Search Results (1,808)

Chronic sleep deprivation (SD) disrupts gut–brain axis (GBA) homeostasis and is closely associated with gut microbiota dysbiosis, neuroinflammation, and depression-like behaviors. This study investigated whether fermentation enhances the antidepressant-like effects of Dendrobium officinale by comparing fermented Dendrobium officinale (FDO) with unfermented Dendrobium officinale (DO) in a chronic SD mouse model. FDO significantly ameliorated anxiety and depressive-like behaviors in SD mice. It reshaped gut microbial structures, enriched beneficial bacteria taxa such as Dubosiella, [Eubacterium]_coprostanoligenes_group, and Allobaculum, and increased SCFA levels. FDO also enhanced colonic ZO-1 and Occludin expression and reduced serum levels of LPS and the pro-inflammatory cytokines. At the central nervous system level, FDO inhibited the activation of hippocampal microglia and astrocytes; alleviated neuroinflammation; restored hippocampal TPH2, 5-hydroxytryptamine (5-HT), and 5-HIAA levels; and modulated the 5-HT_1A/5-HT_2A receptor balance. In addition, FDO upregulated BDNF, PSD-95, and SYN expression and reduced corticosterone (CORT) levels. Compared with DO, FDO showed more pronounced regulatory effects. Correlation analysis suggested that 5-HT may link gut microbial metabolites, inflammation, and synaptic plasticity. In summary, these findings support FDO as a potential GBA-targeted functional food for SD-related depressive-like behaviors. Full article

Background: Chlorella, a unicellular green alga, is currently one of the most popular algae supplements due to its high content of bioactive compounds. Chlorella’s wide range of macro- and micronutrients, including chlorophyll compounds and carotenoids, has been suggested to influence various disorders related to the digestive and nervous systems. This review’s primary purpose was to critically analyze the effects of Chlorella intake on gut microbiota and brain function. Methods: The authors conducted a systematic review with narrative synthesis of peer-reviewed articles written in English and published in PubMed, Web of Science, and Scopus spanning the years 2009 to 2026 (PROSPERO registration number CRD42024527705). The search protocol was performed following PRISMA guidelines. Primary outcomes encompassed physiological variables, such as gut microbial composition, short-chain fatty acids, brain-derived neurotrophic factor, and hippocampal cell density. Secondary outcomes were assessed through neurobehavioral tests and psychological questionnaires. Results: Out of the 1333 articles identified, 47 studies were deemed eligible, and 21 met the predefined criteria, subsequently incorporated into this systematic review. In total, 10 articles documented interventions involving Chlorella and their effects on the gut microbiota, whereas 11 articles investigated several variables pertinent to brain function. Most of the studies included were conducted in animal models, with only a limited number of human trials. Nineteen studies (90%), predominantly preclinical, reported positive associations between Chlorella consumption, gut microbiota modulation, and physiological or neurobehavioral markers related to the gut–brain axis. Conclusions: Chlorella consumption may modulate gut microbiota composition and function, potentially influencing brain-related processes. However, the available literature lacks studies simultaneously addressing both gut microbiota and brain health parameters limiting the understanding of the underlying physiological mechanisms. Full article

Cognitive frailty, characterized by the coexistence of physical frailty and cognitive impairment, has emerged as a major challenge in aging populations and is closely linked to sarcopenia, neurodegeneration, and chronic inflammation. Increasing evidence suggests that the gut microbiota acts as a central regulator of neuromuscular and neurocognitive aging through the integrated gut–brain–muscle axis. This review highlights how microbial dysbiosis, reduced short-chain fatty acid (SCFA) production, systemic endotoxemia, and altered microbial metabolites contribute to mitochondrial dysfunction, neuroinflammation, anabolic resistance, and impaired neuroplasticity. Key signaling mediators, including SCFAs, bile acids, tryptophan-derived metabolites, cytokines, and myokines such as irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B, orchestrate bidirectional communication among the gut, skeletal muscle, and brain. We further discuss the role of exercise-induced microbiota remodeling and muscle endocrine signaling in promoting mitochondrial biogenesis and cognitive resilience. In addition, emerging translational strategies including probiotics, prebiotics, postbiotics, polyphenol-rich functional foods, marine bioactives, and precision nutrition are explored as potential interventions targeting this axis. Collectively, the gut–brain–muscle axis provides a novel systems biology framework for understanding cognitive frailty and developing integrated therapeutic strategies for healthy longevity. Full article

Cardiovascular–kidney–metabolic (CKM) syndrome is a systemic, interdependent disorder arising from the convergence of metabolic dysfunction, chronic kidney disease, and cardiovascular pathology. Anchored in the Developmental Origins of Health and Disease (DOHaD) framework, this review advances a “parallel hit” model, primarily based on evidence from experimental animal studies, particularly rodent models, posited that early-life environmental insults concurrently program structural and functional vulnerabilities in both renal and central nervous system hubs. These early perturbations prime susceptibility long before clinical manifestations emerge. CKM progression is conceptualized as a two-stage trajectory, with an initial phase of parallel programming affecting kidney and brain development, followed by a transition to maladaptive bidirectional crosstalk. In the later phase, heightened efferent sympathetic outflow and aberrant afferent renal signaling—potentiated by uremic toxin accumulation, neuroinflammation, and blood–brain barrier disruption—drive a self-perpetuating cycle that accelerates cardiorenal and metabolic injury. Key integrative mechanisms, including oxidative stress, chronic low-grade inflammation, mitochondrial dysfunction, and gut microbiota dysbiosis, serve as convergent pathways linking early-life exposures to adult CKM phenotypes. These pathways not only sustain disease progression but also represent actionable therapeutic targets. Importantly, this framework underscores the translational potential of early-life “reprogramming” strategies. Interventions such as precision nutrition, antioxidant supplementation, microbiota-directed therapies (including prebiotics, probiotics, and postbiotics), and mechanism-based pharmacotherapies may mitigate or reverse maladaptive programming. However, much of the current mechanistic evidence remains preclinical, and further human studies are needed to validate these pathways and therapeutic approaches. Collectively, this dual-hub paradigm reframes CKM syndrome as a life-course continuum rather than a late-stage comorbidity cluster, emphasizing the necessity of early, mechanism-driven interventions to stabilize the brain–kidney axis and improve long-term cardiovascular–kidney–metabolic outcomes. Full article

Obesity is one of the most serious public health challenges worldwide and has reached the scale of a global epidemic. Its etiology is multifactorial and includes genetic, environmental, hormonal, and neurobiological factors. In recent years, increasing attention has been paid to the role of the gut microbiota in the regulation of energy metabolism, inflammatory processes, and the functioning of the gut–brain axis. An increasing body of evidence suggests that the gut microbiota may influence the dopaminergic system and eating behaviors through bacterial metabolites, immune pathways, and the vagus nerve. Disturbances in microbiota composition may contribute to the development of chronic low-grade inflammation and compulsive consumption of highly processed foods. This article discusses the concept of food addiction as a phenomenon involving loss of control over eating, excessive reward system reactivity, and dopaminergic dysfunction within the mesolimbic reward system. Particular attention is given to the role of the gut microbiota in modulating these processes, including the potential effects of selected commensal bacteria and the importance of dietary interventions such as the ketogenic diet in regulating the gut–brain axis. The presented data suggest that modulation of the gut microbiota may represent a promising supportive strategy in the treatment of obesity and disorders associated with compulsive eating. At the same time, it is emphasized that the current state of knowledge is largely preclinical and observational, highlighting the need for further translational and clinical studies. Full article

Chronic kidney disease (CKD) is a progressive condition characterized by persistent kidney abnormalities with systemic consequences. Beyond its metabolic and cardiovascular complications, CKD has been associated with structural and functional brain alterations that are particularly evident in advanced stages and in patients undergoing hemodialysis (HD). Deficits across multiple cognitive domains are frequently observed and may compromise treatment adherence, clinical management, and quality of life, yet remain largely underrecognized in clinical practice. Older adults are particularly vulnerable. Age-related brain changes and comorbidities may increase susceptibility to CKD-related cerebral alterations, while reduced cognitive reserve may amplify clinical impact. The gut–kidney–brain axis has emerged as a relevant biological pathway, with CKD-related dysbiosis potentially influencing inflammation, metabolic homeostasis, and the generation of uremic metabolites linked to neurological dysfunction. This review examines the mechanisms contributing to brain vulnerability in older adults with CKD, with specific attention to patients undergoing HD, and discusses challenges in the recognition and assessment of cognitive impairment in this population. It further explores microbiota-targeted nutritional strategies as potentially modifiable approaches to modulate gut-derived metabolic and inflammatory processes relevant to brain health, although current evidence for direct effects on cognitive outcomes remains limited. Full article

Dementia, and more specifically Alzheimer’s disease (AD), is a progressive neurodegenerative disorder that has become a growing health menace in the world with an escalation in incidence as well as enormous social and economic consequences. Existing pharmacological treatment including cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists are not very effective in reducing the symptoms and fail to prevent the disease process. The non-pharmacological treatment interventions such as diet, exercise and cognitive training have supportive effects and cannot be used as standalone treatments. Therapeutic gap has resulted in increased interest in complementary and alternative therapies, especially that of pleiotropic action of herbal medicines. Bacopa monnieri (BM) is an Ayurvedic herb that has historically been used to treat memory enhancement and now has both preclinical and clinical evidence supporting its ability to modulate neurotransmission, reduce oxidative stress and suppress neuroinflammation. However, such difficulties as low bioavailability, instability of the environmental factors, and variations in formulations restrict its clinical applicability. New technologies with a lot of potential such as microencapsulation technology can provide the solution to this problem by increasing stability, solubility, and targeted delivery of compounds that will increase treatment efficacy. This narrative review is a synthesis of the existing information on the pathogenesis of dementia, therapeutic approaches, and the effectiveness of BM as a complementary intervention. It points out links between traditional medicine and modern neuroscience, strengths and limitations of on-going evidence, gaps that need further research, such as long-term clinical trials, standardized formulations, and discovery of the role of BM in the gut–brain axis. BM is a prime example of how herbal medicines can be used as a complement to conventional treatment and play a role in multi-modal approaches aimed at reducing the cognitive impairment associated with dementia. Full article

Background/Objectives: The microbiota–gut–brain axis (MGBA) plays a pivotal role in cognitive function, making psychobiotics a promising strategy for managing neurodegenerative diseases. Lactic acid bacteria (LAB) from traditional fermented foods represent a valuable source of candidate strains, and multi-strain consortia may offer enhanced therapeutic efficacy through synergistic effects. This study evaluated the functional and psychobiotic potential of three lactic acid bacteria (LAB) strains isolated from fermented foods, assessed as monocultures and a multi-strain consortium (MIX). Methods: The research encompassed an initial screening of the individual strains and the MIX, assessing their adhesion to mucin, stability in a static in vitro digestion model, and amino acid profiling. Subsequently, the LAB MIX underwent long-term evaluation in a dynamic gastrointestinal model (SHIME^®) inoculated with microbiota from a patient with Alzheimer’s disease, during which alterations in gut microbiota composition and amino acid metabolism were analyzed. Results: The LAB MIX demonstrated high stability under digestive stress and effective mucoadhesive properties. Furthermore, the consortium demonstrated a distinct metabolic signature, driving enhanced functional effects that complemented or exceeded those observed in individual monocultures. In the SHIME^® model, the MIX induced significant, site-specific shifts in microbial composition, notably increasing lactobacilli abundance. These taxonomic changes correlated with an enriched metabolic profile, including elevated levels of GABA precursors and amino acids with antioxidant potential, which are crucial for MGBA modulation. Conclusions: These results identify the LAB consortium as a compelling psychobiotic candidate. Further in-depth in vivo and clinical studies are required to validate its therapeutic potential for MGBA modulation. Full article

Background: Inhibitory processes in the nervous system are traditionally conceptualized as suppressive mechanisms; however, their fundamental role is the refinement and optimization of sensory information. In nociception, this function is mediated by the descending pain inhibitory system (DPIS), which modulates nociceptive transmission at multiple hierarchical levels. Biological sex and gender-related factors significantly influence these inhibitory pathways, yet they are often overlooked in clinical frameworks. Methods: A narrative review was conducted using PubMed, MEDLINE, and Scopus databases, focusing on studies published between 2010 and 2025. Search terms included “descending pain inhibitory system,” “nociplastic pain,” “aging,” “sex differences,” “gender,” and “gut–brain axis.” Approximately 30 key references were synthesized. Results: The DPIS enhances the precision of nociceptive signals through mechanisms analogous to lateral inhibition. In chronic and nociplastic pain, this refinement process is impaired, leading to “sensory blurring.” Aging exacerbates these changes through neurochemical depletion and neuroinflammation. Crucially, this decline follows sex-specific trajectories; estrogen depletion in post-menopausal females accelerates the loss of monoaminergic inhibitory reserves, while gender-related sociocultural stressors can further disrupt top-down executive control. Additionally, alterations in the gut–brain axis signaling—modulated by sex-specific gut microbiota profiles—further disrupt inhibitory control. Conclusions: Chronic pain may be conceptualized as a disorder of sensory refinement rather than excessive nociceptive input. Inclusion of sex and gender as biological variables is essential for precision pain management. Therapeutic strategies should focus on restoring inhibitory precision through both central and systemic approaches, tailored to the patient’s hormonal and physiological profile. Full article

The axis linking the gut to the brain to the immune system connects all tissues involved—bacteria, immune cells, metabolism and the CNS—through a multidirectional communication network. Several studies have confirmed that when this axis is disrupted, it can be responsible for Alzheimer’s disease, Parkinson’s disease, obesity, type 2 diabetes, and NAFLD, and the main consequences come from increased systemic inflammation, altered regulation of immune cells, the production of microbial metabolites that alter signals to the immune cells and nervous system, increase in oxidative stress, breakdown of the gut barrier, and more. In recent years, advanced multi-omics technologies, such as metagenomics, transcriptomics, metabolomics, proteomics, and single-cell sequencing, have provided significant advancement in our understanding of all of the interacting nodes involved in the gut–brain–immune axis. These advanced sequencing technologies can characterize the microbial communities, host immune cells, metabolic profiles, and the degree of cell heterogeneity during a specific disease. Combining multi-omics information can reveal a few shared pathways between neurodegenerative and metabolic disorders, such as NF-κB, NLRP3 inflammasome activation, mitochondrial dysfunction, changes in SCFA metabolism, and the alteration of microbial populations in Alzheimer’s and Parkinson’s disease; metabolic dysbiosis and increased risk for Parkinson’s disease; or changes in gut-to-brain-to-immune signaling contributing to diabetes complications and NAFLD. Artificial intelligence (AI) and machine learning are becoming promising tools for detecting biomarkers from these datasets, extracting knowledge, interpreting systems biology, and helping with developing precision medicine. In this review, we summarize current evidence that supports the role of the gut–brain–immune axis in neurodegenerative and metabolic diseases, highlighting results gained with the utilization of multi-omics approaches. We will describe the key microbial, immune, and metabolic pathways involved in pathogenesis and therapeutic approaches including psychobiotics, tailored nutrition, modulation of the microbiome, and metabolite interventions, discussing future perspectives of the translation of the gut–brain–immune axis knowledge into clinical practice. Full article

Sepsis-associated encephalopathy (SAE) is a frequent neurological complication of sepsis, driven by six interconnected pathophysiological components: (1) systemic inflammation-triggered neuroinflammatory cascades, initiated by systemic recognition of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and propagated by pro-inflammatory mediators; (2) central nervous system (CNS) immune cell-mediated neuroinflammation, wherein microglia, regulatory T cells, and neutrophils dynamically regulate inflammatory progression; (3) blood–brain barrier (BBB) disruption, progressing from functional disturbance to structural damage via tight junction degradation and immune infiltration; (4) multimodal programmed cell death, encompassing autophagy, apoptosis, pyroptosis, and ferroptosis driven by mitochondrial dysfunction; (5) neurotransmitter network imbalance, manifesting as cholinergic deficiency and glutamate excitotoxicity; and (6) gut–brain axis dysregulation, characterized by reduced microbiota-derived metabolites such as butyrate and indolepropionic acid. These components are organized along a core pathological axis comprising four sequential stages: neuroinflammatory storm (encompassing components 1 and 2) → BBB disruption and microcirculatory disturbances (component 3) → multimodal programmed cell death (component 4) → neurotransmitter imbalance (component 5), with the gut–brain axis (component 6) functioning as a bidirectional regulatory node that intersects and modulates all four stages. Mitochondrial dysfunction serves as the central converging node linking these pathological axes. Targeted interventions against neuroinflammation, immune cell modulation, BBB restoration, inhibition of aberrant cell death, neurotransmitter homeostasis, and gut microbiota remodeling hold therapeutic promise. Elucidating the crosstalk among these pathways will accelerate the clinical translation of precision therapies for SAE. Full article

Background: Synaptic plasticity in neurodegenerative disorders (NDs), cognitive impairment, and mental health conditions is regulated by brain-derived neurotrophic factor (BDNF). Even healthy individuals have different levels, which are affected by complex epigenetic, inflammatory, and metabolic regulation. BDNF expression changes are associated with both typical and abnormal aging, as well as mental health conditions. These changes affect brain areas that are crucial for memory, such as the hippocampus and the parahippocampal cortex. Neurotrophins (NTs), including nerve growth factor (NGF) and BDNF, are essential for neuronal differentiation via tropomyosin receptor kinase B (TrkB) and the p75 neurotrophin receptor (p75NTR). Dysregulated NTs signaling contributes to synaptic dysfunction and neuroinflammation. Objective: This systematic review synthesizes preclinical evidence of the potential of naturally derived compounds to modulate NTs for neuroprotection and their incorporation into novel foods. Methodology: A review of major databases found studies that examined the impact of dietary polyphenols and other bioactive substances on NT signaling oxidative stress, inflammation, and neuronal plasticity. Results: Compounds such as epigallocatechin gallate, resveratrol, curcumin, quercetin, and flavanols, can positively impact NTs, reducing reactive oxygen species/reactive nitrogen species, enhancing cell survival, and increasing the expression of trophic factors such as nuclear factor erythroid 2-related factor 2 (Nrf2), NGF, and vascular endothelial growth factor in neural stem cells. However, their bioavailability, optimal dosage, and dietary interactions require further research. Conclusions: The consumption of BDNF-promoting foods can potentially stimulate BDNF synthesis, support optimal neurotransmission, and fortify neural plasticity. Evidence supports a polyphenol-rich diet for preventing NDs and promoting brain health. Observational studies consistently support the protective effects of polyphenols on brain health through their impact on the gut–brain axis. Full article

Bile acids (BA) are increasingly recognized as signaling molecules involved in metabolic regulation and inflammatory processes, both of which are relevant to Parkinson’s disease (PD). However, their role in PD and disease progression remains unclear. In this study, plasma BA profiles were analyzed in 113 participants, including early- and advanced-stage PD patients and age- and sex-matched controls, across three time points over three years. Targeted metabolomics using LC-MS was applied to quantify 20 BA, complemented by analyses of functional ratios, including unconjugated/conjugated and hydrophobic/hydrophilic BA ratios and correlation patterns between BA species. Although most individual BA did not show consistent longitudinal changes, pooled analysis identified significant differences in the unconjugated/conjugated BA ratio between PD patients and controls. In contrast, the hydrophobic/hydrophilic ratio did not differ significantly between groups. Correlation analysis revealed differences in selected BA interrelationships, particularly involving primary and secondary BA, while the overall network structure remained largely preserved. These results indicate that BA metabolism in PD might be characterized rather by subtle, distributed alterations than pronounced changes in individual metabolites. BA profiling may therefore contribute to a broader metabolic characterization of PD, but its utility as a standalone biomarker appears limited. Full article

This study presents an integrated metabolite-centered framework for the comparative evaluation of plant-based substrates through the simultaneous profiling of fermentation-associated short-chain fatty acids (SCFAs) and neuroactive compounds within a single in vitro experimental platform. Unlike conventional studies focusing on individual metabolite classes, the present approach combines in vitro gastrointestinal digestion with simplified bacterial fermentation to characterize substrate-dependent metabolic responses under controlled experimental conditions. Concurrent evaluation of SCFA production and neuroactive compound formation enabled multidimensional assessment of fermentation-associated metabolite profiles and their potential biochemical interrelationships. Significant differences (p < 0.05) were observed among substrates in both SCFA production and neuroactive compound formation. Hemp seed flour exhibited the highest acetate concentration (4.67 mg/100 g) and γ-aminobutyric acid (GABA) level (114.00 µg/g), whereas lentil and corn flour showed elevated propionate levels. Chickpea and bulgur produced the highest butyrate concentrations. Among neuroactive compounds, bulgur exhibited the highest dopamine and serotonin levels, while lentil demonstrated a more balanced metabolite profile. Correlation analysis suggested exploratory associations between SCFA production and neuroactive compound formation. A strong positive correlation between acetate and GABA (r = 0.89) indicated potential co-variation between carbohydrate fermentation and neuroactive metabolite formation, whereas divergent dopamine and serotonin patterns suggested substrate-dependent metabolic differences. Functional mapping further classified substrates into SCFA-oriented, neuroactive compound–dominant, and mixed metabolic profile groups. Collectively, these findings support a metabolite-centered framework for comparative assessment of plant-based substrates based on fermentation-associated metabolite profiles obtained under controlled in vitro conditions. Although the simplified two-strain fermentation model does not reproduce the complexity of the human colonic microbiota, the observed substrate-dependent metabolic differences may provide preliminary insights into biochemical outputs potentially relevant to gut–brain axis-associated pathways. Further studies employing complex microbial communities and in vivo validation are required to confirm the physiological relevance of these findings. Full article

Obesity is a major risk factor for colorectal cancer (CRC) and is increasingly recognized as a contributor to cancer-related cognitive impairment; however, the mechanistic pathways linking metabolic dysfunction, tumor progression, and brain dysfunction remain incompletely defined. Emerging evidence indicates that obesity-induced gut microbial dysbiosis and intestinal barrier disruption may serve as a biologically plausible mechanism connecting these processes via the gut–brain axis although direct clinical causality remains to be firmly established. In obesity, alterations in gut microbiota composition characterized by depletion of barrier-protective taxa and enrichment of pro-inflammatory and genotoxic pathobionts compromise epithelial tight-junction integrity and promote metabolic endotoxemia. The translocation of microbial products, including lipopolysaccharide, sustains chronic systemic inflammation, accelerates CRC progression, and remodels the tumor microenvironment. Notably, these peripheral inflammatory signals extend beyond the intestine and tumor, disrupting blood–brain barrier integrity, activating microglia and astrocytes, and impairing synaptic plasticity within hippocampal and frontal networks. Clinically, these processes manifest as cancer-related cognitive impairment (CRCI), with predominant deficits in attention, processing speed, and working memory, which are often detectable around the time of diagnosis and independent of chemotherapy exposure. This review synthesizes in vivo, in vitro, and human evidence into a proposed theoretical “two-barrier failure” model of obesity-associated CRC and cognitive dysfunction. In addition to mechanistic synthesis, we discuss barrier-centered therapeutic strategies, including targeted probiotics, postbiotics, SCFA supplementation, obesity management through dietary and weight-loss interventions, and potential pharmacological approaches to epithelial and neurovascular barrier protection. We also outline testable clinical trial designs for evaluating these interventions in obesity-associated CRC. Full article