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34 pages, 1035 KB  
Review
Current Evidence from Animal Models on Molecular Changes Underlying Antidepressant Effects of Psychobiotics
by Nevena Todorović Vukotić, Neda Đorđević, Andrijana Stanisavljević Ilić, Svetlana Soković Bajić and Ivana Perić
Pharmaceutics 2026, 18(1), 140; https://doi.org/10.3390/pharmaceutics18010140 - 22 Jan 2026
Abstract
The treatment of depression is an uphill battle due to the low efficiency and delayed clinical response of antidepressants and the fact that most of them cause numerous side effects. Psychobiotics, probiotics that affect brain function and confer mental health benefits, emerged as [...] Read more.
The treatment of depression is an uphill battle due to the low efficiency and delayed clinical response of antidepressants and the fact that most of them cause numerous side effects. Psychobiotics, probiotics that affect brain function and confer mental health benefits, emerged as a promising ally showing protective effects against depressive- and anxiety-like behaviors in various animal models of depression. There is rapidly accumulating evidence that psychobiotics show protective effects at the molecular level as well, affecting several pathophysiological processes implicated in depression. This narrative review summarizes preclinical insights into molecular changes related to the hypothalamic-pituitary-adrenal (HPA) axis, peripheral inflammation, neuroinflammation, neurotransmission and tryptophan metabolism underlying psychobiotic-driven mitigation of depressive and anxiety symptoms in stress-based, corticosterone-induced and inflammation-induced animal models of depression. Research evidence indicates that psychobiotics normalize the activity of the HPA axis, decrease levels of inflammatory mediators in the intestine, circulation, and brain, normalize the levels of neurotransmitters and their receptors, and regulate tryptophan metabolism in various animal models of depression. The main setbacks in this field are the extensive diversity of studied probiotic strains, which are often insufficiently characterized, and the lack of mechanistic studies in animal models. However, despite these challenges, further study of psychobiotics in the pursuit of supportive therapies for depressive disorders is firmly grounded. Full article
48 pages, 3325 KB  
Systematic Review
“Attacking” the Gut–Brain Axis with Psychobiotics: An Umbrella Review of Depressive and Anxiety Symptoms
by Alberto Souza Sá Filho, Tatiane Bastos Souza, José Luís Rodrigues Martins, Gunnar P. H. Dietz, Katia Flávia Fernandes, Stone de Sá, Pedro Augusto Inacio, Iransé Oliveira-Silva, Gustavo Pedrino, Vicente Aprigliano, Gaspar R. Chiappa and James Oluwagbamigbe Fajemiroye
Pharmaceuticals 2026, 19(1), 156; https://doi.org/10.3390/ph19010156 - 15 Jan 2026
Viewed by 315
Abstract
Background/Objectives: This umbrella review critically evaluates the available evidence on psychobiotics for depressive and anxiety symptoms, emphasizing methodological quality, consistency of findings, and persistent gaps in the literature. Methods: A comprehensive search was conducted across PubMed/MEDLINE, Scopus, Web of Science, SciELO, [...] Read more.
Background/Objectives: This umbrella review critically evaluates the available evidence on psychobiotics for depressive and anxiety symptoms, emphasizing methodological quality, consistency of findings, and persistent gaps in the literature. Methods: A comprehensive search was conducted across PubMed/MEDLINE, Scopus, Web of Science, SciELO, Cochrane, and EBSCO (May–June 2025) to identify systematic reviews with meta-analyses of randomized controlled trials examining probiotic, prebiotic, and synbiotic interventions in adults with depressive and/or anxiety symptoms or diagnoses. Two reviewers independently screened studies, extracted data, and evaluated methodological quality using AMSTAR-2. Additional bibliometric, conceptual, and psychometric features were mapped, including geographical origin, publication timeline, scale distribution, and citation-based connectivity. Results: Thirty systematic reviews and meta-analyses were included. Methodological quality was predominantly moderate, low, or critically low in 76.6% of reviews. Probiotic interventions demonstrated consistent benefits for MDD (SMD = −0.50 [95% CI: −0.58 to −0.42], p = 0.0001). However, findings for anxiety were markedly inconsistent, despite the modest improvements in specific subgroups (SMD = −0.19 [95% CI: −0.28 to −0.10]; p < 0.01). Prebiotics for MDD interventions showed limited positive results (SMD = −0.25 [95% CI: −0.47 to −0.03]; p = 0.03). For anxiety, the effects are inconclusive (SMD = −0.07 [95% CI: −0.30 to 0.10]; p = 0.18). Evidence for synbiotics was scarce. Citation-mapping revealed a fragmented and unevenly connected evidence base. Conclusions: The current evidence suggests that probiotics may confer beneficial effects on depressive and anxiety symptoms; however, the same cannot be said for prebiotics and synbiotics. Evidence for the efficacy of prebiotics and synbiotics to treat depression and anxiety is still insufficient or heterogeneous. Registration: CRD420251164884. Full article
(This article belongs to the Special Issue Discovery of Novel Antidepressants and Anxiolytics)
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23 pages, 609 KB  
Review
Microbiota-Driven Strategies for Managing IBD-Associated Risks: From Infections to Mental Health
by Patrycja Krynicka, Pablo Cortegoso Valdivia, Maciej Morawski, Wojciech Marlicz, Karolina Skonieczna-Żydecka and Anastasios Koulaouzidis
Pharmaceuticals 2026, 19(1), 118; https://doi.org/10.3390/ph19010118 - 9 Jan 2026
Viewed by 324
Abstract
Inflammatory bowel diseases (IBD) are increasingly acknowledged not merely as confined gastrointestinal disorders but as systemic immunometabolic syndromes. Central to this paradigm is the gut microbiota including non-bacterial components such as the virome, whose functional disruption marked by reduced short-chain fatty acids (SCFAs), [...] Read more.
Inflammatory bowel diseases (IBD) are increasingly acknowledged not merely as confined gastrointestinal disorders but as systemic immunometabolic syndromes. Central to this paradigm is the gut microbiota including non-bacterial components such as the virome, whose functional disruption marked by reduced short-chain fatty acids (SCFAs), increasingly implicated in pathogenic processes extending beyond intestinal mucosa. This review outlines how these alternations compromise the epithelial barrier and immune regulation, increasing the risk of recurrent Clostridioides difficile infections to anemia, neuropsychiatric comorbidities, and extraintestinal manifestations. We critically evaluate emerging microbiota-targeted strategies, including fecal microbiota transplantation (FMT), live biotherapeutic products (LBPs), and precision postbiotics, positioning them as potential adjuncts to conventional immunosuppression. Finally, we discuss the current barriers to clinical translation, such as safety and heterogeneity, and propose a future framework for personalized, functionally integrated IBD care aimed at restoring long-term microbiota homeostasis. Full article
(This article belongs to the Section Biopharmaceuticals)
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17 pages, 688 KB  
Review
The Immune Mind: Linking Dietary Patterns, Microbiota, and Psychological Health
by Giuseppe Marano, Gianandrea Traversi, Osvaldo Mazza, Emanuele Caroppo, Esmeralda Capristo, Eleonora Gaetani and Marianna Mazza
Nutrients 2026, 18(1), 96; https://doi.org/10.3390/nu18010096 - 27 Dec 2025
Viewed by 804
Abstract
Background/Objectives: Nutritional patterns influence the gut–brain axis and immune signaling with potential consequences for depression and anxiety. We conducted a review focused on clinically meaningful psychiatric outcomes (symptom severity/diagnosis) to synthesize recent evidence (2020–2025) on Mediterranean-style dietary interventions; ultra-processed food (UPF) exposure; and [...] Read more.
Background/Objectives: Nutritional patterns influence the gut–brain axis and immune signaling with potential consequences for depression and anxiety. We conducted a review focused on clinically meaningful psychiatric outcomes (symptom severity/diagnosis) to synthesize recent evidence (2020–2025) on Mediterranean-style dietary interventions; ultra-processed food (UPF) exposure; and psychobiotic/prebiotic strategies, integrating mechanistic insights relevant to practice. Methods: Searches in PubMed/MEDLINE, Scopus, and Web of Science (January 2020–October 2025) combined terms for diet, Mediterranean diet (MD), UPF, microbiota, probiotics, psychobiotics, depression, and anxiety. Eligible designs were randomized/controlled trials (RCTs), prospective cohorts, and systematic reviews/meta-analyses reporting clinical psychiatric outcomes in adults. We prioritized high-quality quantitative syntheses and recent RCTs; data were extracted into a prespecified matrix and synthesized narratively. Results: Recent systematic reviews/meta-analyses support that MD interventions reduce depressive symptoms in adults with major or subthreshold depression, although large, long-term, multicenter RCTs remain a gap. Exposure to UPF is consistently associated with higher risk of common mental disorders and depressive outcomes in large prospective cohorts. Psychobiotics (specific probiotic strains and prebiotics) show small-to-moderate benefits on depressive symptoms across clinical and nonclinical samples, with heterogeneity in strains, dosing, and duration. Mechanistic reviews implicate microbiota-derived metabolites (short-chain fatty acids) and immune–inflammatory signaling (including tryptophan–kynurenine pathways) as plausible mediators. Conclusions: Clinically, emphasizing Mediterranean-style dietary patterns, reducing UPF intake, and considering targeted psychobiotics may complement standard psychiatric care for depression. Future work should prioritize adequately powered, longer RCTs with standardized dietary protocols and microbiome-informed stratification to clarify responders and mechanisms. Full article
(This article belongs to the Special Issue Diet, the Exposome, and Immunity: Microbiota and Beyond)
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5 pages, 169 KB  
Editorial
Probiotics at the Frontline: Redefining Therapeutic Possibilities
by George Stavrou, Alexandra-Eleftheria Menni and Katerina Kotzampassi
Nutrients 2026, 18(1), 48; https://doi.org/10.3390/nu18010048 - 23 Dec 2025
Viewed by 516
Abstract
Recently, advances in microbiome research have emphasized the fundamental role of probiotics—in addition to their inanimate form, postbiotics, and psychobiotics, a rapidly expanding group of probiotics with psychotropic potential [...] Full article
15 pages, 704 KB  
Article
Dual-Strain Psychobiotics Combining Live Lactiplantibacillus plantarum PS128 and Heat-Treated Lacticaseibacillus paracasei PS23 Improve Psychological and Neuroendocrine Outcomes in Stressed Adults: A Randomized, Placebo-Controlled Trial
by Mon-Chien Lee, Ting-An Lin and Chi-Chang Huang
Foods 2025, 14(24), 4190; https://doi.org/10.3390/foods14244190 - 6 Dec 2025
Viewed by 1078
Abstract
Chronic psychological stress impairs neuroendocrine balance and increases the risk of mental health disturbances, including anxiety, sleep disruption, and low mood. The gut–brain axis has emerged as a promising target for stress modulation, particularly through psychobiotic interventions. This randomized, double-blind, placebo-controlled trial evaluated [...] Read more.
Chronic psychological stress impairs neuroendocrine balance and increases the risk of mental health disturbances, including anxiety, sleep disruption, and low mood. The gut–brain axis has emerged as a promising target for stress modulation, particularly through psychobiotic interventions. This randomized, double-blind, placebo-controlled trial evaluated the effects of a combined psychobiotic formulation (Neuralli Mood), comprising live Lactiplantibacillus plantarum PS128 (PS128) and heat-treated Lacticaseibacillus paracasei PS23 (HT-PS23), on the psychological and physiological stress responses in a high-stress occupational population. A total of 116 healthy participants with elevated perceived stress (PSS ≥ 14), primarily firefighters, were randomly assigned to receive the dual-strain supplement or placebo for 8 weeks. Stress-related outcomes were assessed by using validated psychological scales and serum biomarkers. Compared with placebo, the psychobiotics group showed significantly greater reductions in overall job stress perception (JSS), state anxiety (STAI), and insomnia severity (ISI) (all p < 0.05). Additionally, serum adrenocorticotropic hormone (ACTH) and norepinephrine levels were significantly reduced post-intervention, whereas cortisol levels remained unchanged. These findings suggested that combining live and heat-treated psychobiotic strains may provide a safe and effective strategy for alleviating psychological stress and regulating neuroendocrine function in high-risk populations. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Food: Advances and Latest Trends)
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21 pages, 2163 KB  
Review
Psychobiotics at the Frontiers of Neurodegenerative and Neuropsychiatric Research
by Guillermo Roberto Jiménez-Pareyón, José Melesio Cristóbal-Luna, Yuliana García-Martínez, Cynthia Garfias-Noguez, Morayma Ramírez-Damián, Edgar Torres-Maravilla and María Elena Sánchez-Pardo
Microorganisms 2025, 13(12), 2718; https://doi.org/10.3390/microorganisms13122718 - 28 Nov 2025
Viewed by 811
Abstract
Neurodegenerative and neuropsychiatric disorders remain a major public health concern due to their progressive nature, high prevalence, and considerable socioeconomic burden. Conventional treatments often fall short, facing limitations such as pharmacoresistance, adverse effects, and limited efficacy, underscoring the need for complementary approaches. Recent [...] Read more.
Neurodegenerative and neuropsychiatric disorders remain a major public health concern due to their progressive nature, high prevalence, and considerable socioeconomic burden. Conventional treatments often fall short, facing limitations such as pharmacoresistance, adverse effects, and limited efficacy, underscoring the need for complementary approaches. Recent advances highlight the central role of the gut–brain axis (GBA) in neurological health, positioning psychobiotics and probiotic strains with potential mental health benefits, as candidates in adjunctive therapy. This review integrates current evidence on the GBA’s involvement in conditions such as Alzheimer’s disease, Parkinson’s disease, depression, and anxiety. We examine how psychobiotics may modulate neuroinflammation, oxidative stress, and neurotransmitter signaling, thereby contributing to cognitive and emotional regulation. Both preclinical and clinical studies are discussed, with emphasis on biomarker changes, quality-of-life outcomes, and neuropsychiatric comorbidities. We also explore recent innovations, including precision psychobiotics, microbiota–drug synergies, and their relevance to overlapping metabolic and neurodegenerative pathologies. Finally, we address the major translational challenges in the field, strain selection, methodological standardization, biomarker integration, and ethical design, highlighting key perspectives for advancing psychobiotics research toward clinical application. Full article
(This article belongs to the Special Issue Probiotics: Identification and Applications)
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18 pages, 596 KB  
Review
Targeting Irritable Bowel Syndrome Through Diet and Mechanism-Based Therapies: A Pathophysiological Approach
by Ioanna Aggeletopoulou, Katerina Karaivazoglou, Maria Kalafateli and Christos Triantos
Nutrients 2025, 17(22), 3595; https://doi.org/10.3390/nu17223595 - 17 Nov 2025
Cited by 1 | Viewed by 1867
Abstract
Irritable Bowel Syndrome (IBS) is a prevalent and heterogeneous functional gastrointestinal disorder with a complex and multifactorial pathophysiology. Traditional treatment approaches have focused on symptom relief, often overlooking the underlying biological mechanisms driving the disease. Τhis review summarizes the current evidence linking core [...] Read more.
Irritable Bowel Syndrome (IBS) is a prevalent and heterogeneous functional gastrointestinal disorder with a complex and multifactorial pathophysiology. Traditional treatment approaches have focused on symptom relief, often overlooking the underlying biological mechanisms driving the disease. Τhis review summarizes the current evidence linking core pathophysiological pathways of IBS with mechanism- and diet- based therapeutic strategies to guide personalized treatment. Serotonergic signaling, microbial dysbiosis, immune activation, epithelial barrier dysfunction, and bile acid malabsorption interact to shape the diverse phenotypes of IBS, contributing to altered motility, visceral hypersensitivity, and gut-brain axis dysregulation. Increasing evidence supports that targeted dietary and biological interventions including low-FODMAP and Mediterranean low-FODMAP diets, targeted use of probiotics and psychobiotics, and vitamin D supplementation can modulate microbial composition, reduce luminal irritants, support barrier integrity, and attenuate immune system activation. Similarly, pharmacologic therapies including serotonergic receptor modulators, bile acid sequestrants and neuroimmune agents act on specific mechanistic pathways, reflecting a shift from symptom-based to mechanism-driven management. Collectively, these findings highlight that integrating dietary, microbial, neuroimmune, and serotonergic modulation within a unified therapeutic framework can support a more rational and individualized approach to IBS management and long term symptom control. Full article
(This article belongs to the Special Issue Advances in Nutrition and Dietetics in Gastroenterology)
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27 pages, 1272 KB  
Review
The Pediatric Microbiota–Gut–Brain Axis: Implications for Neuropsychiatric Development and Intervention
by Giuseppe Marano, Greta Sfratta, Ester Maria Marzo, Giorgia Cozzo, Francesca Abate, Gianandrea Traversi, Osvaldo Mazza, Esmeralda Capristo, Eleonora Gaetani and Marianna Mazza
Children 2025, 12(11), 1561; https://doi.org/10.3390/children12111561 - 17 Nov 2025
Viewed by 2286
Abstract
Background: The gut microbiota plays a crucial role in brain development and function, especially in early life. Disruptions in the pediatric microbiota–gut–brain axis have been linked to neurodevelopmental and psychiatric disorders. We hypothesize that early-life dysbiosis can perturb neurodevelopment via the pediatric microbiota–gut–brain [...] Read more.
Background: The gut microbiota plays a crucial role in brain development and function, especially in early life. Disruptions in the pediatric microbiota–gut–brain axis have been linked to neurodevelopmental and psychiatric disorders. We hypothesize that early-life dysbiosis can perturb neurodevelopment via the pediatric microbiota–gut–brain axis, increasing risk and/or severity of neuropsychiatric outcomes, and that microbiota-targeted strategies may mitigate this risk. Methods: We conducted a narrative review by searching PubMed, Scopus, and Web of Science up to January 2025 for studies addressing pediatric microbiota, neuropsychiatric development, and interventions. Human and animal studies were included if they provided mechanistic or clinical insights. Results: Key determinants of microbiota development in childhood include mode of delivery, feeding practices, antibiotic exposure, diet, and environment. Altered microbial composition has been associated with autism spectrum disorder, attention-deficit/hyperactivity disorder, mood disorders, anxiety, and anorexia nervosa. Mechanistic pathways involve immune modulation, neural signaling (including the vagus nerve and enteric nervous system), and microbial metabolites such as short-chain fatty acids. Interventions targeting the microbiota—ranging from dietary strategies and probiotics to psychobiotics and fecal microbiota transplantation—show promise but require further pediatric-focused trials. Conclusions: The pediatric microbiota–gut–brain axis represents a critical window for neuropsychiatric vulnerability and intervention. Early-life strategies to support a healthy microbiota may help reduce the risk or severity of psychiatric disorders. Future research should prioritize longitudinal pediatric cohorts and clinical trials to translate mechanistic insights into precision interventions. Full article
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14 pages, 805 KB  
Article
Impact of Kefir on the Gut–Brain Axis: Serotonin Metabolism and Signaling in Pediatric Rats
by Mehmet Gazi Boyaci, Ayhan Pektaş, Fadime Topal, Nur Önen and Bilgehan Mehmet Pektaş
Microorganisms 2025, 13(11), 2536; https://doi.org/10.3390/microorganisms13112536 - 5 Nov 2025
Viewed by 2197
Abstract
Serotonin (5-hydroxytryptamine) is a key neurotransmitter involved in gastrointestinal and central nervous system functions. Given that approximately 90% of serotonin is synthesized in the gut, dietary interventions targeting the gut microbiota have emerged as promising strategies to modulate serotonin homeostasis. Kefir, a fermented [...] Read more.
Serotonin (5-hydroxytryptamine) is a key neurotransmitter involved in gastrointestinal and central nervous system functions. Given that approximately 90% of serotonin is synthesized in the gut, dietary interventions targeting the gut microbiota have emerged as promising strategies to modulate serotonin homeostasis. Kefir, a fermented milk beverage rich in probiotics and bioactive compounds, has been suggested to influence gut–brain axis signaling, yet its effects in the pediatric period remain insufficiently characterized. This study aimed to investigate the impact of kefir supplementation on serotonin biosynthesis, receptor expression, and metabolic pathways in a pediatric rat model, focusing on molecular markers across brain, jejunum, and serum tissues. Sixteen male Wistar rats (four weeks old) were divided into kefir and control groups. The kefir group received daily oral gavage of kefir (1 mL/100 g) for eight weeks, while controls received saline. Gene and protein expression levels of serotonergic markers (5-HT, TPH1, TPH2, SLC6A4, VMAT2, 5-HTR2B, 5-HTR3A, and 5-HTR4) were analyzed using quantitative PCR, ELISA, and Western blotting. Serotonin turnover was assessed via 5-HIAA levels. Kefir supplementation significantly increased 5-HT and TPH1 expression in both brain and jejunum tissues. In the brain, kefir elevated TPH2 and upregulated 5-HTR3A and 5-HTR2B, while reducing 5-HIAA levels, suggesting decreased serotonin degradation. In the jejunum, 5-HTR4 expression was markedly increased. Serum analyses revealed reduced TPH1/TPH2 expression but elevated 5-HTR4 levels, indicating systemic modulation of serotonergic signaling. Kefir exerts multifaceted effects on the serotonergic system in pediatric rats by enhancing serotonin biosynthesis, modulating receptor expression, and reducing serotonin turnover. These findings highlight kefir as a potential psychobiotic capable of influencing the gut–brain axis during early life, with implications for pediatric neurodevelopment and mental health. Further research, including clinical trials, is warranted to confirm its translational potential. Full article
(This article belongs to the Special Issue Role of Dietary Nutrients in the Modulation of Gut Microbiota)
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25 pages, 625 KB  
Review
The Gut Microbiome and Its Impact on Mood and Decision-Making: A Mechanistic and Therapeutic Review
by Pierluigi Diotaiuti, Francesco Misiti, Giulio Marotta, Lavinia Falese, Giovanna Elisa Calabrò and Stefania Mancone
Nutrients 2025, 17(21), 3350; https://doi.org/10.3390/nu17213350 - 24 Oct 2025
Cited by 1 | Viewed by 5757
Abstract
Background/Objectives: The gut microbiome is increasingly recognized as a key modulator of central nervous system function through the gut–brain axis. Dysbiosis has been associated with neuropsychiatric disorders such as depression, anxiety, impulsivity, cognitive decline, and addiction. This review aims to synthesize mechanistic [...] Read more.
Background/Objectives: The gut microbiome is increasingly recognized as a key modulator of central nervous system function through the gut–brain axis. Dysbiosis has been associated with neuropsychiatric disorders such as depression, anxiety, impulsivity, cognitive decline, and addiction. This review aims to synthesize mechanistic insights and therapeutic perspectives on how gut microbiota influence mood regulation, decision-making, and cognitive processes. Methods: A comprehensive narrative review was conducted using peer-reviewed articles retrieved from PubMed, Scopus, and Web of Science up to August 2025. Studies were included if they explored microbiota-related effects on behavior, mood, cognition, or decision-making using human or animal models. Emphasis was placed on molecular mechanisms, microbiome-targeted therapies, and multi-omics approaches. Results: Evidence indicates that gut microbiota modulate neurochemical pathways involving serotonin, dopamine, GABA, and glutamate, as well as immune and endocrine axes. Microbial imbalance contributes to low-grade systemic inflammation, impaired neuroplasticity, and altered stress responses, all of which are linked to mood and cognitive disturbances. Specific microbial taxa, dietary patterns, and interventions such as probiotics, prebiotics, psychobiotics, and fecal microbiota transplantation (FMT) have shown promise in modulating these outcomes. The review highlights methodological advances including germ-free models, metagenomic profiling, and neuroimaging studies that clarify causal pathways. Conclusions: Gut microbiota play a foundational role in shaping emotional and cognitive functions through complex neuroimmune and neuroendocrine mechanisms. Microbiome-based interventions represent a promising frontier in neuropsychiatric care, although further translational research is needed to define optimal therapeutic strategies and address individual variability. Full article
(This article belongs to the Section Prebiotics, Probiotics and Postbiotics)
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39 pages, 1299 KB  
Review
Precision Nutrition and Gut–Brain Axis Modulation in the Prevention of Neurodegenerative Diseases
by Dilyar Tuigunov, Yuriy Sinyavskiy, Talgat Nurgozhin, Zhibek Zholdassova, Galiya Smagul, Yerzhan Omarov, Oksana Dolmatova, Ainur Yeshmanova and Indira Omarova
Nutrients 2025, 17(19), 3068; https://doi.org/10.3390/nu17193068 - 26 Sep 2025
Cited by 4 | Viewed by 2961
Abstract
In the recent years, the accelerating global demographic shift toward population aging has been accompanied by a marked increase in the prevalence of neurodegenerative disorders, notably Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Among emerging approaches, dietary interventions targeting the [...] Read more.
In the recent years, the accelerating global demographic shift toward population aging has been accompanied by a marked increase in the prevalence of neurodegenerative disorders, notably Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Among emerging approaches, dietary interventions targeting the gut–brain axis have garnered considerable attention, owing to their potential to modulate key pathogenic pathways underlying neurodegenerative processes. This review synthesizes current concepts in precision nutrition and elucidates neurohumoral, immune, and metabolic regulatory mechanisms mediated by the gut microbiota, including the roles of the vagus nerve, cytokines, short-chain fatty acids, vitamins, polyphenols, and microbial metabolites. Emerging evidence underscores that dysbiotic alterations contribute to compromised barrier integrity, the initiation and perpetuation of neuroinflammatory responses, pathological protein aggregations, and the progressive course of neurodegenerative diseases. Collectively, these insights highlight the gut microbiota as a pivotal target for the development of precision-based dietary strategies in the prevention and mitigation of neurodegenerative disorders. Particular attention is devoted to key bioactive components such as prebiotics, probiotics, psychobiotics, dietary fiber, omega-3 fatty acids, and polyphenols that critically participate in regulating the gut–brain axis. Contemporary evidence on the contribution of the gut microbiota to the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis is systematically summarized. The review further discusses the prospects of applying nutrigenomics, chrononutrition, and metagenomic analysis to the development of personalized dietary strategies. The presented findings underscore the potential of integrating precision nutrition with targeted modulation of the gut–brain axis as a multifaceted approach to reducing the risk of neurodegenerative diseases and preserving cognitive health. Full article
(This article belongs to the Section Nutrition and Neuro Sciences)
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25 pages, 1446 KB  
Review
Lactiplantibacillus plantarum as a Psychobiotic Strategy Targeting Parkinson’s Disease: A Review and Mechanistic Insights
by Wu-Lin Chen, Fu-Sheng Deng and Ying-Chieh Tsai
Nutrients 2025, 17(19), 3047; https://doi.org/10.3390/nu17193047 - 24 Sep 2025
Cited by 1 | Viewed by 3073
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the pathological aggregation of α-synuclein (α-syn), the loss of dopaminergic neurons, and the appearance of both motor and non-motor symptoms. Emerging evidence suggests a bidirectional influence of the microbiota–gut–brain axis in PD pathogenesis, [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the pathological aggregation of α-synuclein (α-syn), the loss of dopaminergic neurons, and the appearance of both motor and non-motor symptoms. Emerging evidence suggests a bidirectional influence of the microbiota–gut–brain axis in PD pathogenesis, where gut dysbiosis contributes to increased intestinal barrier permeability, immune activation, chronic inflammation, oxidative stress, α-syn misfolding, and neurotransmitter imbalance. These findings are increasing interest in probiotics as microbiota-targeted interventions that restore intestinal and systemic homeostasis. Lactiplantibacillus plantarum, a probiotic species with remarkable environmental adaptability and genomic plasticity, has emerged as a promising candidate for PD management. Preclinical studies demonstrate that specific Lpb. plantarum strains, such as PS128 or CCFM405, can beneficially modulate gut microbial communities, reinforce barrier integrity, regulate bile acid metabolism, attenuate neuroinflammatory responses, and improve motor deficits in PD-like mice. In addition, Lpb. plantarum DP189 or SG5 interventions can significantly reduce α-syn aggregation in the brain via suppression of oxidative stress, modulation of neuroinflammatory responses, and activation of neurotrophic factors. Recent evidence even suggests that Lpb. plantarum-derived extracellular vesicles may possess anti-PD activity by influencing host gene expression, neuronal function, and immune modulation. Although robust clinical data are still limited, preliminary clinical trials indicate that supplementation with PS128 or certain Lpb. plantarum-contained consortiums can alleviate constipation, improve gastrointestinal function, reduce systemic inflammation, and even ameliorate motor symptoms when used alongside standard dopaminergic therapies. In this review, we provide an integrated overview of preclinical, clinical, and mechanistic insights, and evaluate the translational potential of Lpb. plantarum as a safe and diet-based strategy to target the microbiota-gut–brain axis in PD. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics: Past, Present and Future)
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17 pages, 6419 KB  
Article
Lactiplantibacillus plantarum HY7715 Alleviates Restraint Stress-Induced Anxiety-like Behaviors by Modulating Oxidative Stress, Apoptosis, and Mitochondrial Function
by Kippuem Lee, Daehyeop Lee, Haeryn Jeong, Joo Yun Kim, Jae Jung Shim and Jae Hwan Lee
Int. J. Mol. Sci. 2025, 26(18), 9251; https://doi.org/10.3390/ijms26189251 - 22 Sep 2025
Viewed by 1026
Abstract
Anxiety disorders are closely associated with oxidative stress-mediated neuronal damage, mitochondrial dysfunction, and apoptosis. In this study, we investigated the neuroprotective effects of Lactiplantibacillus plantarum HY7715 in a mouse model of restraint stress-induced anxiety, and in neuronal cell models (HT-22 mouse hippocampal neuroblast [...] Read more.
Anxiety disorders are closely associated with oxidative stress-mediated neuronal damage, mitochondrial dysfunction, and apoptosis. In this study, we investigated the neuroprotective effects of Lactiplantibacillus plantarum HY7715 in a mouse model of restraint stress-induced anxiety, and in neuronal cell models (HT-22 mouse hippocampal neuroblast cell and SH-SY5Y human neuroblastoma cells). Oral administration of HY7715 (1 × 109 CFU/kg/day) alleviated anxiety-like behaviors significantly, as shown by increased central exploration in the open field test and prolonged open-arm activity in the elevated plus maze. HY7715 reduced serum norepinephrine levels elevated by stress, and restored hippocampal expression of brain-derived neurotrophic factor, while suppressing pro-inflammatory (NF-κB, IL-6) and pro-apoptotic (BAX, caspase-3) markers. It also increased expression of mitochondrial regulatory genes (SIRT1, mTOR), and decreased that of cytochrome c, in brain tissue. Histological analysis revealed that HY7715 preserved neuronal integrity in the CA1 and CA3 hippocampal regions. In vitro, HY7715 attenuated oxidative stress-induced cytotoxicity, decreased intracellular ROS accumulation, maintained mitochondrial activity, and inhibited apoptosis of both neuronal cell types, showing greater efficacy than the strain type L. plantarum KCTC3108. These findings suggest that HY7715 exerts neuroprotective effects by modulating oxidative stress/apoptosis/mitochondrial pathways, and highlight its potential as a psychobiotic for stress-related neuropsychiatric disorders. Full article
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27 pages, 1023 KB  
Review
Psychobiotics in Aquaculture: Harnessing the Microbiome–Gut–Brain Axis for Stress Management and Production Enhancement in Fish
by Mikhail Nikolaevich Churilov, Evgeniya Valeryevna Prazdnova and Dmitry Vladimirovich Rudoy
Animals 2025, 15(18), 2726; https://doi.org/10.3390/ani15182726 - 18 Sep 2025
Viewed by 1903
Abstract
Intensified aquaculture production has significantly increased farmed fish exposure to various stressors that compromise welfare and productivity, demanding innovative approaches to enhance sustainable production. Aquaculture environments subject fish to multiple stressors. These include high-density housing, handling, transportation, and fluctuating water quality. Such stressors [...] Read more.
Intensified aquaculture production has significantly increased farmed fish exposure to various stressors that compromise welfare and productivity, demanding innovative approaches to enhance sustainable production. Aquaculture environments subject fish to multiple stressors. These include high-density housing, handling, transportation, and fluctuating water quality. Such stressors activate the hypothalamic–pituitary–interrenal axis, resulting in a cascade of endocrine responses. This subsequently impairs feeding behavior, growth performance, and immune function. Psychobiotics exert beneficial effects by producing neuroactive compounds, including gamma-aminobutyric acid, short-chain fatty acids, serotonin, and dopamine. Key bacterial genera such as Lactobacillus, Bifidobacterium, Bacillus, and Enterococcus demonstrate significant psychobiotic properties. Experimental evidence from zebrafish and commercially relevant species demonstrates that psychobiotic interventions consistently reduce cortisol levels, normalize stress responses, and improve behavioral outcomes. These effects occur through the microbiome–gut–brain axis, a bidirectional system connecting the nervous and gastrointestinal systems by neural, endocrine, and immune pathways. Nevertheless, significant challenges persist, such as species-specific efficacy, limitations in mechanistic understanding, and the need for standardized evaluation protocols. This review examines psychobiotics as promising interventions for stress management in aquaculture systems. We conclude that psychobiotics may offer a sustainable approach for mitigating aquaculture stress responses and enhancing both fish welfare and production efficiency through targeted microbiome modulation. Full article
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