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.

Phage-mediated horizontal transfer of virulence genes can enhance the transmission and pathogenicity of Salmonella enterica (S. enterica), a process potentially regulated by its regulatory mechanisms. In this study, we explored the global dynamics of phage-mediated horizontal transfer in S. enterica and investigated the role of its regulatory mechanisms in transduction. A total of 5178 viral sequences encoding 12 S. enterica virulence genes were retrieved from the Integrated Microbial Genomes and Virome (IMG/VR) database, alongside 466,136 S. enterica genomes from EnteroBase. Virulence genes, including iacP (acyl carrier protein), mgtB (P-type Mg²⁺ transporter), misL (autotransporter porin), and fliC (flagellar filament protein), were widely distributed in phages and S. enterica across North America, Europe, and Asia. Phylogenetic analysis revealed close genetic affinity between phage- and bacterial-encoded virulence genes, suggesting shared ancestry and historical horizontal gene transfer events. The global regulator carbon storage regulator A (csrA) was highly conserved and ubiquitous in S. enterica. Overexpression of csrA inhibited prophage cyclization and release by upregulating the prophage cI repressor during horizontal gene transfer. Overall, these findings enhance our understanding of phage-mediated horizontal transfer of virulence genes, explore new areas of bacterial regulators that inhibit gene exchange and evolution by affecting phage life cycles, and offer a novel approach to controlling the transmission of phage-mediated S. enterica virulence genes.

Multiple factors, including genetics, nutrition, and health, influence the vertical transmission of microbiota from mothers to their offspring. Recent studies have shown that avian microbiota can be passed to the next generation via the eggshell and egg albumen. However, it remains unclear whether these microbial communities are regulated by nutrition and how they are associated with the host genotype. Chickens, with their controlled rearing conditions and stable genotypes, provide a promising model for investigating microbiome transmission in birds. This study aims to determine whether host genotype-associated bacteria are vertically transmitted between generations, and how maternal nutritional intervention with soyasaponin modulates this microbial transfer, thereby shaping chick intestinal development and informing effective nutritional strategies. We established a microbial vertical transmission model across various anatomical sites in breeder hens, chicken embryos, and chicks. Avian gut microbiota and reproductive tract microbiota can both be found in chicks at various developmental stages. Supplementing breeder hen diets with soyasaponin interacts with vertically transmitted Bifidobacterium adolescentis to produce γ-aminobutyric acid. This compound modulates offspring intestinal development through distinct mechanisms in chick epithelial cells, including the inhibition of LC3 and caspase3-associated autophagy and apoptosis pathways, as well as the promotion of proliferation and differentiation pathways mediated by LGR5 and Olfm4. Our study highlights that avian gut and reproductive tract microbiota are transmitted to chicks through the cloaca, with the yolk sac also being instrumental in this vertical transfer. The incorporation of soyasaponin in avian diets affects microbial transfer, providing a theoretical basis for studying maternal effects in poultry and formulating corresponding dietary strategies.

Incremental evidence on the effect of cold atmospheric plasma (CAP) in specifically killing transformed cells and advances in sequencing technologies at multiple omics have led to the demand of in-depth exploration on the mechanisms of action driving the potency of CAP against cancer cells at the molecular level. However, high-throughput data detailing the effect of CAP on cancer cells is lacking, let alone the corresponding database and analytical tool. Here, we sequenced the whole transcriptome, proteome, phosphorylome, acetylome, and lactylome of transformed cells in response to CAP using breast cancer cells as the disease model; and advanced our previously developed Hiplot platform by establishing a focus-driven tumor-specific module, namely CAP medicine in breast cancer (CAPmed-BC) (https://capbc.hiplot.com.cn). CAPmed-BC is the first multi-omics data resource in plasma medicine for analyzing the treatment response of breast cancer cells to CAP. It can analyze each type of omics data regarding differentially expressed biomarkers, expression landscape, gene ontology analysis, pathway interpretation, gene set enrichment analysis, and protein-protein interaction network. It can also interrogate the dynamic fluctuation, functional activity, and metabolic vulnerability of cancer cells in response to CAP by combinatorially analyzing omics at multiple carefully defined dimensions. We also built in a visualization module to support users for producing personalized graphs via adjusting parameters. We believe that CAPmed-BC will become a valuable resource for characterizing the outcome of CAP on breast cancers at the omics and molecular levels, and make considerable contributions to both plasma medicine and oncology.

The gut microbiota is a highly dynamic and complex ecosystem. However, the processes by which its members respond to dietary fibers remain incompletely understood. Here, we performed daily sampling over a 14-day observational period under the habitual diet, followed by a 14-day dietary fiber intervention in overweight participants with and without type 2 diabetes mellitus. By combining daily sampling, guild-level approach, and time-series analysis, we revealed diverse temporal response patterns among various microbiota members that are often missed by conventional sampling. These patterns were closely linked to their genetic capacities for carbohydrate utilization and transport. Moreover, time-delayed analysis of longitudinal multi-omics data identified specific metabolites that potentially mediate the beneficial effects of gut microbiota on host metabolism. Overall, our findings demonstrate the necessity of high-frequency sampling for capturing dynamic microbial responses and offer reliable targets for mechanistic investigations.

Microbiome and resistome transmission from mother to child, as well as from animal to environment, has been widely discussed in recent years. Dairy cows mainly provide milk and meat. However, in the dairy production system, the characteristics and transmission trends of resistome assembly and the microbiome in the gastrointestinal tract (GIT) remain unclear. In this study, we sequenced the GIT (rumen fluid and feces) microbiome of dairy cow populations from two provinces in China (136 cows and 36 calves), determined the characteristics of their resistome profiles and the distribution of antibiotics resistance genes (ARGs) across bacteria and further tracked the temporal dynamics of the resistome in offspring during early life using multi-omics technologies (16S ribosomal RNA [rRNA] sequencing, metagenome, and metatranscriptome). We characterized the GIT resistome in cows, distinguished by gut sites and regions. The abundance of ARGs in calves peaked within the first 3 days after birth, with Enterobacteriaceae as the dominant microbial host. As calves aged, resistome composition stabilized, and overall ARG abundance gradually decreased. Both diet and age influenced carbohydrate-active enzymes and ARG profiles. Resistance profiles in ecological niches (meconium, colostrum, soil, and wastewater) were unique, resembling maternal sources. Mobile genetic elements (MGEs), mainly found in soil and wastewater, played an important role in mediating these interactions. Multidrug resistance consistently emerged as the most significant form of resistance at the both the metagenome and metatranscriptome levels. Several antibiotic classes showed higher proportions at the RNA level than at the DNA level, indicating that even low-abundance gene groups can have a considerable influence through high expression. This study broadens our understanding of ARG dissemination in livestock production systems, providing a foundation for developing future preventive and control strategies.

The involvement of gut microbiota in calcific aortic valve disease (CAVD) pathogenesis remains underexplored. Here, we provide evidence for a strong association between the gut microbiota and CAVD development. ApoE^−/− mice were stratified into easy- and difficult- to calcify groups using neural network and cluster analyses, and subsequent faecal transplantation and dirty cage sharing experiments demonstrated that the microbiota from difficult-to-calcify mice significantly ameliorated CAVD. 16S rRNA sequencing revealed that reduced abundance of Faecalibacterium prausnitzii (F. prausnitzii) was significantly associated with increased calcification severity. Association analysis identified F. prausnitzii-derived butyric acid as a key anti-calcific metabolite. These findings were validated in a clinical cohort (25 CAVD patients vs. 25 controls), where serum butyric acid levels inversely correlated with disease severity. Functional experiments showed that butyric acid effectively hindered osteogenic differentiation in human aortic valve interstitial cells (hVICs) and attenuated CAVD progression in mice. Isotope labeling and ¹³C flux analyses confirmed that butyric acid produced in the intestine can reach heart tissue, where it reshapes glycolysis by specifically modifying GAPDH. Mechanistically, butyric acid-induced butyrylation (Kbu) at lysine 263 of GAPDH competitively inhibited lactylation (Kla) at the same site, thereby counteracting glycolysis-driven calcification. These findings uncover a novel mechanism through which F. prausnitzii and its metabolite butyric acid contribute to the preservation of valve function in CAVD, highlighting the gut microbiota-metabolite-glycolysis axis as a promising therapeutic target.

Early gastric cancer (EGC) represents a critical stage in preventing and controlling the progression from gastritis to advanced gastric cancer (AGC). Therefore, identifying the single-cell characteristics of EGC, particularly the cellular composition of the tumor microenvironment (TME), as well as identifying potential predictive markers and therapeutic targets, could significantly enhance the monitoring of gastric cancer and improve clinical cure rates. We constructed a comprehensive single-cell RNA sequencing atlas for 184,426 high-quality gastric cancer cells from various stages, utilizing clinical biopsies and surgical samples. Our single-cell atlas highlights the cellular and molecular characteristics of EGC. Eight distinct cell lineage states were identified, and it was observed that the number of epithelial cell meta-clusters gradually decreased, while the number of T&NK, B, plasma, fibroblast, myeloid, and endothelial cells increased with disease progression. Certain epithelial subclusters (metaplastic stem-like cells (MSCs), pit mucous-like cells (PMC-like), proliferating cells), T-cell subclusters (T_reg, CCR7⁺ naive, CH25H⁺ CD4⁺, T_EM CD8⁺, and GFPT2⁺ CD8⁺ T cells), and endothelial subclusters (IL-33⁺ Venous-1 and AMAMTSL2⁺ Artery-2) were found to be increased in EGC. The Venous-1 subcluster was found to express high levels of IL-33. Mechanistically, it was revealed that IL-33 enhances the survival and angiogenesis of endothelial cells by upregulating the expression of adhesion proteins CD34 and PECAM1. Patient-derived EGC and AGC organoids were subsequently generated, and it was demonstrated that endothelial-derived IL-33 promoted the growth of both EGC and AGC organoids ex vitro and in vivo. Furthermore, IL-33 was found to increase the expression of KRT17 in EGC organoids. Notably, we also found that high expression of IL-33 was positively correlated with the depth of invasion and malignancy of EGC. This study provides novel insights into the single-cell components involved in EGC and reveals the role of the IL-33⁺ endothelial subcluster in EGC progression.

Plant growth-promoting rhizobacteria (PGPR) represent a sustainable method to improve crop productivity. Synthetic microbial consortia have emerged as a powerful tool for engineering rhizosphere microbiomes. However, designing functionally stable consortia remains challenging due to an insufficient understanding of bacterial social interactions. In this study, we investigated the effects of Bacillus velezensis SQR9 (i.e., a commercially important PGPR) on social interactions within the rhizosphere community, particularly among Bacillus species. SQR9 inoculation significantly enhanced cucumber plant growth and altered the structure of rhizosphere Bacillus and its related bacterial communities. The results of swarm boundary and carbon utilization assays, revealed that phylogenetically closer Bacillus strains exhibited increased social cooperation and increased metabolic niche overlap. Building on these social interactions, we designed 30 consortia comprising both highly related (HR) and moderately related (MR) types across four richness levels (1, 2, 3, and 4 strains), with MR consortia demonstrating superior PGP effects through enhanced plant growth, root colonization, indole-3-acetic acid production, and siderophore production, than the HR consortia. Expanding these findings to 300 consortia across four richness levels (1, 2, 4, and 8 strains) confirmed enhanced PGP effects in MR consortia with increasing richness. These findings highlight the importance of bacterial interactions and phylogenetic relationships in shaping rhizosphere communities and designing synthetic microbial consortia. Specifically, this study provides a framework for assembling Bacillus consortia that enhance cooperation, which would aid in improving their stability and effectiveness in agricultural applications.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a significant global health challenge. Recent advancements in gut microbiota (GM) research have shed light on the intricate relationship between GM and TB, suggesting that GM alterations may influence host susceptibility, disease progression, and response to antituberculosis drugs. This review systematically synthesizes and analyzes the current research progress on the relationship between GM and TB, focusing on six key aspects: (1) bidirectional effects between GM dynamics and TB progression; (2) the interaction between GM and anti-TB drugs; (3) GM and TB immune response; (4) GM as a potential target for diagnosis and treatment of TB; (5) multi-omics and artificial intelligence (AI) technologies in GM-TB research; (6) current challenges and future directions in GM-TB research. We highlight the bidirectional nature of the GM–TB interaction, where MTB infection can lead to GM dysbiosis, and changes can affect the host's immune response, contributing to TB onset and progression. Advanced molecular techniques, such as next-generation sequencing and metagenomics, along with AI, play pivotal roles in elucidating these complex interactions. Future research directions include investigating the relationship between GM and TB vaccine efficacy, exploring GM's potential in TB prevention, developing microbiome-based diagnostic and prognostic tools, and examining the role of GM in TB recurrence. By addressing these areas, we aim to provide a comprehensive perspective on the latest advancements in GM and TB research and offer insights for future studies and clinical applications. Ultimately, the development of novel microbiome-based strategies may offer new tools and insights for the effective control and management of TB, a disease that continues to pose a significant threat to public health.