搜索结果：Animal microbiome

The main objective of this study was to develop economic selection indices (IM€T) for different dairy production systems (conventional, cheese-oriented, grazing, and organic) by incorporating production, functional, and sustainability-related traits, including enteric methane and feed intake. The potential inclusion of microbiome-derived information was also evaluated in conventional and organic production systems. Relative to a baseline scenario without emphasis on sustainability, the new indices assigned a negative economic weight (1%) to methane emissions. Organic systems, with a larger economic value applied on methane, resulted in a relative weight of 11% for methane production. Feed intake also received a negative economic weight, ranging from 13 to 15% across production systems. The inclusion of sustainability-related traits primarily reduced the economic emphasis on milk and protein yield, with the largest trade-offs observed in organic systems. Longevity also showed a slight reduction in relative economic weight when dry matter intake and methane production were included in the breeding goal. Grazing and organic systems applied a larger weight on longevity, in comparison to IM€T_milk. Predicted genetic responses indicated the greatest expected improvements in reduced methane emissions and enhanced feed efficiency, although these gains were accompanied by lower rates of genetic progress for production traits and longevity. Substituting methane emission and feed intake traits with microbiome-derived information resulted in larger predicted reductions in methane emissions and feed costs, while also improving genetic gain for fat yield. The expected increase in overall genetic gain for profit ranged from 10 to 30% when microbiome information was incorporated. The inclusion of methane emissions and feed intake in selection indices is expected to contribute to shaping the phenotype of future dairy cattle by 2050, emphasizing environmental efficiency alongside traditional productivity traits. Rumen microbiome information showed strong genetic correlations with methane emissions (|r| > 0.74) and feed efficiency (|r| > 0.64), suggesting that it may represent a novel trait for inclusion in dairy breeding programs, although further research is required to validate its utility.

The objective of this experiment was to determine the effect of increasing doses of a phytogenic product based on condensed tannins and spices (CTS) on production performance of lactating dairy cows fed a low protein diet. Eight rumen-cannulated Holstein Friesian dairy cows (140 ± 86 DIM; 39.0 ± 5 kg/d milk yield; mean ± SD), were used in a replicated 4 × 4 Latin Square design experiment with 4-wk periods. Treatments were: 0, 10, 20 and 30 g/d CTS (CTR, 10CTS, 20CTS, and 30CTS, respectively). The grass silage and corn silage-based diet was 55.2% forage, 38.7% NDF, 21.0% total starch, and 14.6% CP. Orthogonal contrasts were used to evaluate the linear and quadratic effect of increasing doses of CTS. Results follow the order: CTR, 10CTS, 20CTS, and 30CTS. Increasing doses of CTS quadratically increased DMI (25.4, 25.9, 26.1, and 25.1 kg/d) and milk yield (37.1, 38.5, 37.7, and 36.3 kg/d), tended to increase fat-and-protein-corrected milk (36.9, 37.6, 37.4, and 36.1 kg/d), and did not affect feed or N efficiency (1.45 ± 0.2 and 32.0 ± 2.3%, respectively). Treatments did not affect milk fat yield (1.48 ± 0.2 kg/d) but increasing doses of CTS increased milk protein yield quadratically (1.22, 1.27, 1.26, and 1.20 kg/d). Intermediate doses of CTS tended to increase de novo fatty acid yield (352, 369, 373, and 356 g/d) and decrease trans-10 C18:1 (4.31, 4.05, 4.05, and 4.24 g/d) compared with CTR and 30CTS. Treatments did not affect milk urea concentration (17.8 ± 1.7 mg/dL) or milk crude protein (3.39 ± 0.2%) or fat (4.06 ± 0.2%) content. Rumen pH and time below rumen pH of 5.8 were not affected by level of CTS supplementation. A treatment by time interaction for rumen ammonia concentration indicated that 20CTS and 30CTS increased ammonia concentration 3 h post-feeding compared with CTR and 10CTS (7.72, 7.94, 13.7, and 14.1 mg/dL). The 10CTS treatment decreased rumen propionate concentration only at 3 h post-feeding compared with the other treatments. Apparent DM and NDF total-tract digestibility were not affected by treatments. Shotgun metagenomics were used to evaluate the impact of CTS supplementation on the solid- and liquid-associated rumen microbiome. Treatment effects were only observed in the solid-associated microbiome. Supplementation of CTS linearly decreased α diversity at both the taxa and functional levels, indicating promotion of a leaner microbial community with higher doses of CTS. Differential abundance analysis identified 26 species with large fold changes, including some species with a high presence of cellulases and significant correlations with phenotypic parameters such as DMI, N efficiency, and milk production. In conclusion, a mixture of CTS affected microbiome and rumen metabolism, increasing fat-and-protein-corrected milk yield when fed at 10 and 20 g/d only. This experiment demonstrates the importance of in vivo dose response experiments with phytogenic products to determine optimum dosage for improved rumen metabolism and performance.

Acute appendicitis is one of the leading causes of surgical emergency hospitalizations. However, the mechanisms leading to the development of appendicitis are poorly understood. Current knowledge suggests an interplay probably led by dietary habits with impact on the microbiome which elicits responses in genetically predisposed individuals. The aim of this review is to assess the nutrition-microbiome-genetic axis associated with acute appendicitis development. The main dietary and nutritional patterns associated to acute appendicitis were low consumption of fiber, water and fish oil, and high levels of saturated fat, salt, processed meat and ultra-processed foods. Collectively, these westernised dietary patterns (WDP) may increase more than 40% the risk of developing acute appendicitis. The WDP are associated to shifts in the microbiome observed in inflamed appendices such as an increased abundance of Fusobacteria together with a lower level of Proteobacteria. While dietary patterns and associated changes in the microbiome may affect a large proportion of the population, only a relatively small percentage develop acute appendicitis suggesting the existence of predisposing genetic factors. Several single nucleotide polymorphisms (SNP) have been identified linking nutrition and microbiome to the genetic background in acute appendicitis. These include the HLA-C SNP rs2524046, associated with coeliac disease, and the variant rs9953918 of NEDD4L (involved in fluid/water mobilisation). A hypothetical allergy model for appendicitis has been recently proposed providing a preliminary groundwork that identifies SNPs in or near IL-6, IL-10 and IL-13, NOD2, CCL22 and CTLA4 involved in the pathogenesis of both inflammatory diseases.

The current study investigated the rumen microbiome of Holstein-Friesian (HF) and Holstein-Friesian × Jersey crossbred (JFX) dairy cows grazing three sward systems; a perennial ryegrass (Lolium perenne) monoculture receiving 250 kg nitrogen (N)/ha/year (PRG), perennial ryegrass with white clover receiving 125 kg N/ha/year (PRGWC), and a multispecies sward, consisting of grasses, clovers and herbs which also received 125 kg N/ha/year (MSS). Rumen fluid samples were collected at two time points, early-August and mid-October. Sward system had no effect on microbiome alpha or beta diversity. The bacterial genera Lachnospira and Prevotellaceae Ga6A1 group were both more abundant in PRGWC and MSS compared with PRG while Pseudoramibacter was more abundant in MSS compared with the other two sward systems. There was no difference in the total abundance of methanogenic archaea between swards (expressed as the ratio of archaea to bacteria) although the Methanosphaera genus was more abundant and the Methanobrevibacter genus was less abundant in PRGWC and MSS compared with PRG. The analysis also revealed a minor difference in microbiome beta diversity between the two dairy cow breeds, reflecting global microbiome configuration differences. Four specific bacterial genera were less abundant in JFX compared with HF. The JFX cows also had slightly greater Methanobrevibacter and slightly lower Methanosphaera abundance compared with the HF cows although total methanogen abundance was not different. The results from this study demonstrate that increasing sward species diversity has limited influence on the core rumen microbiome while crossbreeding HF with Jersey did have some influence. Both factors also altered the composition of the rumen methanogenic community. Further research is required to understand the relationship between these alterations and enteric methane emissions.

The gut microbiome modulates host neuropathology, but the mechanisms linking specific microbial genes and metabolites to host phenotypes remain poorly defined. Here, we identify microbiome-derived vitamin B6 (VB6) and its biosynthesis gene as key regulators of host dopaminergic homeostasis. Metagenomic analysis of fecal samples from Parkinson's disease (PD) patients revealed enrichment of biosynthetic pathways for pyridoxal-5'-phosphate (PLP), the active form of VB6, and tyrosine decarboxylase genes. Using E. coli-C. elegans symbiotic models, we demonstrate that the bacterial pdxJ gene, encoding a key enzyme in de novo VB6 synthesis, is essential in regulating host dopaminergic homeostasis. Colonization with pdxJ-deficient bacteria led to reduced host VB6 and dopamine levels, reduced dopaminergic enzyme activity, and altered motor behavior, which were all rescued by VB6 supplementation. In PD-relevant C. elegans models, bacterial PLP biosynthesis modulated α-synuclein aggregation and behavioral deficits associated with human LRRK2 mutations. In mice, colonization with pdxJ-deficient bacteria reduced serum VB6 levels, decreased tyrosine hydroxylase staining in the substantia nigra, and impaired motor coordination, which were rescued by VB6 supplementation. Overall, our results define a bacterial pdxJ-PLP-dopamine axis that links gut microbial metabolism to host dopaminergic phenotypes and suggest bacterial VB6 biosynthesis as a potential modifier of PD risk and a context-dependent therapeutic target.

Dysglycaemia and periodontal inflammation frequently co-occur during pregnancy, but the microbial mechanisms linking these conditions and their potential for intervention remain incompletely understood. Here, we establish prospective pregnancy cohorts including more than 2500 volunteers and longitudinally profile oral microbiome dynamics in 534 pregnant women. We show that gestational diabetes mellitus (GDM) is associated with a progressive shift from Streptococcus-dominated oral microbiota to Prevotella/Porphyromonas-enriched dysbiosis. In mouse and cellular models, this dysbiotic oral microbiota induces periodontal inflammation, systemic IL-17 and IL-1β responses, suppression of glucagon-like peptide-1 and insulin, and exacerbation of hyperglycemia. Conversely, oral microbiota remodeling through transplantation of Streptococcus-dominated bacteria attenuates periodontal inflammation, restores glucagon-like peptide-1 and insulin levels, and improves glycaemic status in mice. Salivary metabolomics identifies docosahexaenoic acid (DHA) depletion in GDM, and in vitro assays show selective suppression of dysbiosis-associated oral pathogens by DHA. We therefore test topical gingival DHA in a double-blind randomized controlled trial of 40 pregnant women with GDM (ChiCTR2400080741), with probing depth and fasting blood glucose as primary endpoints and gingival index, attachment loss and plaque index as secondary endpoints. Daily gingival DHA application for six weeks improves probing depth and attenuates fasting glucose increase compared with placebo, with median fasting glucose changes from baseline of 0.10 versus 0.27 mmol/L. Together, these findings identify oral dysbiosis as a microbial driver of periodontal and glycaemic deterioration during pregnancy and support oral microbiome modulation as a potential adjunctive strategy for pregnancy care, although the clinical findings remain preliminary and require validation in larger trials with broader glycaemic endpoints.

Rodent models are critical tools in the study of trauma and burn injury, giving mechanistic insights into the unique pathophysiological response and the systemic complications that follow. These models allow researchers to control injury patterns, longitudinally assess immune and metabolic responses, and evaluate therapeutic strategies in ways that are not feasible in human subjects. In this second part of our review, we examine how experimental trauma and burn models have evolved to better replicate the clinical trajectory of critically ill patients, with emphasis on polytrauma, burn injury, and translational relevance. We also highlight the role of the gut microbiome in the pathogenesis of shock within sepsis, trauma, and burn and review how rodent models have been used to investigate dysbiosis and test microbiome-targeted interventions. Although interspecies differences pose translational challenges, ongoing refinements in model selection, injury models, microbiome characterization, and reverse-translational approaches continue to expand the utility of rodent models, allowing researchers to discover vital insights into the complex pathophysiology of these critically ill patients and potential therapeutic targets that guide further investigation.

Skeletal maldevelopment is a significant challenge in broiler production, causing substantial economic losses. Vitamin D₃ (VD₃) plays a critical role in poultry skeletal health, but its optimal dietary inclusion level for medium-growth broilers remains to be determined due to bioavailability differences among forms. This study investigated the effects of dietary VD₃ levels (conventional vs. nano-formulated) on growth performance, bone development, and gut microbiota composition and metabolite profile in broilers. A total of 420 one-day-old male Luhua broilers were randomly assigned to four groups in an 84-day experiment: a control group fed a basal diet, and three treatment groups supplemented with 3,750 IU/kg conventional VD₃ (CVD), 2,500 IU/kg low-dose nano-VD3 (LNVD), or 3,750 IU/kg high-dose nano-VD3 (HNVD). Both CVD and LNVD significantly enhanced average daily gain (ADG) and bone development by improving bone mineral content (BMC) and bone mineral density (BMD), mechanical properties (yield strength, stiffness, Elastic modulus), increasing calcium and ash content, and upregulating osteogenic gene expression (ALP, OC, OPG, BMP1) in the femur and tibia. Compared to CVD, LNVD led to significantly higher ADG from days 1-84 and greater bone indices at days 28, 56 and 84, including fresh bone weight (FBW), fat-free dry weight (FFDW), yield strength, elastic modulus, and calcium and ash content in the femur and tibia. In contrast, HNVD significantly decreased ADG and bone indices. Furthermore, cecal microbiome and metabolomics analysis showed that LNVD increased the relative abundance of beneficial bacteria (e.g., Ligilactobacillus, Muribaculaceae, NK4A214_group) and key metabolites (e.g., butyric acid, kynurenic acid, glutathione), while reducing harmful taxa (e.g., Desulfovibrio, Campylobacter_jejuni) and detrimental metabolites (e.g., leukotriene E3, 4-hydroxy-2-nonenal-Cys-Gly conjugate). These shifts significantly correlated with improved growth and bone traits. In summary, 2,500 IU/kg nano-VD₃ is recommended as the optimal supplementation level for Luhua broilers under the conditions of this study, offering a strategy to enhance VD₃ nutrition and skeletal health.

The ensiling of woody biomass, specifically Caragana korshinskii, presents a substantial challenge for sustainable forage production primarily due to recalcitrant fermentation characteristics. To overcome these limitations, this study investigated the regulatory effects of niche-adapted Lactobacillus strains-originally isolated from oat silage-on the microbial community and biochemical profiles during a 60-day ensiling period. Targeted inoculation, particularly with a mixed lactic acid bacterial consortium (LM), effectively modulated the silage microbiome. This treatment accelerated the establishment of a Lactiplantibacillus-dominated homofermentative phase, followed by a controlled transition to Lentilactobacillus-mediated heterofermentation. This specific microbial succession suppressed undesirable proteolytic activity and inhibited spoilage-associated taxa. Furthermore, integrated metabolomic profiling indicated that this optimized microbial assembly significantly enriched amino acid metabolism and ABC transporter pathways. This metabolic regulation facilitated precise nutrient flux, resulting in enhanced lactic acid accumulation and improved crude protein retention. These findings demonstrate that the strategic assembly of niche-adapted microbiota offers a robust strategy for converting lignocellulosic biomass into high-quality forage. By optimizing specific metabolic pathways, this approach significantly improves both the microbial stability and nutritional quality of the resulting silage.

Animal gastrointestinal tracts generally evolved towards a diverse and spatially structured organ system for efficient food digestion. In it, food is chemically broken down and bacterial load reduced by gastric acid in the stomach, acting as a "gatekeeper" for microbes entering the intestines where chyme nutrients and water are absorbed. The natural microbiota across gastrointestinal tract zones support digestion, compete with ingested pathogens and acts itself as an immune stimulus. Despite its important role, several lineages of fish, such as pipefishes, have secondarily lost their stomach and evolved agastric digestion, with unknown consequences to their intestines' microbiomes. Here, we test how stomach loss might affect the microbiome by investigating the fore-, mid- and hindgut's autochthonous microbiota of the Baltic Sea broadnosed pipefish, Syngnathus typhle, and comparing it to the stomach, fore- and hindgut's autochthonous microbiota of the sympatric and ecologically similar three-spine stickleback, Gasterosteus aculeatus. Using 16S-rRNA gene sequencing and qPCR, we show that microbial abundance is high in the stomach, accompanied by high alpha diversity, but low in the intestine of G. aculeatus, although microbial diversity remains at intermediate levels - a pattern almost inversed in S. typhle. G. aculeatus' stomach has the most distinct microbiota across gastrointestinal zones; however, this species' intestines' microbes are also found in S. typhle. In contrast, the pipefish's hindgut is the most distinct zone, and many microbes shared across its whole intestine are not found in the G. aculeatus. Our data supports the notion of the stomach and its distinct microbiome being an immunological gatekeeper for the gut, but also suggests that S. typhle might benefit from the additional microbes as many indicator taxa are suspected to act as mutualistic symbionts. Stomach-loss may therefore be a trade-off between improved chemical digestion capabilities and an immunological gate-keeper vs. improved microbial digestion and increased immune stimulation.

The rapid advancement of human-relevant in vitro skin models has been driven by increasingly stringent regulatory restrictions on animal testing and the growing recognition that conventional animal and two-dimensional cell culture systems fail to accurately predict human skin biology and clinical outcomes. Three-dimensional reconstructed human skin models, ex vivo human skin platforms, and next-generation bioengineered systems have been recognized as critical tools for dermatological research, cosmetic safety assessment, and pharmaceutical development. This review focuses on commercially available in vitro human skin models currently used in regulatory and research settings, as well as emerging technologies under active development. We provide an overview of reconstructed human epidermis and full-thickness skin equivalents, functional variants incorporating pigmentation and microbiome support, and ex vivo human skin models derived from surgical tissues. Additionally, we discuss cutting-edge platforms, including vascularized and perfused skin models, immune-competent skin constructs, organoid-based appendage-containing models, and microbiome-integrated platforms. Furthermore, we highlight current limitations, regulatory gaps, and future directions for standardization, scalability, and clinical translation. Collectively, advanced human skin models are expected to significantly enhance dermatological research by enabling predictive, ethical, and mechanistically informative testing strategies that bridge the gap between in vitro experimentation and clinical outcomes.

Oral health's inextricable links to systemic health are highlighted by the emerging oral-gut-brain axis and other well-known axes. There is growing evidence of a complex oral-gut-brain axis linking mouth and gut microbiomes with the central nervous system. Axis disruptions, characterized as oral and gut dysbiosis or microbial imbalances, can trigger oral and systemic inflammation and neuroinflammation, contributing to diseases such as Alzheimer's disease and Parkinson's disease. We summarize the oral-gut-brain axis mechanistic pathways, key evidence from human clinical and animal studies, and how the oral microbiome modulates human health and disease. Periodontal disease (PD) is associated with increased oral pathogen presence in diseased tissues throughout the human body. Preclinical models recapitulate these findings. Experimental periodontal infection induces dysbiosis that is linked to activation of inflammatory pathways that promote diseased phenotypes. Novel therapeutic approaches, including the probiotic fbacteriocin nisin, are increasingly recognized for targeted microbiome therapy at multiple inflection points across the axis. Nisin restores microbial balance, reduces inflammation, inhibits end-organ pathology, prevents periodontal bone loss, and reduces brain amyloid/tau accumulation and cytokine expression. These findings highlight the complexity of the oral-gut-brain axis and the ability to modulate the axis using bacteriocin-based approaches. Future probiotic or antimicrobial strategies aimed at ameliorating neuroinflammatory and metabolic diseases via microbiome-targeted therapy hold clinical promise.

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Heart rot, caused by the basidiomycete fungus Fomitopsis subpinicola, poses a severe threat to the health of Abies georgei var. smithii, a keystone conifer dominating subalpine forests on Sejila Mountain in southeastern Xizang (Tibet), China. To understand the microbial dynamics associated with disease progression, we used 16S rRNA and internal transcribed spacer high-throughput sequencing combined with multivariate and co-occurrence network analyses to characterize structural changes in the trunk endophytic microbiota across healthy, asymptomatic (heartwood decay without external symptoms), and symptomatic (fruiting bodies present) trees. Heart rot progression is the dominant factor associated with microbial succession, explaining more variation than tissue compartment. The bark-associated microbiome exhibited the earliest and strongest shifts and may provide a useful target for future early assessment of heartwood decay. Microbial interaction networks, particularly cross-kingdom (bacteria-fungi) associations, exhibited a significant increase in negative correlations as disease progressed, suggesting a shift from predominantly positive or neutral associations toward more antagonistic interactions, which may reflect increasing ecological competition and progressive destabilization of the trunk microbiome during decay. A pivotal finding was the dynamic microbial response observed during the asymptomatic stage. At this stage, fungal communities had already diverged markedly, and disease-associated shifts involving taxa such as Vibrisseaceae and Microbacteriaceae suggested that microbial restructuring had begun before obvious external symptoms appeared.IMPORTANCEOur findings show that shifts in endophytic microbiome structure and network stability are detectable during heart rot progression. In particular, bark-associated communities responded earlier and more strongly than near-pith communities, suggesting their potential value in future microbiome-informed, less destructive approaches for early assessment of cryptic stem diseases.

Vitamin B12 (cobalamin) is an essential micronutrient whose biological importance extends beyond its traditional classification as a haematinic vitamin. This third and final part of a review covering work published between 2020 and 2025 synthesises selected illustrative studies that have advanced understanding of B12 physiology, nutrition, deficiency, delivery, and systems-level biology. At the molecular level, B12 functions as a cofactor in one‑carbon metabolism and mitochondrial pathways, influencing DNA synthesis, methylation capacity, and energy metabolism. These biochemical roles translate into organism-level consequences, particularly in the nervous system, where deficiency may cause irreversible neurological injury even in the absence of overt haematological abnormalities.Population-level analyses show that B12 status reflects the interaction of didetary intake, absorption efficiency, life stage, and food-system dynamics. Although animal-source foods remain the most reliable sources, shifts towards plant-based diets and inconsistent fortification practices are altering risk profiles. Clinical evidence further indicates that B12 deficiency is heterogeneous, frequently under-recognised, and complicated by the limitations of conventional biomarkers. Advances in delivery science point towards more controlled and targeted interventions, including encapsulation technologies, alternative administration routes, and receptor-mediated transport strategies. Emerging evidence also suggests biological activities for cobalamin derivatives beyond classical cofactor function, while microbiome research increasingly implicates corrinoid metabolism in host-microbe interactions relevant to immune and metabolic regulation. These developments support an integrated systems-level view of B12 biology spanning dietary supply, physiology, microbial ecology, and therapeutic innovation. SYNOPSIS: The final part of this review examines recent advances in vitamin B12 biology, spanning physiology, nutrition, deficiency, biomarker limitations, therapeutic delivery, and microbiome-linked corrinoid metabolism. These developments support an integrated systems-level view linking molecular function, dietary ecology, population health, and emerging therapeutic opportunities.

The transition period in dairy cows is accompanied by profound shifts in mineral homeostasis and gut microbial ecology. While endocrine regulation of hypocalcemia has been extensively characterized, adaptive responses to hypophosphatemia-and the potential involvement of the gut microbiota-have received far less attention. Twenty-four Holstein dairy cows were randomly assigned to control or low-phosphorus groups. Hypophosphatemia was induced by dietary supplementation with 300 g/d synthetic zeolite from 21 days prepartum to 3 days postpartum. Blood and feces samples were collected at -21, -7, 0, 1, and 3 d relative to calving for longitudinal analysis of physiology, hindgut microbiome and plasma metabolomics to investigate host-microbiome adaptation to peripartum hypophosphatemia in dairy cows. Cows with hypophosphatemia exhibited pronounced compositional remodeling of their hindgut microbiota and extensive, persistent alterations in their plasma metabolome, with glycerophospholipid metabolism being a consistently affected pathway. Integrated correlation and mediation analyses revealed close associations between hindgut microbial variation, host metabolic reprogramming, and circulating phosphorus dynamics. In addition, a plasma feature putatively annotated as α-methyl-m-tyrosine (AMT) was identified as a candidate statistical mediator associated with the observed relationships between Lachnospiraceae_NK3A20_group abundance with systematic phosphorus concentrations. Collectively, these findings indicate that peripartum hypophosphatemia in dairy cows is accompanied by coordinated host metabolic and hindgut microbial remodeling, supporting a hindgut-centered host-metabolite-microbiome framework for understanding phosphorus adaptation during early lactation.

Host cultivar identity can influence rhizosphere microbiomes, yet its relative importance compared with soil amendment regime in saline-alkali farmland remains insufficiently resolved. Here, we compared how two oat (Avena sativa) cultivars shape soil microbial communities and functions under contrasting amendment regimes. In a field experiment, two oat cultivars, Tianyan 60 (TY60) and Musite (MST), were grown under five treatments: control, bacterial agent, organic manure, silica fume, and their combination. Soil physicochemical properties, enzyme activities, and metagenomic sequencing were used to characterize microbial taxonomic and functional profiles. Amendment regimes strongly altered soil nutrient and enzyme variables, whereas cultivar identity explained more variation than amendment regime in microbial community structure and beta diversity under the tested field conditions. Taxonomically, TY60 showed stronger amendment-associated reassembly, including enrichment of Bacteroidota, Pseudomonadota, and Ascomycota under selected treatments, whereas MST retained a comparatively more stable higher-rank backbone. Network analysis further indicated cultivar-associated differences in microbial community organization. Functionally, organic manure and the combination treatments (MIX3) produced the broadest shifts in C, N, P, and S cycling gene modules, particularly in TY60-associated soils. Null-model analyses showed that stochastic assembly dominated overall, but the dominant stochastic component differed among kingdoms, with bacteria mainly governed by drift, archaea by homogeneous dispersal, and fungi by a more balanced contribution of the drift and homogeneous dispersal. These results indicate that cultivar identity played a stronger role than amendment regime in shaping amendment-associated microbiome and functional shifts in this two-cultivar comparison, highlighting the potential value of combining cultivar choice with organic-microbial inputs to improve rhizosphere multifunctionality in saline-alkali agroecosystems.

Soil microbiomes are critical for ecosystem functioning, yet the global influences of climate and agricultural practices on their diversity and structure remain incompletely characterized. Here we analyzed 1921 soil samples from 33 countries worldwide across diverse biomes to assess how climate gradients and agricultural inputs, including pesticides and fertilizers, shape prokaryotic and fungal communities. We found that microbial diversity peaks at intermediate temperatures and differs markedly between natural and agricultural soils, with agriculture increasing microbial diversity while altering community composition and ecological guilds. Pesticide use selectively reduced bacterial diversity and shifted fungal guilds, decreasing ectomycorrhizal fungi while increasing saprotrophs, whereas fertilization reduced microbial network cohesion, with organic and inorganic fertilizers eliciting distinct community responses. These findings reveal that climatic factors and agricultural management jointly influence soil microbial diversity, community structure, and network connectivity, with implications for soil health and ecosystem resilience in managed landscapes. Overall, our results demonstrate that agricultural practices, including the use of pesticides and both organic and inorganic fertilizers, act as strong ecological filters that reshape soil microbiomes worldwide-enhancing apparent diversity but driving a functional shift toward less mutualistic, more fragmented, and potentially less resilient communities.

Longevity pharmacology has evolved from descriptive gerontology into a mechanistically driven field aiming to modulate fundamental processes of biological aging. Despite rapid scientific advances, whether this progress has translated into meaningful clinical outcomes remains uncertain. This critical perspective evaluates recent developments in longevity pharmacology and examines whether they represent genuine clinical progression or continued translational delay. A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science to identify English-language publications related to longevity pharmacology, gerotherapeutics, biomarkers of aging, and translational geroscience published between January 2000 and April 2026. We review evidence from senescence biology (including frailty), autophagy and mitophagy modulation, metabolic and nutrient-sensing pathways, stem cell and natural product - based rejuvenation strategies, microbiome-targeted interventions, and AI-enabled biomarker development. Particular emphasis is placed on systemic chronic inflammation as a central integrative driver of age-related disease. While selected interventions show early clinical signals, most remain preclinical or lack long-term validation. Key barriers include biomarker deficits, biological heterogeneity, safety concerns, regulatory misalignment, and limitations of animal models. Although mechanistic maturity is advancing rapidly, clinical translation remains incremental and fragmented. Near-term progress is most likely to arise from low-risk, system-level interventions supported by validated biomarkers and geroscience-informed clinical trial designs.