Search Results (509)

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, frequently arising from chronic inflammatory states such as metabolic dysfunction-associated steatotic liver disease and cirrhosis. While extensive epidemiological data demonstrate a strong, dose-dependent inverse association between habitual coffee consumption and HCC incidence, the underlying molecular causality remains incompletely understood. In this comprehensive review, we elucidate the “Coffee Paradox” through the lens of nutriepigenomics. We demonstrate how coffee-derived bioactives—specifically chlorogenic acids, diterpenes, and microbially derived short-chain fatty acids—function as a coordinated epigenetic defense system. These compounds actively inhibit DNA methyltransferases, serve as endogenous histone deacetylase inhibitors via the gut–liver axis, and induce post-transcriptional, tumor-suppressive microRNA networks to halt oncogenic progression. However, to provide a critical and balanced perspective, we also address significant translational challenges. We evaluate conflicting null associations from recent Mendelian randomization studies and highlight the profound variability introduced by specific brewing methods, roasting profiles, and individual pharmacogenomics (e.g., CYP1A2 polymorphisms). Finally, we outline the future of precision hepatology, emphasizing the critical transition from observational epidemiology to clinical application via the utilization of circulating exosomal microRNAs as dynamic liquid biopsies and the development of standardized epi-nutraceuticals. Ultimately, this multi-layered epigenetic framework provides a robust foundation for integrating targeted dietary interventions into the primary prevention of HCC. Full article

The global demand for Salvia miltiorrhiza Bunge in the botanical medicine market is steadily increasing. However, its production has long relied on asexual root propagation, making it highly susceptible to germplasm degradation. Transitioning to seed reproduction offers the advantage of genetic renewal, yet it is constrained by unstable seed vigor and slow seedling growth. In the present study, comprehensive physiological and microbiome analyses of S. miltiorrhiza seeds from 14 regions across 7 provinces in China were conducted to elucidate the association between the seed microbiome and vigor, and to identify plant growth-promoting (PGP) strains. The results demonstrated: (1) Seed physical traits and germination characteristics varied significantly across geographic origins. Seed vigor, exhibiting the highest coefficient of variation, served as a key parameter reflecting germination quality. (2) High-vigor seeds harbored distinct microbial communities characterized by higher diversity indices, greater network complexity, and the significant enrichment of potentially beneficial bacteria (e.g., Pseudomonas). (3) Through correlation-directed screening of isolated pure cultures, Pseudomonas mendocina P-6 and Enterobacter ludwigii BM-12 were identified as exhibiting robust, multi-trait PGP capacity. In planta validation showed that these two strains significantly promoted the growth of 1-month-old S. miltiorrhiza seedlings, increasing total fresh weight by 33.9–71.3%. This study reveals the microecological drivers of seed vigor and provides candidate strains for inoculant development, thereby supporting the sustainable, seed-based propagation of S. miltiorrhiza. Full article

To investigate how steam-explosion pretreatment affects humification during sawdust composting, an aerobic composting experiment was conducted using sawdust, chicken manure, and spent mushroom substrate as feedstocks. Two treatments were established—a steam-explosion-pretreated sawdust group (SEW) and an untreated sawdust control (CK)—each with three replicate reactors. Samples were collected dynamically at five key composting stages (initial, heating, thermophilic, cooling, and maturation) for physicochemical, enzymatic, and microbial community analyses. Linear mixed-effects model analysis revealed that enzyme activities were significantly affected by treatment, composting time, and their interaction. SEW significantly enhanced cellulase and polyphenol oxidase activities, and increased laccase and peroxidase activities at specific stages. Compared with CK (humic substances, 75.30 g/kg), SEW promoted higher humic substance accumulation (120.80 g/kg) and altered the dynamics of dissolved organic carbon. Microbial co-occurrence networks in SEW (50 nodes, 602 edges) were more complex than CK (49 nodes, 464 edges), indicating tighter microbial interactions. Path analysis revealed that HS in CK was mainly influenced by DOC and temperature, while HS in SEW was associated with enzyme activities, microbial diversity, and Pseudogracilibacillus. These results suggest that steam-explosion pretreatment enhances substrate transformation and humic substance formation during composting. Full article

Triplophysa yarkandensis (Cypriniformes: Nemacheilidae), a rare endemic fish in the Tarim River Basin, Xinjiang, China, plays a pivotal role in maintaining the stability of plateau saline–alkaline aquatic ecosystems, yet its survival is increasingly threatened by habitat salinization. However, the multi-dimensional synergistic adaptation mechanisms linking its phenotypic variation, intestinal structure, and associated microbial communities to extreme saline–alkaline stress remain poorly understood. In this study, we innovatively integrated morphological/intestinal histological characterization, 16S rRNA gene sequencing, and microbial ecological analyses (co-occurrence networks and assembly processes) to systematically decode its adaptive strategies. Results revealed that T. yarkandensis exhibits a streamlined body shape, morphological variability, and elongated intestinal villi that may support locomotion and nutrient/ion uptake under osmotic stress. Its gut exerts a stringent selective filter, driving distinct differentiation between water and gut microbial communities—with gut-enriched core taxa (Aurantimicrobium and Aestuariivirga) and functional pathways (unsaturated fatty acid biosynthesis and ABC transporters) specialized for osmoregulation. Notably, the water microbial assembly is dominated by stochastic processes, while the gut assembly relies on host-driven deterministic selection, forming a habitat-specific adaptive pattern. These findings uncover the synergistic adaptation system of host phenotype and gut microbiota for survival in extreme saline–alkaline habitats, advancing our understanding of fish–microbe co-evolution in extreme ecosystems and providing critical theoretical support for the conservation of rare plateau fish, as well as guidance for the utilization of saline–alkaline water resources in aquaculture. Full article

Phosphorus (P) limitation is prevalent in terrestrial ecosystems. Plants can improve soil P availability through the exudation of organic acids and symbiotic interactions with microorganisms. However, associations between different plant functional groups and phosphorus cycling in P limited karst ecosystems remain poorly understood. To investigate this, the exudation rates of oxalic, citric and acetic acids from fine roots, the contents of carbon, nitrogen, and P in leaves and fine roots, and the contents of oxalic, citric and acetic acids, total P, available P (AP), and microbial biomass P in rhizosphere soils were measured across different plant functional groups in a karst ecosystem in southwestern China. Additionally, the activities of acid and alkaline phosphatases were also analyzed, as well as the relative abundance, community structure, diversity, and co-occurrence network patterns of arbuscular mycorrhizal fungi (AMF) and alkaline phosphatase-encoding (phoD) gene-harboring bacteria. The results showed that both the exudation rates and the contents of organic acids and AP were highest in the tree group, followed by the shrub and grass groups. The AP content of the legume group was significantly higher than that of the non-legume group. The exudation rates of oxalic acid were significantly greater than those of citric and acetic acids. AMF diversities were highest in the shrub and legume groups. The diversities of phoD-harboring bacteria decreased from the tree group to the shrub group and then to the grass group, yet there were no significant differences between the legume and non-legume groups. The communities of both AMF and phoD-harboring bacteria exhibited significant differences among these plant functional groups. The prevalent genera of phoD-harboring bacteria across all groups were Pseudomonas and Halomonas, with Halomonas being particularly prevalent in the legume group. The AMF community was dominated by Glomus, which attained its highest relative abundance in the tree and legume groups. Furthermore, the increased exudation rate and content of oxalic acid were associated with higher relative abundances of Glomus in AMF and Pseudomonas and Bacillus among phoD-harboring bacteria. Structural Equation Model (SEM) analysis demonstrated that plant-exuded organic acids, especially oxalic acid, were positively associated with P availability indirectly through their linkages with the diversity and abundance of AMF and phoD-harboring bacteria. The crucial role of oxalic acid was particularly prominent in the tree and legume groups. Our findings suggest that screening AMF and phoD-harboring bacteria with highly efficient P transformation activity and inoculating them into the rhizosphere of plants with high oxalic acid exudation could help improve plant resilience to P limitation and support sustainable restoration in karst ecosystems. Full article

The prized wild mushroom Tricholoma matsutake maintains distinctive microbiota within its dominant zone; however, the spatial and seasonal reorganization of microbiota from taxonomic and functional perspectives remain poorly understood. High-throughput amplicon sequencing was performed in warming (March–June) and cooling (September–December) seasons to compare microbial communities among T. matsutake-dominant (present, visible mycelium) and -nondominant soils (transition, adjacent with present; control, distant from fairy ring). Fungal and bacterial community structures in T. matsutake-dominant soils were obviously distinct (ANOSIM, R > 0.6, p = 0.001), and bacterial communities exhibited clear seasonal separation. The relative abundances of Ascomycota and Mortierellomycota significantly reduced, whereas mycorrhiza-helper bacteria, including Paenibacillus, Bacillus, and Cohnella, were enriched. Functional predictions suggested that the potential expression of cofactor and vitamin biosynthesis, nutrient degradation, and inorganic nutrient metabolism pathways may be enriched in T. matsutake-dominant soil. During the fruiting period, the expression of the predicted amino acid biosynthesis pathway may be reduced, whereas that of the cofactor/carrier/vitamin biosynthesis pathway may be enriched. Our findings suggest that T. matsutake dominance could be associated with the spatial and seasonal restructuring of soil microbial communities, potentially leading to the formation of functionally interconnected microbial networks. Therefore, this study predicts hidden ecological insights that, once biochemically validated, may be used to develop important strategies for the sustainable conservation and artificial cultivation of T. matsutake. Full article

Background: Root-knot nematodes (RKNs) are destructive parasites affecting both agricultural and natural plants. Fagopyrum tataricum, a phenolic-rich edible and medicinal plant, has antidiabetic, anti-inflammatory, and anticancer properties, yet the impact of RKN infection on its rhizosphere microbiome remains unclear. Methods: We employed full-length 16S rRNA gene sequencing (FL16S) to profile bacterial communities in the rhizosphere of healthy and RKN-infected F. tataricum plants. Results: FL16S classified 78.41% of operational taxonomic units (OTUs) at the genus level and 69.18% at the species level. Healthy plants showed higher richness, diversity, and evenness, while principal co-ordinate analysis (PCoA) and PERMANOVA indicated significant RKN-associated shifts in community composition. Dominant phyla included Bacteroidota, Proteobacteria, Patescibacteria, Verrucomicrobiota, Actinobacteriota, Acidobacteriota, and Chloroflexi, with Abditibacteriota enriched in healthy and Acidobacteriota in diseased rhizospheres. At the OTU level, 66 differentially abundant taxa were identified, including nine hub OTUs in healthy plants, suggesting keystone roles in network stability. Network analyses revealed reduced diversity, interactions, and altered intra- and inter-phylum dynamics under RKN infection. Conclusions: These findings provide insight into rhizosphere microbial responses to RKN parasitism in F. tataricum and identify potential microbial biomarkers and biocontrol targets, supporting microbiome-based management strategies. Full article

Background and Objectives: Gastric cancer remains a leading cause of cancer-related mortality worldwide and develops through complex interactions between environmental factors, microbial dysbiosis, and host molecular pathways. Although Helicobacter pylori infection is a well-established risk factor, emerging evidence suggests that broader alterations in the gastric microbiome may also contribute to carcinogenesis. However, the associations between gastric cancer-associated microbial taxa and host gene expression profiles remain insufficiently characterized. This study aimed to identify host gene signatures associated with gastric cancer-related microbial taxa through a descriptive analysis integrating microbiome-derived taxa with transcriptome data. Materials and Methods: Microbial taxa associated with gastric cancer were systematically retrieved from the Disbiome database. Taxon set enrichment analysis (TSEA) was performed using the MicrobiomeAnalyst platform to identify host genes associated with gastric cancer-associated taxa. Importantly, TSEA relies on healthy reference data from the Human Microbiome Project and does not establish gastric cancer-specific interactions or causal relationships. Gene expression levels were subsequently evaluated using The Cancer Genome Atlas (TCGA) PanCancer stomach adenocarcinoma (STAD) dataset by comparing tumor and matched normal gastric tissues. Gene interaction network and transcription factor (TF) enrichment analyses were conducted to explore predicted regulatory relationships. Results: Among 64 microbial taxa associated with gastric cancer, 43 were reported as elevated. After removing overlapping taxa across studies, 37 elevated and 21 reduced taxa were retained for analysis. TSEA identified 11 host genes associated with gastric cancer-related microbial taxa. Transcriptomic analysis demonstrated significant downregulation of DPP6 and DLG2, while KDM4D, USP34, and VDR were significantly upregulated in gastric cancer tissues compared with normal controls. Network and TF enrichment analyses revealed predicted co-expression and co-localization patterns among these genes, suggesting their potential involvement in immune-related processes, epigenetic regulation, and cellular organization. Conclusions: This descriptive study identifies distinct host gene expression signatures associated with gastric cancer-associated microbial dysbiosis. This study is purely associative and hypothesis-generating; no causal or mechanistic inferences are made. TSEA used healthy reference data and therefore does not reflect gastric cancer-specific host–microbe interactions. The findings provide a basis for future hypothesis-driven research but require validation in independent cohorts. Full article

Schizopygopsis younghusbandi is an endemic and economically important fish in the Qinghai-Xizang Plateau, but its aquaculture is limited by harsh environmental conditions and incomplete understanding of host–microbiome–environment interactions. This study applied metagenomic sequencing to examine how different culture environments affect growth, water microbial communities, and gut microbiome network stability. Three-year-old juveniles (initial body weight 50.57 ± 1.88 g) were reared for 90 days in five systems: conventional pond (P), wetland (WL), concrete tank (G), river (R), and recirculating aquaculture system (RC). No significant differences in initial body weight or length were observed among groups (p > 0.05). Fish in the RC system achieved the highest final body weight, weight gain rate, and specific growth rate (p < 0.05), while survival rates were highest in the river and RC groups and lowest in ponds (p < 0.05). Microbial diversity and community composition differed significantly among culture modes, with bacterial and protozoan communities showing the strongest environmental responsiveness. Co-occurrence network analyses revealed that RC and G systems exhibited higher network complexity, density, and proportion of positive correlations, reflecting enhanced microbial interaction and ecological stability, whereas the WL system showed reduced network connectivity. Correlation analysis indicated that bacterial abundance was positively associated with total nitrogen, total phosphorus, and dissolved oxygen (p < 0.05), highlighting environmental regulation of microbial assemblages. Overall, the aquaculture environment shapes gut microbial networks, which closely relate to growth performance. Recirculating aquaculture systems can mitigate growth limitations in plateau fish by stabilizing the environment and reinforcing gut microbial communities, providing a sustainable strategy for high-altitude aquaculture development. Full article

Aquatic–terrestrial ecotones are highly dynamic biogeochemical hotspots where hydrological fluctuations profoundly influence microbial community structure and ecosystem functioning. However, the mechanisms underlying microbial community responses across hydrological gradients remain insufficiently understood. In this study, 16S rRNA gene sequencing was used to comparatively analyze bacterial communities in the waterward and landward zones of the drawdown area of the Danjiangkou Reservoir. The results showed that bacterial community composition differed significantly between the two zones, and waterlogging markedly increased bacterial α-diversity. Community variation was primarily associated with key environmental factors, including total phosphorus (TP), soil moisture content (SMC), and nitrate nitrogen (NO₃⁻-N). Compared with the landward zone, stochastic processes contributed more to community assembly in the waterward zone, which also exhibited higher network complexity and topological stability. In addition, several keystone taxa were identified, suggesting their potential roles in maintaining network structure and ecological stability. Functional prediction further revealed distinct metabolic potentials between zones, with enhanced anaerobic and redox-related functions in the waterward zone and predominantly aerobic metabolism in the landward zone. These findings suggest that hydrological fluctuations reshape bacterial community structure and potential ecological functions by jointly regulating water availability and nutrient dynamics. This study provides new insights into microbial ecological processes in reservoir riparian zones and offers a scientific basis for the management of aquatic–terrestrial ecotone ecosystems. Full article

Ticks harbor complex microbial communities composed of symbionts, commensals, and tick-borne pathogens (TBPs). Together, these microorganisms form the tick holobiont. Within this system, the tick’s physiological architecture structures microbial communities by distributing microorganisms across distinct tissues. This compartmentalization creates spatially distinct ecological niches, which in turn shape how microbial communities assemble and interact. In this review, we integrate ecological theory with current knowledge of tick microbiome research to examine how pathogen–pathogen and pathogen–microbiome interactions emerge within these tissue-structured microbial communities. We first outline how baseline ecological filters, including tick species, developmental stage, tissue identity, vertical transmission, and environmental context, shape the microbiome configuration through community assembly processes. We then examined how TBPs, as high-impact colonizers, can further modify microbial networks by altering host-mediated selective pressures, influencing interaction topology, and reshaping community stability. Based on these observations, we propose a dual selective pressure framework in which (i) baseline ecological structuring processes and (ii) pathogen-associated selective pressures interact to determine the microbial network configuration and functional outcomes within the tick holobiont. These interacting forces may drive shifts in diversity, modularity, keystone taxa emergence, and network resilience, ultimately influencing vector competence. This review frames the microbial communities within the tick holobiont as spatially structured ecological systems shaped by multilevel selective pressures. This conceptual foundation provides a coherent framework for understanding microbial interactions in arthropod vectors and highlights avenues for mechanistic research and microbiome-based strategies to mitigate tick-borne diseases. Full article

The microbiota–gut–brain axis (MGBA) is a complex bidirectional communication network integrating neural, endocrine, immune, and metabolic pathways linking intestinal microbiota to central nervous system function. Increasing evidence indicates that microbiota-derived signals are critical regulators of neurodevelopment and may contribute to vulnerability to neurodegenerative disorders across the lifespan. In this narrative review, we synthesize experimental and clinical evidence to define the key biological mechanisms underlying microbiota–brain interactions. Converging data indicate that immune activation, barrier dysfunction, and microbial metabolites, particularly short-chain fatty acids and tryptophan-derived compounds, represent central mediators linking gut dysbiosis to neuroinflammatory and neurodegenerative processes. Early-life microbial perturbations, driven by factors such as antibiotic exposure, diet, and psychosocial stress, appear to induce long-term immunometabolic programming that may increase susceptibility to neurological disorders later in life. Clinical studies consistently associate dysbiosis with neurodevelopmental conditions and major neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease; however, causal relationships remain incompletely defined due to heterogeneity and the predominance of observational data. Overall, the available evidence supports a lifespan model in which microbiota-driven immune and metabolic dysregulation contributes to both early neurodevelopmental trajectories and late-life neurodegeneration. While microbiome-based biomarkers and therapeutic strategies show promise, their clinical translation requires validation in longitudinal and interventional studies. Full article

Astragalus membranaceus is an important perennial medicinal plant whose roots constitute its primary medicinal organ; however, its cultivation is severely constrained by root rot caused by Fusarium oxysporum. This study aimed to characterize differences in the rhizosphere microbiome between healthy and diseased plants, identify antagonistic microorganisms from healthy rhizosphere soils, and investigate their suppressive effects on F. oxysporum and the associated host metabolic responses. High-throughput sequencing was used to compare bacterial and fungal communities in the rhizospheres of healthy and diseased plants. Microorganisms were isolated from healthy rhizosphere soils and screened for antagonistic activity against F. oxysporum, followed by validation in pot experiments. Metabolomic analysis was further conducted to assess host metabolic responses to microbial treatment. Root rot disease significantly altered the dominant composition of rhizosphere microbial communities and was associated with reduced fungal diversity and lower bacterial richness in diseased soils. Co-occurrence network analysis revealed increased complexity in bacterial networks and strengthened positive correlations among fungal taxa under diseased conditions. A total of 81 microbial strains were isolated from healthy rhizosphere soils, among which Penicillium halotolerans exhibited the strongest inhibitory activity against the mycelial growth of F. oxysporum. Pot experiments further supported its suppressive effect on Astragalus root rot. Metabolomic analysis indicated that P. halotolerans treatment was associated with changes in host metabolic profiles related to energy metabolism, defense-associated protein synthesis, and nutrient uptake. Overall, this study identified P. halotolerans as a fungal strain with antagonistic activity against F. oxysporum and provided initial evidence for its association with the suppression of Astragalus root rot. These findings offer candidate microbial resources and mechanistic insights for understanding rhizosphere-associated disease suppression in Astragalus membranaceus. Full article

Inflammatory bowel diseases (IBD), encompassing ulcerative colitis and Crohn’s disease, are associated with an increased risk of colorectal cancer through mechanisms driven by persistent mucosal inflammation. Chronic inflammatory signaling, recurrent epithelial injury, and altered tissue repair processes progressively reshape the intestinal microenvironment, promoting genomic instability and facilitating the development of colitis-associated colorectal cancer (CAC). Despite the well-established link between inflammation and tumorigenesis, only a subset of patients with long-standing IBD develops malignancy, highlighting the complexity of the regulatory effects of the ongoing inflammation on the tumor initiation and progression. This review discusses the multifaceted roles of innate and adaptive immune responses in CAC pathogenesis. Innate immune signaling mediated by pattern recognition receptors, particularly Toll-like receptors, integrates microbial and damage-associated signals to activate inflammatory pathways that regulate epithelial proliferation, survival, and tumor-promoting cytokine networks. Tumor-associated macrophages, neutrophils, and myeloid-derived suppressor cells contribute to carcinogenesis by sustaining chronic inflammation, promoting immunosuppression, and remodeling the tumor microenvironment, although under specific conditions these cells can also support antitumor immunity. Innate lymphocyte subsets participate in immune surveillance and epithelial homeostasis, yet may also amplify inflammatory circuits that influence tumor development. Adaptive immune populations further shape CAC evolution, as CD4⁺ T-helper subsets, CD8⁺ cytotoxic T lymphocytes, regulatory T cells, and B cells exert divergent effects depending on cytokine milieu, immune context, and disease stage. Understanding immune-cell plasticity and the molecular pathways governing these processes may facilitate the identification of predictive biomarkers and the development of targeted immunomodulatory strategies aimed at preventing CAC. Full article

Kopi Luwak (civet coffee), produced from coffee beans recovered from the feces of the Asian palm civet, is among the most expensive specialty coffees worldwide for its unique sensory characteristics. In this study, a multi-omics strategy was employed to elucidate the impact of drying on the microbial community structure and metabolic profiles of Typica Kopi Luwak beans. Drying induced pronounced shifts in the microbial composition, with a significant enrichment of Sphingobacterium and depletion of Streptococcus at the genus level. Concurrently, drying resulted in substantial metabolic remodeling, characterized by increased levels of prenol lipids, fatty acyls, carboxylic acids and derivatives, steroids and steroid derivatives, and organooxygen compounds, accompanied by a marked reduction in flavonoids. KEGG pathway analysis indicated that both altered microbial taxa and metabolites were associated with lipid metabolism, carbohydrate metabolism, amino acid metabolism, and the biosynthesis of other secondary metabolites. Correlation network analysis further revealed the associations between key microbial genera and specific classes of differential metabolites. Collectively, these findings suggest the potential role of post-excretion sun-drying in shaping the microbiome and metabolome of Typica Kopi Luwak beans, offering a scientific basis for controlled or in vitro fermentation strategies to produce coffees with reproducible quality attributes. Full article