Search Results (776)

Chronic kidney disease (CKD) is characterized by the progressive accumulation of uremic toxins (UTs), which contribute to systemic complications, increased cardiovascular risk, and disease progression. Epidemiological and experimental evidence demonstrate pronounced sex differences in CKD progression and outcomes, yet the mechanisms underlying sex-specific uremic toxicity remain unclear. This review synthesizes current knowledge on sex differences in the origin, metabolism, transport, and biological effects of UTs, with a focus on sex-dependent regulatory mechanisms along the gut–liver–kidney axis. Sex hormones influence key determinants of toxin handling, including gut microbiota composition, hepatic enzyme activity, plasma protein binding, membrane transporter expression, and intracellular signaling pathways. Together, these factors regulate systemic toxin exposure and tissue susceptibility to injury. CKD also disrupts endocrine homeostasis, creating bidirectional interactions between hormonal regulation and toxin accumulation. Experimental and limited clinical evidence suggest that sex may influence circulating toxin profiles and susceptibility to toxin-associated complications. Collectively, sex is an important modulator of uremic toxicity, with sex hormones mediating at least part of the sex differences. A sex-informed framework may improve fundamental understanding through mechanistic studies and future clinical research may help clarify its relevance for biomarker development and support the development of personalized therapeutic strategies for CKD. Full article

The survival of complex multicellular organisms depends on continuous inter-organ communication networks that coordinate organism-wide responses across physiological conditions and stress states, including adaptation to environmental challenges, infection, and injury. Rather than operating as isolated units, organ systems are integrated through interconnected signaling networks that transmit biological information across tissues. Building on prior work examining individual physiological pathways, this review introduces a unified systems-level framework that integrates inter-organ communication into a coherent model of organism-wide regulation. This review proposes a systems-level framework in which homeostasis is maintained through eight principal communication systems: neural, endocrine, immune-inflammatory, vascular, lymphatic, metabolic, microbiome–gut, and mechanical-structural. Epithelial barriers function as dynamic signaling interfaces within multiple systems, while extracellular vesicles act as cross-system mediators of information transfer rather than as independent communication networks. These systems operate across distinct temporal scales to coordinate host defense, metabolic adaptation, vascular regulation, and tissue repair. The framework further introduces a temporal hierarchy of signaling dynamics that links communication systems to phase-specific responses during physiological stress. Within this integrated network, glucocorticoid receptor α (GRα) is proposed to function as a systems-level regulator of inter-organ communication, supported by converging mechanistic, experimental, and clinical evidence, with variability in the strength of evidence across domains. In contrast to prior reviews, which addressed GRα function within individual systems, this work conceptualizes GRα as a central rheostat coordinating cross-system signaling and temporal transitions in homeostatic correction. Evidence was identified through hypothesis-driven searches using the Consensus AI platform and verified through manual review of primary biomedical literature. GRα, a ligand-activated transcription factor expressed in most nucleated cells, enables hormonal stress signals to coordinate gene-expression programs across tissues, modulating neuroendocrine responses, endothelial function, inflammatory signaling, metabolic regulation, microbiome–host interactions, and tissue remodeling. Systemic responses to stress progress through three phases of homeostatic correction—Priming, Modulatory, and Restorative—within which GRα supports integrated organism-wide adaptation. This integrative framework provides a mechanistic basis for understanding the emergence and temporal evolution of biological responses in health and critical illness. Full article

The weaning-to-estrus interval (WEI) is an important indicator of sow reproductive performance, yet the mechanisms underlying post-weaning anestrus in Tibetan sows remain unclear. In this study, multiparous Tibetan sows were classified into an estrus group (FQ) and an anestrus group (WQ) based on estrus status after weaning. Serum reproductive hormones, hematological parameters, gut microbiota (16S rRNA sequencing), and fecal metabolites (untargeted metabolomics) were analyzed. Compared with the FQ group, the WQ group showed significantly lower estradiol (E₂) and higher progesterone (P) levels (p < 0.01), along with a decreased proportion of neutrophils and an increased proportion of lymphocytes (p < 0.05). No significant differences in alpha diversity were observed, whereas PLS-DA revealed differences in microbial community structures between groups. LEfSe analysis indicated that Methanobrevibacter and Acinetobacter were enriched in the FQ group, whereas Muribaculaceae and Prevotella were enriched in the WQ group. Differential metabolites were mainly involved in amino acid and lipid metabolism and enriched in pathways related to steroid hormone biosynthesis, oocyte maturation, and tryptophan metabolism. These findings suggest that post-weaning anestrus may be associated with endocrine imbalances, immune changes, and gut microbiota–metabolite interactions. They may provide a basis for future studies in Tibetan pig breeding and genetic improvement. Full article

Zn-CS chelate has shown beneficial effects on gut health and growth in piglets, but its impact on weaned foals remains largely unknown. This study evaluated the effects of dietary Zn-CS supplementation on growth performance, nutrient digestibility, physiological status, and fecal microbiota in weaned Ili foals. Thirty-two six-month-old foals were randomly assigned to four treatment groups receiving 0, 2, 4, or 6 mg Zn-CS/kg body weight per day for 90 days. Growth performance, nutrient digestibility, plasma biochemical parameters, liver function enzymes, serum hormones, antioxidant indices, fecal pH, volatile fatty acids, and fecal microbial composition were measured. Dietary Zn-CS supplementation significantly increased final body weight, total weight gain, and average daily gain (p < 0.05), while linearly improving body size indicators. Apparent digestibility of dry matter, digestible energy, metabolizable energy, and acid detergent fiber was markedly enhanced (p < 0.05). Zn-CS supplementation also effectively regulated plasma albumin and total cholesterol levels and hepatic enzyme activities, and strongly enhanced antioxidant function by increasing superoxide dismutase, glutathione peroxidase, catalase activities, and total antioxidant capacity, while reducing malondialdehyde content (p < 0.01). Additionally, Zn-CS upregulated plasma growth hormone, insulin, and triiodothyronine concentrations, decreased somatostatin secretion (p < 0.05), reduced fecal pH, and increased VFA contents. Notably, Zn-CS reshaped the fecal microbial structure by increasing beneficial bacteria and inhibiting potential pathogens. In conclusion, dietary Zn-CS supplementation effectively promotes growth and health in weaned Ili foals, with 6 mg/kg BW/day being the optimal supplemental dose under experimental conditions. Full article

Background/Objectives: Intermittent fasting (IF) has been widely investigated for its metabolic effects, including improvements in insulin sensitivity, lipid metabolism, and inflammatory markers. However, its psychological and experiential dimensions remain comparatively underexplored. The present narrative review examines IF within a psychobiological framework, integrating evidence from metabolic science, neuroendocrinology, and affective neuroscience to explore its potential impact on emotional regulation and interoceptive processes. Methods: A structured narrative literature search was conducted across PubMed, Scopus, and Google Scholar, focusing on studies published between 2010 and 2025. Eligible studies included human and relevant animal research addressing metabolic, hormonal, interoceptive, and psychological responses to IF. Evidence was synthesized thematically to identify convergent mechanisms linking metabolic adaptations to emotional and regulatory outcomes. Results: Available literature suggests that IF is associated with a metabolic shift toward lipid utilization, characterized by increased ketone body production, particularly β-hydroxybutyrate. These adaptations appear to be accompanied by modulation of neuroendocrine pathways and may influence central nervous system functioning through mechanisms potentially related to neuroinflammation, mitochondrial efficiency, and synaptic plasticity. Emerging evidence further suggests that IF may modulate BDNF signaling and gut–brain axis activity, although direct causal pathways in humans remain to be established. At the psychological level, IF is associated with heterogeneous emotional outcomes: structured fasting protocols have been linked to modest improvements in perceived stress and mood in metabolically healthy individuals, whereas irritability, anxiety, or behavioral rigidity may emerge in those with pre-existing psychological vulnerabilities. Individual differences in interoceptive sensitivity, emotion regulation strategies, and moderating biological factors—including sex, circadian timing, and habitual physical activity—appear to influence these responses. Conclusions: Overall, IF may be conceptualized as a context-dependent psychobiological stressor whose effects extend beyond metabolic regulation to include interoceptive and emotional processes. These effects appear bidirectional, potentially promoting psychological resilience in some individuals while increasing the risk of affective destabilization or maladaptive behaviors in others. Current evidence remains limited by a lack of integrative and longitudinal studies combining metabolic and psychological measures. Future research adopting multidisciplinary approaches is needed to clarify the mechanisms underlying individual variability and to better define the potential benefits and risks of IF in both clinical and non-clinical populations. Full article

Bergamot essential oil (BEO) has demonstrated antidepressant potential, but its oral application is limited by poor water solubility and undesirable organoleptic properties. In this study, a BEO-loaded beverage was developed based on a whey protein-stabilized oil-in-water emulsion system. The optimal formulation, determined via single-factor experiments combined with orthogonal optimization, consisted of inulin (0.5 g/50 g), milk powder (2.0 g/50 g), sucralose (0.008 g/50 g), and sodium carboxymethyl cellulose (0.04 g/50 g). The resulting beverage remained stable without visible phase separation during 4 months of storage at 4 °C. In a chronic corticosterone treatment (CCT)-induced mouse model of depression, oral administration of the BEO beverage increased activity in the central area of the open field test and exploratory behavior in the elevated plus maze, while reducing repetitive stereotyped behaviors in the marble burying test. At the molecular level, the BEO beverage was associated with reduced levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and corticosteroid (CORT), and increased levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), serotonin (5-HT), dopamine (DA), and norepinephrine (NE). Additionally, the BEO beverage was associated with observed alleviation of neuronal damage in the hippocampal CA3 region, upregulation of brain-derived neurotrophic factor (BDNF), improved gut microbial diversity, and altered host metabolic profiles. Collectively, these findings suggest that the BEO emulsion beverage is a feasible intervention for alleviating depression-like behaviors in the mouse model, and provide initial associative evidence supporting its potential as a functional food for mood management. Full article

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex, multi-system disorder involving interactions among metabolic dysfunction, chronic low-grade inflammation, and neuroendocrine dysregulation, rather than a condition confined to the ovary. While current management strategies primarily target symptomatic manifestations, such as menstrual irregularity, hyperandrogenism, and insulin resistance, they do not directly address the underlying integrative pathways linking the gut microbiome, cellular energy sensing, and hypothalamic reproductive control. This review proposes a mechanistic framework in which algae-derived bioactives modulate a gut–SIRT1–kisspeptin axis, thereby offering a systems-level perspective on PCOS pathophysiology and intervention. Gut dysbiosis in PCOS contributes to altered bile acid signaling, disrupted microbial metabolite profiles, and increased inflammatory tone, all of which may impair both metabolic and reproductive functions. Concurrently, reduced activity of the NAD⁺-dependent deacetylase SIRT1 has been documented across ovarian, endometrial, and metabolic tissues, linking energy imbalance to oxidative stress, inflammation, and impaired steroidogenesis. At the neuroendocrine level, dysregulated kisspeptin signaling contributes to abnormal gonadotropin-releasing hormone pulsatility and luteinizing hormone hypersecretion, key features of PCOS. Algae-derived compounds, including polysaccharides, phlorotannins, fucoidan, fucoxanthin, and microalgae bioactives, exhibit prebiotic, anti-inflammatory, and metabolic regulatory properties that intersect with these pathways, particularly through modulation of gut microbiota and activation of AMPK/SIRT1 signaling. The central proposition of this review is that algae-derived bioactives may act across interconnected biological layers: reshaping gut microbial ecology, restoring SIRT1-mediated metabolic balance, and retuning kisspeptin-driven neuroendocrine activity. While individual components of this axis are supported by substantial evidence, direct experimental validation of the complete pathway remains limited. Therefore, this framework is positioned as a translationally grounded but hypothesis-driven model that integrates currently fragmented findings into a coherent and testable paradigm. Future research should prioritize multi-level experimental and clinical studies that simultaneously assess microbiota composition, metabolic signaling, and reproductive neuroendocrine outcomes to establish the therapeutic potential of algae-based interventions in PCOS. Full article

Dietary sodium excess is a primary driver of hypertension, yet individuals differ markedly in their blood pressure response to salt. This variation, termed salt sensitivity, cannot currently be predicted from clinical variables alone. This review examines three aspects of salt-gut physiology: intestinal sodium handling, salt-induced changes in gut microbiome composition, and microbiota-mediated effects on immune function, metabolite production, and gut barrier integrity. The intestine absorbs dietary sodium through regulated transporters whose activity adapts to luminal and hormonal conditions, making the gut a key regulator of sodium balance. High salt intake consistently alters gut microbiota composition in animal models, most reproducibly depleting Lactobacillus species, with variable effects on overall diversity. These compositional shifts, supported by human data, activate intestinal Th17 cells and deplete short-chain fatty acid producers, contributing to systemic inflammation and elevated blood pressure. The presence of inducible osmoadaptation responses varies substantially across microbes, though activation under dietary sodium conditions has not been demonstrated in vivo. If salt-driven microbial changes contribute causally to hypertension, microbiota-targeted interventions could complement sodium restriction in patients for whom long-term dietary adherence is poor. Controlled sodium intervention studies in animals and humans are needed to establish whether such a causal contribution exists. Full article

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by complex and interconnected pathophysiological mechanisms, including mitochondrial dysfunction, oxidative stress, neuroinflammation, lysosomal impairment, and altered neurotransmitter metabolism. Unlike cerebrospinal fluid or blood, urine offers a truly non-invasive source of biomarkers, reflecting systemic metabolic changes and renal protein excretion linked to neurodegeneration. This review aims to critically synthesize current evidence on urinary biomarkers in PD and to organize this heterogeneous literature into pathophysiologically meaningful domains. Methods: A comprehensive literature search of human studies investigating urinary biomarkers in PD was performed. Eligible studies were comprehensively analyzed and classified according to dominant biological pathways. To facilitate interpretation, findings were organized into six thematic domains: genetic and protein-based biomarkers; metabolic pathways and mitochondrial dysfunction; oxidative stress and neuroinflammation; gut–brain-axis-related metabolites; hormonal and systemic biomarkers; and emerging exploratory markers. Results were summarized in domain-specific tables and integrated using a conceptual framework. Results: A total of 32 human studies met the inclusion criteria, revealing diverse urinary molecular signatures associated with PD across multiple biological domains. Genetic and protein-based markers, including LRRK2-related proteins, α-synuclein species, and lysosomal lipids, showed potential for disease stratification. Metabolomic studies consistently identified alterations in acylcarnitines, organic acids, and amino acid metabolism, reflecting mitochondrial dysfunction. Biomarkers related to oxidative stress, immune activation, gut microbiota metabolism, and hormonal regulation further highlighted the systemic nature of PD. However, most individual biomarkers lacked disease specificity and exhibited methodological heterogeneity. Conclusions: Current evidence supports urine as a valuable source of systemic biomarkers reflecting multiple pathophysiological processes in PD. While single urinary markers remain insufficient for clinical application, integrated omics-based approaches—particularly metabolomics and peptidomics/proteomics—hold promise for identifying combinatorial biomarker signatures. Future longitudinal and standardized studies are required to enhance specificity and translational potential for non-invasive diagnosis and disease monitoring in PD. Full article

Enhancing egg production in geese without antibiotics remains a challenge in poultry science. This study compared the effects of Lactobacillus (LAB) and Bacillus (BAC) probiotics on laying performance, gut microbiota, and serum metabolism in Zhedong White geese. Birds were fed a control diet or diets supplemented with LAB or BAC. Egg production and quality were monitored throughout the trial. Serum metabolomics and fecal 16S rRNA sequencing were integrated with KEGG enrichment and correlation analyses to uncover functional mechanisms. Both probiotics improved laying performance and egg quality. Total egg production of the LAB group was 8.5% higher than that of the BAC group (p < 0.05). The LAB group’s advantage in egg production was consistent with its stronger activation of the steroid hormone biosynthesis pathway (elevated serum corticosterone and tetrahydrocorticosterone indicated an overall enhancement of steroidogenic flux). Simultaneously, the LAB group exhibited a more efficient conversion of L-phenylalanine to catecholamine precursors, which drove activation of the neuroendocrine reproductive axis. The BAC group showed more significant changes in nitrogen and energy metabolism pathways and a more pronounced expansion of energy-harvesting Firmicutes. These findings reveal two strain-specific regulatory pathways: LAB functions through the “aromatic amino acid–neuroendocrine–steroid hormone axis,” while BAC relies on the “gut microbiota–energy metabolism” pathway, with direct implications for the precise application of probiotics under antibiotic-free farming conditions. Full article

Epimedium is a traditional Chinese tonic used to tonify the kidneys, enhance sexual function, and strengthen muscles and bones. However, the potential effects of Epimedium on the semen quality of Bama boars remain incompletely elucidated. The objective of this study was to evaluate the effects of dietary Epimedium ultrafine powder (EP) supplementation on the semen quality of Bama boars and to explore the underlying mechanisms. The objective of this study was to evaluate the effects of dietary EP supplementation on the semen quality of Bama boars and to explore the underlying mechanisms. Eighteen healthy, sexually mature adult male Bama boars were randomly divided into three groups (n = 6) and fed either a basal diet (CON) or the basal diet supplemented with 0.3% (EP3) or 0.5% (EP5) Epimedium ultrafine powder for five weeks. This study employed enzyme-linked immunosorbent assay (ELISA), 16S RNA gene sequencing, non-targeted metabolomics (CON and EP5), and Spearman correlation analysis, among other methods. The results indicated that dietary Epimedium (0.3% and 0.5%) increased the levels of serum TP, FSH, and SOD and decreased the abnormal sperm rate and the levels of serum TBA, TNF-α, and IL-6. Among them, adding 0.5% Epimedium in the diet increased sperm motility and the levels of serum T, LH, and IgG. 16S rRNA gene sequencing analysis revealed that both 0.3% and 0.5% Epimedium supplementation reduced the abundance of Streptococcus. Specifically, the 0.3% dose decreased Prevotella abundance, while the 0.5% dose reduced Escherichia-Shigella abundance. PICRUSt2 analysis revealed that the pathways of phenylalanine, butanoate, biotin, and arachidonic acid metabolism were significantly enriched in the Epimedium group. A non-targeted metabolomics analysis identified that indole-3-acrylic acid, DL-tryptophan, 2-hydroxyphenylalanine, and propionylcarnitine showed significant upregulation after Epimedium supplementation. Spearman correlation analysis indicated that Streptococcus was negatively correlated with sperm motility and serum-related parameters (TP, T, LH, IgM, and IgG). Streptococcus and Escherichia-Shigella were negatively correlated with indole-3-acrylic acid, DL-tryptophan, and biotin. In conclusion, Epimedium has a positive impact on the seminal quality, reproductive hormones, and immune–antioxidant levels of Bama boars by regulating the composition and metabolites of the intestinal microbiota. Full article

Alcohol use disorder (AUD) is associated with gut dysbiosis through interactions with the immune system. The present study aimed to investigate whether endotoxin lipopolysaccharides (LPS) and high-mobility group box-1 protein (HMGB1), a key inflammatory mediator, as well as the metabolic fat mass hormone leptin, are reliable biomarkers for the estimation of alcohol dependence and abstinence. AUD outpatients (N = 122) and healthy volunteers (N = 63) were recruited and assessed by using the Psychiatric Research Interview for Substance and Mental Disorders according to DSM-IV-TR after blood extraction. The results indicated that AUD patients had higher plasma concentrations of LPS and HMGB1, and lower plasma concentrations of leptin and SDF-1α compared to healthy subjects. Two logistic models, including HMGB1, leptin and SDF-1α (model 1) or LPS (model 2), provided high discriminatory powers to identify AUD patients [prognostic probability: model 1 = 0.90 (0.78); model 2 = 0.86 (0.79); p < 0.001]. LPS and HMGB1 positively correlated with alcohol abstinence duration in male AUD patients only. Linear logistic regression included LPS, HMGB1, fractalkine, SDF-1α and/or leptin to accurately estimate the duration of problematic alcohol use and alcohol abstinence when sexes were analyzed separately. These results suggest that LPS and HMGB1 are relevant sex-specific actors for predicting alcohol abstinence and problematic alcohol use in AUD patients. Full article

Clutch persistence, defined as the ability to sustain consecutive egg-laying cycles, is a pivotal determinant of profitability in the poultry industry, particularly for aging laying hens (≥65 weeks). However, the molecular mechanisms governing this trait remain elusive, largely due to the traditional “ovary-centric” paradigm that overlooks systemic regulation by the gut microbiota. To address this knowledge gap, the present study aimed to dissect the comprehensive regulatory network governing clutch persistence using integrated multi-omics analyses. A total of 20 sixty-five-week-old Rhode Island Red (RIR) laying hens with cumulative egg production exceeding 300 eggs but distinct clutch persistence were stratified into a high-clutch persistence group (HCP, ≥25 clutches, n = 10) and a low-clutch persistence group (LCPLCP, ≤15 clutches, n = 10). Multi-omics profiling, including ovarian transcriptomics, proteomics, and metabolomics; serum metabolomics; and cecal microbiota 16S rRNA sequencing was performed. Data integration and association mining were conducted via Spearman correlation analysis with stringent thresholds (r > 0.6, p < 0.01). Integrated analyses revealed a “gut–ovary axis” regulatory model mediated by a lipid mediator network, operating through a three-tiered mechanism: (1) Gut Initiation: The HCP group exhibited enriched cecal γ-Proteobacteria, which promoted biosynthesis of lipid precursors. (2) Serum Transport: Key serum lipid mediators, most notably LysoPC (22:6) (VIP = 4.5) and cholesterol ester CE (20:4), served as critical carriers transducing gut-derived signals to the ovary. (3) Ovarian Execution: These lipid signals activated a core ovarian metabolic pathway centered on the PLA2G6-ALOX15B-AGPAT3 axis, which coordinated follicular development and ovulation by supplying steroid hormone synthesis substrates, exerting anti-inflammatory effects, and stabilizing membrane structures. Collectively, this study demonstrates that gut microbiota modulates clutch persistence in aging laying hens via lipid mediators, orchestrating a systemic “gut–serum–ovary” regulatory cascade. These findings provide a novel molecular framework for extending the economic egg-laying cycle through the targeted manipulation of intestinal microbiota or serum lipid metabolism. Full article

Background/Objectives: Bile acids, synthesized from cholesterol in the liver, are amphipathic molecules that play an integral role in lipid digestion and absorption, while also serving as systemic endocrine hormones. They continuously undergo enterohepatic circulation, where they interact with various transporter proteins. Dysregulated bile acid transport is associated with the pathogenesis of liver disease. This review summarizes the key findings relating to bile acid transport expression and activity in the pathogenesis of liver disease. Methods: A review of the literature was performed using PubMed and relevant terms including, but not limited to, “bile acid transporters”, “liver disease”, and “bile acid uptake and efflux”. Studies published in peer-reviewed journals relevant to this review were considered and reviewed. Results: Within the gut and liver, several key bile acid and xenobiotic transporters within the enterohepatic circulation are dysregulated. The directionality and extent of changes are cell- and disease-specific. Many of the regulatory processes are driven by changes in bile acid signaling, although further work is needed to expand on post-translational modification of bile acid transporters in liver disease. Conclusions: Bile acid transporters are dynamically regulated in liver diseases with distinct etiologies. Therefore, restoring BA transporter function represents an actionable therapeutic approach to liver disease. Full article

The gut microbiota plays a multifaceted role in calcium homeostasis and bone metabolism —acting through metabolic, immunological, and hormonal pathways that collectively constitute the gut–bone axis. The microbiota influences calcium bioavailability through several overlapping mechanisms that act in the intestine. Moreover, microbial fermentation products may directly impact the osteoblast–osteoclast interplay and, by modulating immune and endocrine functions, are crucial for bone metabolism. A healthy microbiota supports bone formation; however, intestinal dysbiosis may impair bone structure and function. This narrative review aims to present pathways linking the gut microbiota to bone metabolism, both in health and disease. First, we will discuss the influence of gut microbiota on calcium absorption. We will then outline the role that microbial metabolites, such as bile acids and short-chain fatty acids (SCFAs), play in regulating bone structure and function. In the following section, we will discuss the role of the microbiota in the immunological and hormonal modulation of bone metabolism. Finally, we will discuss how dysbiosis affects bone and how therapeutic interventions, such as probiotics, prebiotics, and postbiotics, may influence bone tissue quality. Full article