Search Results (130)

The gut microbiota and its interaction with the nervous system through the gut–brain axis (MGB) have been the subject of growing interest in biomedical research. It has been proposed that modulation of microbiota using probiotics could offer a promising therapeutic alternative for mood regulation and the treatment of anxiety and depression disorders. The findings indicate that several probiotic strains, such as Lactobacillus and Bifidobacterium, have demonstrated anxiolytic and antidepressant effects in pre and clinical studies. These effects seem to be mediated by the regulation of the hypothalamic–pituitary–adrenal axis (HPA), the synthesis of neurotransmitters such as serotonin (5-HT) and Gamma-amino-butyric acid (GABA), as well as the modulation of systemic inflammation. However, the lack of standardization in dosing and strain selection, in addition to the scarcity of large-scale clinical studies, limit the applicability of these findings in clinical therapy. Additional research is required to establish standardized therapeutic protocols and better understand the role of probiotics in mental health. The aim of this narrative review is to discuss the relationship between the gut microbiota and the MGB axis in the context of anxiety and depression disorders, the underlying neurobiological mechanisms, as well as the preclinical evidence for the effect of probiotics in modulating these disorders. In this way, an exhaustive search was carried out in scientific databases including PubMed, ScienceDirect, Scopus, and Web of Science. Preclinical research evaluating the effects of different probiotic strains in animal models during chronic treatment was selected, excluding those studies that did not provide access to the full text. Full article

Plateau environments present unique mental health challenges owing to stressors including hypoxia, low temperatures, and intense ultraviolet (UV) radiation. These factors induce structural and functional alterations in the gut microbiota, disrupting gut-brain axis homeostasis and contributing to the higher prevalence of depression in plateau regions relative to flatland areas. For example, studies report that 28.6% of Tibetan adults and 29.2% of children/adolescents on the Qinghai-Tibet Plateau experience depression, with increasing evidence linking this trend to alterations in the gut microbiota. Dysbiosis contributes to depression through three interconnected mechanisms: (1) Neurotransmitter imbalance: Reduced bacterial diversity impairs serotonin synthesis, disrupting emotional regulation. (2) Immune dysregulation: Compromised gut barrier function allows bacterial metabolites to trigger systemic inflammation via toll-like receptor signaling pathways. (3) Metabolic dysfunction: Decreased short-chain fatty acid levels weaken neuroprotection and exacerbate hypothalamic-pituitary-adrenal axis stress responses. Current interventions—including dietary fiber, probiotics, and fecal microbiota transplantation—aim to restore microbiota balance and increase short-chain fatty acids, alleviating depressive symptoms. However, key knowledge gaps remain in understanding the underlying mechanisms and generating population-specific data. In conclusion, existing evidence indicates an association between plateau environments, the gut microbiota, and depression, but causal relationships and underlying mechanisms require further empirical investigation. Integrating multiomics technologies to systematically explore interactions among high-altitude environments, the microbiota and the brain will facilitate the development of precision therapies such as personalized nutrition and tailored probiotics to protect mental health in high-altitude populations. Full article

Anxiety disorders are among the most common psychiatric conditions that significantly impair one’s quality of life and place a significant burden on healthcare systems. Conventional treatments have certain restraints, such as potential side effects and limited efficacy. Τhe underlying pathophysiological mechanisms of anxiety are not fully understood. A comprehensive literature search was performed in MEDLINE and Scopus databases for original English-language articles published between January 2014 and December 2024. Study selection, data extraction, and screening were independently carried out by multiple investigators using predefined criteria. Our review aimed to help better comprehend the molecular basis of anxiety, focusing on the hypothalamic–pituitary–adrenal (HPA) axis, serotonergic signaling, and gamma-aminobutyric acid (GABA) neurotransmission. In addition, we addressed the role of epigenetics and pharmacogenomics in personalized treatment. Although novel anxiety treatments are promising, they are predominantly preclinical and highly heterogeneous, which poses a challenge to achieving reliable therapeutic efficacy. Our findings could potentially contribute to the development of new therapeutic interventions. Further research is warranted, especially in human subjects, with an aim to combine genetic and epigenetic profiles to refine treatment approaches and develop innovative therapeutics. Full article

Numerous scientific findings indicate that excess adipose tissue, particularly visceral fat, is associated with a chronic inflammatory state manifested by elevated levels of proinflammatory cytokines and an imbalance in the T helper type 1/type 2 (Th1/Th2) response, which carries numerous metabolic consequences. Obesity induces, among other effects, the activation of the kynurenine pathway and a reduction in serotonin synthesis, alterations in adipokine profiles, modifications of the hypothalamic–pituitary–adrenal (HPA) axis, disturbances in fatty acid ratios, oxidative stress, and dysfunction of the gamma-aminobutyric acid (GABA)ergic system. These neuroimmunological and metabolic disturbances, along with obesity-induced neurotransmission abnormalities that may represent a common underlying model of depression, could provide valuable insights into the pathomechanisms of depression, allowing for prediction of disease progression and individualized therapeutic strategies in overweight patients. Furthermore, the analysis of inflammation-associated biomarkers opens up new therapeutic perspectives, suggesting that interventions aimed at reducing inflammation might lead to potential advances in the treatment of depression. Full article

Inhibitors of cytosolic phospholipase A₂ (GIVA cPLA₂) have received great attention, since this enzyme is involved in a number of inflammatory diseases, including cancer and auto-immune and neurodegenerative diseases. Traditionally, the effects of GIVA cPLA₂ inhibitors in cells have been studied by determining the inhibition of arachidonic acid release. However, although to a lesser extent, GIVA cPLA₂ may also hydrolyze glycerophospholipids, releasing other free fatty acids (FFAs), such as linoleic acid or oleic acid. In the present work, we applied a liquid chromatography–high-resolution mass spectrometry method to study the levels of intracellular FFAs, after treating cells with selected GIVA cPLA₂ inhibitors. Six inhibitors belonging to different chemical classes were studied, using SH-SY5Y neuroblastoma cells as a model. This lipidomic approach revealed that treatment with each inhibitor created a distinct intracellular FFA profile, suggesting not only inhibitory potency against GIVA cPLA₂, but also other parameters affecting the outcome. Potent inhibitors were found to reduce not only arachidonic acid, but also other long-chain FAs, such as adrenic or linoleic acid, even medium-chain FAs, such as caproic or caprylic acid, suggesting that GIVA cPLA₂ inhibitors may affect FA metabolic pathways in general. The downregulation of intracellular FFAs may have implications in reprogramming FA metabolism in neurodegenerative diseases and cancer. Full article

Arachidonic acid levels are elevated in the colonic mucosa of patients with inflammatory bowel disease (IBD). Fecal metabolites are emerging as valuable diagnostic tools for IBD. This study aimed to investigate associations between 31 fecal fatty acids, including arachidonic acid, to identify potential correlations with disease severity. Among the 31 fatty acids analyzed in feces, dihomo-γ-linolenic acid, arachidonic acid, and adrenic acid were significantly increased in patients with IBD compared to controls. In contrast, levels of linoleic acid and γ-linolenic acid, the precursors of arachidonic acid, were similar between both groups. No significant differences in fatty acid levels were observed between patients with Crohn’s disease and ulcerative colitis. Arachidonic acid and adrenic acid levels positively correlated with fecal calprotectin, a clinically established marker of IBD severity, but showed no association with stool consistency or the Gastrointestinal Symptom Rating Scale. This suggests that these fatty acids are linked to disease severity rather than disease-related symptoms. Current IBD-specific medications had no significant impact on the fecal levels of any of the 31 fatty acids. In summary, this study demonstrates elevated fecal levels of dihomo-γ-linolenic acid, arachidonic acid, and adrenic acid in IBD patients. Normal levels of precursor fatty acids suggest that impaired downstream metabolism may contribute to the accumulation of these n-6 polyunsaturated fatty acids. Full article

Hemorrhagic shock from traumatic injury results in a massive systemic response with activation of the hypothalamic–pituitary–adrenal (HPA) axis, pro-thrombotic and clot-lysis pathways as well as development of an endotheliopathy. With ongoing hemorrhage, these responses become dysregulated and are associated with worsening coagulopathy, microvascular dysfunction, and increased transfusion requirements. Our transfusion practices as well as our understanding of the molecular response to hemorrhage have undergone significant advancement during war. Currently, resuscitation practices address the benefit of the early recognition and management of acute coagulopathy and advocates for balanced resuscitation with either whole blood or a 1:1 ratio of packed red blood cells to fresh frozen plasma (respectively). However, a significant volume of evidence in the last two decades has recognized the importance of the early modulation of traumatic endotheliopathy and the HPA axis via the early administration of plasma, whole blood, and adjunctive treatments such as tranexamic acid (TXA) and calcium. This evidence compels us to rethink our understanding of ‘balanced resuscitation’ and begin creating a more structured practice to address additional competing priorities beyond coagulopathy. The following manuscript reviews the benefits of addressing the additional interrelated physiologic responses to hemorrhage and seeks to expand beyond our understanding of ‘balanced resuscitation’. Full article

Psychobiotics, live microorganisms that provide mental health by interacting with the gut microbiota, are emerging as a promising therapeutic option for psychiatric and neurodevelopmental disorders. Their effectiveness in addressing conditions such as depression, anxiety, insomnia, stress, autism spectrum disorder (ASD), and eating disorders were examined through a comprehensive analysis of existing studies up to the first half of 2024, based on data from reliable electronic databases. We found that psychobiotics can significantly reduce symptoms of various psychiatric disorders by influencing neurotransmitter levels, regulating the hypothalamic-pituitary-adrenal (HPA) axis, and improving gut barrier function through short-chain fatty acids (SCFAs) and other metabolites. However, several limitations were identified, including inconsistent study methodologies, small sample sizes, and a lack of data on long-term safety. Addressing these limitations through rigorous research is essential for establishing standardized protocols and fully confirming the therapeutic potential of psychobiotics. In conclusion, psychobiotics show great promise as complementary treatments for mental health conditions, but continued research is necessary to refine their application and integrate them into clinical practice effectively. Full article

Chronic hyperglycemia is a major driver of neurovascular damage in diabetic retinopathy (DR), a leading cause of preventable blindness in adults. DR progression is often undetected until its advanced stages, with oxidative stress recognized as a primary contributor. In diabetes, oxidative stress disrupts retinal cellular balance, damaging proteins, DNA, and lipids, and triggering photoreceptor degeneration. Pterostilbene (Pter), a polyphenol with antioxidant properties, has demonstrated protective effects in DR animal models and was assessed in a pilot clinical study. DR patients treated with 250 mg/day of oral Pter showed a reduction in the development of retinal vascular alterations characteristic of the disease. Urinary analyses confirmed Pter’s role in reducing the lipid peroxidation of polyunsaturated fatty acids (PUFAs), including arachidonic and adrenic acids, indicators of oxidative damage in DR. Pter also improved the GSH/GSSG ratio, reflecting a restored redox balance. However, after six months without treatment, retinal damage indicators reappeared, highlighting the importance of sustained intervention. These findings suggest that Pter may help slow the progression of DR by protecting against oxidative stress and highlight the importance of implementing antioxidant therapies from the diagnosis of diabetes, although its long-term impact and the development of consistent biomarkers deserve more research to optimize DR management. Full article

Depression and anxiety are two common mental health issues that require serious attention, as they have significant impacts on human well-being, with both being emotionally and physically reflected in the increasing number of suicide cases globally. The World Health Organization (WHO) estimated that about 322 million people around the world experienced mental illnesses in 2017, and this number continues to increase. Cortisol is a major stress-controlled hormone that is regulated by the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis has three main components, including the hypothalamus, pituitary gland, and adrenal gland, where cortisol, the primary stress hormone, is released. It plays crucial roles in responding to stress, energy balance, and the immune system. The cortisol level in the bloodstream usually increases when stress develops. Molecularly imprinted polymers (MIPs) have been highlighted in terms of creating artificial bioreceptors by mimicking the shape of detected biomolecules, making natural bioreceptor molecules no longer required. MIPs can overcome the limitations of chemicals and physical properties reducing over time and the short-time shelf life of natural bioreceptors. MIPs’ benefits are reflected in their ease of use, high sensitivity, high specificity, reusability, durability, and the lack of requirement for complicated sample preparation before use. Moreover, MIPs incur low costs in manufacturing, giving them a favorable budget for the market with simple utilization. MIPs can be formulated by only three key steps, including formation, the polymerization of functional monomers, and the creation of three-dimensional cavities mimicking the shape and size of targeting molecules. MIPs have a high potential as biosensors, especially working as bioanalytics for protein, anti-body, antigen, or bacteria detection. Herein, this research proposes an MIP-based cortisol biosensor in which cortisol is imprinted on methyl methacrylate (MMA) and methacrylic acid (MAA) produced by UV polymerization. This MIP-based biosensor may be an alternative method with which to detect and monitor the levels of hormones in biological samples such as serum, saliva, or urine due to its rapid detection ability, which would be of benefit for diagnosing depression and anxiety and prescribing treatment. In this study, quantitative detection was performed using an electrochemical technique to measure the changes in electrical signals in different concentrations of a cortisol solution ranging from 0.1 to 1000 pg/mL. The MIP-based biosensor, as derived by calculation, achieved its best detection limit of 1.035 pg/mL with a gold electrode. Tests were also performed on molecules with a similar molecular structure, including Medroxyprogesterone acetate and drospirenone, to ensure the sensitivity and accuracy of the sensors, demonstrating a low sensitivity and low linear response. Full article

Chronic stress poses threats to the physical and psychological well-being of dogs. Resveratrol (Res) is a polyphenol with antidepressant properties and has rarely been studied in dogs. This study aimed to investigate the stress-relieving effects and underlying mechanism of Res in dogs. Dogs were fed a basal diet supplemented with Res for 35 days. The fecal microbiota of the dogs was cultured with Res in vitro. The results show that Res improved the stress-related behaviors and increased the serum levels of 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), immunoglobulin A, and antioxidant capacity in dogs. Res downregulated the hormones of the hypothalamic–pituitary–adrenal axis. The abundance of butyric-producing bacteria, like Blautia, increased, while the growth of Fusobacterium related to gut inflammation was inhibited in the Res group. A higher content of fecal butyric acid was observed in the Res group. The metabolome indicated that Res increased the fecal and serum levels of tryptophan (Trp) and decreased the consumption of Trp by microorganisms. A chronic unpredictable mild stress mouse model was established, and Res was administered for 35 days. The results show that Res ameliorated the stress-related behavior and increased the levels of Trp and 5-HT in the whole brains of mice. The relative mRNA expression of genes associated with the tight junction protein, aryl hydrocarbon receptor, and Trp transporters in the colon were upregulated. In conclusion, Res could ameliorate canine stress by increasing 5-HT, BDNF, and the antioxidant capacity and improving the immune function and stress response, which was attributed to the role of Res in the restructuring of gut microbiota and the modulation of tryptophan metabolism. Full article

The gut–brain axis (GBA) is a complex communication network connecting the gastrointestinal tract (GIT) and the central nervous system (CNS) through neuronal, endocrine, metabolic, and immune pathways. Omega-3 (n-3) fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are crucial food components that may modulate the function of this axis through molecular mechanisms. Derived mainly from marine sources, these long-chain polyunsaturated fatty acids are integral to cell membrane structure, enhancing fluidity and influencing neurotransmitter function and signal transduction. Additionally, n-3 fatty acids modulate inflammation by altering eicosanoid production, reducing proinflammatory cytokines, and promoting anti-inflammatory mediators. These actions help preserve the integrity of cellular barriers like the intestinal and blood–brain barriers. In the CNS, EPA and DHA support neurogenesis, synaptic plasticity, and neurotransmission, improving cognitive functions. They also regulate the hypothalamic–pituitary–adrenal (HPA) axis by reducing excessive cortisol production, associated with stress responses and mental health disorders. Furthermore, n-3 fatty acids influence the composition and function of the gut microbiota, promoting beneficial bacterial populations abundance that contribute to gut health and improve systemic immunity. Their multifaceted roles within the GBA underscore their significance in maintaining homeostasis and supporting mental well-being. Full article

Lysosomal acid lipase deficiency (LAL-D) is an ultra-rare lysosomal storage disease with two distinct phenotypes, an infantile-onset form (formerly Wolman disease) and a later-onset form (formerly cholesteryl ester storage disease). The objective of this narrative review is to examine the most important aspects of the diagnosis and treatment of LAL-D and to provide practical expert recommendations. The infantile-onset form occurs in the first weeks of life and is characterized by malnourishment and failure to thrive due to gastrointestinal impairment (vomiting, diarrhea, malabsorption), as well as systemic inflammation, hepatosplenomegaly, and adrenal calcifications. Mortality is close to 100% before one year of life in the absence of specific treatment. The later-onset form can be diagnosed in childhood or adulthood and is characterized by chronic liver injury and/or lipid profile alterations. When LAL-D is suspected, enzyme activity should be determined to confirm the diagnosis, with analysis from a dried blood spot sample being the quickest and most reliable method. In infantile-onset LAL-D, the initiation of enzyme replacement therapy (sebelipase α) and careful nutritional management with a low-lipid diet is very urgent, as prognosis is directly linked to the early initiation of specific treatment. In recent years, our knowledge of the management of LAL-D has increased considerably, with improvements regarding the initial enzyme replacement therapy dose and careful nutritional treatment with a low-lipid diet to decrease lipid deposition and systemic inflammation, leading to better outcomes. In this narrative review we offer a quick guide for the initial management of infantile-onset LAL-D. Full article

Introduction: Arterial hypertension is a major contributor to a wide range of health complications, with cardiac hypertrophy and chronic kidney disease being among the most prevalent. Consequently, novel strategies for the treatment and prevention of hypertension are actively being explored. Recent research has highlighted a potential link between hypertension and the gut–brain axis. A bidirectional communication between the microbiota and the brain via the vagus nerve, enteric nervous system, hypothalamus–pituitary–adrenal axis, secreted short-chain fatty acids, and neurotransmitter metabolism. Materials and methods: A comprehensive literature search was conducted using databases such as PubMed to identify studies exploring the relationship between gut microbiota and hypertension, along with the effects of dietary interventions and probiotics on blood pressure regulation. Discussion: Studies in both animal models and human subjects have demonstrated a strong correlation between alterations in gut microbiota composition and the development of hypertension. By influencing blood pressure, the gut microbiota can potentially affect the progression of cardiovascular and kidney disorders. Modulating gut microbiota through dietary interventions and probiotics has shown promise in regulating blood pressure and reducing systemic inflammation, offering a novel approach to managing hypertension. Diets such as the Mediterranean diet, which is rich in polyphenols and omega-3 fatty acids and low in sodium, promote the growth of beneficial gut bacteria that support cardiovascular health. Additionally, probiotics have been found to enhance gut barrier function, reduce inflammation, and modulate the Renin–Angiotensin System, all of which contribute to lowering blood pressure. Conclusions: Further research is needed to determine the mechanisms of action of the microbiota in hypertension. The aim of this study was to evaluate the influence of gut microbiota on blood pressure regulation and the progression of hypertension-related complications, such as cardiovascular and kidney disorders. Full article

Background: The aim of this study was to identify the blood lipidomic profile associated with a healthy eating pattern in a middle-aged US population sample and to determine its relationship with metabolic disorders and cardiovascular risk (CVR). Methodology: Self-reported information about diet and blood samples were obtained from 2114 adult participants in the Midlife in the United States study (MIDUS). Food intake data were used to design a Healthy Diet Index (MIDUS-HEI) and to evaluate the predictive value by examining its association with health variables. The associated lipid signature (HEI-LS) was constructed using Lasso regression, from lipidomic data (LC/MS). Associations between HEI-LS, cardiometabolic biomarkers, and estimated CVR were assessed using multiple linear regression. Results: MIDUS-HEI score was a robust indicator of dietary quality and inversely associated with body mass index (p < 0.001) and metabolic syndrome (p = 0.012). A lipidomic signature comprising 57 distinct lipid species was highly correlated with the MIDUS-HEI score (r = 0.39, p < 10⁻¹⁶). It was characterized by lower levels of saturated fatty acid and adrenic acid (n-6) and higher levels of docosahexaenoic acid (n-3). Healthier HEI-LS scores were strongly associated with better cardiometabolic indicators and lower estimated CVR (OR 0.89 CI 95% 0.87–0.91). Conclusions: The MIDUS-HEI effectively assessed dietary quality, confirming the link between poor diet quality and metabolic disorders in American population. Lipidomic profiling offered an objective assessment of dietary patterns and provided insights into the relationship between diet quality, metabolic responses, and CVR. This approach supports precision nutrition strategies for at-risk populations. Full article