Microbiome最新文献

This editorial piece co-authored by the Senior Editors at Microbiome aims to highlight current challenges in the field of environmental and host-associated microbiome research. We also take the opportunity to clarify our expectations for the articles submitted to the journal. At Microbiome, we are seeking studies that provide either new mechanistic insights into the role of microbiomes in health and environmental systems or substantial conceptual or technical advances. Manuscripts need to meet high standards of language accuracy, quality of microbiome analyses, and data and protocol availability, including detailed reporting of wet-lab and in silico protocols, all of which can critically enhance transparency and reproducibility. We think that such efforts are essential to push the boundaries of our knowledge on microbiomes in a concerted, international effort.

Background: Candidate Phyla Radiation (CPR) represents a unique superphylum characterized by ultra-small cell size and symbiotic lifestyle. Although CPR bacteria have been identified in varied environments, their broader distribution, associations with hosts, and ecological roles remain largely unexplored. To address these knowledge gaps, a serpentinite-like environment was selected as a simplified model system to investigate the CPR communities in hyperalkaline environments and their association with hosts in extreme conditions. Additionally, the enzymatic activity, global distribution, and evolution of the CPR-derived genes encoding essential metabolites (e.g., folate or vitamin B₉) were analyzed and assessed.

Results: In the highly alkaline serpentinite-like ecosystem (pH = 10.9-12.4), metagenomic analyses of the water and sediment samples revealed that CPR bacteria constituted 1.93-34.8% of the microbial communities. Metabolic reconstruction of 12 high-quality CPR metagenome-assembled genomes (MAGs) affiliated to the novel taxa from orders UBA6257, UBA9973, and Paceibacterales suggests that these bacteria lack the complete biosynthetic pathways for amino acids, lipids, and nucleotides. Notably, the CPR bacteria commonly harbored the genes associated with essential folate cofactor biosynthesis and metabolism, including dihydrofolate reductase (folA), serine hydroxymethyltransferase (glyA), and methylenetetrahydrofolate reductase (folD). Additionally, two presumed auxotrophic hosts, incapable of forming tetrahydrofolate (THF) due to the absence of folA, were identified as potential hosts for some CPR bacteria harboring folA genes. The functionality of these CPR-derived folA genes was experimentally verified by heterologous expression in the folA-deletion mutant Escherichia coli MG1655 ΔfolA. Further assessment of the available CPR genomes (n = 4,581) revealed that the genes encoding the proteins for the synthesis of bioactive folate derivatives (e.g., folA, glyA, and/or folD genes) were present in 90.8% of the genomes examined. It suggests potential widespread metabolic complementarity in folate biosynthesis between CPR and their hosts.

Conclusions: This finding deepens our understanding of the mechanisms of CPR-host symbiosis, providing novel insight into essential cofactor-dependent mutualistic CPR-host interactions. Our observations suggest that CPR bacteria may contribute to auxotrophic organisms and indirectly influence biogeochemical processes. Video Abstract.

Background: Gut microbiota plays a critical role in counteracting enteric viral infection. Our previous study demonstrated that infection of porcine deltacoronavirus (PDCoV) disturbs gut microbiota and causes intestinal damage and inflammation in piglets. However, the influence of gut microbiota on PDCoV infection remains unclear.

Results: Firstly, the relationship between gut microbiota and disease severity of PDCoV infection was evaluated using 8-day-old and 90-day-old pigs. The composition of gut microbiota was significantly altered in 8-day-old piglets after PDCoV infection, leading to severe diarrhea and intestinal damage. In contrast, PDCoV infection barely affected the 90-day-old pigs. Moreover, the diversity (richness and evenness) of microbiota in 90-day-old pigs was much higher compared to the 8-day-old piglets, suggesting the gut microbiota is possibly associated with the severity of PDCoV infection. Subsequently, transplanting the fecal microbiota from the 90-day-old pigs to the 3-day-old piglets alleviated clinical signs of PDCoV infection, modulated the diversity and composition of gut microbiota, and maintained the physical and chemical barrier of intestines. Additionally, metabolomic analysis revealed that the fecal microbiota transplantation (FMT) treatment upregulated the swine intestinal arginine biosynthesis, FMT significantly inhibited the inflammatory response in piglet intestine by modulating the TLR4/MyD88/NF-κB signaling pathway.

Conclusions: PDCoV infection altered the structure and composition of the gut microbiota in neonatal pigs. FMT treatment mitigated the clinical signs of PDCoV infection in the piglets by modulating the gut microbiota composition and intestinal barrier, downregulating the inflammatory response. The preventive effect of FMT provides novel targets for the development of therapeutics against enteropathogenic coronaviruses. Video Abstract.

Background: Antimicrobial resistance is a major global health concern, with the environment playing a key role in its emergence and spread. Understanding the relationships between environmental factors, microbial communities, and resistance mechanisms is vital for elucidating environmental resistome dynamics. In this study, we characterized the environmental resistome of the Baltic Sea and evaluated how environmental gradients and spatial variability, alongside its microbial communities and associated functional genes, influence resistome diversity and composition across geographic regions.

Results: We analyzed the metagenomes of benthic sediments from 59 monitoring stations across a 1,150 km distance of the Baltic Sea, revealing an environmental resistome comprised of predicted antimicrobial resistance genes (ARGs) associated with resistance against 26 antibiotic classes. We observed spatial variation in its resistance profile, with higher resistome diversity in the northern regions and a decline in the dead zones and the southern areas. The combined effects of salinity and temperature gradients, alongside nutrient availability, created a complex environmental landscape that shaped the diversity and distribution of the predicted ARGs. Salinity predominantly influenced microbial communities and predicted ARG composition, leading to clear distinctions between high-saline regions and those with lower to mid-level salinity. Furthermore, our analysis suggests that microbial community composition and mobile genetic elements might be crucial in shaping ARG diversity and composition.

Conclusions: We presented that salinity and temperature were identified as the primary environmental factors influencing resistome diversity and distribution across geographic regions, with nutrient availability further shaping these patterns in the Baltic Sea. Our study also highlighted the interplay between microbial communities, resistance, and associated functional genes in the benthic ecosystem, underscoring the potential role of microbial and mobile genetic element composition in ARG distribution. Understanding how environmental factors and microbial communities modulate environmental resistomes will help predict the impact of future environmental changes on resistance mechanisms in complex aquatic ecosystems. Video Abstract.

Background: The Porcine Epidemic Diarrhea Virus (PEDV) is one of the major challenges facing the global pig farming industry, and vaccines and treatments have proven difficult in controlling its spread. Faecalibacterium prausnitzii (F.prausnitzii), a key commensal bacterium in the gut, has been recognized as a promising candidate for next-generation probiotics due to its potential wide-ranging health benefits. A decrease in F.prausnitzii abundance has been associated with certain viral infections, suggesting its potential application in preventing intestinal viral infections. In this study, we utilized a piglet model to examine the potential role of F.prausnitzii in PEDV infections.

Results: A piglet model of PEDV infection was established and supplemented with F.prausnitzii, revealing that F.prausnitzii mitigated PEDV infection. Further studies found that outer membrane vesicles (OMVs) are the main functional components of F.prausnitzii, and proteomics, untargeted metabolomics, and small RNA-seq were used to analyze the composition of OMVs. Exhaustion of the gut microbiota demonstrated that the function of Fp. OMVs relies on the presence of the gut microbiota. Additionally, metagenomic analysis indicated that Fp. OMVs altered the gut microbiota composition, enhancing the abundance of Faecalibacterium prausnitzii, Prevotellamassilia timonensis, and Limosilactobacillus reuteri. Untargeted metabolomics analysis showed that Fp. OMVs increased phosphatidylcholine (PC) levels, with PC identified as a key metabolite in alleviating PEDV infection. Single-cell sequencing revealed that PC altered the relative abundance of intestinal cells, increased the number of intestinal epithelial cells, and reduced necroptosis in target cells. PC treatment in infected IPEC-J2 and Vero cells alleviated necroptosis and reduced the activation of the RIPK1-RIPK3-MLKL signaling axis, thereby improving PEDV infection.

Conclusion: F.prausnitzii and its OMVs play a critical role in mitigating PEDV infections. These findings provide a promising strategy to ameliorate PEDV infection in piglets. Video Abstract.

Background: Alterations in the composition and function of the intestinal microbiota have been observed in organismal aging across a broad spectrum of animal phyla. Recent findings, which have been derived mostly in simple animal models, have even established a causal relationship between age-related microbial shifts and lifespan, suggesting microbiota-directed interventions as a potential tool to decelerate aging processes. To test whether a life-long microbiome rejuvenation strategy could delay or even prevent aging in non-ruminant mammals, we performed recurrent fecal microbial transfer (FMT) in mice throughout life. Transfer material was either derived from 8-week-old mice (young microbiome, yMB) or from animals of the same age as the recipients (isochronic microbiome, iMB) as control. Motor coordination and strength were analyzed by rotarod and grip strength tests, intestinal barrier function by serum LAL assay, transcriptional responses by single-cell RNA sequencing, and fecal microbial community properties by 16S rRNA gene profiling and metagenomics.

Results: Colonization with yMB improved coordination and intestinal permeability compared to iMB. yMB encoded fewer pro-inflammatory factors and altered metabolic pathways favoring oxidative phosphorylation. Ecological interactions among bacteria in yMB were more antagonistic than in iMB implying more stable microbiome communities. Single-cell RNA sequencing analysis of intestinal mucosa revealed a salient shift of cellular phenotypes in the yMB group with markedly increased ATP synthesis and mitochondrial pathways as well as a decrease of age-dependent mesenchymal hallmark transcripts in enterocytes and TA cells, but reduced inflammatory signaling in macrophages.

Conclusions: Taken together, we demonstrate that life-long and repeated transfer of microbiota material from young mice improved age-related processes including coordinative ability (rotarod), intestinal permeability, and both metabolic and inflammatory profiles mainly of macrophages but also of other immune cells. Video Abstract.

Background: Lignin, as the most abundant recalcitrant organic carbon in terrestrial ecosystems, plays a crucial role in the Earth's carbon cycle. After lignin entering aquatic environments, portion of it tends to accumulate in sediments, forming a stable carbon relatively reservoir. However, the increasing temperature caused by human activities may impact microbial-mediated lignin decomposition, thereby affecting sedimentary carbon reservoirs. Therefore, revealing how temperature affects microbial-mediated lignin decomposition in river sediment, a topic that remains elusive, is essential for comprehending the feedbacks between river carbon reservoirs and climate. To address this, we conducted stable isotope probing of river surface sediment using ¹³C-lignin and ¹³C-vanillin, and utilized a series of techniques, including CO₂ production analysis, 16S rRNA gene amplicon sequencing, metagenomics, and metatranscriptomics, to identify the lignin-decomposing microbes and the effects of temperature on microbial-mediated lignin decomposition.

Results: We found that elevated temperatures not only increased the total sediment respiration (total CO₂) and the CO₂ emissions from lignin/vanillin decomposition, but also enhanced priming effects. The ¹³C-labled taxa, including Burkholderiales, Sphingomonadales, and Pseudomonadales, were identified as the main potential lignin/vanillin decomposers, and their abundances and activity significantly increased as temperature increased. Furthermore, we observed that increasing temperature significantly increased the activity of lignin decomposing pathways, including β-aryl ether fragments and 4,5-PDOG pathway. Additionally, as temperature increases, the transcriptional abundances of other carbon cycling related genes, such as pulA (starch decomposition) and xyla (hemicellulose decomposition), also exhibited increasing trends. Overall, our study elucidated the potential lignin-decomposing microbes and pathways in river sediment and their responses to temperature increasing.

Conclusions: Our study demonstrated that the temperature increasing can increase the rate of lignin/vanillin decomposition via affecting the activity of lignin-decomposing microbes. This finding indicates that the ongoing intensification of global warming may enhance the decomposition of recalcitrant organic carbon in river sediment, thereby impacting global carbon cycling. Video Abstract.

The human microbiome, a complex ecosystem of microorganisms inhabiting the body, plays a critical role in human health. Investigating its association with host traits is essential for understanding its impact on various diseases. Although shotgun metagenomic sequencing technologies have produced vast amounts of microbiome data, analyzing such data is highly challenging due to its sparsity, noisiness, and high feature dimensionality. Here, we develop MIOSTONE, an accurate and interpretable neural network model for microbiome-disease association that simulates a real taxonomy by encoding the relationships among microbial features. The taxonomy-encoding architecture provides a natural bridge from variations in microbial taxa abundance to variations in traits, encompassing increasingly coarse scales from species to domains. MIOSTONE has the ability to determine whether taxa within the corresponding taxonomic group provide a better explanation in a data-driven manner. MIOSTONE serves as an effective predictive model, as it not only accurately predicts microbiome-trait associations across extensive simulated and real datasets but also offers interpretability for scientific discovery. Both attributes are crucial for facilitating in silico investigations into the biological mechanisms underlying such associations among microbial taxa. Video Abstract.

Background: In humans and pigs, altered composition of the microbiota associated with the epithelium of the palatine tonsils has been associated with bacterial or viral infection and lymphoid tissue inflammation. Tonsil lymphoid tissue is important for immunity and considered an important portal of entry for pathogens such as Streptococcus suis. Little is known about correlations between tonsil-associated microbiota, tonsillar infections, and the species that might confer colonization resistance against pathogens. Here, we describe a large collection of representative bacterial species from the tonsil surface biofilm and used genome mining and in vitro assays to assess their potential as probiotics to reduce infections by S. suis and other pathogens.

Results: Data on tonsil microbiota composition from over 100 piglets from 11 farms and 3 countries revealed a core microbiota comprising Actinobacillus, Streptococcus, and Moraxella and 11 other less abundant but prevalent genera. To establish a collection of culturable core species, we plated 5 tonsil swabs taken from healthy piglets on different farms and countries on 8 different media and isolated 518 pure cultures belonging to 23 genera. To identify candidate probiotic strains, we tested for antagonistic activity against a panel of pathogens and in silico genome mining to find biosynthetic gene clusters (BGCs) in isolates that might produce antimicrobial compounds. We identified two novel species with potential probiotic activities: a Brevibacterium species and Corynebacterium species producing a heat and proteolytically stable lanthipeptide variant of flavucin, inhibiting in vitro growth of the opportunistic pathogens S. suis and Staphylococcus aureus.

Conclusions: We defined the core tonsil microbiota of piglets and cultured representative single bacterial isolates for research on microbiota-host interactions in the oral cavity. Several isolates inhibiting the growth of bacterial pathogens that might be exploited as probiotics to promote colonization resistance were deposited in publicly available strain repositories. Our mining of genomes from cultured isolates suggests that the tonsil microbiota is an untapped source of novel antimicrobials Video Abstract.

Background: Fatty liver hemorrhage syndrome (FLHS) has become one of the major factors leading to the death of laying hen in caged egg production. FLHS is commonly associated with lipid peroxidation, hepatocyte injury, decreased antioxidant capacity, and inflammation. However, there are limited evidences regarding the preventive effect of Lactiplantibacillus plantarum on FLHS in laying hens and its mechanisms. Our previous results showed that Lp. plantarum FRT4 alleviated FLHS by regulating lipid metabolism, but did not focus on its antioxidant and anti-inflammatory functions and mechanisms. Therefore, this study aimed to investigate the preventive mechanisms of Lp. plantarum FRT4 in alleviating FLHS, with a focus on its role in antioxidant activity and inflammation regulation.

Results: Supplementation with Lp. plantarum FRT4 enhanced the levels of T-AOC, T-SOD, and GSH-Px, while reducing the levels of TNF-α, IL-1β, IL-8, and NLRP3 in the liver and ovary of laying hens. Additionally, Lp. plantarum FRT4 upregulated the mRNA expressions of SOD1, SOD2, CAT, and GPX1, downregulated the mRNA expressions of pro-inflammatory factors IL-1β, IL-6, and NLRP3, and upregulated the mRNA expressions of anti-inflammatory factors IL-4 and IL-10. Lp. plantarum FRT4 improved the structure and metabolic functions of gut microbiota, and regulated the relative abundances of dominant phyla (Bacteroidetes, Firmicute, and Proteobacteria) and genera (Prevotella and Alistipes). Additionally, it influenced key KEGG pathways, including tryptophan metabolism, amino sugar and nucleotide sugar metabolism, insulin signaling pathway, FoxO signaling pathway. Spearman analysis revealed that the abundance of microbiota at different taxonomic levels was closely related to antioxidant enzymes and inflammatory factors. Furthermore, Lp. plantarum FRT4 modulated the mRNA expressions of related factors in the FoxO/TLR-4/NF-κB signaling pathway by regulating gut microbiota. Moreover, the levels of E₂, FSH, and VTG were significantly increased in the ovary after Lp. plantarum FRT4 intervention.

Conclusions: Lp. plantarum FRT4 effectively ameliorates FLHS in laying hens. This efficacy is attributed to its antioxidant and anti-inflammatory properties, which are mediated by modulating the structure and function of gut microbiota, and further intervening in the FoxO/TLR-4/NF-κB signaling pathway. These actions enhance hepatic and ovarian function and increase estrogen levels. Video Abstract.