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The gut microbiota (GM) plays a crucial role in maintaining the overall health and well-being of the host. Recent studies have demonstrated that the GM may significantly influence bone metabolism and degenerative skeletal diseases, such as osteoporosis (OP). Interventions targeting GM modification, including probiotics or antibiotics, have been found to affect bone remodeling. This review provides a comprehensive summary of recent research on the role of GM in regulating bone remodeling and seeks to elucidate the regulatory mechanism from various perspectives, such as the interaction with the immune system, interplay with estrogen or parathyroid hormone (PTH), the impact of GM metabolites, and the effect of extracellular vesicles (EVs). Moreover, this review explores the potential of probiotics as a therapeutic approach for OP. The insights presented may contribute to the development of innovative GM-targeted therapies for OP.

Although previous studies using phenotypic or/and genomic approaches monitoring have revealed the spatiotemporal distribution of antimicrobial resistance (AMR) in Salmonella in local areas, their geographical patterns and driving factors remain largely unknown at a global scale. Here, we performed an analysis of publicly available data of 208,233 Salmonella genomes in 148 countries/regions between 1900 and 2023 and explored driving indicators of AMR. Overall, we found that the geographic distribution of AMR varied depending on the location, source, and serovar. The proportion of AMR levels increased across six continents, especially in serovars Agona, Dublin, I 1,4,[5],12:i:-, Muenchen, Senftenberg, Mbandaka mainly from chickens, food, wild animals, and the environment, while decreased in Schwarzengrund and Saintpaul mainly from cattle, pigs, and turkeys. We also found that S . Typhimurium exhibiting macro, red, dry, and rough was detected as early as 1992 in the USA, earlier than in China. Moreover, we identified that antibiotic consumption, agriculture, climate, urban, health, and socioeconomic factors contribute to the development of AMR in Salmonella . We present a globally high-resolution genetic atlas of Salmonella and also identify some factors driving the rise of AMR, which can provide valuable information for understanding the transmission dynamics and evolutionary trajectories of Salmonella . Salmonella is a major cause of foodborne disease worldwide. Authors created a Salmonella database and present a genetic atlas of antimicrobial resistance, identifying some socioeconomic and environmental drivers for the rise of resistance globally.

Polymyxins are the last line of defense against lethal infections caused by multidrug resistant Gram-negative pathogens. Very recently, the use of polymyxins has been greatly challenged by the emergence of the plasmid-borne mobile colistin resistance gene (mcr-1). However, the mechanistic aspects of the MCR-1 colistin resistance are still poorly understood. Here we report the comparative genomics of two new mcr-1-harbouring plasmids isolated from the human gut microbiota, highlighting the diversity in plasmid transfer of the mcr-1 gene. Further genetic dissection delineated that both the trans-membrane region and a substrate-binding motif are required for the MCR-1-mediated colistin resistance. The soluble form of the membrane protein MCR-1 was successfully prepared and verified. Phylogenetic analyses revealed that MCR-1 is highly homologous to its counterpart PEA lipid A transferase in Paenibacili, a known producer of polymyxins. The fact that the plasmid-borne MCR-1 is placed in a subclade neighboring the chromosome-encoded colistin-resistant Neisseria LptA (EptA) potentially implies parallel evolutionary paths for the two genes. In conclusion, our finding provids a first glimpse of mechanism for the MCR-1-mediated colistin resistance.

Background Antibiotic-resistant pathogens pose high risks to human and animal health worldwide. In recent years, the role of gut microbiota as a reservoir of antibiotic resistance genes (ARGs) in humans and animals has been increasingly investigated. However, the structure and function of the gut bacterial community, as well as the ARGs they carry in migratory birds remain unknown. Results Here, we collected samples from migratory bird species and their associated environments and characterized their gut microbiomes and resistomes using shotgun metagenomic sequencing. We found that migratory birds vary greatly in gut bacterial composition but are similar in their microbiome metabolism and function. Birds from the same environment tend to harbor similar bacterial communities. In total, 1030 different ARGs (202 resistance types) conferring resistance to tetracycline, aminoglycoside, β-lactam, sulphonamide, chloramphenicol, macrolide-lincosamide-streptogramin (MLS), and quinolone are identified. Procrustes analysis indicated that microbial community structure is not correlated with the resistome in migratory birds. Moreover, metagenomic assembly-based host tracking revealed that most of the ARG-carrying contigs originate from Proteobacteria . Co-occurrence patterns revealed by network analysis showed that emrD , emrY , ANT(6)-Ia , and tetO , the hubs of ARG type network, are indicators of other co-occurring ARG types. Compared with the microbiomes and resistomes in the environment, migratory birds harbor a lower phylogenetic diversity but have more antibiotic resistance proteins. Interestingly, we found that the mcr-1 resistance gene is widespread among different birds, accounting for 50% of the total samples. Meanwhile, a large number of novel β-lactamase genes are also reconstructed from bird metagenomic assemblies based on fARGene software. Conclusions Our study provides a comprehensive overview of the diversity and abundance of ARGs in migratory birds and highlights the possible role of migratory birds as ARG disseminators into the environment. 9vRT3BmK5LZQjoS1YmKYZo Video abstract.

The human gut microbiota is a reservoir of antibiotic resistance genes, but little is known about their diversity and richness within the gut. Here we analyse the antibiotic resistance genes of gut microbiota from 162 individuals. We identify a total of 1,093 antibiotic resistance genes and find that Chinese individuals harbour the highest number and abundance of antibiotic resistance genes, followed by Danish and Spanish individuals. Single-nucleotide polymorphism-based analysis indicates that antibiotic resistance genes from the two European populations are more closely related while the Chinese ones are clustered separately. We also confirm high abundance of tetracycline resistance genes with this large cohort study. Our study provides a broad view of antibiotic resistance genes in the human gut microbiota. The appearance of antibiotic resistance has been attributed to the misuse of antibiotics. By analysing the diversity of antibiotic resistance genes present in 162 human gut microbiota samples, the authors find that Chinese individuals harbour a larger pool of resistance genes than Spanish or Danish counterparts.

Gut microbial reference genomes and gene catalogs are necessary for understanding the chicken gut microbiome. Here, we assembled 12,339 microbial genomes and constructed a gene catalog consisting of ~16.6 million genes by integrating 799 public chicken gut microbiome samples from ten countries. We found that 893 and 38 metagenome-assembled genomes (MAGs) in our dataset were putative novel species and genera, respectively. In the chicken gut, Lactobacillus aviarius and Lactobacillus crispatus were the most common lactic acid bacteria, and glycoside hydrolases were the most abundant carbohydrate-active enzymes (CAZymes). Antibiotic resistome profiling results indicated that Chinese chicken samples harbored a higher relative abundance but less diversity of antimicrobial resistance genes (ARGs) than European samples. We also proposed the effects of geography and host species on the gut resistome. Our study provides the largest integrated metagenomic dataset from the chicken gut to date and demonstrates its value in exploring chicken gut microbial genes.Feng et al. include genome recovery and data analysis of large number of chicken gut metagenomic datasets which significantly expands the reference genomes available from the chicken gut microbial communities, and catalog the genes prevalent in the gut systems. They further depict the countryspecific chicken gut antibiotic resistomes and the effects of geography and host species on the gut resistome.

The antibiotic resistance is natural in bacteria and predates the human use of antibiotics. Numerous antibiotic resistance genes （ARGs） have been discovered to confer resistance to a wide range of antibiotics. The ARGs in natural environments are highly integrated and tightly regulated in specific bacterial metabolic networks. However, the antibiotic selection pressure conferred by the use of antibiotics in both human medicine and agriculture practice leads to a significant increase of antibiotic resistance and a steady accumulation of ARGs in bacteria. In this review, we summarized, with an emphasis on an ecological point of view, the important research progress regarding the collective ARGs （antibiotic resistome） in bacterial communities of natural environments, human and animals, i.e., in the one health settings. We propose that the resistance gene flow in nature is ＂from the natural environments＂ and ＂to the natural environments＂; human and animals, as intermediate recipients and disseminators, contribute greatly to such a resistance gene ＂circulation.＂

Accumulated evidence supports the beneficial role of inulin in alleviating metabolic dysfunction-associated fatty liver disease (MAFLD) by modulating gut microbiota. However, the underlying mechanisms are not fully understood. Here we used high-fat diet (HFD)-induced laying hen model of MAFLD to investigate the effect of inulin on ameliorating MAFLD and found that the inulin-enriched Megamonas genus was inversely correlated with hepatic steatosis-related parameters. Oral administration of a newly isolated commensal bacterium by culturomics, M. funiformis CML154, to HFD-fed hens and mice ameliorated MAFLD, changed liver gene expression profiles, and increased intestinal propionate concentration. Further evidence demonstrated that the anti-MAFLD effect of M. funiformis CML154 is attributed to propionate-mediated activation of the APN - AMPK - PPARα signaling pathway, thereby inhibiting fatty acid de novo synthesis and promoting β-oxidation. These findings establish the causal relationships among inulin, M. funiformis , and MAFLD, and suggest that M. funiformis CML154 is a probiotic candidate for preventative or therapeutic intervention of MAFLD.

Cross talk occurs between the human gut and the lung through a gut-lung axis involving the gut microbiota. However, the signatures of the human gut microbiota after active infection have not been fully understood. Here, we investigated changes in the gut microbiota in tuberculosis (TB) patients by shotgun sequencing the gut microbiomes of 31 healthy controls and 46 patients. We observed a dramatic changes in gut microbiota in tuberculosis patients as reflected by significant decreases in species number and microbial diversity. The gut microbiota of TB patients were mostly featured by the striking decrease of short-chain fatty acids (SCFAs)-producingbacteria as well as associated metabolic pathways. A classification model based on the abundance of three species, , and , performed well for discriminating between healthy and diseased patients. Additionally, the healthy and diseased states can be distinguished by SNPs in the species of . We present a comprehensive profile of changes in the microbiota in clinical TB patients. Our findings will shed light on the design of future diagnoses and treatments for infections.

Revealing the assembly and succession of the chicken gut microbiota is critical for a better understanding of its role in chicken physiology and metabolism. However, few studies have examined dynamic changes of absolute chicken gut microbes using the quantitative microbiome profiling (QMP) method. Here, we revealed the developmental trajectory of the broiler chicken gut bacteriome and mycobiome by combining high‐throughput sequencing with a microbial load quantification assay. We showed that chicken gut microbiota abundance and diversity reached a plateau at 7 days posthatch (DPH), forming segment‐specific community types after 1 DPH. The bacteriome was more impacted by deterministic processes, and the mycobiome was more affected by stochastic processes. We also observed stage‐specific microbes in different gut segments, and three microbial occurrence patterns including “colonization,” “disappearance,” and “core” were defined. The microbial co‐occurrence networks were very different among gut segments, with more positive associations than negative associations. Furthermore, we provided links between the absolute changes in chicken gut microbiota and their serum metabolite variations. Time‐course untargeted metabolomics revealed six metabolite clusters with different changing patterns of abundance. The foregut microbiota had more connections with chicken serum metabolites, and the gut microbes were closely related to chicken lipid and amino acid metabolism. The present study provided a full landscape of chicken gut microbiota development in a quantitative manner, and the associations between gut microbes and chicken serum metabolites further highlight the impact of gut microbiota in chicken growth and development. In this study, we revealed the developmental trajectory of the broiler chicken gut bacteriome and mycobiome by combining high‐throughput sequencing with a microbial load quantification assay. Furthermore, we provided links between the absolute changes in chicken gut microbiota and their serum metabolite variations. The present study provided a full landscape of chicken gut microbiota development in a quantitative manner, and the associations between gut microbes and chicken serum metabolites further highlight the impact of gut microbiota in chicken growth and development. Highlights The developmental trajectory of the broiler chicken gut microbiota is revealed by a quantitative microbiome profiling approach. The chicken gut microbiota displays gut segment‐specific community types and growth stage‐specific microbes. The chicken gut microbes have different colonization abilities, forming different developmental patterns. The chicken gut microbiota development is associated with the chicken serum metabolite changes.