched case-control study. Postgrad Med J 2025:qgaf077. [PMID: 40387251 DOI: 10.1093/postmj/qgaf077] [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: 12/24/2024] [Revised: 03/18/2025] [Accepted: 04/29/2025] [Indexed: 05/20/2025]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are widely prescribed, but their link to migraine risk, especially in Asian populations, remains unclear. This longitudinal study aimed to answer the following question: Does PPI exposure show a dose-dependent risk of migraine, varying by subtype and PPI indication in an Asian population? METHOD Using Taiwan's National Health Insurance Research Database (2000-15), we conducted a matched case-control study on PPI exposure. Adults prescribed PPIs for peptic ulcers, gastroesophageal reflux disease, or upper gastrointestinal bleeding were included, excluding those with prior migraines or incomplete data. Controls were matched 1:1 by age, sex, and residence. PPI exposure was measured in cumulative defined daily doses (cDDDs). RESULT The study included 22 834 PPI users (11 417 cases, 11 417 controls) with a mean follow-up of 4.1 ± 3.3 years. The study population comprised 65.6% females and 34.4% males, with no significant sex difference (P = 1.000). Mean age was 47.27 ± 15.16 years in cases and 47.42 ± 15.14 years in controls (P = .444). The average interval from PPI initiation to migraine diagnosis was 2.4 ± 1.9 years. Compared with those with the lowest PPI exposure (cDDD ≤30), migraine risk progressively increases with greater cumulative exposure: cDDD 31-120 [aOR = 1.22, 95% confidence interval (CI) = 1.15-1.30], cDDD 121-365 (aOR = 1.42, 95% CI = 1.32-1.52), and cDDD >365 (aOR = 1.60, 95% CI = 1.41-1.80). This dose-dependent relationship was consistent across migraine subtypes and PPI indications. CONCLUSION This large-scale Asian population study revealed a significant dose-dependent association between PPI exposure and increased migraine risk, emphasizing the need for cautious prescribing and monitoring of migraine symptoms in long-term PPI users, particularly in Asian populations.
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Affiliation(s)
- Yuan-Zhen Ruan
- Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu District, Taipei City 114202, Taiwan
| | - Fu-Chi Yang
- Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu District, Taipei City 114202, Taiwan
| | - Ya-Mei Bai
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Sec. Shihpai Road, Beitou District, Taipei 11217, Taiwan
- Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St. Beitou Dist., Taipei City 112304, Taiwan
| | - Chia-Fen Tsai
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Sec. Shihpai Road, Beitou District, Taipei 11217, Taiwan
- Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St. Beitou Dist., Taipei City 112304, Taiwan
| | - Chih-Sung Liang
- Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, No. 60, Xinmin Rd., Beitou Dist., Taipei City 112003, Taiwan
- Department of Psychiatry, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City 11490, Taiwan
| | - Tung-Ping Su
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Sec. Shihpai Road, Beitou District, Taipei 11217, Taiwan
- Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St. Beitou Dist., Taipei City 112304, Taiwan
- Department of Psychiatry, General Cheng Hsin Hospital, No. 45, Cheng Hsin St., Beitou Dist., Taipei City 11220, Taiwan
| | - Shih-Jen Tsai
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Sec. Shihpai Road, Beitou District, Taipei 11217, Taiwan
- Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St. Beitou Dist., Taipei City 112304, Taiwan
| | - Tzeng-Ji Chen
- Department of Family Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City 11217, Taiwan
- Institute of Hospital and Health Care Administration, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St. Beitou Dist., Taipei City 112304, Taiwan
| | - Chia-Kuang Tsai
- Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu District, Taipei City 114202, Taiwan
| | - Mu-Hong Chen
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Sec. Shihpai Road, Beitou District, Taipei 11217, Taiwan
- Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St. Beitou Dist., Taipei City 112304, Taiwan
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Barber TM, Kabisch S, Pfeiffer AFH, Weickert MO. The Gut Microbiome as a Key Determinant of the Heritability of Body Mass Index. Nutrients 2025; 17:1713. [PMID: 40431453 PMCID: PMC12114430 DOI: 10.3390/nu17101713] [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: 04/19/2025] [Revised: 05/15/2025] [Accepted: 05/16/2025] [Indexed: 05/29/2025] Open
Abstract
The pathogenesis of obesity is complex and incompletely understood, with an underlying interplay between our genetic architecture and obesogenic environment. The public understanding of the development of obesity is shrouded in myths with widespread societal misconceptions. Body Mass Index (BMI) is a highly heritable trait. However, despite reports from recent genome-wide association studies, only a small proportion of the overall heritability of BMI is known to be lurking within the human genome. Other non-genetic heritable traits may contribute to BMI. The gut microbiome is an excellent candidate, implicating complex interlinks with hypothalamic control of appetite and metabolism via entero-endocrine, autonomic, and neuro-humeral pathways. The neonatal gut microbiome derived from the mother via transgenerational transmission (vaginal delivery and breastfeeding) tends to have a permanence within the gut. Conversely, non-maternally derived gut microbiota manifest mutability that responds to changes in lifestyle and diet. We should all strive to optimize our lifestyles and ensure a diet that is replete with varied and unprocessed plant-based foods to establish and nurture a healthy gut microbiome. Women of reproductive age should optimize their gut microbiome, particularly pre-conception, ante- and postnatally to enable the establishment of a healthy neonatal gut microbiome in their offspring. Finally, we should redouble our efforts to educate the populace on the pathogenesis of obesity, and the role of heritable (but modifiable) factors such as the gut microbiome. Such renewed understanding and insights would help to promote the widespread adoption of healthy lifestyles and diets, and facilitate a transition from our current dispassionate and stigmatized societal approach towards people living with obesity towards one that is epitomized by understanding, support, and compassion.
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Affiliation(s)
- Thomas M. Barber
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK;
- Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Human Metabolism Research Unit, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK
| | - Stefan Kabisch
- Department of Endocrinology and Metabolic Medicine, Campus Benjamin Franklin, Charité University Medicine, Hindenburgdamm 30, 12203 Berlin, Germany (A.F.H.P.)
- Deutsches Zentrum für Diabetesforschung e.V., Geschäftsstelle am Helmholtz-Zentrum München, Ingolstädter Landstraße, 85764 Neuherberg, Germany
| | - Andreas F. H. Pfeiffer
- Department of Endocrinology and Metabolic Medicine, Campus Benjamin Franklin, Charité University Medicine, Hindenburgdamm 30, 12203 Berlin, Germany (A.F.H.P.)
- Deutsches Zentrum für Diabetesforschung e.V., Geschäftsstelle am Helmholtz-Zentrum München, Ingolstädter Landstraße, 85764 Neuherberg, Germany
| | - Martin O. Weickert
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK;
- Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Human Metabolism Research Unit, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK
- Centre for Sport, Exercise and Life Sciences, Faculty of Health & Life Sciences, Coventry University, Coventry CV1 5FB, UK
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Li L, Du F, Liu X, Song M, Grosso G, Battino M, Boesch C, Li H, Liu X. Effect of Supplementation with Probiotics in Patients with Schizophrenia: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. Foods 2025; 14:1773. [PMID: 40428552 PMCID: PMC12111037 DOI: 10.3390/foods14101773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 05/01/2025] [Accepted: 05/06/2025] [Indexed: 05/29/2025] Open
Abstract
Supplementation with probiotics seems to confer protective effects in individuals with schizophrenia (SZ), although available results are inconclusive. The aim of this study was to systematically review existing randomized clinical trials (RCTs) to critically assess the effect of probiotics on psychiatric symptoms, anthropometric indicators, lipid profiles, glycemic indices, inflammation, and oxidative stress in adults with SZ. A systematic search was conducted in four databases from inception until January 2025. Six RCTs were included in the quantitative analysis that demonstrated beneficial effects of probiotics on SZ severity determined via the Positive and Negative Syndrome Scale (PANSS), with significant reductions in PANSS (MD = -0.50, p = 0.001), PANSS Negative (MD = -0.31, p = 0.050), and PANSS General scores (MD = -0.33, p = 0.036), alongside reductions in body weight (MD = -0.92, p = 0.000), body mass index (MD = -0.53, p = 0.016), and total cholesterol (SMD = -0.34, p = 0.005). Furthermore, probiotic interventions reduced baseline glucose (SMD = -0.59, p = 0.000), insulin (MD = -0.68, p = 0.000), and measures of insulin sensitivity/resistance and significantly improved biomarkers of inflammation and oxidative stress. To summarize, this meta-analysis suggests that probiotics may confer beneficial effects in patients with SZ through improving psychiatric symptoms as well as markers of body weight, lipid and glucose metabolism, inflammation, and oxidative stress.
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Affiliation(s)
- Lu Li
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (F.D.); (X.L.); (M.S.); (H.L.)
| | - Fengqi Du
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (F.D.); (X.L.); (M.S.); (H.L.)
| | - Xilong Liu
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (F.D.); (X.L.); (M.S.); (H.L.)
| | - Mengyao Song
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (F.D.); (X.L.); (M.S.); (H.L.)
| | - Giuseppe Grosso
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy;
| | - Maurizio Battino
- International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing, Jiangsu University, Zhenjiang 212013, China;
- Dipartimento di Scienze Cliniche Specialistiche e Odontostomatologiche, Università Politecnica delle Marche, Via Ranieri 65, 60130 Ancona, Italy
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres 21, 39011 Santander, Spain
| | - Christine Boesch
- School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK;
| | - He Li
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (F.D.); (X.L.); (M.S.); (H.L.)
| | - Xinqi Liu
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (F.D.); (X.L.); (M.S.); (H.L.)
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Wang G, Ma T, Liu R, Gu H, Zhou ZY, Wan Z. Comparisons of metabolites and gut microbiota profiles for both young and middle-aged APPSwe/PS1De9 mice. Neuroscience 2025; 577:54-63. [PMID: 40355072 DOI: 10.1016/j.neuroscience.2025.04.053] [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: 09/28/2024] [Revised: 04/24/2025] [Accepted: 04/30/2025] [Indexed: 05/14/2025]
Abstract
The research focused on exploring the differences and relationships between gut microbiota and metabolites at various stages of Alzheimer's disease (AD), specifically using APP/PS1 mice at the ages of 6 months and 10 months. To assess metabolites in serum and cortex, and to evaluate gut microbiota profiles in cecal content, UPLC-MS/MS and 16S rRNA sequencing techniques were utilized, respectively. Findings indicated that, in comparison to younger mice, serum concentrations of L-Leucine, thymine, and Glucosamine 6-phosphate were lower, whereas levels of Sorbitol and Palmitic acid were higher. Furthermore, measurements of the ACE and Chao1 indices significantly declined in the older cohort. At the phylum level, the relative abundance of Bacteroidetes showed a decline, while there was an increase in Actinobacteria and TM7 bacteria among the middle-aged subjects. The novelty of this study is we found there were notable alterations in both gut microbiota and metabolites within serum and cortex when comparing young and older APP/PS1 mice, emphasizing the important connections between metabolites and gut microbiota throughout the progression of AD. These results indicate that manipulating metabolites and gut flora may serve as a vital strategy for the prevention and management of AD.
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Affiliation(s)
- Guiping Wang
- Laboratory Animal Center, Medical College of Soochow University, 199 Ren'ai Road, Suzhou, China
| | - Tongtong Ma
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou, China
| | - Ruitong Liu
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou, China
| | - Huiwen Gu
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou, China
| | - Zheng-Yu Zhou
- Laboratory Animal Center, Medical College of Soochow University, 199 Ren'ai Road, Suzhou, China.
| | - Zhongxiao Wan
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou, China.
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Mei S, Deng Z, Meng FY, Guo QQ, Tao HY, Zhang L, Xi C, Zhou Q, Tian XF. Sini Powder Alleviates Stress Response and Suppresses Hepatocellular Carcinoma Development by Restoring Gut Microbiota. Chin J Integr Med 2025:10.1007/s11655-025-4127-z. [PMID: 40338446 DOI: 10.1007/s11655-025-4127-z] [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: 10/09/2024] [Indexed: 05/09/2025]
Abstract
OBJECTIVES To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). METHODS The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice. RESULTS The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased. CONCLUSION SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
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Affiliation(s)
- Si Mei
- Faculty of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Zhe Deng
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Fan-Ying Meng
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Qian-Qian Guo
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - He-Yun Tao
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Lin Zhang
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Chang Xi
- School of Humanities and Management, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Qing Zhou
- The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410007, China
| | - Xue-Fei Tian
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China.
- Faculty of International Education, Hunan University of Chinese Medicine, Changsha, 410208, China.
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Li CC, Hsieh K, Chang PC, Chang HJ. Prevalence of suicide attempts and related factors among adolescents in Taiwan using a nationally representative survey. J Formos Med Assoc 2025:S0929-6646(25)00201-3. [PMID: 40335425 DOI: 10.1016/j.jfma.2025.04.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 03/30/2025] [Accepted: 04/23/2025] [Indexed: 05/09/2025] Open
Abstract
PURPOSE This study aimed to apply stress-diathesis model to investigate the prevalence of suicide attempts and associated factors in a nationally representative sample of adolescents. METHODS A cross-sectional design and secondary data analysis were conducted using the parent study "Taiwan Youth Health Survey" data. A total of 5511 junior high school students were included. The outcome variable was self-reported suicide attempts, and the independent variables included self-reported stress and diathesis factors. RESULTS The prevalence of suicide attempts among adolescents was 7.7 %, with rates of 6.1 % for boys and 9.4 % for girls. The multiple logistic regression revealed that girls, loneliness, suicide ideation and plans, smoking, drinking alcohol, consumption of carbonated soft drinks (CSDs), eating fast food, experiencing a severe injury, being bullied, and lacking close friends were associated with an increased risk for attempting suicide. For boys, anxiety, smoking, experiencing severe injuries were identified as significant risk factors. For girls, loneliness, drinking alcohol, consuming CSDs, eating fast food, being bullied, and less parental supervision were identified as significant risk factors. The derived prediction score for the total group, boys, and girls yielded areas under the cure of 0.85, 0.82, and 0.87, respectively. The regression model, which incorporated interaction terms, demonstrated that loneliness, consumption of CSDs, and less parental supervision are gender-specific risk factors. CONCLUSION It is essential to consider gender differences in preventive measures. Appropriate interventions should be tailored to address both predispositions and stress unique to each gender, ensuring that gender-specific risk factors are managed more comprehensively.
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Affiliation(s)
- Chia-Chi Li
- School of Nursing, College of Nursing, Taipei Medical University, 250 Wu-Xing St., Taipei, 11031, Taiwan, ROC.
| | - Kelly Hsieh
- Department of Disability and Human Development, University of Illinois Chicago1640 Roosevelt Rd, Chicago, IL, 60609, USA.
| | - Pi-Chen Chang
- School of Nursing, College of Nursing, Taipei Medical University, 250 Wu-Xing St., Taipei, 11031, Taiwan, ROC.
| | - Hsiu-Ju Chang
- Department of Nursing, College of Nursing, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong Street, Taipei, 112, Taiwan, ROC; Efficient Smart Care Research Center, College of Nursing, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong Street, Taipei, 112, Taiwan, ROC.
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21
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Chen Y, Peng Y, Niu Q, Jiang Y, Ni H, Chen L, Lin Y. The impact of probiotics therapy on cognitive and metabolic characteristics in patients with cognitive impairment: An umbrella review of meta-analysis of randomized controlled trials. Eur J Pharmacol 2025; 994:177326. [PMID: 39914784 DOI: 10.1016/j.ejphar.2025.177326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 01/29/2025] [Accepted: 01/30/2025] [Indexed: 03/15/2025]
Abstract
BACKGROUND While existing meta-analysis suggest that probiotic therapies may enhance cognitive functions and influence metabolic characteristics, the findings have been inconclusive. In light of these discrepancies, our study undertakes an umbrella review to more precisely determine the aggregate effects and rigorously evaluate the credibility and quality of evidence. METHODS We conducted a systematic search across seven databases, including PubMed, Embase, the Cochrane Library, ProQuest, Web of Science, CINAHL, and Scopus, from their inception to June 20, 2024. We utilized the AMSTAR-2 tool to evaluate the quality of the meta-analyses and applied the GRADE system to rate the quality of the evidence. We estimated the final effect sizes (ESs) along with their 95% confidence intervals (CI) and performed both sensitivity and subgroup analyses to explore the sources of heterogeneity. RESULTS Among the 314 articles identified in our search, 13 meta-analysis that met the criteria were included in the study. The quality of the evidence in these studies was graded from high to very low. Our results demonstrate that probiotic treatment significantly enhances cognitive function in patients (ESSMD = 0.39, 95%CI: 0.19 to 0.59, p < 0.001). Moreover, probiotic treatment notably decreased level of serum malondialdehyde (MDA), insulin resistance as detected by homeostasis model assessment method (HOMA-IR) and high-sensitivity C-reactive protein (hs-CRP) (p < 0.001). Conversely, probiotic treatment did not significantly impact triglycerides and very-low-density lipoprotein (VLDL) in patients (p > 0.05). CONCLUSION Although preliminary evidence indicated that probiotic therapy may positively impact cognitive function, MDA, HOMA-IR, and hs-CRP, the overall quality of the existing evidence is insufficient to provide strong support. Therefore, future research must employ more rigorous designs or initiate larger clinical trials to produce more compelling evidence to further validate the efficacy of probiotic therapy on cognitive function of patients with cognitive dysfunction.
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Affiliation(s)
- Yaqin Chen
- School of Nursing, Fujian Medical University, Fuzhou, Fujian, China
| | - Yanchun Peng
- Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Qi Niu
- School of Nursing, Fujian Medical University, Fuzhou, Fujian, China
| | - Yan Jiang
- School of Nursing, Fujian Medical University, Fuzhou, Fujian, China
| | - Hong Ni
- Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Liangwan Chen
- Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Fujian Provincial Special Reserve Talents Laboratory, Fuzhou, Fujian, China.
| | - Yanjuan Lin
- Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
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22
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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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23
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Camarda L, Mattioli LB, Corazza I, Marzetti C, Budriesi R. Targeting the Gut-Brain Axis with Plant-Derived Essential Oils: Phytocannabinoids and Beyond. Nutrients 2025; 17:1578. [PMID: 40362887 PMCID: PMC12074236 DOI: 10.3390/nu17091578] [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: 04/02/2025] [Revised: 04/28/2025] [Accepted: 05/01/2025] [Indexed: 05/15/2025] Open
Abstract
Background: The gut-brain axis (GBA) is a complex bidirectional communication system that links the gastrointestinal tract and the central nervous system. Essential oils (EOs) have emerged as promising natural compounds capable of modulating this axis. Methods: A comprehensive analysis of the recent literature was conducted, focusing on studies investigating the effects of EOs on the GBA. Particular attention was given to the endocannabinoid system, the role of cannabis-derived EOs, and other plant-based EOs with potential neuroprotective and gut microbiota-modulating effects. Results: Among the EOs analyzed, cannabis essential oil (CEO) gained attention for its interaction with cannabinoid receptors (CBR1 and CBR2), modulating gut motility, immune responses, and neurotransmission. While acute administration of the CEO reduces inflammation and gut permeability, chronic use has been associated with alterations in gut microbiota composition, potentially impairing cognitive function. Other EOs, such as those from rosemary, lavender, eucalyptus, and oregano, demonstrated effects on neurotransmitter modulation, gut microbiota balance, and neuroinflammation, supporting their potential therapeutic applications in GBA-related disorders. Conclusions: EOs demonstrate promising potential in modulating the GBA through mechanisms including neurotransmitter regulation, gut microbiota modulation, and anti-inflammatory activity. At the same time, phytocannabinoids offer therapeutic value; their long-term use warrants caution due to potential impacts on microbiota. Future research should aim to identify EO-based interventions that can synergistically restore GBA homeostasis and mitigate neurodegenerative and gastrointestinal disorders.
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Affiliation(s)
- Luca Camarda
- Department of Pharmacy and Biotechnology (FaBiT), Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy; (L.B.M.); (R.B.)
| | - Laura Beatrice Mattioli
- Department of Pharmacy and Biotechnology (FaBiT), Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy; (L.B.M.); (R.B.)
- Health Sciences and Technologies-Interdepartmental Center for Industrial Research (CIRI-SDV), Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy;
| | - Ivan Corazza
- Health Sciences and Technologies-Interdepartmental Center for Industrial Research (CIRI-SDV), Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy;
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy
| | | | - Roberta Budriesi
- Department of Pharmacy and Biotechnology (FaBiT), Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy; (L.B.M.); (R.B.)
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24
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Nikolova VL, Cleare AJ, Young AH, Stone JM. Exploring the mechanisms of action of probiotics in depression: Results from a randomized controlled pilot trial. J Affect Disord 2025; 376:241-250. [PMID: 39924003 DOI: 10.1016/j.jad.2025.01.153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 01/27/2025] [Accepted: 01/31/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND We previously reported greater reductions in depression and anxiety following probiotic supplementation in people with major depressive disorder (MDD) in a randomised double-blind placebo-controlled pilot trial (Nikolova et al., 2023). Here, we investigate the mechanisms underlying these effects. METHODS 49 people with MDD received a multi-strain probiotic (n = 24) or placebo (n = 25) for 8 weeks in addition to their antidepressant. Stool and blood samples were collected to analyse gut microbiota composition and inflammatory cytokines. Stool samples from 25 matched healthy volunteers (HVs) were also obtained. RESULTS Within the probiotic group, there was a significant increase in richness according to Chao1(bias-corrected) (w4 p = 0.04) and a trend for increased Total count (w4 p = 0.06, w8 p = 0.09) compared to baseline, but not to placebo. When compared to HVs post-treatment, only the placebo group had a significant decrease in Shannon' entropy (p = 0.03) and a trend for decreased Total count (p = 0.08) and Simpson's index (p = 0.09). Between-group differences in beta diversity were observed at week 4 (p = 0.04), but not week 8. Consistent between-group differences were seen in family Bacilleceae post-treatment (FDR p < 0.05), which correlated with decreases in anxiety (FDR p < 0.05). There were no differences in inflammatory markers. LIMITATIONS This study was limited by data loss during the COVID-19 Pandemic. CONCLUSION Probiotics may positively impact the microbiota by normalising diversity and increasing levels of health-related taxa, which may partially account for their benefits in MDD. Understanding how these changes relate to symptom improvement can inform their targeted use in clinical practice. Larger trials incorporating functional multi-omics are needed. TRIAL REGISTRATION NCT03893162.
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Affiliation(s)
- Viktoriya L Nikolova
- Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; ADM Health & Wellness, ADM Protexin Ltd., Somerset, UK.
| | - Anthony J Cleare
- Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, UK; South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, UK.
| | - Allan H Young
- Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, UK; South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, UK.
| | - James M Stone
- Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; Brighton and Sussex Medical School, Brighton BN1 9PX, UK.
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25
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Lai Y, Xiong P. Analysis of gut microbiota and depression and anxiety: Mendelian randomization from three datasets. Gen Hosp Psychiatry 2025; 94:206-218. [PMID: 40154232 DOI: 10.1016/j.genhosppsych.2025.03.012] [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: 10/11/2024] [Revised: 03/14/2025] [Accepted: 03/14/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Emerging evidence supports gut microbiota's association with mental distress, particularly depression and anxiety, the microbiota-gut-brain axis was the believed to be the underlying mechanism. This study investigated the causal relationships between specific gut microbiota and depression and anxiety disorders using large-scale genome-wide association study (GWAS) data. METHODS A two-sample bidirectional Mendelian randomization (MR) analysis was conducted to explore the causal effects of 211 microbial taxa on depression and anxiety across three large GWAS databases: FinnGen, Pan-UKBB, and PGC. Sensitive analyses were followed to validate the robustness of results. Random-effect meta-analysis was further performed to enhance the statistical power. RESULTS The MR analysis revealed that the Bifidobacteriales (IVW: OR 0.90, 95 %CI 0.83 to 0.98) and Bifidobacteriaceae (IVW: OR 0.90, 95 %CI 0.83 to 0.98) had a protective effect against depression. Clostridiales (cML-MA: OR 0.88, 95 %CI 0.81 to 0.95) and Parasutterella (cML-MA: OR 0.75, 95 %CI 0.64 to 0.88) showed negative associations with depression. Increased abundance of Oxalobacteraceae (cML-MA: OR 1.78, 95 %CI 1.24 to 2.56), Deltaproteobacteria (cML-MA: OR 2.17, 95 %CI 1.38 to 3.40), and Desulfovibrionales (cML-MA: OR 2.22, 95 %CI 1.41 to 3.49) was associated with a higher risk of depression. For anxiety, protective effects were found for Actinobacteria (phylum: IVW: OR 0.83, 95 %CI 0.76 to 0.87; class: IVW: OR 0.84, 95 %CI 0.75 to 0.93), Bifidobacteriales (IVW: OR 0.80, 95 %CI 0.75 to 0.85), Bifidobacteriaceae (IVW: OR 0.80, 95 %CI 0.75 to 0.85) and Bifidobacterium [g] (IVW: OR 0.79, 95 %CI 0.74 to 0.84). Lactobacillaceae [f] (cML-MA: OR 1.18, 95 %CI 1.08 to 1.28), Clostridia [c] (cML-MA: OR 1.15, 95 %CI 0.1.06 to 1.26) and Clostridiales [o] (IVW: OR 1.15, 95 %CI 1.05 to 1.27) were associated with increased anxiety risk. Meta-analysis results indicated significant associations, particularly the protective effects of Actinobacteria (OR 0.90, 95 % CI, 0.83 to 0.98) and Clostridiaceae1 (OR 0.91, 95 % CI, 0.83 to 0.99) on depression and several taxa on anxiety. No significant instrumental variables for depression or anxiety on gut microbiota were identified. CONCLUSIONS Our findings highlight specific gut microbiota that are associated with depression and anxiety, underscoring the causal relationships between these intestinal microbes and psychiatric disorders. These results suggest potential strategies for mitigating disease symptoms and improving quality of life through microbiome-targeted therapies. Further studies, including randomized controlled trials and investigations into sex-specific effects, are essential to validate and expand upon these findings.
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Affiliation(s)
- Yaoyong Lai
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Peng Xiong
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China.
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26
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McHenry LC, Schürch R, Council-Troche M, Gross AD, Johnson LE, Ohlinger BD, Couvillon MJ. Sublethal glyphosate exposure reduces honey bee foraging and alters the balance of biogenic amines in the brain. J Exp Biol 2025; 228:jeb250124. [PMID: 40326703 DOI: 10.1242/jeb.250124] [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: 05/21/2024] [Accepted: 03/17/2025] [Indexed: 05/07/2025]
Abstract
Glyphosate is a broad-spectrum herbicide that inhibits the shikimate pathway, which honey bees (Apis mellifera), a non-target beneficial pollinator, do not endogenously express. Nonetheless, sublethal glyphosate exposure in honey bees has been correlated to impairments in gustation, learning, memory and navigation. While these impacted physiologies underpin honey bee foraging and recruitment, the effects of sublethal glyphosate exposure on these important behaviors remain unclear, and any proximate mechanism of action in the honey bee is poorly understood. We trained cohorts of honey bees from the same hives to forage at one of two artificial feeders offering 1 mol l-1 sucrose solution, either unaltered (N=40) or containing glyphosate at 5 mg acid equivalent (a.e.) l-1 (N=46). We then compared key foraging behaviors and, on a smaller subset of bees, recruitment behaviors. Next, we quantified protein levels of octopamine, tyramine and dopamine, and levels of the amino acid precursor tyrosine in the brains of experimental bees collected 3 days after the exposure. We found that glyphosate treatment bees reduced their foraging by 13.4% (P=0.022), and the brain content of tyramine was modulated by a crossover interaction between glyphosate treatment and the number of feeder visits (P=0.004). Levels of octopamine were significantly correlated with its precursors tyramine (P=0.011) and tyrosine (P=0.018) in glyphosate treatment bees, but not in control bees. Our findings emphasize the critical need to investigate impacts of the world's most-applied herbicide and to elucidate its non-target mechanism of action in insects to create better-informed pollinator protection strategies.
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Affiliation(s)
- Laura C McHenry
- Department of Entomology, Virginia Tech, Blacksburg, VA 24060, USA
| | - Roger Schürch
- Department of Entomology, Virginia Tech, Blacksburg, VA 24060, USA
| | | | - Aaron D Gross
- Department of Entomology, Virginia Tech, Blacksburg, VA 24060, USA
| | | | - Bradley D Ohlinger
- Department of Entomology, Virginia Tech, Blacksburg, VA 24060, USA
- Odum School of Ecology, University of Georgia, Athens, GA 30602, USA
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27
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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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Kimmel M, Tong B, Devall AE, Björvang RD, Schuppe-Koistinen I, Engstrand L, Fransson E, Skalkidou A, Hugerth LW. Investigating the Microbiome in Relation to Mental Distress Across Two Points During Pregnancy: Data From U.S. and Swedish Cohorts. BIOLOGICAL PSYCHIATRY GLOBAL OPEN SCIENCE 2025; 5:100453. [PMID: 40115744 PMCID: PMC11925571 DOI: 10.1016/j.bpsgos.2025.100453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 01/12/2025] [Accepted: 01/15/2025] [Indexed: 03/23/2025] Open
Abstract
Background In this study, we aimed to characterize the gut microbiome and its potential functioning in 2 populations at 2 time points during pregnancy in relation to mental distress. Methods During the second and third trimester, individuals from the United States and Sweden completed the Edinburgh Postnatal Depression Scale and provided fecal samples for whole-genome metagenomics. A total of 832 and 161 samples were sequenced and analyzed from the Swedish cohort and the U.S. cohort, respectively. Multiple characterizations of the microbial community were analyzed in relation to distress measured using the Edinburgh Postnatal Depression Scale. Principal coordinate analysis and distance-based redundancy analysis assessed variation in functional gut-brain modules. For the U.S. cohort, the Trier Social Stress Test was administered 8 weeks postpartum while collecting salivary cortisol. Results Principal coordinate analysis identified 4 sample clusters based on the gut-brain modules distinguished by functions such as short-chain fatty acid synthesis and cortisol degradation. While with distance-based redundancy analysis, mental distress subtypes did not significantly contribute to variation in gut-brain modules (p = .085 for Sweden, p = .23 for the U.S.), a U.S. sample cluster distinguished by lower cortisol degradation from another cluster with higher gut microbial cortisol degradation abundance had significantly higher odds of being associated with depression (p = .024). The U.S. sample cluster with lower gut microbial cortisol degradation abundance also had significantly higher cortisol levels after a postpartum social stressor. Conclusions Further studies are warranted to investigate the potential for the gut microbiome to serve as biomarkers of gut-brain axis health during pregnancy across disparate populations.
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Affiliation(s)
- Mary Kimmel
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Department of Psychiatry, Washington University, St. Louis, Missouri
| | - Bangzhuo Tong
- Department of Medical Biochemistry and Microbiology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
| | - Alfons Edbom Devall
- Department of Medical Biochemistry and Microbiology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
- Department of Molecular Biology, Umeå University, Umeå, Sweden
| | - Richelle D Björvang
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Ina Schuppe-Koistinen
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Lars Engstrand
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Emma Fransson
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Alkistis Skalkidou
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Luisa W Hugerth
- Department of Medical Biochemistry and Microbiology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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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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Knobbe TJ, Kremer D, Bültmann U, Annema C, Navis G, Berger SP, Bakker SJ, Meuleman Y. Insights Into Health-Related Quality of Life of Kidney Transplant Recipients: A Narrative Review of Associated Factors. Kidney Med 2025; 7:100986. [PMID: 40182980 PMCID: PMC11964492 DOI: 10.1016/j.xkme.2025.100986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2025] Open
Abstract
Life expectancy and graft survival continue to improve after transplantation. However, improved posttransplant clinical outcomes do not necessarily translate into improved health-related quality of life (HRQoL). Therefore, there is an increased focus on HRQoL in kidney transplant recipients (KTRs). The HRQoL of KTRs is worse than that of the general population, but interventions that improve HRQoL in KTRs are scarce, and health care professionals in nephrology care do not routinely address HRQoL. To improve HRQoL, it is essential to understand which factors play a role in HRQoL and to pinpoint areas for intervention. This narrative review maps the concept of HRQoL within the KTR population and provides a comprehensive overview of factors associated with posttransplant HRQoL. The results are structured using an easy-to-understand conceptual model of HRQoL, which is instrumental for understanding how HRQoL is constituted of many clinical and nonclinical factors. We conclude that symptom burden among KTRs is high, which is likely a key driver of the limited HRQoL in this population. Moreover, myriad other clinical and nonclinical factors are associated with HRQoL, but the majority of the evidence is observational.
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Affiliation(s)
- Tim J. Knobbe
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Daan Kremer
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ute Bültmann
- Community and Occupational Medicine, Department of Health Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Coby Annema
- Section of Nursing Science, Department of Health Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Gerjan Navis
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Stefan P. Berger
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Stephan J.L. Bakker
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Yvette Meuleman
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
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31
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Zou M, Li X, Li C, Pei H, Kang R, Liu L, Gao L. Comparative Analysis of Gut Bacteria of Four Waterbirds Species in Taolimiao-Alashan Nur (T-A Nur) in Erdos Relic Gull National Nature Reserve, Inner Mongolia, China. Ecol Evol 2025; 15:e71432. [PMID: 40370353 PMCID: PMC12074897 DOI: 10.1002/ece3.71432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 04/15/2025] [Accepted: 04/28/2025] [Indexed: 05/16/2025] Open
Abstract
Taolimiao-Alashan Nur (T-A Nur) is an important breeding site for the Relict Gulls (Larus relictus) and many other waterbirds. To understand the gut health status of rare bird species living there and to protect these bird species, this study analyzed the gut microbiota of four waterbird species, including Relict Gull (L. relictus), Black-necked Grebe (Podiceps nigricollis), Greylag Goose (Anser anser), and Ruddy Shelduck (Tadorna ferruginea), using 16S rRNA high-throughput sequencing. Results showed that the gut microbiota of Ruddy Shelduck had the highest α-diversity, while Greylag Goose had the lowest. The composition of gut microbiota varied significantly among the bird species. The dominant bacterial phylum in the guts of Black-necked Grebe, Greylag Goose, and Ruddy Shelduck was Firmicutes, while it was Pseudomonadota in Relict Gull. At the genus level, the dominant bacteria were Halomonas in Black-necked Grebe, Escherichia-Shigella in Relict Gull, Ligilactobacillus in Greylag Goose, and Enterococcus in Ruddy Shelduck. Correlation analysis revealed significant relationships among gut bacterial communities, suggesting that gut bacteria can regulate host metabolism and physiological state by their interactions. KEGG functional predictions indicated that gut microbiota were primarily involved in metabolism. The abundance of metabolism-related microorganisms in Relict Gull was significantly lower than in Greylag Goose and Ruddy Shelduck, indicating that the gut microbiota of Greylag Goose and Ruddy Shelduck can provide stronger metabolic functions for the hosts. Additionally, microorganisms related to human diseases were more abundant in the gut of Relict Gull compared to Ruddy Shelduck and Black-necked Grebe, and in Greylag Goose compared to Ruddy Shelduck. These findings suggested that the gut microbiota of birds in this area harbor some human pathogens, which warrants attention and preventive measures.
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Affiliation(s)
- Mingxin Zou
- College of Ecology and EnvironmentBaotou Teacher's CollegeBaotouChina
| | - Xuanyu Li
- College of Ecology and EnvironmentBaotou Teacher's CollegeBaotouChina
| | - Chunyu Li
- College of Ecology and EnvironmentBaotou Teacher's CollegeBaotouChina
| | - Hongda Pei
- College of Ecology and EnvironmentBaotou Teacher's CollegeBaotouChina
| | - Ruobing Kang
- College of Ecology and EnvironmentBaotou Teacher's CollegeBaotouChina
| | - Li Liu
- College of Ecology and EnvironmentBaotou Teacher's CollegeBaotouChina
| | - Li Gao
- College of Ecology and EnvironmentBaotou Teacher's CollegeBaotouChina
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32
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Xu M, Li W, Hu X, Zhang J. Arecoline Alleviates Depression via Gut-Brain Axis Modulation, Neurotransmitter Balance, Neuroplasticity Enhancement, and Inflammation Reduction in CUMS Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:10201-10213. [PMID: 40257350 DOI: 10.1021/acs.jafc.4c11643] [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: 04/22/2025]
Abstract
This study evaluated the antidepressant effects of arecoline, a bioactive alkaloid derived from areca nuts, using a mouse model of depression induced by chronic unpredictable mild stress. Arecoline treatment significantly alleviated depression-like behaviors, including anxiety, anhedonia, and despair, as evidenced by behavioral tests. Mechanistically, arecoline restored serotonin and norepinephrine levels in the brain and serum, reduced pro-inflammatory markers such as IL-1β and LPS in both serum and colon, and enhanced hippocampal neuroplasticity through increased BDNF and PSD-95 expression. Moreover, arecoline modulated gut microbiota composition, particularly enriching beneficial species like Bifidobacterium pseudolongum and Ligilactobacillus murinus, and regulated serum metabolites associated with tryptophan metabolism, neurotransmitter synthesis, and oxidative stress. These findings demonstrate that arecoline exerts its antidepressant effects via a multitargeted approach involving the gut-brain axis, neurotransmitter modulation, and neuroplasticity enhancement. This study highlights arecoline as a promising therapeutic candidate for depression, emphasizing its potential to address both central and peripheral mechanisms.
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Affiliation(s)
- Meng Xu
- School of Food Science and Engineering, Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Hainan University, Haikou 570228, China
- Collaborative Innovation Center of One Health, Hainan University, Haikou 570228, China
| | - Wanggao Li
- School of Food Science and Engineering, Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Hainan University, Haikou 570228, China
- Collaborative Innovation Center of One Health, Hainan University, Haikou 570228, China
| | - Xiaosong Hu
- School of Food Science and Engineering, Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Hainan University, Haikou 570228, China
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Jiachao Zhang
- School of Food Science and Engineering, Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Hainan University, Haikou 570228, China
- Collaborative Innovation Center of One Health, Hainan University, Haikou 570228, China
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Lee SH, Han C, Shin C. IUPHAR Review: Microbiota-Gut-Brain Axis and its role in Neuropsychiatric Disorders. Pharmacol Res 2025; 216:107749. [PMID: 40306604 DOI: 10.1016/j.phrs.2025.107749] [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: 03/23/2025] [Revised: 04/20/2025] [Accepted: 04/25/2025] [Indexed: 05/02/2025]
Abstract
The human gut microbiome, composed of a vast array of microorganisms that have co-evolved with humans, is crucial for the development and function of brain systems. Research has consistently shown bidirectional communication between the gut and the brain through neuronal, endocrine, and immunological, and chemical pathways. Recent neuroscience studies have linked changes in the microbiome and microbial metabolites to various neuropsychiatric disorders such as autism, depression, anxiety, schizophrenia, eating disorders, and neurocognitive disorders. Novel metagenome-wide association studies have confirmed these microbiome variations in large samples and expanded our understanding of the interactions between human genes and the gut microbiome. The causal relationship between gut microbiota and neuropsychiatric disorders is being elucidated through the establishment of large cohort studies incorporating microbiome data and advanced statistical techniques. Ongoing animal and human studies focused on the microbiota-gut-brain axis are promising for developing new prevention and treatment strategies for neuropsychiatric conditions. The scope of these studies has broadened from microbiome-modulating therapies including prebiotics, probiotics, synbiotics and postbiotics to more extensive approaches such as fecal microbiota transplantation. Recent systematic reviews and meta-analyses have strengthened the evidence base for these innovative treatments. Despite extensive research over the past decade, many intriguing aspects still need to be elucidated regarding the role and therapeutic interventions of the microbiota-gut-brain axis in neuropsychiatric disorders.
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Affiliation(s)
- Seung-Hoon Lee
- Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Changsu Han
- Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheolmin Shin
- Department of Psychiatry, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
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Sun YF, Han ZX, Yao XK, Meng J, Ren WL, Wang CK, Yuan XX, Zeng YQ, Wang YF, Sun ZW, Wang JW. Effects of Different Stages of Training on the Intestinal Microbes of Yili Horses Analyzed Using Metagenomics. Genes (Basel) 2025; 16:504. [PMID: 40428326 PMCID: PMC12111061 DOI: 10.3390/genes16050504] [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: 04/04/2025] [Revised: 04/24/2025] [Accepted: 04/25/2025] [Indexed: 05/29/2025] Open
Abstract
Objectives: The aim of this study was to investigate the effects of different stages of training on the intestinal microbial abundance of Yili horses. Methods: Ten Yili horses, all aged 2 years old and weighing 305 ± 20 kg, were selected and divided into a training group and an untrained group. The training group performed riding training 6 days a week, and the untrained group moved freely in the activity circle every day. Fecal samples were collected on days 30 and 60, and the intestinal microorganisms were detected and analyzed using metagenomics. Results: Compared with the 30-day untrained group, the relative abundances of Bacteroidetes were significantly increased in the 30-day training group (p < 0.01). Conversely, the abundances of Clostridiaceae, Clostridium, and Ruminococcus were significantly decreased (p < 0.01), whereas those of Prevotella, Bacteroideaceae, and Bacteroidetes were significantly increased (p < 0.05). Additionally, the relative abundances of Firmicutes and Actinomycetes were significantly decreased (p < 0.05). Compared with the 60-day untrained group, no significant differences in the phyla Bacteriaceae and Bacteriae of the 60-day training group (p > 0.05) were observed. In the linear discriminant analysis effect size analysis, seven significantly different bacteria were detected in the fecal flora of horses in the 30-day training group versus the untrained 30-day group, but only one significantly different bacterium was detected after 60 days. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes were related to metabolism and the environmental information processing pathway, carbohydrate metabolism, and membrane transport pathways. Conclusions: Therefore, training seems to affect the diversity and composition of the gut microbiota of Yili horses, especially during the first 30 days of training.
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Affiliation(s)
- Yuan-Fang Sun
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
| | - Zi-Xiang Han
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
| | - Xin-Kui Yao
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
- Xinjiang Key Laboratory of Horse Breeding and Exercise Physiology, Urumqi 830052, China
| | - Jun Meng
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
- Xinjiang Key Laboratory of Horse Breeding and Exercise Physiology, Urumqi 830052, China
| | - Wan-Lu Ren
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
| | - Chuan-Kun Wang
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
| | - Xin-Xin Yuan
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
| | - Ya-Qi Zeng
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
- Xinjiang Key Laboratory of Horse Breeding and Exercise Physiology, Urumqi 830052, China
| | - Yong-Fa Wang
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
| | - Zhi-Wen Sun
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
| | - Jian-Wen Wang
- College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China; (Y.-F.S.); (Z.-X.H.); (X.-K.Y.); (J.M.); (W.-L.R.); (C.-K.W.); (X.-X.Y.); (Y.-Q.Z.); (Y.-F.W.); (Z.-W.S.)
- Xinjiang Key Laboratory of Horse Breeding and Exercise Physiology, Urumqi 830052, China
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Jiang D, Zhang J, Ji Y, Dai Z, Yang Y, Wu Z. Glutamate Supplementation Regulates Nitrogen Metabolism in the Colon and Liver of Weaned Rats Fed a Low-Protein Diet. Nutrients 2025; 17:1465. [PMID: 40362775 PMCID: PMC12073364 DOI: 10.3390/nu17091465] [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: 03/10/2025] [Revised: 04/03/2025] [Accepted: 04/11/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Glutamate, a nutritionally non-essential amino acid, is a key intermediate in nitrogen metabolism. Despite more studies on its functional role in intestine health, it remains unknown how glutamate regulates nitrogen metabolism in animals fed a low-protein diet. Methods: Herein, we investigated the effects of glutamate supplementation on colonic amino acid transport, barrier protein expression, microbiota alterations, fecal nitrogen emissions, hepatic amino acid transport, and protein synthesis in weaned rats. Results: We found that protein restriction diminished the mucus thickness, reduced goblet cell numbers, and the expression of EAAT3, y+LAT2 in the colon. In contrast, glutamate supplementation reversed these effects, increasing the colon length and enhancing the expression of ZO-1, Occludin, and Claudin-1 in the colon. At the genus level, glutamate increased the abundance of Lactococcus and Clostridia_sensu_stricto_18. Additionally, glutamate supplementation resulted in an increased apparent nitrogen digestibility, reduced the ratio of fecal nitrogen to total nitrogen intake, and increased the ratio of fecal microbial nitrogen to total nitrogen intake. Protein restriction decreased the mRNA level of ATP1A1, EAAT3, SNAT9/2, and ASCT2, and the protein level of p-mTOR, mTOR, p-mTOR/mTOR, and p-p70S6K/p70S6K as well as p-4EBP1/4EBP1 in the liver. These effects were reversed by glutamate supplementation. Conclusions: In conclusion, glutamate supplementation upregulates amino acid transporters and barrier protein expression in the colon, modulates microbiota composition to reduce fecal nitrogen excretion, and enhances amino acid transport and protein synthesis in the liver by activating the mTOR/p70S6K/4EBP1 pathway, which influences nitrogen metabolism in weaned rats fed a low-protein diet.
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Affiliation(s)
| | | | | | | | | | - Zhenlong Wu
- State Key Laboratory of Animal Nutrition and Feed Science, China Agricultural University, Beijing 100193, China; (D.J.); (J.Z.); (Y.J.); (Z.D.); (Y.Y.)
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36
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Saniotis A, Henneberg M, Mohammadi K. Evolutionary medicine and bioastronautics: an innovative approach in addressing adverse mental health effects to astronauts during long term space missions. Front Physiol 2025; 16:1558625. [PMID: 40342860 PMCID: PMC12058484 DOI: 10.3389/fphys.2025.1558625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Accepted: 04/08/2025] [Indexed: 05/11/2025] Open
Abstract
Although evolutionary medicine has produced several novel insights for explaining prevalent health issues, it has yet to sufficiently address possible adverse mental health effects of humans during long-term space missions While evolutionary applications to medicine have increased over the past 20 years, there is scope for the integration of evolutionary applications in the new branch of space medicine called bioastronautics, which analyses the effects on human bodies when in outer space. Evolutionary principles may explain what kinds of space environments increase mental health risks to astronauts, both in the short and long term; secondly, evolutionary principles may provide a more informed understanding of the evolutionary mismatch between terrestrial and space environments in which astronauts exist. This information may assist in developing frameworks for improving mental health of astronauts and future space colonists. Consequently, this paper will focus on some of the major evolutionary mismatches currently confronting astronauts' mental health, with an aim to improve medical knowledge. It will also provide possible therapeutic countermeasures based on evolutionary principles for reducing adverse mental effects on astronauts.
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Affiliation(s)
- Arthur Saniotis
- Department of Medical Microbiology, Cihan University-Erbil, Erbil, Iraq
- School of Biomedicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia
| | - Maciej Henneberg
- School of Biomedicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia
- Institute of Evolutionary Medicine, University of Zurich, Zurich, Switzerland
| | - Kazhaleh Mohammadi
- Department of Medical Microbiology, College of Science, Knowledge University, Erbil, Iraq
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Cho MY, Eom JH, Choi EM, Yang SJ, Lee D, Kim YY, Kim HS, Hwang I. Recent advances in therapeutic probiotics: insights from human trials. Clin Microbiol Rev 2025:e0024024. [PMID: 40261032 DOI: 10.1128/cmr.00240-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/24/2025] Open
Abstract
SUMMARYRecent advances in therapeutic probiotics have shown promising results across various health conditions, reflecting a growing understanding of the human microbiome's role in health and disease. However, comprehensive reviews integrating the diverse therapeutic effects of probiotics in human subjects have been limited. By analyzing randomized controlled trials (RCTs) and meta-analyses, this review provides a comprehensive overview of key developments in probiotic interventions targeting gut, liver, skin, vaginal, mental, and oral health. Emerging evidence supports the efficacy of specific probiotic strains and combinations in treating a wide range of disorders, from gastrointestinal (GI) and liver diseases to dermatological conditions, bacterial vaginosis, mental disorders, and oral diseases. We discuss the expanding understanding of microbiome-organ connections underlying probiotic mechanisms of action. While many clinical trials demonstrate significant benefits, we acknowledge areas requiring further large-scale studies to establish definitive efficacy and optimal treatment protocols. The review addresses challenges in standardizing probiotic research methodologies and emphasizes the importance of considering individual variations in microbiome composition and host genetics. Additionally, we explore emerging concepts such as the oral-gut-brain axis and future directions, including high-resolution microbiome profiling, host-microbe interaction studies, organoid models, and artificial intelligence applications in probiotic research. Overall, this review offers a comprehensive update on the current state of therapeutic probiotics across multiple domains of human health, providing insights into future directions and the potential for probiotics to revolutionize preventive and therapeutic medicine.
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Affiliation(s)
- Mu-Yeol Cho
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
| | - Je-Hyun Eom
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
| | - Eun-Mi Choi
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
| | | | - Dahye Lee
- Department of Orthodontics, Apple Tree Dental Hospital, Goyang-si, South Korea
| | - Young Youn Kim
- Department of Oral and Maxillofacial Surgery, Apple Tree Dental Hospital, Goyang-si, South Korea
| | - Hye-Sung Kim
- Department of Oral and Maxillofacial Surgery, Apple Tree Dental Hospital, Goyang-si, South Korea
| | - Inseong Hwang
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
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38
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Duru IC, Lecomte A, Laine P, Shishido TK, Suppula J, Paulin L, Scheperjans F, Pereira PAB, Auvinen P. Comparison of phage and plasmid populations in the gut microbiota between Parkinson's disease patients and controls. Sci Rep 2025; 15:13723. [PMID: 40258842 PMCID: PMC12012184 DOI: 10.1038/s41598-025-96924-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 04/01/2025] [Indexed: 04/23/2025] Open
Abstract
The aging population worldwide is on the rise, leading to a higher number of Parkinson's disease (PD) cases each year. PD is presently the second most prevalent neurodegenerative disease, affecting an estimated 7-10 million individuals globally. This research aimed to identify mobile genetic elements in human fecal samples using a shotgun metagenomics approach. We identified over 44,000 plasmid contigs and compared plasmid populations between PD patients (n = 68) and controls (n = 68). Significant associations emerged between groups (control vs PD) based on plasmid alpha and beta diversity. Moreover, the gene populations present on plasmids displayed marked differences in alpha and beta diversity between PD patients and controls. We identified a considerable number of phage contigs that were differentially abundant in the two groups. We also developed a predictive machine learning model based on phage abundance data, achieving a mean Area Under the Curve (AUC) of 0.74 with a standard deviation of 0.105 and a mean F1 score of 0.68 with a standard deviation of 0.14 across cross-validation folds, indicating moderate discriminatory power. Additionally, when tested on external data, the model yielded an AUC of 0.74 and an F1 score of 0.8, further demonstrating the predictive potential of phage populations in Parkinson's disease. Further, we improved the continuity and identification of the protein coding regions of the phage contigs by implementing alternative genetic codes.
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Affiliation(s)
- Ilhan Cem Duru
- Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
| | - Alexandre Lecomte
- Institute of Biotechnology, University of Helsinki, Helsinki, Finland
| | - Pia Laine
- Institute of Biotechnology, University of Helsinki, Helsinki, Finland
| | | | - Joni Suppula
- Institute of Biotechnology, University of Helsinki, Helsinki, Finland
| | - Lars Paulin
- Institute of Biotechnology, University of Helsinki, Helsinki, Finland
| | - Filip Scheperjans
- Department of Neurology, Helsinki University Hospital and Clinicum, University of Helsinki, Helsinki, Finland
| | - Pedro A B Pereira
- Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
- Department of Neurology, Helsinki University Hospital and Clinicum, University of Helsinki, Helsinki, Finland.
| | - Petri Auvinen
- Institute of Biotechnology, University of Helsinki, Helsinki, Finland
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Hajjeh O, Rajab I, Bdair M, Saife S, Zahran A, Nazzal I, AbuZahra MI, Jallad H, Abukhalil MM, Hallak M, Al-Said OS, Al-Braik R, Sawaftah Z, Milhem F, Almur O, Saife S, Aburemaileh M, Abuhilal A. Enteric nervous system dysfunction as a driver of central nervous system disorders: The Forgotten brain in neurological disease. Neuroscience 2025; 572:232-247. [PMID: 40088964 DOI: 10.1016/j.neuroscience.2025.03.015] [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: 01/30/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/17/2025]
Abstract
The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered neurotransmission, gut microbiota imbalance, and neuroinflammation contribute to disease pathogenesis. The GBA enables bidirectional communication through the vagus nerve, gut hormones, immune signaling, and microbial metabolites, linking gut health to neurological function. ENS dysregulation is implicated in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), influencing systemic and CNS pathology through neuroinflammation and impaired barrier integrity. This review highlights emerging therapeutic strategies targeting ENS dysfunction, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and vagus nerve stimulation, which offer novel ways to modulate gut-brain interactions. Unlike previous perspectives that view the ENS as a passive disease marker, this review repositions it as an active driver of neurological disorders. By integrating advances in ENS biomarkers, therapeutic targets, and GBA modulation, this article presents a paradigm shift-emphasizing ENS dysfunction as a fundamental mechanism in neurodegeneration and neurodevelopmental disorders. This perspective paves the way for innovative diagnostics, personalized gut-targeted therapies, and a deeper understanding of the ENS's role in brain health and disease.
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Affiliation(s)
- Orabi Hajjeh
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Islam Rajab
- Internal Medicine Department, St. Joseph's University Medical Center, 703 Main St, Paterson, NJ 07503, USA
| | - Mohammad Bdair
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Sarah Saife
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Anwar Zahran
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Iyad Nazzal
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Mohammad Ibrahem AbuZahra
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Hammam Jallad
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
| | - Maram M Abukhalil
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Mira Hallak
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Osama S Al-Said
- Department Of Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Rama Al-Braik
- Department Of Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Zaid Sawaftah
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Fathi Milhem
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Omar Almur
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Sakeena Saife
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Mohammed Aburemaileh
- Department Of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Anfal Abuhilal
- Neuroscience Initiative, Advanced Science Research Center, The City University of New York (CUNY) Graduate Center, New York, NY 10031, USA
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40
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Zhao M, Xing L, Li Y, Zhang J, Liu Y, Ye F, Chen S. Multiomics-based analysis of key genes, metabolites and pathways unveils mechanism associated with social rank in Chickens. Poult Sci 2025; 104:105192. [PMID: 40319585 DOI: 10.1016/j.psj.2025.105192] [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: 01/06/2025] [Revised: 03/27/2025] [Accepted: 04/18/2025] [Indexed: 05/07/2025] Open
Abstract
Social rank plays a crucial role in shaping physiological, psychological and immune responses in animals. Our previous study found that gut microbes and short-chain fatty acids as well as brain neurotransmitters are involved with the mechanism of social hierarchy. Nevertheless, how these gut and brain metabolites interact to affect the mechanism of social hierarchy in chickens is not yet known. In this study, 40 hens were randomly divided into four groups at the age of 49 days, and social rank of each hen was determined by 6 times according to the feeding competition tests. Then hens ranked 1/2 were named High Social Rank (HSR, n = 8) and hens ranked 9/10 were named Low Social Rank (LSR, n = 8). We use multiomics to explore gut metabolites, neurotransmitters, and brain transcriptome, neurotransmitters and related gene expression in 91-day-old chickens, so as to better understand the underpinning mechanism that regulates the social hierarchy. We found that the pro-inflammatory genes were significantly lower while anti-inflammatory factor in spleen was higher in HSR chickens than in LSR chickens (P<0.05). Besides, seven immune-related genes were significantly different in the amygdala between HSR and LSR (P < 0.05). In addition, AVP, RXFP3, VIP and NKX2-1 were associated with the social rank through GABAergic neurons and neuroactive ligand-receptor pathways, with the up-regulation of 5-HT in the amygdala of LSR. Genes SLC11A2 and HMOX1 in ferroptosis pathway influenced the cecum metabolite l-glutamate and tyrosine. While fumaric, l-glutamic and 4-Oxoproline were found enriched in "alanine, aspartate and glutamate metabolism" and "arginine biosynthesis". In conclusion, social rank affects the immunity, in which higher ranking hens show better anti-inflammatory and lower pro-inflammatory than lower ranking hens. Genes TAP2, PLD4, P2RX7, ALDH9A1, SLC11A2, ADM, C3, AVP, RXFP3, VIP, NKX2-1, SLC11A2 and HMOX1 may play an important regulatory role on GABAergic neurons, neuroactive ligand-receptor and ferroptosis pathways related to neuron, immune, and stress behaviour, and in turn affects social rank. Fumaric, l-glutamic and 4-Oxoproline, may regulate social rank through the "alanine, aspartate and glutamate metabolism" and "arginine biosynthesis".
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Affiliation(s)
- Mengqiao Zhao
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan, PR China
| | - Limin Xing
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan, PR China
| | - Yushan Li
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan, PR China
| | - Jiaxin Zhang
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan, PR China
| | - Yinghui Liu
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan, PR China
| | - Fei Ye
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan, PR China
| | - Siyu Chen
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan, PR China.
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41
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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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42
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Parthasarathy S, Giridharan B, Panigrahi J, Konyak LM, Jamir N, Tharumasivam SV. Abnormal microbiota due to prenatal antibiotic as a possible risk factor for Attention-Deficit / Hyperactivity Disorder (ADHD). INTERNATIONAL REVIEW OF NEUROBIOLOGY 2025; 180:299-328. [PMID: 40414636 DOI: 10.1016/bs.irn.2025.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2025]
Abstract
One of the major issues modern medicine faces is the increasing use of antibiotics in reaction to the increased incidence of infectious agents. The current trend of antibiotic overuse contributes to microbial dysbiosis. Recent studies have hypothesized that antibiotic exposure during pregnancy, which alters the composition of the microbiome, might increase the likelihood of attention deficit hyperactivity disorder (ADHD). In addition to the ongoing discussion about the potential links between antibiotic usage, microbiome dysbiosis, and ADHD, there is a rising interest in integrating AI and ML into healthcare practices. Diagnosis, treatment plans, and prognoses are all enhanced by these technological advancements. Remote monitors or telemedicine monitoring are among the management techniques described in this chapter for effectively managing illnesses. Also discussed are ways to halt the progression of diseases by preventative measures that use biosensor technology and dietary approaches. Personalized treatment programs, disease progression stages, and prognosis evaluations are all made possible with the use of artificial intelligence and machine learning. By using these technologies to provide individualized therapy, healthcare practitioners may get a better understanding of ADHD and perhaps improve patient outcomes.
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Affiliation(s)
| | - Bupesh Giridharan
- Department of Forestry, Nagaland University (Hqrs.), Lumami, Nagaland, India; Department of Biotechnology, Berhampur University, Bhanja Bihar, Ganjam, Odisha, India.
| | - Jogeswar Panigrahi
- Department of Biotechnology, Berhampur University, Bhanja Bihar, Ganjam, Odisha, India
| | - Longnyu M Konyak
- Department of Forestry, Nagaland University (Hqrs.), Lumami, Nagaland, India
| | - Nokenketla Jamir
- Department of Forestry, Nagaland University (Hqrs.), Lumami, Nagaland, India
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43
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Wang Y, Guo C, Zang B, Wang P, Yang C, Shi R, Kong Y, Sui A, Li S, Lin Y. Anxiolytic effects of accelerated continuous theta burst stimulation on mice exposed to chronic restraint stress and the underlying mechanism involving gut microbiota. J Affect Disord 2025; 375:49-63. [PMID: 39848468 DOI: 10.1016/j.jad.2025.01.104] [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: 10/01/2024] [Revised: 01/10/2025] [Accepted: 01/20/2025] [Indexed: 01/25/2025]
Abstract
BACKGROUND Accelerated continuous theta burst stimulation (acTBS) is a more intensive and rapid protocol than continuous theta burst stimulation (cTBS). However, it remains uncertain whether acTBS exhibits anxiolytic effects. The aim of this study was to investigate the impact of acTBS on anxiety model mice and elucidate the underlying mechanisms involved, in order to provide a more comprehensive understanding of its effects. METHODS Chronic restraint stress (CRS) model was employed to observe the anxiolytic effects of acTBS. The study focused on evaluating the impact of acTBS on behavior, neuroinflammation, gut and gut microbiota in mice with anxiety induced by CRS. RESULTS The application of acTBS ameliorated anxiety-like behaviors in CRS-induced mice. Notably, it effectively suppressed the activation of microglia and reduced the level pro-inflammatory cytokines in PFC, hippocampus, and amygdala of anxiety mice. Additionally, acTBS alleviated astrocyte activation specifically in hippocampus. The NF-κB signaling pathway involved in the anti-inflammatory effects of acTBS. Furthermore, acTBS ameliorated inflammation and histological damage in colon. 16S rRNA analysis revealed that acTBS significantly enhanced the relative abundance of Lactobacillus, while normalized the dysregulated levels of Coriobacterales, Bacteroides, and Parabacteroides caused by CRS. These changes facilitated chemoheterotrophic and fermentation functions within the microbiota. Importantly, changes in microbiota composition influenced by acTBS was found to be correlated with anxiety-like behaviors and neuroinflammation. CONCLUSIONS acTBS exerted anxiolytic effects on mice exposed to CRS, which was associated with the modulation of gut microbiota.
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Affiliation(s)
- Yihan Wang
- Department of Neurology, The Second Hospital of Dalian Medical University, Dalian 116021, China
| | - Cong Guo
- Department of Neurology, The Second Hospital of Dalian Medical University, Dalian 116021, China
| | - Bowen Zang
- Department of Neurology, The Second Hospital of Dalian Medical University, Dalian 116021, China
| | - Peng Wang
- Department of Neurology, The Second Hospital of Dalian Medical University, Dalian 116021, China
| | - Chuyan Yang
- Department of Neurology, The Second Hospital of Dalian Medical University, Dalian 116021, China
| | - Ruifeng Shi
- Department of Neurology, The Second Hospital of Dalian Medical University, Dalian 116021, China
| | - Yue Kong
- Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian 116044, China
| | - Aoran Sui
- Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian 116044, China
| | - Shao Li
- Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian 116044, China.
| | - Yongzhong Lin
- Department of Neurology, The Second Hospital of Dalian Medical University, Dalian 116021, China.
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44
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Bonomo MG, D’Angelo S, Picerno V, Carriero A, Salzano G. Recent Advances in Gut Microbiota in Psoriatic Arthritis. Nutrients 2025; 17:1323. [PMID: 40284188 PMCID: PMC12030176 DOI: 10.3390/nu17081323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/04/2025] [Accepted: 04/08/2025] [Indexed: 04/29/2025] Open
Abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.
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Affiliation(s)
- Maria Grazia Bonomo
- Department of Health Sciences, University of Basilicata, Viale dell’ Ateneo Lucano 10, 85100 Potenza, Italy; (S.D.); (G.S.)
| | - Salvatore D’Angelo
- Department of Health Sciences, University of Basilicata, Viale dell’ Ateneo Lucano 10, 85100 Potenza, Italy; (S.D.); (G.S.)
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Via Potito Petrone, 85100 Potenza, Italy; (V.P.); (A.C.)
| | - Valentina Picerno
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Via Potito Petrone, 85100 Potenza, Italy; (V.P.); (A.C.)
| | - Antonio Carriero
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Via Potito Petrone, 85100 Potenza, Italy; (V.P.); (A.C.)
| | - Giovanni Salzano
- Department of Health Sciences, University of Basilicata, Viale dell’ Ateneo Lucano 10, 85100 Potenza, Italy; (S.D.); (G.S.)
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45
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Johnson KVA, Steenbergen L. Probiotics reduce negative mood over time: the value of daily self-reports in detecting effects. NPJ MENTAL HEALTH RESEARCH 2025; 4:10. [PMID: 40205027 PMCID: PMC11982403 DOI: 10.1038/s44184-025-00123-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 03/06/2025] [Indexed: 04/11/2025]
Abstract
The burgeoning field of the microbiome-gut-brain axis has inspired research into how the gut microbiome can affect human emotion. Probiotics offer ways to investigate microbial-based interventions but results have been mixed, with more evidence of beneficial effects in clinically depressed patients. Using a randomised, double-blind, placebo-controlled design in 88 healthy volunteers, we conduct a comprehensive study into effects of a multispecies probiotic on emotion regulation and mood through questionnaires, emotional processing tests and daily reports. We find clear evidence that probiotics reduce negative mood, starting after two weeks, based on daily monitoring, but few other changes. Our findings reconcile inconsistencies of previous studies, revealing that commonly used pre- versus post-intervention assessments cannot reliably detect probiotic-induced changes in healthy subjects' emotional state. We conclude that probiotics can benefit mental health in the general population and identify traits of individuals who derive greatest benefit, allowing future targeting of at-risk individuals.
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Affiliation(s)
- Katerina V-A Johnson
- Clinical Psychology Unit, Leiden University, Institute of Psychology, Leiden, The Netherlands.
- Department of Psychiatry, University of Oxford, Oxford, UK.
| | - Laura Steenbergen
- Clinical Psychology Unit, Leiden University, Institute of Psychology, Leiden, The Netherlands
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46
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Kalkan AE, BinMowyna MN, Raposo A, Ahmad MF, Ahmed F, Otayf AY, Carrascosa C, Saraiva A, Karav S. Beyond the Gut: Unveiling Butyrate's Global Health Impact Through Gut Health and Dysbiosis-Related Conditions: A Narrative Review. Nutrients 2025; 17:1305. [PMID: 40284169 PMCID: PMC12029953 DOI: 10.3390/nu17081305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
Short-chain fatty acids (SCFAs), mainly produced by gut microbiota through the fermentation process of dietary fibers and proteins, are crucial to human health, with butyrate, a famous four-carbon SCFA, standing out for its inevitably regulatory impact on both gut and immune functions. Within this narrative review, the vital physiological functions of SCFAs were examined, with emphasis on butyrate's role as an energy source for colonocytes and its ability to enhance the gut barrier while exhibiting anti-inflammatory effects. Knowledge of butyrate synthesis, primarily generated by Firmicutes bacteria, can be influenced by diets with specifically high contents of resistant starches and fiber. Butyrate can inhibit histone deacetylase, modulate gene expression, influence immune functionality, and regulate tight junction integrity, supporting the idea of its role in gut barrier preservation. Butyrate possesses systemic anti-inflammatory properties, particularly, its capacity to reduce pro-inflammatory cytokines and maintain immune homeostasis, highlighting its therapeutic potential in managing dysbiosis and inflammatory diseases. Although butyrate absorption into circulation is typically minimal, its broader health implications are substantial, especially regarding obesity and type 2 diabetes through its influence on metabolic regulation and inflammation. Furthermore, this narrative review thoroughly examines butyrate's growing recognition as a modulator of neurological health via its interaction with the gut-brain axis. Additionally, butyrate's neuroprotective effects are mediated through activation of specific G-protein-coupled receptors, such as FFAR3 and GPR109a, and inhibition of histone deacetylases (HDACs). Research indicates that butyrate can alleviate neurological disorders, including Alzheimer's, Parkinson's, autism spectrum disorder, and Huntington's disease, by reducing neuroinflammation, enhancing neurotransmitter modulation, and improving histone acetylation. This focus will help unlock its full therapeutic potential for metabolic and neurological health, rather than exclusively on its well-known benefits for gut health, as these are often interconnected.
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Affiliation(s)
- Arda Erkan Kalkan
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17100, Turkey;
| | - Mona N. BinMowyna
- College of Education, Shaqra University, Shaqra 11911, Saudi Arabia;
| | - António Raposo
- CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal
| | - Md Faruque Ahmad
- Department of Clinical Nutrition, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia; (M.F.A.); (A.Y.O.)
| | - Faiyaz Ahmed
- Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, P.O. Box 6666, Buraydah 51452, Saudi Arabia;
| | - Abdullah Y. Otayf
- Department of Clinical Nutrition, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia; (M.F.A.); (A.Y.O.)
| | - Conrado Carrascosa
- Department of Animal Pathology and Production, Bromatology and Food Technology, Faculty of Veterinary, Universidad de Las Palmas de Gran Canaria, Trasmontaña s/n, 35413 Arucas, Spain;
| | - Ariana Saraiva
- Research in Veterinary Medicine (I-MVET), Faculty of Veterinary Medicine, Lisbon University Centre, Lusófona University, Campo Grande 376, 1749-024 Lisboa, Portugal;
- Veterinary and Animal Research Centre (CECAV), Faculty of Veterinary Medicine, Lisbon University Centre, Lusófona University, Campo Grande 376, 1749-024 Lisboa, Portugal
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17100, Turkey;
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47
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Xiang F, Hu L, Zhang S, Lv P, Wei G, Yan Z. Integration of network pharmacology and untargeted metabolomics reveals Changpu San's antidepressant mechanisms via tryptophan metabolism. JOURNAL OF ETHNOPHARMACOLOGY 2025; 345:119590. [PMID: 40064322 DOI: 10.1016/j.jep.2025.119590] [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: 11/06/2024] [Revised: 12/25/2024] [Accepted: 03/05/2025] [Indexed: 03/18/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Changpu San (CPS) is a traditional Chinese medicine (TCM) formula historically used to treat symptoms resembling depression. However, its antidepressant effects and underlying mechanisms remain unclear. AIM OF THE STUDY This study aims to evaluate CPS's antidepressant effects and elucidate its mechanisms by combining network pharmacology with untargeted metabolomics. MATERIALS AND METHODS A chronic unpredictable mild stress (CUMS) mouse model was used to assess CPS's antidepressant effects via behavioral tests and body weight monitoring. By integrating network pharmacology and untargeted metabolomics, both based on UPLC-Q-Exactive-Orbitrap-MS for CPS chemical profiling and serum metabolite analysis, a key pathway was identified. This pathway was validated through UPLC-QQQ-MS/MS and ELISA by measuring relevant biomarkers, while its association with colonic microbiota was further investigated using 16S rDNA sequencing. RESULTS CPS alleviated depression-like behaviors in CUMS mice. A total of 140 compounds were identified in CPS, revealing 140 core targets related to depression. Metabolomics analysis identified 42 serum metabolites significantly altered in CUMS mice, with tryptophan metabolism emerging as a shared pathway across both approaches. Experimental validation showed CPS partially reversed tryptophan metabolism dysregulation, significantly increasing tryptophan levels and reducing kynurenine levels in the brain. Moreover, CPS modulated the colonic microbiota, with key genera such as Prevotella and Bacillus showing correlations with tryptophan metabolism and inflammation. CONCLUSION CPS shows promise as an effective antidepressant, potentially through modulating tryptophan metabolism and reshaping colonic microbiota. This study provides valuable insights into its mechanisms and offers a methodological reference for researching other TCM formulas.
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Affiliation(s)
- Fangrui Xiang
- School of Life Science and Engineering, Southwest Jiaotong University, Cheng du, P.R. China.
| | - Lin Hu
- School of Life Science and Engineering, Southwest Jiaotong University, Cheng du, P.R. China.
| | - Shengqi Zhang
- School of Life Science and Engineering, Southwest Jiaotong University, Cheng du, P.R. China.
| | - Pengcheng Lv
- School of Life Science and Engineering, Southwest Jiaotong University, Cheng du, P.R. China.
| | - Guihua Wei
- School of Life Science and Engineering, Southwest Jiaotong University, Cheng du, P.R. China.
| | - Zhiyong Yan
- School of Life Science and Engineering, Southwest Jiaotong University, Cheng du, P.R. China.
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48
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Xiao B, Fu L, Yang Z, Yu G. Effect of probiotics on cognitive function and cardiovascular risk factors in mild cognitive impairment and Alzheimer's disease: an umbrella meta-analysis. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:109. [PMID: 40200373 PMCID: PMC11980270 DOI: 10.1186/s41043-025-00816-3] [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: 02/03/2025] [Accepted: 03/03/2025] [Indexed: 04/10/2025]
Abstract
BACKGROUND This umbrella meta-analysis evaluates the effects of probiotics on cognitive function and metabolic health in Alzheimer's disease (AD) and mild cognitive impairment (MCI) by synthesizing findings from meta-analyses of randomized controlled trials (RCTs), as existing evidence remains inconclusive. METHODS A systematic search was conducted in PubMed, Web of Science, and Scopus to identify meta-analyses of RCTs investigating the impact of probiotic supplementation on cognitive function and metabolic biomarkers. The random-effects model was used. Heterogeneity and publication bias were assessed. RESULTS Thirteen meta-analyses, comprising 3910 patients, were included. Probiotics significantly improved cognitive function in AD (SMD = 0.78, 95% CI: 0.33 to 1.23) and MCI (SMD = 0.43, 95% CI: 0.15 to 0.70). Probiotics also increased total antioxidant capacity (SMD = 0.40, 95% CI: 0.11 to 0.70) and reduced MDA (SMD = - 0.35, 95% CI: - 0.62 to - 0.09) and hs-CRP (SMD = - 0.59, 95% CI: - 0.87 to - 0.30). Insulin resistance improved, as reflected by decreased HOMA-IR (SMD = - 0.34, 95% CI: - 0.43 to - 0.26). No significant effects were observed on glutathione, nitric oxide, or lipid profiles. CONCLUSION Probiotic supplementation appears to enhance cognitive function and metabolic parameters in individuals with MCI and AD, likely through mechanisms involving inflammation reduction, oxidative stress modulation, and improved insulin sensitivity. Further high-quality RCTs are required to validate these findings and determine optimal probiotic formulations.
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Affiliation(s)
- Bin Xiao
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Lina Fu
- The People's Hospital of Danyang, Zhenjiang, Jiangsu Province, China
| | - Zhe Yang
- Taizhou School of Clinical Medicine, Nanjing Medical University, Jiangsu, China.
| | - Guran Yu
- Department of Neurology, Jiangsu Province Hospital of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210019, Jiangsu Province, China.
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49
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Li N, Fang X, Li H, Liu J, Chen N, Zhao X, Yang Q, Chen X. Ginsenoside CK modulates glucose metabolism via PPARγ to ameliorate SCOP-induced cognitive dysfunction. Metab Brain Dis 2025; 40:168. [PMID: 40178645 DOI: 10.1007/s11011-025-01596-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 03/23/2025] [Indexed: 04/05/2025]
Abstract
Ginsenoside compound K (CK) exhibits neuroprotective properties; however, the underlying mechanisms behind these effects have not been investigated thoroughly. CK is the primary active compound derived from ginseng and is metabolized in the gut. It enhances neuronal function by modulating the gut microflora. Therefore, the present study aimed to elucidate the mechanism through which CK enhances cognitive function, employing gut microbiome and microarray analyses. The results revealed that CK upregulated the expression of peroxisome proliferator-activated receptor gamma (PPARγ), suppressed amyloid-β (Aβ) aggregation in hippocampal neurons, and influenced the expression of cyclin-dependent kinase-5 (CDK5), (including insulin receptor substrate 2) IRS2, insulin-degrading enzyme (IDE), glycogen synthase kinase-3 beta (GSK-3β), glucose transporter type 1 (GLUT1), and glucose transporter type 3 (GLUT3) proteins. These proteins play crucial roles in regulating brain glucose metabolism, increasing neuronal energy, and reducing neuronal apoptosis, thereby ameliorating cognitive impairment in mice.
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Affiliation(s)
- Na Li
- Jinlin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, P.R. China
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119077, Singapore
| | - Xingyu Fang
- Jinlin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, P.R. China
| | - Hui Li
- Qian Wei Hospital of Jilin Province, Changchun, 130117, Jilin, P.R. China
| | - Jian Liu
- Jinlin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, P.R. China
| | - Nan Chen
- Jinlin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, P.R. China
| | - Xiaohui Zhao
- Jinlin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, P.R. China
| | - Qing Yang
- Jinlin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, P.R. China.
| | - Xijun Chen
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, P.R. China.
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50
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Marano G, Rossi S, Sfratta G, Traversi G, Lisci FM, Anesini MB, Pola R, Gasbarrini A, Gaetani E, Mazza M. Gut Microbiota: A New Challenge in Mood Disorder Research. Life (Basel) 2025; 15:593. [PMID: 40283148 PMCID: PMC12028401 DOI: 10.3390/life15040593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 03/30/2025] [Accepted: 04/01/2025] [Indexed: 04/29/2025] Open
Abstract
The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the latest findings on the gut-microbiota-brain axis and elucidates how alterations in gut microbiota composition can influence this axis, leading to changes in brain function and behavior. Although dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation have yielded encouraging results, significant advances are needed to establish next-generation approaches that precisely target the neurobiological mechanisms of mood disorders. Future research must focus on developing personalized treatments, facilitated by innovative therapies and technological progress, which account for individual variables such as age, sex, drug history, and lifestyle. Highlighting the potential therapeutic implications of targeting the gut microbiota, this review emphasizes the importance of integrating microbiota research into psychiatric studies to develop more effective and personalized treatment strategies for mood disorders.
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Affiliation(s)
- Giuseppe Marano
- Unit of Psychiatry, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (G.S.); (M.B.A.); (M.M.)
- Department of Neurosciences, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Sara Rossi
- Unit of Psychiatry, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (G.S.); (M.B.A.); (M.M.)
- Department of Neurosciences, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Greta Sfratta
- Unit of Psychiatry, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (G.S.); (M.B.A.); (M.M.)
- Department of Neurosciences, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Gianandrea Traversi
- Unit of Medical Genetics, Department of Laboratory Medicine, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy
| | - Francesco Maria Lisci
- Unit of Psychiatry, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (G.S.); (M.B.A.); (M.M.)
- Department of Neurosciences, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Maria Benedetta Anesini
- Unit of Psychiatry, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (G.S.); (M.B.A.); (M.M.)
- Department of Neurosciences, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Roberto Pola
- Section of Internal Medicine and Thromboembolic Diseases, Department of Internal Medicine, Fondazione Poli-Clinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Eleonora Gaetani
- Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Unit of Internal Medicine, Cristo Re Hospital, 00167 Rome, Italy
| | - Marianna Mazza
- Unit of Psychiatry, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (G.S.); (M.B.A.); (M.M.)
- Department of Neurosciences, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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