Search Results (773)

Transitioning to sustainable, plant-forward diets, such as the Planetary Health Diet is a global priority; however, the palatability gap remains a formidable barrier, as consumers often perceive low-sodium, plant-centric diets as sensory-deficient. While aromatic herbs could bridge this gap, the current literature rarely integrates their sensory, ecological, phytochemical, and cultural dimensions. This narrative review explores how Mediterranean aromatic plants indigenous to the Maltese Islands function as sensory and molecular catalysts to bridge this gap. Through a thematic synthesis (2005–2026) integrating ethnobotanical evidence with molecular nutrition and sensory science, the Maltese archipelago is examined as a small-island ecological model. Chronic abiotic stressors, including high salinity and intense solar exposure, induce phytochemical priming, significantly enhancing secondary metabolites like polyphenols and terpenoids. These compounds establish a folk–medicine bridge, where traditional culinary practices align with modern biochemical validation. These bioactives demonstrate a capacity to modulate the NF-κB inflammatory axis, mitigate systemic inflammaging, and support the gut–microbiome–brain axis. Furthermore, these aromatics serve as translational tools for EAT-Lancet 2025 targets by facilitating cross-modal sensory compensation for sodium reduction and improving nutrient bioaccessibility via the culinary entourage effect. The TASTE-MED framework positions culinary nutrition as a vital translational bridge, asserting that flavour is a prerequisite for dietary sustainability and aligning individual molecular resilience with broader planetary health goals. Full article

Obesity is increasingly recognized as a complex systemic disorder rather than a simple consequence of excess energy intake and fat accumulation. This review presents a systems biology framework that examines how obesity-driven disruption of inter-organ communication networks contributes to chronic disease susceptibility, with particular emphasis on colorectal cancer (CRC). Disrupted signaling among the brain, adipose tissue, liver, skeletal muscle, gut, and immune system generates maladaptive feedback loops that promote chronic metabolic inflammation (metaflammation), loss of physiological resilience, and progressive metabolic dysfunction. Within this framework, obesity is redefined as a network disease characterized by neuroendocrine dysregulation, adipose tissue remodeling, immune dysfunction, impaired organ crosstalk, and alterations in the gut microbiome. A central feature of this dysregulation is persistent low-grade inflammation driven by immune-metabolic reprogramming and sustained activation of inflammatory pathways. Obesity-associated metaflammation is further linked to accelerated biological aging through mechanisms involving cellular senescence, mitochondrial dysfunction, oxidative stress, and impaired metabolic resilience. These interconnected processes create a tumor-promoting environment by enhancing oncogenic signaling, disrupting intestinal barrier integrity, altering microbial and metabolic signaling, impairing immune surveillance, and promoting epithelial dysfunction, thereby increasing susceptibility to CRC. The review also examines how behavioral, circadian, environmental, and socioeconomic factors influence metabolic health and cancer risk. Finally, emerging translational opportunities, including biomarker-guided risk stratification, precision prevention, metabolic network restoration, and integrative lifestyle and pharmacological interventions, are discussed. Collectively, this review reframes obesity as a whole-body regulatory disorder and provides an integrated conceptual framework linking metabolism, inflammation, aging, and colorectal carcinogenesis to inform future prevention and therapeutic strategies. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, tau hyperphosphorylation, neuroinflammation, mitochondrial dysfunction, and oxidative stress. Despite recent advances, current therapies offer little benefit, and AD remains a significant challenge. Polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have attracted attention for their neuroprotective effects primarily through anti-inflammatory and antioxidant properties, but also for their ability to influence membrane fluidity and neuronal function. DHA is the predominant omega-3 PUFA in nerve cell membranes and is critical for synaptic plasticity and cognitive function. Some evidence has demonstrated that marine omega-3 supplementation reduces Aβ deposition, modulates microglial activation, and prevents cognitive decline in animal models. Even with heterogeneous results, preclinical and clinical studies suggest that long-term DHA/EPA supplementation can improve cognitive function in subjects with mild cognitive impairment (MCI) and reduce neuroinflammation markers. However, individual variability and brain bioavailability pose significant challenges. This review summarizes and discusses the current knowledge on the importance of PUFAs for human health, exploring novel mechanistic hypotheses, such as the effect of omega-3 fatty acids on brain iron homeostasis, the microbiota–gut–brain axis, the glymphatic system, and miRNAs. Furthermore, it focuses on the therapeutic potential of PUFAs in the treatment of AD and proposes future directions for translational research. Full article

The gut–microbiota–brain axis (GMBA), an intricate network connecting the gastrointestinal (GI) tract and the brain, plays a pivotal role in maintaining overall health and influencing disease processes. The human gut microbiota, comprising over 3000 bacterial species, regulates immune responses, hormonal signals, and metabolite production, maintaining homeostasis under normal conditions. Dysbiosis, or microbial imbalance, has been linked to various central nervous system (CNS) disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and autism spectrum disorder (ASD). Given the growing interest in this topic and the limited effectiveness of current therapeutic strategies for managing patients with AD, the purpose of the current narrative review is to analyze the pathophysiological role of the GMBA in the pathogenesis of AD and assess potential therapeutic strategies targeting the GMBA, particularly the microbiome and its metabolites. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science to identify clinical studies, experimental research, and review articles examining the GMBA in health and AD, as well as related therapeutic strategies. The search terms included “Alzheimer’s disease”, “neuroinflammation”, “amyloid-beta”, “tau”, “gut–brain axis”, “microbiome”, “short-chain fatty acids”, “probiotics”, “prebiotics”, and “fecal microbiota transplantation”. In AD, altered gut microbiota composition is associated with neuroinflammation, neurodegeneration, and exacerbation of disease progression. Probiotics have shown potential in enhancing cognitive function and reducing neuroinflammation by modulating microbiota composition and influencing brain-derived neurotrophic factor (BDNF) levels. Prebiotics, through their impact on gut microbiota and metabolite production, also offer therapeutic promise by improving cognitive function and mitigating neuroinflammation. With its historical and modern applications, fecal microbiota transplantation (FMT) may represent a potential strategy for addressing dysbiosis and its neurological implications. This manuscript focuses on GMBA and its effects on neuroinflammation, neurodegeneration, and CNS health while emphasizing the need for further research into microbiome-based therapies and the gut–brain relationship in patients with AD. Full article

The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) central to metabolic regulation, and its potential modulation by dietary phytochemicals is increasingly recognized as physiologically relevant. Understanding how such compounds interact with GLP-1R is important for clarifying mechanisms that may contribute to gut-to-brain signaling. In this study, we examined three structurally related dietary ginsenosides, Rg1, Rg2, and Rg3, as potential modulators of GLP-1R using luciferase reporter assays and computational analyses. Despite sharing similar molecular weights, a common dammarane scaffold, and comparable sugar moieties, the three ginsenosides displayed distinct effects on GLP-1R activity: Rg2 and Rg3 potently reduced receptor activation in a dose-dependent manner when co-administered with Exendin-4, whereas Rg1 had minimal effect. Computational screening of the GLP-1R structure for binding sites identified a putative extracellular pocket on the protein that can accommodate these compounds, while molecular docking and binding free energy calculations provided predicted affinities qualitatively reflecting the phytochemicals’ experimental activities. These findings point to a plausible extracellular mechanism through which dietary ginsenosides may influence GLP-1R responsiveness at the intestinal interface. Our results point to the possibility that non-absorbed phytochemicals can differentially modulate gut-expressed receptors, suggesting a novel pathway for dietary signaling relevant to ethnopharmacology and metabolic health. 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

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: 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

The gut microbiome plays a pivotal role in modulating multiple physiological processes from the earliest stages of life. However, the complete scope of its effects during childhood is yet to be fully elucidated, which underscores the importance of enhancing the understanding of this emerging area of research. This narrative review provides an overview of the influence of the gut microbiome in early human ontogeny by examining its role in brain and immune development, as well as its involvement in neurodevelopmental disorders and early-life mental health. The gut microbiome contributes to shaping the development and function of both the brain and the immune system. Its influence appears to be primarily mediated through the synthesis of neurotransmitters and microbial metabolites, as well as through the activation of specific pathways within the hypothalamic–pituitary–adrenal axis. Nevertheless, the exact mechanisms through which the gut microbiome exerts these effects, and the full extent of its impact on neurodevelopmental and immune health, remain incompletely understood and continue to be active areas of research and scientific debate. Ultimately, advances revealing how the gut microbiome shapes early brain and immune system development will create new opportunities for innovative interventions and predictive strategies aimed at transforming pediatric health outcomes. Full article

Selenium (Se) is an essential trace element that exerts pleiotropic effects on host physiology, yet the mechanisms by which it coordinates systemic health remain incompletely understood. Emerging evidence regards the gut microbiota as a key mediator of Se biological functions, giving rise to the Se–gut–tissue axis. This review synthesizes the current research progresses on how dietary Se may shape gut microbial composition and metabolism, and how these microbial shifts are associated with protective effects in both intestinal and extra-intestinal tissues. Se sources (particularly organic or new synthetic form) may bidirectionally interact with gut bacteria by enriching beneficial genera such as Akkermansia, Lactobacillus, and butyrate-producing Clostridia, while suppressing opportunistic pathogens. This microbial remodeling strengthens intestinal barrier integrity, enhances antioxidant and anti-inflammatory responses (e.g., via GPX, TrxR, and NF-κB suppression), and generates bioactive metabolites, notably short-chain fatty acids and secondary bile acids. Through these mechanisms, the Se–gut–microbiota axis may regulate distal organ homeostasis, including the liver (ameliorating NAFLD and acute injury), brain (counteracting neurodegeneration and modulating serotonin/GABA), muscle (improving mass and Se deposition), kidney (attenuating uremic toxin-induced ferroptosis), and reproductive organs. Despite encouraging progress, challenges remain in establishing causality, optimizing dose–response relationships, and translating findings into precision interventions. Full article

Microplastics (MPs) are increasingly detected environmental contaminants in both marine and freshwater ecosystems, with reported concentrations ranging from a few to thousands of particles per cubic meter depending on location and methodology. Although growing evidence suggests potential risks to aquatic organisms, the extent of their ecological and biological impacts is still under active investigation. Their size, persistence and capacity to transport chemical additives and co-contaminants allow them to enter biological systems by ingestion and respiration. When ingested, MPs cause oxidative stress, inflammation, and metabolic disorders, resulting in the destruction of vital tissues in major body organs including liver, gills, intestines, and brain. They also change gene expression, cause endocrine and immune pathway perturbation, induce apoptosis, and cause gut microbiome dysbiosis, all of which worsen the health and survival of the organism. MPs also serve as vectors of heavy metals, antibiotics, pesticides, and pathogens and enhance toxicity due to the Trojan horse effect and enable bioaccumulation in food webs. Due to their widespread presence in water, soil, air, and food, MP pollution has direct effects on human, animal, and ecosystem health. This review synthesizes current knowledge on the sources of MPs, the mode of exposure, and the mechanism of toxicity and new ecological implications. It also presents mitigation measures, and stresses a One Health paradigm as the key to taking concerted action on the international level to minimize MP pollution and protect both the environment and human health. Full article

Alterations in gastrointestinal function (digestion, absorption, motility, secretion, and elimination) play important roles in the pathophysiology of many gastrointestinal disorders. Food also strongly influences gastrointestinal health and disease. Some foods act as antigens that trigger an enteric immune response, while others can serve as substrates with direct or indirect biological effects. Food can also be metabolized by gut microbes into bioactive molecules that alter physiology. This review discusses the current research evidence and the clinical use of “food as medicine” through dietary therapies for the management of various gastrointestinal conditions, including disorders of gut–brain interaction, eosinophilic esophagitis, celiac disease, inflammatory bowel disease, gastroparesis, and short bowel syndrome with intestinal failure. Full article