Search Results (4,678)

Ascosphaera apis, an obligate lethal fungal pathogen that infects bee larvae, and causes chalkbrood disease, poses a significant threat to the global beekeeping industry. Long non-coding RNAs (lncRNAs) are employed by pathogens to enhance infectivity and evade host immunity. Here, lncRNAs in A. apis spores (AaCK group) and the guts of 4-, 5-, and 6-day-old Apis cerana cerana worker larvae inoculated with A. apis spores (AaT1, AaT2, and AaT3 groups) were identified, characterized, and validated. Additionally, the expression pattern of fungal lncRNAs during infection was analyzed, followed by an investigation of the regulatory manners and roles of differentially expressed lncRNAs (DElncRNAs). A total of 1379 lncRNAs were identified in AaCK, AaT1, AaT2, and AaT3 groups using bioinformatics, involving various types such as sense lncRNAs, antisense lncRNAs, bidirectional lncRNAs, intergenic lncRNAs, and intronic lncRNAs. Additionally, 4, 9, and 75 up-regulated lncRNAs as well as 2, 1, and 15 down-regulated ones were identified in the 4-, 5-, and 6-day-old larval guts following A. apis inoculation. Fifteen DElncRNAs as potential antisense lncRNAs may interact with 15 sense-strand mRNAs in the AaCK vs. AaT3 comparison group. Cis-acting analysis identified 10, 16, and 136 upstream and downstream genes of DElncRNAs in the aforementioned comparison groups, involving a series of GO terms and KEGG pathways like metabolic process and biosynthesis of secondary metabolites. Following the trans-acting investigation, 752, 821, and 1327 co-transcribed genes with DElncRNAs were discovered, spanning an array of functional terms and pathways such as biological processes and glycerophospholipid metabolism. Analysis of a competing endogenous RNA (ceRNA) network indicated that 1 and 5 DElncRNAs in the AaCK vs. AaT1 and AaCK vs. AaT3 comparison groups potentially targeted 1 and 2 miRNAs, further targeting 208 and 286 mRNAs, respectively. Further analysis identified one ceRNA axis relevant to the MAPK signaling pathway and several ceRNA networks associated with the biosynthesis of secondary metabolites. Finally, RT-qPCR results confirmed that the expression trends of six randomly selected DElncRNAs were consistent with those in the transcriptome data. These findings not only offer a foundation for elucidating the mechanisms underlying DElncRNA-mediated A. apis infection but also enrich our understanding of honeybee host–fungal pathogen interactions. Full article

Bovine colostrum (COL) is widely used in dietary supplements, and previous studies have suggested its potential benefits for immune function, selected clinical conditions, wound healing, and athletic performance. This systematic review analyzed clinical trials published between 2001 and 2025 that investigated the effects of COL on human body fat and blood lipid profiles. The review was conducted in accordance with PRISMA guidelines, and study quality was assessed using Cochrane risk-of-bias tools. Thirteen studies were included. One study in older adults reported that COL supplementation at 60 g/day for 8 weeks significantly reduced body fat percentage by 0.4% (p < 0.05). Another study found that COL supplementation at 10 g/day combined with plant proteins for 12 weeks significantly attenuated the increase in leg tissue fat percentage compared with placebo (PLA) (0.48 ± 1.29% vs. 1.12 ± 1.27%, respectively; p < 0.05). Changes in blood lipid profiles were reported in two studies. In individuals with type 2 diabetes, COL supplementation at 10 g/day for 4 weeks significantly reduced total cholesterol (TC) and triglyceride levels in both men and women, by 8.27% vs. 7.62% and 11.96% vs. 21.46%, respectively. In another study involving older adults, COL supplementation at 30 g/day for 12 weeks significantly reduced TC (5.88 to 5.38 mmol/L) and low-density lipoprotein cholesterol (LDL-C) (3.68 to 3.28 mmol/L) compared with PLA. Owing to substantial methodological heterogeneity and inconsistent findings, further randomized, double-blind trials are needed in larger groups of overweight or obese participants, with intervention periods lasting at least six months. Future studies should use a standardized COL dose of 20–25 g/day, controlled caloric deficits, and a four-arm design comparing placebo and COL under normocaloric and energy-restricted dietary conditions. Assessments should include blood metabolic biomarkers, body composition measured by dual-energy X-ray absorptiometry, gut microbiome composition, and fecal short-chain fatty acids to determine whether any observed benefits are attributable to COL alone or to its combination with dietary intervention. 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

Akkermansia muciniphila (A. muciniphila) is a bacterium that breaks down mucus and is studied for its effects on metabolism and the immune system. Studies show that it affects Alzheimer’s disease (AD) by protecting the gut barrier, reducing inflammation, and influencing communication between the immune system, the brain, and mitochondria. This review summarizes mechanistic, preclinical, and translational evidence connecting A. muciniphila to AD, including products such as short-chain fatty acids (SCFAs), and structural or secreted proteins including Amuc_1100 and extracellular vesicles (AmEVs). We also discuss differences between bacterial strains, differences in research methods, and findings that change under different conditions, which make the results harder to interpret. Animal studies suggest neuroprotective effects, but clinical evidence is still limited. Clinical use will need human studies at the strain level, confirmation in humanized models, and early trials using biomarkers to test safety and causal effects. Full article

Background/Objectives: The gut microbiome is a critical regulator of host metabolism, immunity, and the gut–brain axis. Exercise is a promising non-pharmacological modulator of microbial ecology, yet human evidence remains heterogeneous and the translational gap persists. This narrative review synthesizes mechanisms, human and animal evidence, and future directions for the exercise–gut microbiome axis. Methods: PubMed, Scopus, Web of Science, and SID were searched for articles published between January 2000 and February 2025. Keywords included exercise, physical activity, gut microbiome, gut microbiota, short-chain fatty acids, and gut–muscle axis. From 218 initial records, 89 original studies (47 human, 42 animal) met inclusion criteria and were critically appraised. Results: Exercise modulates the gut microbiome via splanchnic hypoperfusion, hyperthermia, altered transit time, and immune-mediated barrier regulation. Moderate-intensity continuous training consistently increases alpha diversity and enriches butyrate-producing taxa (Faecalibacterium prausnitzii, Roseburia hominis) and mucin-degrading Akkermansia muciniphila. High-intensity interval training transiently increases intestinal permeability in untrained individuals but, following adaptation, stimulates butyrate production via lactate cross-feeding metabolism—a recent breakthrough. Effects are transient and reversible upon detraining. Animal models establish causality through fecal microbiota transplantation; human randomized controlled trials demonstrate modest, intensity-dependent, and highly individualistic responses. Emerging evidence supports the gut–muscle axis in sarcopenia and personalized exercise prescription guided by microbiome profiling. Conclusion: Exercise shows promise as a low-cost modulator of the gut microbiome for enriching health-associated taxa and improving metabolic outcomes. Definitive evidence linking exercise-induced microbial shifts to enhanced athletic performance in humans remains lacking. Future research requires diet-controlled randomized controlled trials with ≥12-week interventions, shotgun metagenomics, and mechanistic validation of the gut–muscle axis in humans. Full article

Diet is a modifiable factor that influences multiple pathways relevant to hematologic malignancy, including systemic inflammation, immune cell activity, gut microbiota composition, and cancer cell metabolism. Translation of preclinical findings into clinical practice for hematologic malignancies remains nascent, although momentum is building to evaluate dietary interventions as a component of supportive and disease-modifying care. This review examines the mechanistic rationale for dietary interventions across the spectrum of clonal hematologic disorders and synthesizes current clinical evidence. Anti-inflammatory dietary patterns, particularly the Mediterranean diet, have demonstrated reductions in pro-inflammatory cytokines and may attenuate the inflammatory milieu that fuels clonal expansion. Obesity, which elevates the risk of developing hematologic malignancies and worsens clinical outcomes in diseases such as acute lymphoblastic leukemia (ALL) and acute myeloid leukemia, may be addressed through calorie-restricted, low-fat, or plant-based dietary strategies. Gut microbiota dysbiosis induced by chemotherapy represents another target, with high-fiber and plant-based diets showing promise in restoring microbial diversity and potentially enhancing treatment efficacy. Early-phase clinical trials in multiple myeloma, acute lymphoblastic leukemia, and myeloproliferative neoplasms have established feasibility and yielded preliminary signals warranting larger confirmatory studies. Larger, rigorously designed trials are needed to establish dietary interventions as legitimate therapeutic tools in the management of hematologic malignancies. Full article

Background: Gestational diabetes mellitus (GDM) is an increasingly prevalent metabolic disorder of pregnancy. Beyond its well-established metabolic consequences, growing evidence suggests that exposure to maternal hyperglycemia during fetal life may influence immune system development and increase the risk of allergic diseases in offspring. Objective: This study aimed to systematically review the available evidence on the association between gestational diabetes mellitus and the development of allergic diseases in children, with particular emphasis on immunological mechanisms and the role of early-life gut microbiota. Methods: A systematic review was conducted using the PubMed and Scopus databases. Original human and animal studies, including cohort, case–control, cross-sectional, and clinical studies, were eligible for inclusion. Study selection followed PRISMA guidelines and was performed independently by three reviewers. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) Critical Appraisal Tools. Results: The included studies suggest that children born to mothers with GDM may have an increased risk of developing allergic diseases, particularly atopic dermatitis, food allergy, allergic rhinitis, and urticaria. Associations with childhood asthma were less consistent and appeared to depend on maternal body mass index, glycemic control, and duration of follow-up. Evidence suggests that maternal hyperglycemia may disrupt fetal immune programming through chronic low-grade inflammation, oxidative stress, altered cytokine profiles, and impaired regulatory T-cell development. Additionally, GDM has been associated with early alterations in neonatal gut microbiota composition and metabolic pathways, which may further contribute to immune dysregulation and increased susceptibility to allergic diseases. Importantly, effective metabolic control during pregnancy was associated with a lower risk of adverse allergic outcomes in offspring. Conclusions: GDM may represent an important prenatal exposure associated with altered immune maturation and a higher risk of allergic diseases in offspring. Early metabolic disturbances, immune dysregulation, and alterations in gut microbiota appear to be key mechanisms underlying this association. Optimizing glycemic control during pregnancy and implementing early-life preventive strategies may reduce the long-term burden of allergic diseases. Further well-designed longitudinal and mechanistic studies are required to clarify causal pathways and identify effective preventive interventions. Full article

Food allergy is a chronic immune-mediated condition that must be understood not only as a biological disorder but also as a biopsychosocial condition with significant psychological and neurodevelopmental consequences. Beyond the management of acute allergic reactions, individuals living with food allergy experience ongoing threat appraisal, dietary restriction, and social constraints, shaping emotional regulation, cognition, and wellbeing. This review adopts a psychology-led biopsychosocial and neuropsychological framework to examine the mechanisms through which immune activation and food avoidance influence psychological functioning. Drawing on medical psychology, psychoneuroimmunology, and gut–brain research, we explore how threat perception, interoceptive awareness, learning processes, stress physiology, and family context interact to shape emotional and behavioural responses to food allergy. Particular attention is given to the role of risk perception, vigilance, and learned avoidance in driving anxiety and reduced quality of life. By integrating evidence across psychological and biological domains, this review argues for a more comprehensive model of food allergy that recognises the cumulative emotional and neuropsychological burden associated with living with chronic dietary risk. Greater integration of psychological perspectives within allergy care may help support adaptive coping, reduce unnecessary restriction, and improve quality-of-life outcomes for individuals and families affected by food allergy. Full article

Background: Macrophages were long regarded as passive executors of erythrophagocytosis responsible for systemic iron recycling. However, increasing evidence has reframed them as immunometabolic hubs that sense diverse environmental cues to modulate systemic iron homeostasis. Main body: This review examines the molecular architecture underlying macrophage iron metabolism and outlines how iron metabolic processes are dynamically regulated across spatial and temporal scales through the integration of mechanotransductive, mitochondrial, and epigenetic signaling pathways. Across disease contexts, macrophage iron handling displays marked heterogeneity, exemplified by contact-dependent iron transfer in tumors and ferroptosis-driven instability in cardiovascular disease. In cardiovascular pathologies, iron overload is associated with enhanced ferroptosis-related cascades that contribute to atherosclerotic plaque instability. Furthermore, at mucosal interfaces, host–pathogen competition over nutritional immunity highlights epigenetic strategies by which pathogens perturb host iron machinery. Conclusions: Linking these mechanistic insights to clinical translation, emerging therapeutic strategies are discussed that move beyond non-specific systemic iron chelation toward more targeted interventions. These include engineering macrophages for targeted drug delivery, exploiting nanomedicine-based redox modulation to influence macrophage phenotypes, and non-invasive regulation via the gut microbiota–epigenetic axis. Collectively, elucidating macrophage iron metabolic networks provides a conceptual framework for the development of precision approaches to inflammatory, metabolic, and malignant diseases. Full article

The effects of dietary tributyrin (TB) supplementation in juvenile Litopenaeus vannamei fed a high-soybean-meal diet were evaluated in an 8-week growth trial. The basal diet contained 24% fishmeal, while the experimental diet was supplemented with TB at 2.24 g kg⁻¹. Tanks were randomly assigned each dietary treatment in triplicate, with each tank consisting of 50 shrimp with 1.66 ± 0.24 g as an initial weight. Shrimp fed with the control diet exhibited the lowest growth, whereas supplementation with TB improved growth performance. For ADCs (apparent digestibility coefficients), non-significant variances were detected in dry matter, crude lipid, and crude protein; however, ash was highly significant in the control (0.00) group. Moreover, gross energy was highly significant in the TB-supplemented group. Whole-body and dorsal muscle proximate composition showed no substantial differences (p > 0.05), except that ash was highly significant in the whole body for the control diet, while lipids were highly significant in dorsal muscles for the TB diet. The biochemical, antioxidant and immune parameters of the hepatopancreas and hemolymph showed non-significant changes in both groups, except total protein (TP) and triglycerides (TGs) were highly significant in the TB-supplemented group in both the hemolymph and hepatopancreas. Conversely, malondialdehyde (MDA) was highly significant in the control group in the hemolymph. Non-significant changes were detected among treatment groups for most of the textural properties of the shrimp; however, hardness was highly significant in the control group. The TB group showed a highly significantly larger intestinal villus height (p < 0.05). Compared with shrimp fed a control diet, those receiving the tributyrin-supplemented diet showed improved gut morphology and structure, as well as enhanced histological characteristics of the hepatopancreas. Overall, TB supplementation significantly enhanced the specific growth rate, weight gain rate, final body weight, and intestinal morphology. Although some indicators were not affected, these results indicate that TB has potential as a valuable dietary supplement in aquaculture. Full article

Background: The gut microbiome contributes to immune–metabolic homeostasis through microbial-derived metabolites such as short-chain fatty acids (SCFAs). However, whether early disruption of the gut microbiome–SCFA axis identifies impaired clinical recovery in pediatric intensive care unit (PICU) patients remains unclear. Biological markers reflecting the recovery trajectory beyond conventional severity scores remain poorly characterized in pediatric critical illness. We therefore investigated whether early microbiome disruption and fecal SCFA profiles are associated with recovery trajectory in critically ill children. Methods: In this prospective observational study (N = 26), fecal samples were collected within 5 days of PICU admission. Microbial diversity was assessed using 16S rRNA gene sequencing (Shannon index), and fecal SCFAs were quantified using targeted metabolomics. Disease severity was assessed using the Pediatric Index of Mortality 3 (PIM3). The primary outcome was PICU length of stay (LOS) as a pragmatic indicator of metabolic and functional recovery trajectory in critically ill children. Results: Younger age and higher disease severity showed a trend toward reduced microbial diversity (β = 0.066, p = 0.089, and β = −0.054, p = 0.089). Early loss of gut microbial diversity was associated with reduced fecal butyric acid concentrations (r = 0.440, p = 0.024). Importantly, lower microbial diversity in the early sampling window showed a significant inverse correlation with PICU LOS (ρ = −0.428, p = 0.029), whereas fecal butyric acid alone was not directly associated with LOS (p = 0.321). In multivariable regression models adjusting for age, disease severity, and clinical exposures, microbial diversity showed a consistent inverse association with PICU LOS, although statistical significance was not reached. Conclusions: Early disruption of the gut microbiome–SCFA axis, characterized by reduced microbial diversity and lower fecal butyrate, showed trend-level associations with delayed clinical recovery in this pilot cohort. Gut microbial ecosystem integrity may serve as a biologically relevant marker of recovery trajectory beyond conventional severity scoring. Full article

Neurodevelopment is a dynamic and multifactorial process, critical in the early stages of life, involving the formation of neural networks, the establishment of synapses, and the maturation of cognitive, social and emotional circuits. In this context, the gut microbiome emerges as an essential regulator of neurodevelopment, exerting influences through multiple biochemical and immunological mechanisms that define the “gut-brain axis”. The microbiota modulates neurodevelopment by regulating neurotransmitters (serotonin, dopamine, GABA), the production of microbial metabolites, including short-chain fatty acids, the modulation of inflammatory cytokines, and vagal signaling to the central nervous system. Recent evidence highlights the role of microbiota in modulating microglia, synaptogenesis, dendritic maturation, and neuronal plasticity, emphasizing how these processes are influenced by microbial activity rather than providing a comprehensive treatise on plasticity itself. Gut microbiota disturbances, or dysbiosis, have been associated with various neuropsychiatric and neurodevelopmental disorders, contributing to cognitive, behavioral, and emotional dysfunctions. This article summarizes, in a narrative manner, the main dysbiosis patterns identified in these disorders and the biological mechanisms by which the microbiome influences neuronal development and function, including immune–neuronal interactions, metabolomic modulation, and neuroendocrine signaling. Finally, emerging directions of intervention aimed at adjusting the microbial profile, such as dietary adjustment, the use of probiotics, prebiotics, symbiotics, and fecal microbiota transplantation, are presented with the aim of positively influencing neurodevelopment and preventing or ameliorating associated dysfunctions. This review emphasizes the need for longitudinal, rigorous, and controlled clinical trials to validate the efficacy of microbiota modulation strategies and to substantiate their integration into individualized pediatric management protocols. Full article

The gut microbiota plays a crucial role in human metabolism, and disruptions to its composition, particularly reductions in bacterial diversity, have been increasingly associated with the development of metabolic syndrome (MetS). MetS encompasses a constellation of interrelated metabolic risk factors, including central obesity, insulin resistance, dyslipidemia, and hypertension, which collectively elevate the risk of cardiovascular and cerebrovascular disease. A comprehensive understanding of the mechanisms underlying MetS is therefore critical for the development of effective preventive and therapeutic strategies. Complex interactions between the gut microbiota and host metabolic pathways are mediated by multiple factors, including microbial metabolites, inflammatory signaling, and host immune responses. This narrative review characterizes the clinical manifestations of MetS and alterations in gut microbiota composition, characterized by an overrepresentation of potentially pathogenic taxa and a concomitant decline in beneficial microbial species. In addition, we discuss current and emerging approaches to microbiota modulation, including prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation, and evaluate their potential roles in the prevention and management of MetS. We identify critical evidence gaps and propose research priorities for evidence-based clinical strategies for MetS management and prevention. Full article

Once written off as nothing more than a waste product of glycolysis, lactic acid is now seen as a key signaling molecule that operates across a wide range of physiological and pathological processes, from immune regulation and tumor metabolism to neural function. But its role goes beyond energy metabolism and cell signaling. Recent studies have uncovered a new type of post-translational modification called histone lactylation, in which lactate itself provides the lactoyl group attached to lysine residues on histones. This modification directly ties a cell’s metabolic state to the epigenetic control of gene expression. For example, histone lactylation helps shift macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype by fine-tuning gene transcription. In this review, we walk through the discovery and biochemical foundation of histone lactylation; discuss the likely writer and eraser enzymes that manage its dynamic changes; and highlight recent advances in understanding the role of this modification in inflammation, tumorigenesis, neurological disorders, and interactions with gut microbes. We also lay out key unanswered questions and consider why targeting protein lactylation might open up new therapeutic possibilities. Full article

The gut microbiota, often referred to as the “forgotten organ”, plays an indispensable role in maintaining host physiological metabolism, immune function, and nutrient absorption. Moreover, the gut microbiome serves as a critical biological barrier against viral infections and is increasingly recognized as a potential target to augment antiviral therapies. Recent studies have revealed that microbial ligands and metabolites derived from the gut microbiota are pivotal in modulating respiratory immune responses, providing compelling evidence of the complex interaction network between microorganisms and the host, particularly the signaling pathways linking the gut to distal organs such as the lungs. This review examines the communication and regulatory mechanisms between the gut microbiota and pulmonary mucosal surfaces during influenza virus infection, emphasizing how gut microbial communities and probiotics influence host immune responses, promote the production of immune-related molecules, and enhance antiviral defenses. The aim is to provide comprehensive insights into the gut–lung axis and its implications for respiratory health. Full article