Multi-omics sequencing and correlation analysis identified the beneficial role of Faecalibacterium prausnitzii (F. prausnitzii)-derived butyric acid (BA) as a key metabolite in the restoration of valve function in calcific aortic valve disease (CAVD). The therapeutic efficacy of BA in attenuating CAVD progression was confirmed in vitro, ex vivo, and in vivo. Subsequent mechanistic investigations revealed that BA reshape glycolysis through site-specific inhibition of lactylation at the Lys-263 residue of GAPDH, which is mediated by competitive inhibition of butyrylation at the same site.

Using metagenomic sequencing and bioinformatics analysis of fecal samples from rectal cancer patients and corresponding mouse models, our study identifies a strong association between Lactobacillus abundance and acute chemoradiotherapy-induced intestinal injury (ACRIII). Elevated Lactobacillus levels before treatment were consistently linked to reduced intestinal damage. From patients who achieved complete tumor remission without developing ACRIII, we isolated 10 novel Lactobacillus strains. Among these, Lacticaseibacillus rhamnosus DY801 emerged as the most effective in mitigating ACRIII. Multi-omics analysis revealed that DY801 modulates methionine metabolism in host lymphoid tissue inducer (Lti) cells, leading to increased histone H3 lysine 4 trimethylation (H3K4me3). This epigenetic modification suppresses the secretion of pro-inflammatory cytokines IL-17A and IL-22, ultimately alleviating intestinal injury.

This study revealed spatio-temporal characteristics of gastrointestinal resistome in a cow-to-calf model and the pattern of their spread to the environment and offspring in the dairy production system. The gastrointestinal tract of dairy cows is a natural reservoir of resistomes and distinguished by gut sites and regions. The resistance profiles of different ecological niches (meconium, colostrum, soil, and water) were unique, and most of the features were shared with the maternal source. In the early life, antibiotics resistance genes may acquire from the maternal source, and diet and age are the primary regulatory factors of the resistome. Mobile genetic elements are an important medium between various ecological niches interactions which may occur most frequently from the soil and waste water.

In this study, 19 overweight participants, with or without type 2 diabetes mellitus, underwent 14 days of normal-diet observation followed by 14 days of dietary fiber intervention. Fecal samples and continuous glucose monitoring data were collected daily throughout the 28-day period. Using guild-based analysis of individual-level networks and time-series approaches, we captured the dynamic responses of gut microbiota, revealing multiple abundance-shift patterns that are often overlooked by conventional sampling strategies. By integrating multi-omics data with time-delayed analysis, we further identified key microbial members and metabolites associated with host metabolic improvements, thereby providing reliable targets for subsequent mechanistic investigations.

This study identified 10 reliable quantitative trait loci (QTLs) governing cotton resistance to V. dahliae in various environments through a genome-wide association analysis (GWAS) using an upland cotton population. The pyramid of these 10 elite alleles reduced the disease index of cotton to V. dahliae from 70 to 20. Trace analysis of these elite alleles revealed that the increased utilization of Lsnp1R, Lsnp4R, Lsnp5R, Lsnp8R, and Lsnp9R since the 1990s aligned with Chinese cotton breeding programs, offering new insights into interpreting the advancements in cotton breeding for Verticillium wilt resistance in China. Analysis of 1152 transcriptomes under normal and V. dahliae-stress conditions elucidated the regulatory network governing cotton's response to V. dahliae, highlighting the regulation of reactive oxygen species (ROS) homeostasis and immune response. By combining genome-wide association analysis and transcriptome-wide association studies, 15 candidate causal genes were pinpointed, with GhARM identified as a negative regulator of cotton resistance to V. dahliae through the modulation of ROS homeostasis.

The human body is inhabited by trillions of microorganisms that play a crucial role in health and diseases. Although our understanding of the species and functional composition of the human gut microbiome is rapidly expanding, species–function heterogeneity and dynamic activities in human microecosystem niches remain unclear. By applying a novel gut-specific single-microbe RNA sequencing and analytical framework on three healthy donors with distinct enterotypes, we created a comprehensive transcriptional landscape of human gut microbiome. We investigated the functional redundancy and complementarity involved in central carbon metabolism and studied the heterogeneity and covariation of single-microbe metabolic capacity. We demonstrated Megamonas funiformis, a keystone species in Asian populations, can effectively improve mineral absorption through exogenous phytic acid degradation.

Metaproteomics within the multi-omics framework provides a comprehensive view of microbial systems by identifying proteins, quantifying their levels, detecting posttranslational modifications (PTMs), mapping protein–protein interactions (PPIs), and localizing proteins. It complements other omics techniques, such as metagenomics, metatranscriptomics, and metabolomics, to deepen our understanding of microbiome dynamics across various research domains.

Single-cell analyst is a user-friendly, web-based platform designed for comprehensive multi-omics single-cell data analysis. Supporting six single-cell omics types and spatial transcriptomics, it eliminates the need for coding, making advanced data analysis accessible to researchers of all expertize levels. The platform automates key analytical steps, including quality control, data processing, and phenotypic analysis, while generating interactive, publication-ready visualizations. By streamlining complex multi-omics workflows, single-cell analyst empowers users to efficiently explore and interpret single-cell data without requiring extensive computational skills.

Prenatal exposure to glucocorticoids is linked to long-term health risks in offspring, but the role of maternal gut microbiota in mediating these effects remains unclear. Here, we demonstrate that prenatal prednisone therapy (PPT) in humans and prenatal prednisone exposure (PPE) in rats result in sex-specific long bone dysplasia in offspring, including reduced peak bone mass (PBM) and heightened osteoporosis risk in female offspring. Multi-omics profiling and fecal microbiota transplantation show that PPE alters maternal gut microbiota composition and depletes the microbial metabolite daidzein (DAI). DAI deficiency suppresses Hoxd12 expression, impairs osteogenesis, and leads to PBM decline in female offspring. In bone marrow-derived mesenchymal stem cells from PPE female offspring, DAI promoted Hoxd12 expression and osteogenic differentiation. Notably, DAI supplementation restored H3K9ac levels, enhanced Hoxd12 expression, and promoted osteogenic differentiation through the ERβ/KAT6A pathway. Furthermore, maternal DAI supplementation during pregnancy prevented osteoporosis susceptibility in PPE female offspring and alleviated functional abnormalities in multiple organs, including the liver, hippocampus, ovary, and adrenal gland. In conclusion, PPE induces multiorgan dysplasia and increases disease predisposition (e.g., osteoporosis) in female offspring by disrupting maternal gut microbiota and depleting DAI. Maternal DAI supplementation provides a promising preventive strategy to counteract these adverse outcomes.

We employed bulk RNA-seq and scRNA-seq techniques to analyze the immune dysregulation in patients with intracerebral hemorrhage (ICH). The study revealed that excessive inflammatory responses, neutrophil activation, and T-cell dysfunction are the main characteristics of ICH. A multi-machine learning framework was utilized to construct a predictive model for ICH risk in hypertensive patients. Molecular docking and simulation results demonstrated that NXPE3 is a potential therapeutic target, and dihydroergotamine (DHE) exhibits a strong binding affinity to NXPE3. In vivo experiments indicated that DHE can reduce the incidence of spontaneous ICH and modulate the immune-inflammatory response. These results support DHE targeting NXPE3 as a potential therapeutic strategy for hypertension-related ICH.

Microbial communities play critical roles in various ecosystems. Despite extensive research on the taxonomic and functional diversity of microbial communities, effective approaches to regulate targeted microbial functions remain limited. Here, we present an innovative methodology that integrates core enzyme identification, protein structural characterization, regulator virtual screening, and functional validation to achieve precise microbiome functional regulation. As a proof of concept, we focused on the regulation of urea decomposition by the rumen microbiota in ruminants. Through metagenomic analysis, we identified the core urease gene and its corresponding microbial genome (MAG257) affiliated with the unclassified Succinivibrionaceae, and reconstructed its complete gene cluster. Structural analysis of the urease catalytic subunit (UreC) via cryo-electron microscopy (cryo-EM) revealed detailed features of its active site, guiding molecular docking studies that identified epiberberine, a natural compound with potent urease inhibitory activity. Validation in a rumen simulation system demonstrated that epiberberine significantly reduced urea decomposition and enhanced nitrogen utilization. This study establishes a robust framework that combines structural biology and computational screening to achieve targeted microbiome functional regulation, offering a promising tool for microbiome engineering and broader applications in animal productivity, human health, environmental improvement, and biotechnology.

In this study, 102 cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) who received neoadjuvant RC48-ADC combined with immunotherapy were included. We evaluated the pathological responses and explored multiple clinical characteristics to identify independent predictive indicators of the efficacy. The results showed that neoadjuvant RC48-ADC combined with immunotherapy had promising efficacy. Furthermore, we collected 11 MIBC samples and performed single-cell RNA sequencing. All BLCA epithelial cells were identified as four subclusters. We conducted differential gene expression/functional enrichment analysis, cell proportion analysis, cell cycle analysis, CNV analysis, and pseudotemporal analysis on all tumor cells to evaluate potential efficacy-predictive biomarkers and the evolutionary patterns of tumor cells during neoadjuvant treatment. The results indicated that the combined detection of HER2 and HSPA1A expression in C3 subcluster based on single-cell RNA sequencing is a potential strategy for predicting efficacy. In addition, C3 plays a dominant role in the emergence of drug-resistance during the evolution of BLCA epithelial cells.

Since its initial release in 2022, ggClusterNet has become a vital tool for microbiome research, enabling microbial co-occurrence network analysis and visualization in over 300 studies. To address emerging challenges, including multi-factor experimental designs, multi-treatment conditions, and multi-omics data, we present a comprehensive upgrade with four key components: (1) A microbial co-occurrence network pipeline integrating network computation (Pearson/Spearman/SparCC correlations), visualization, topological characterization of network and node properties, multi-network comparison with statistical testing, network stability (robustness) analysis, and module identification and analysis; (2) Network mining functions for multi-factor, multi-treatment, and spatiotemporal-scale analysis, including Facet.Network() and module.compare.m.ts(); (3) Transkingdom network construction using microbiota, multi-omics, and other relevant data, with diverse visualization layouts such as MatCorPlot2() and cor_link3(); and (4) Transkingdom and multi-omics network analysis, including corBionetwork.st() and visualization algorithms tailored for complex network exploration, including model_maptree2(), model_Gephi.3(), and cir.squ(). The updates in ggClusterNet 2 enable researchers to explore complex network interactions, offering a robust, efficient, user-friendly, reproducible, and visually versatile tool for microbial co-occurrence networks and indicator correlation patterns. The ggClusterNet 2R package is open-source and available on GitHub (https://github.com/taowenmicro/ggClusterNet).

A better understanding of the characteristic serum metabolites and microbiota from the gut and oral cavity in centenarians could contribute to elucidating the mutual connections among them and would help provide information to achieve healthy longevity. Here, we have recruited a total of 425 volunteers, including 145 centenarians in Suixi county — the first certified “International Longevity and Health Care Base” in China. An integrative analysis for the serum metabolites, gut, and oral microbiota of centenarians (aged 100–120) was compared with those of centenarians' lineal relatives (aged 24–86), the elderly (aged 65–88) and young (aged 23–54). Strikingly distinct metabolomic and microbiological profiles were observed within the centenarian signature, longevity family signature, and aging signature, underscoring the metabolic and microbiological diversity among centenarians and their lineal relatives. Within the centenarian between healthy and frail individuals, significant differences in metabolite profiles and microbiota compositions are observed, suggesting that healthy longevity is associated with unique metabolic and microbiota patterns. Through an integrative analysis, the tryptophan pathway has been revealed to be an important potential mechanism for individuals to achieve healthy longevity. Specifically, a key tryptophan metabolite, 5-methoxyindoleacetic acid (5-MIAA), was revealed to be associated with the genus Christensenellaceae R-7 group, and it exhibited effects of delaying cell senescence, promoting lifespan, and alleviating inflammation. Our characterization of the extensive metabolomic and microbiota remodeling in centenarians may offer new scientific insights for achieving healthy longevity.

Our study provides a comprehensive multi-omics profile of aging, integrating proteomic, metabolomic, and metagenomic analyses across diverse tissues and plasma. We identified the synergistic amplification of the circulating complement system and tissue-wide immunoglobulin accumulation as key molecular drivers of inflammaging. Furthermore, we uncovered gut microbiota dysbiosis, characterized by a significant decrease in Escherichia and an increase in Helicobacter, which contributes to lipid metabolic reprogramming, particularly the dysregulation of polyunsaturated fatty acid metabolism across multiple tissues. By elucidating the intricate interplay between inflammaging and dysbiosis-induced fatty acid metabolic remodeling in mammalian aging, our study highlights promising gero-protective targets and pathways that could mitigate aging-related diseases and enhance health span. These insights pave the way for developing novel therapeutic strategies to promote healthy aging.

Here, we conducted a large-scale investigation of vertebrate viruses in soils and found soil was a mediator of vertebrate viruses. Compared to natural soils, agricultural soils possessed distinct prevalence patterns, with a higher detection rate and richness for vertebrate viruses and higher potential health risks.

This study explored the effect of plant-derived indigo supplementation on intestinal inflammation using in vivo, in vitro, and clinical sample analyses. Our results showed that indigo decreased mucosal inflammation by regulating CD4+ T cell differentiation in a gut microbiota-dependent manner. Microbes transferred from indigo-treated mice, indigo-induced enrichment of Roseburia intestinalis, and its metabolite butyrate played a role in Th17/Treg immunity similar to that of indigo in intestinal inflammation, which was involved in mTORC1/HIF-1α signal-mediated reprogrammed glucose metabolism. We further showed that patients with ulcerative colitis exhibited significant gut dysbiosis and CD4+ T cell differentiation abnormalities. Our findings provide new insights into the gut-immune axis in ulcerative colitis, offering a novel microbial-based immunotherapy for the treatment of inflammatory bowel disease.

This study identifies the potential quorum sensing (QS) bacteria in wastewater treatment plants (WWTPs) and constructs a QS communication network through the establishment of a local QS bacterial database with six languages and the analysis of over 1000 activated sludge microbiome samples collected from 269 WWTPs. The results not only advance the understanding of bacterial communication in WWTPs but also provide a valuable tool for developing regulatory strategies to optimize the functionality of these vital ecosystems.

This study identifies the potential quorum sensing (QS) bacteria in wastewater treatment plants (WWTPs) and constructs a QS communication network through the establishment of a local QS bacterial database with six languages and the analysis of over 1000 activated sludge microbiome samples collected from 269 WWTPs. The results not only advance the understanding of bacterial communication in WWTPs but also provide a valuable tool for developing regulatory strategies to optimize the functionality of these vital ecosystems.

Compared to healthy controls, children with food-sensitized tolerance and food allergy showed reduced fecal short-chain fatty acids (SCFAs), particularly butyrate. In an ovalbumin-sensitized mouse model, butyrate outperformed other SCFAs in alleviating allergic responses. Butyrate suppressed reactive oxygen species production in intestinal epithelial cells, downregulated the Notch ligand Jagged1 expression, and reduced Notch intracellular domain nuclear translocation, thereby inhibiting the Notch downstream gene Hes1. Consequently, enhanced tight junctions protein expression improved barrier integrity, limiting food allergen permeation and subsequent Th2 immune responses. This attenuated mast cell degranulation (e.g., histamine and mouse mast cell protease 1 (mMCP-1)) and alleviated allergy symptoms. The study highlighted the therapeutic potential of butyrate-enhancing strategies-including dietary fibers, prebiotics, and probiotics-as modalities for allergy prevention or treatment.

Spaceflight reshapes microbiota and immune function, mitigating some ageing effects while accelerating immune aging, revealing crucial insights for astronaut health and longevity in space missions.

EasyMetagenome is a user-friendly shotgun metagenomics pipeline designed for comprehensive microbiome analysis, supporting quality control, host removal, read-based, assembly-based, binning, genome and pan-genome analysis. It offers customizable settings, data visualizations, and parameter explanations. The pipeline is freely available at https://github.com/YongxinLiu/EasyMetagenome.

The concept of “gut–X axis”: the intestine and intestinal microbiota are proven to be able to modulate the pathophysiologic progressions of the extraintestinal organs' diseases. The bioactive chemicals and/or intestinal immune cells can translocate into the circulatory system and other organs and influence the immune reactions, metabolic status, cells physiology, and so forth of extraintestinal organs, finally regulating these organs' homeostasis. Meanwhile, other organs may reversely impact the intestine, namely such regulatory axis is bidirectional.

Fastp is a widely adopted tool for FASTQ data preprocessing and quality control. It is ultrafast and versatile and can perform adapter removal, global or quality trimming, read filtering, unique molecular identifier processing, base correction, and many other actions within a single pass of data scanning. Fastp has been reconstructed and upgraded with some new features. Compared to fastp 0.20.0, the new fastp 0.23.2 is even 80% faster.

Representative visualization results of ImageGP. ImageGP supports 16 types of images and four types of online analysis with up to 26 parameters for customization. ImageGP also contains specialized plots like volcano plot, functional enrichment plot for most omics-data analysis, and other 4 specialized functions for microbiome analysis. Since 2017, ImageGP has been running for nearly 5 years and serving 336,951 visits from all over the world. Together, ImageGP (http://www.ehbio.com/ImageGP/) is an effective and efficient tool for experimental researchers to comprehensively visualize and interpret data generated from wet-lab and dry-lab.

The ggtree object is designed to store phylogenetic tree and associated data, and the object itself is a graphic object that can be rendered as an image file. This work will increase the reproducibility and reusability of phylogenetic data, as well as facilitate integrative and comparative studies.

A new release of PhyloSuite, capable of conducting tree-based analyses. Detailed guidelines for each step of phylogenetic and tree-based analyses, following the “What? Why? and How?” structure. This protocol will help beginners learn how to conduct multilocus phylogenetic analyses and help experienced scientists improve their efficiency.