mSystems最新文献

{"title":"Multi-omics mechanical analysis of gut microbiota, carboxylic acids, and cardiac gene expression interaction triggering diabetic cardiomyopathy.","authors":"Meixin Shi, Bingbing Zhao, Wenjie Cai, Hui Yuan, Xiao Liang, Zhitao Li, Xinyu Liu, Ye Jin, Xi Liu, Can Wei","doi":"10.1128/msystems.01450-24","DOIUrl":"10.1128/msystems.01450-24","url":null,"abstract":"<p><p>It is well known that gut microbial imbalance is a potential factor for the occurrence and development of diabetes mellitus (DM) and its complications. Moreover, the heart and gut microbiota can regulate each other through the gut-metabolite-heart axis. In this study, metagenomics, metabolomics, and transcriptomics were chosen to sequence the changes in gut microbiota, serum metabolite levels, and differentially expressed genes (DEGs) in leptin receptor-deficient db/db mice and analyze the correlation between serum metabolites and gut microbiota or DEGs. According to the results, there were significant differences in the 1,029 cardiac genes and 353 serum metabolites in diabetic mice of the db/db group, including DEGs enriched in the PPAR signaling pathway and increased short-chain carboxylic acids (CAs), when compared with the normal db/m group. According to metagenomics, the gut microbiota of mice in the db/db group were disrupted, and particularly Lachnospiraceae bacteria and Oscillospiraceae bacteria significantly decreased. Also, according to the Pearson correlation analysis, a significant positive correlation was found between CAs and PPAR signaling pathway-related DEGs, and a negative correlation was found between CAs and the abundance of the above-mentioned species. To sum up, type 2 diabetes mellitus (T2DM) can upregulate the expression of partial cardiac genes through the levels of serum short-chain CAs affected by gut microbiota, thus playing a role in the occurrence and development of diabetic cardiomyopathy (DCM).</p><p><strong>Importance: </strong>Our research results clearly link the changes in heart genes of T2DM and normal mice with changes in serum metabolites and gut microbiota, indicating that some genes in biological processes are closely related to the reduction of protective microbiota in the gut microbiota. This study provides a theoretical basis for investigating the mechanism of DCM and may provide preliminary evidence for the future use of gut microbiota therapy for DCM.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0145024"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles from fifth-stage larval <i>Angiostrongylus cantonensis</i> upregulate cholesterol biosynthesis and suppress NLRP2-associated inflammatory responses in mouse astrocytes.","authors":"Chien-Ju Cheng, Lian-Chen Wang, Lichieh Julie Chu, Kuang-Yao Chen, Ching-Yun Huang, Kuo-Lun Lan, Kuo-Yang Huang","doi":"10.1128/msystems.01014-24","DOIUrl":"10.1128/msystems.01014-24","url":null,"abstract":"<p><p><i>Angiostrongylus cantonensis</i> is a zoonotic parasite that causes severe symptoms in humans, including eosinophilic meningitis and eosinophilic meningoencephalitis. Extracellular vesicles (EVs) derived from helminthes have been implicated in regulating host survival and immune response. However, the roles of <i>A. cantonensis</i> EVs in modulating parasite pathogenesis and host immune response remain poorly understood. Herein, we characterized EVs derived from <i>A. cantonensis</i> fifth-stage larvae (L5) and adult worms. Ultrastructural features showed that EVs from adult worms are smaller in size compared with those from L5. Proteomic analysis identified stage-specific proteins packaged in L5 and adult worm EVs. To investigate the crosstalk between L5 EVs and host cells, RNA sequencing analysis was conducted to identify the differentially expressed genes (DEGs) and enriched biological pathways in mouse astrocytes treated with L5 EVs. GO and KEGG enrichment analysis demonstrated that the pathways related to \"cholesterol biosynthesis\" are significantly upregulated in L5 EV-treated astrocytes. Based on the transcriptomic data, we observed a downregulated trend of NOD-like receptors (NLRs) protein 2 (NLRP2), a key regulator of brain inflammation, in mouse astrocytes treated with L5 EVs. To validate this result, we utilized ATP to induce the expression of NLRP2 inflammasome-related genes and proteins, as well as the secretion of downstream cytokines. Notably, ATP-induced overexpression of NLRP2 inflammasome-related molecules was significantly reduced in mouse astrocytes upon L5 EV treatment. Collectively, our data suggest that <i>A. cantonensis</i> L5 EVs enhance cholesterol synthesis and potentially modulate immune response by reducing NLRP2 inflammasome-related signaling in non-permissive host cells.IMPORTANCE<i>Angiostrongylus cantonensis</i> is a significant causative agent of eosinophilic meningitis and eosinophilic meningoencephalitis in humans. Helminth-derived extracellular vesicles (EVs) are known to play a crucial role in parasite pathogenesis and host immunomodulation. However, the protein compositions of <i>A. cantonensis</i> EVs and their roles in parasite pathogenesis and host immune response remain unclear. Our results demonstrate for the first time the distinct protein compositions in <i>A. cantonensis</i> L5 and adult worm EVs. The highly abundant proteins in L5 EVs that have immunomodulatory or pathogenic potential in the host deserve further investigation. Additionally, the uptake of L5 EVs by mouse astrocytes significantly upregulates cholesterol synthesis and suppresses ATP-induced NLRP2 inflammasome-related signaling. This study highlights the immunomodulatory roles of L5 EVs in non-permissive hosts, suggesting their potential as therapeutic targets and vaccine candidates against <i>A. cantonensis</i>.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0101424"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing host-associated microbiomes using the consumer/resource model.","authors":"Germán Plata, Karthik Srinivasan, Madan Krishnamurthy, Lukas Herron, Purushottam Dixit","doi":"10.1128/msystems.01068-24","DOIUrl":"10.1128/msystems.01068-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;A key step toward rational microbiome engineering is &lt;i&gt;in silico&lt;/i&gt; sampling of realistic microbial communities that correspond to desired host phenotypes, and vice versa. This remains challenging due to a lack of generative models that simultaneously capture compositions of host-associated microbiomes and host phenotypes. To that end, we present a generative model based on the mechanistic consumer/resource (C/R) framework. In the model, variation in microbial ecosystem composition arises due to differences in the availability of effective resources (inferred latent variables), while species' resource preferences remain conserved. Simultaneously, the latent variables are used to model phenotypic states of hosts. &lt;i&gt;In silico&lt;/i&gt; microbiomes generated by our model accurately reproduce universal and dataset-specific statistics of bacterial communities. The model allows us to address three salient questions in host-associated microbial ecologies: (i) which host phenotypes maximally constrain the composition of the host-associated microbiomes? (ii) how context-specific are phenotype/microbiome associations, and (iii) what are plausible microbiome compositions that correspond to desired host phenotypes? Our approach aids the analysis and design of microbial communities associated with host phenotypes of interest.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Generative models are extremely popular in modern biology. They have been used to model the variation of protein sequences, entire genomes, and RNA sequencing profiles. Importantly, generative models have been used to extrapolate and interpolate to unobserved regimes of data to design biological systems with desired properties. For example, there has been a boom in machine-learning models aiding in the design of proteins with user-specified structures or functions. Host-associated microbiomes play important roles in animal health and disease, as well as the productivity and environmental footprint of livestock species. However, there are no generative models of host-associated microbiomes. One chief reason is that off-the-shelf machine-learning models are data hungry, and microbiome studies usually deal with large variability and small sample sizes. Moreover, microbiome compositions are heavily context dependent, with characteristics of the host and the abiotic environment leading to distinct patterns in host-microbiome associations. Consequently, off-the-shelf generative modeling has not been successfully applied to microbiomes.To address these challenges, we develop a generative model for host-associated microbiomes derived from the consumer/resource (C/R) framework. This derivation allows us to fit the model to readily available cross-sectional microbiome profile data. Using data from three animal hosts, we show that this mechanistic generative model has several salient features: the model identifies a latent space that represents variables that determine the growth and, therefore, relative abunda","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0106824"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modification and analysis of context-specific genome-scale metabolic models: methane-utilizing microbial chassis as a case study.","authors":"M A Kulyashov, R Hamilton, Y Afshin, S K Kolmykov, T S Sokolova, T M Khlebodarova, M G Kalyuzhnaya, I R Akberdin","doi":"10.1128/msystems.01105-24","DOIUrl":"10.1128/msystems.01105-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Context-specific genome-scale model (CS-GSM) reconstruction is becoming an efficient strategy for integrating and cross-comparing experimental multi-scale data to explore the relationship between cellular genotypes, facilitating fundamental or applied research discoveries. However, the application of CS modeling for non-conventional microbes is still challenging. Here, we present a graphical user interface that integrates COBRApy, EscherPy, and RIPTiDe, Python-based tools within the BioUML platform, and streamlines the reconstruction and interrogation of the CS genome-scale metabolic frameworks via Jupyter Notebook. The approach was tested using -omics data collected for &lt;i&gt;Methylotuvimicrobium alcaliphilum&lt;/i&gt; 20Z&lt;sup&gt;R&lt;/sup&gt;, a prominent microbial chassis for methane capturing and valorization. We optimized the previously reconstructed whole genome-scale metabolic network by adjusting the flux distribution using gene expression data. The outputs of the automatically reconstructed CS metabolic network were comparable to manually optimized &lt;i&gt;i&lt;/i&gt;IA409 models for Ca-growth conditions. However, the CS model questions the reversibility of the phosphoketolase pathway and suggests higher flux via primary oxidation pathways. The model also highlighted unresolved carbon partitioning between assimilatory and catabolic pathways at the formaldehyde-formate node. Only a very few genes and only one enzyme with a predicted function in C1 metabolism, a homolog of the formaldehyde oxidation enzyme (&lt;i&gt;fae1-2&lt;/i&gt;), showed a significant change in expression in La-growth conditions. The CS-GSM predictions agreed with the experimental measurements under the assumption that the Fae1-2 is a part of the tetrahydrofolate-linked pathway. The cellular roles of the tungsten (W)-dependent formate dehydrogenase (&lt;i&gt;fdhAB&lt;/i&gt;) and &lt;i&gt;fae&lt;/i&gt; homologs (&lt;i&gt;fae1-2&lt;/i&gt; and &lt;i&gt;fae3&lt;/i&gt;) were investigated via mutagenesis. The phenotype of the f&lt;i&gt;dhAB&lt;/i&gt; mutant followed the model prediction. Furthermore, a more significant reduction of the biomass yield was observed during growth in La-supplemented media, confirming a higher flux through formate. &lt;i&gt;M. alcaliphilum&lt;/i&gt; 20Z&lt;sup&gt;R&lt;/sup&gt; mutants lacking &lt;i&gt;fae1-2&lt;/i&gt; did not display any significant defects in methane or methanol-dependent growth. However, contrary to &lt;i&gt;fae1,&lt;/i&gt; the &lt;i&gt;fae1-2&lt;/i&gt; homolog failed to restore the formaldehyde-activating enzyme function in complementation tests. Overall, the presented data suggest that the developed computational workflow supports the reconstruction and validation of CS-GSM networks of non-model microbes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;The interrogation of various types of data is a routine strategy to explore the relationship between genotype and phenotype. An efficient approach for integrating and cross-comparing experimental multi-scale data in the context of whole-genome-based metabolic network reconstruction becomes a powerful tool that facilitates fundamental and appli","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0110524"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prebiotic potential of dietary onion extracts: shaping gut microbial structures and promoting beneficial metabolites.","authors":"Yebeen Yoo, Seongok Kim, WonJune Lee, Jinwoo Kim, Bokyung Son, Kwang Jun Lee, Hakdong Shin","doi":"10.1128/msystems.01189-24","DOIUrl":"10.1128/msystems.01189-24","url":null,"abstract":"<p><p>Onions are well-known vegetables that offer various health benefits. This study explores the impact of onion extracts on gut microbiome using an <i>in vitro</i> fecal incubation model and metabolome analysis. Fecal samples were collected from 19 healthy donors and incubated in the presence or absence of onion extracts for 24 h. To reduce inter-individual variability in the gut microbiome, we employed enterotyping based on baseline fecal microbiota: 14 subjects with a <i>Bacteroides</i>-dominant type (enterotype B) and 5 subjects with <i>Prevotella</i>-dominant type (enterotype P). Alpha diversity was significantly reduced in the onion-treated group compared to the non-treated control group in both <i>Bacteroides</i>- and <i>Prevotella</i>-dominant types. However, significant structural differences in bacterial communities were observed based on weighted UniFrac distance. Notably, short-chain fatty acid (SCFA)-producing bacteria, such as <i>Bifidobacterium</i>_388775, <i>Feacalibacterium</i>, and <i>Fusicatenibacter</i>, were overrepresented in response to onion extracts in enterotype B. Furthermore, genes related to butyrate production were significantly overrepresented in the onion-treated group within enterotype B. Consistent with the enriched taxa and the predicted metabolic pathways, SCFAs and their related metabolites were significantly enriched in the onion-treated group. Additionally, tryptophan metabolism-derived metabolites, including indolelactate (ILA) and indolepropionate (IPA), were elevated by 4- and 32-fold, respectively, in the onion-treated group compared to the control group. <i>In vitro</i> growth assays showed an increase in lactobacilli strains in the presence of onion extracts. These results provide evidence that onion extracts could serve as promising prebiotics by altering gut microbial structure and promoting the production of beneficiary metabolites, including SCFAs and indole derivatives, and enhancing the growth of probiotics.IMPORTANCEThis study is significant as it provides compelling evidence that onion extracts have the potential to serve as effective prebiotics. Utilizing an <i>in vitro</i> fecal incubation model and enterotyping to reduce inter-individual variability, the research demonstrates how onion extracts can alter gut microbial structure and promote the production of beneficial metabolites, including SCFAs and indole derivatives like ILA and IPA. Additionally, onion extract treatment enhances the growth of beneficial probiotics. The findings underscore the potential of onion extracts to improve gut health by enriching specific beneficial bacteria and metabolic pathways, thereby supporting the development of functional foods aimed at improving gut microbiota composition and metabolic health.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0118924"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omic signatures of host response associated with presence, type, and outcome of enterococcal bacteremia.","authors":"Charlie Bayne, Dominic McGrosso, Concepcion Sanchez, Leigh-Ana Rossitto, Maxwell Patterson, Carlos Gonzalez, Courtney Baus, Cecilia Volk, Haoqi Nina Zhao, Pieter Dorrestein, Victor Nizet, George Sakoulas, David J Gonzalez, Warren Rose","doi":"10.1128/msystems.01471-24","DOIUrl":"https://doi.org/10.1128/msystems.01471-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Despite the prevalence and severity of enterococcal bacteremia (EcB), the mechanisms underlying systemic host responses to the disease remain unclear. Here, we present an extensive study that profiles molecular differences in plasma from EcB patients using an unbiased multi-omics approach. We performed shotgun proteomics and metabolomics on 105 plasma samples, including those from EcB patients and healthy volunteers. Comparison between healthy volunteer and EcB-infected patient samples revealed significant disparities in proteins and metabolites involved in the acute phase response, inflammatory processes, and cholestasis. Several features distinguish these two groups with remarkable accuracy. Cross-referencing EcB signatures with those of &lt;i&gt;Staphylococcus aureus&lt;/i&gt; bacteremia revealed shared reductions in cholesterol metabolism proteins and differing responses in platelet alpha granule and neutrophil-associated proteins. Characterization of &lt;i&gt;Enterococcus&lt;/i&gt; isolates derived from patients facilitated a nuanced comparison between EcB caused by &lt;i&gt;Enterococcus faecalis&lt;/i&gt; and &lt;i&gt;Enterococcus faecium,&lt;/i&gt; uncovering reduced immunoglobulin abundances in &lt;i&gt;E. faecium&lt;/i&gt; cases and features capable of distinguishing the underlying microbe. Leveraging extensive patient metadata, we now have identified features associated with mortality or survival, revealing significant multi-omic differences and pinpointing histidine-rich glycoprotein and fetuin-B as features capable of distinguishing survival status with excellent accuracy. Altogether, this study aims to culminate in the creation of objective risk stratification algorithms-a pivotal step toward enhancing patient management and care. To facilitate the exploration of this rich data source, we provide a user-friendly interface at https://gonzalezlab.shinyapps.io/EcB_multiomics/.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;&lt;i&gt;Enterococcus&lt;/i&gt; infections have emerged as the second most common nosocomial infection, with enterococcal bacteremia (EcB) contributing to thousands of patient deaths annually. To address a lack of detailed understanding regarding the specific systemic response to EcB, we conducted a comprehensive multi-omic evaluation of the systemic host response observed in patient plasma. Our findings reveal significant features in the metabolome and proteome associated with the presence of infection, species differences, and survival outcome. We identified features capable of discriminating EcB infection from healthy states and survival from mortality with excellent accuracy, suggesting potential practical clinical utility. However, our study also established that systemic features to distinguish &lt;i&gt;Enterococcus faecalis&lt;/i&gt; from &lt;i&gt;Enterococcus faecium&lt;/i&gt; EcB show only a moderate degree of discriminatory accuracy, unlikely to significantly improve upon current diagnostic methods. Comparisons of differences in the plasma proteome relative to healthy samples between bacteremia caused by &lt;i&gt;","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0147124"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serine/threonine protein kinase mediates rifampicin resistance in <i>Brucella melitensis</i> through interacting with ribosomal protein RpsD and affecting antioxidant capacity.","authors":"Yaqin Yuan, Wenqing Ning, Junjie Chen, Jiquan Li, Tianqi Xue, Cuihong An, Lingling Mao, Guangzhi Zhang, Shizhong Zhou, Jiabo Ding, Xiaowen Yang, Jianqiang Ye","doi":"10.1128/msystems.01109-24","DOIUrl":"10.1128/msystems.01109-24","url":null,"abstract":"<p><p>Brucellosis, a zoonotic disease, has re-emerged in both humans and animals, causing significant economic losses globally. Recently, an increasing number of rifampicin-resistant <i>Brucella</i> strains have been isolated worldwide without detectable mutations in known antibiotic resistance genes. Here, this study identified the deletion of serine/threonine protein kinase (STPK) gene in <i>B. melitensis</i> as an efficient trigger for rifampicin resistance using bioinformatics predictions, a transposon mutant library, and gene mutation strains. Notably, the absence of the STPK could increase the expression of ribosomal proteins and genes involved in sulfur metabolism and reduced glutathione, and decrease NADPH oxidase activity and NADP⁺/NADPH ratio, which is associated with the antioxidant capacity of <i>B. melitensis</i>. Moreover, co-immunoprecipitation revealed that STPK could efficiently interact with the ribosomal protein RpsD, possibly altering protein translation and riboswitch expression. These findings demonstrate that the STPK gene mediates resistance by regulating sulfur metabolism to counteract the reactive oxygen species induced by rifampicin. Furthermore, the approaches developed in this study provide a platform for screening new resistance genes in <i>Brucella</i> spp., and the identified STPK or its pathway can serve as a potential target for new drug development against rifampicin-resistant <i>Brucella</i> spp.</p><p><strong>Importance: </strong>New rifampicin resistance gene in <i>Brucella melitensis</i> is identified via bioinformatics predictions and a whole-genome transposon mutant library, new mechanisms of rifampicin resistance in <i>B. melitensis</i>, and new function of serine/threonine protein kinase gene and its interaction proteins.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0110924"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections.","authors":"Emily Lydon, Christina M Osborne, Brandie D Wagner, Lilliam Ambroggio, J Kirk Harris, Ron Reeder, Todd C Carpenter, Aline B Maddux, Matthew K Leroue, Nadir Yehya, Joseph L DeRisi, Mark W Hall, Athena F Zuppa, Joseph Carcillo, Kathleen Meert, Anil Sapru, Murray M Pollack, Patrick McQuillen, Daniel A Notterman, Charles R Langelier, Peter M Mourani","doi":"10.1128/msystems.01335-24","DOIUrl":"10.1128/msystems.01335-24","url":null,"abstract":"<p><p>Viral lower respiratory tract infection (vLRTI) is a leading cause of hospitalization and death in children worldwide. Despite this, no studies have employed proteomics to characterize host immune responses to severe pediatric vLRTI in both the lower airway and systemic circulation. To address this gap, gain insights into vLRTI pathophysiology, and test a novel diagnostic approach, we assayed 1,305 proteins in tracheal aspirate (TA) and plasma from 62 critically ill children using SomaScan. We performed differential expression (DE) and pathway analyses comparing vLRTI (<i>n</i> = 40) to controls with non-infectious acute respiratory failure (<i>n</i> = 22), developed a diagnostic classifier using LASSO regression, and analyzed matched TA and plasma samples. We further investigated the impact of viral load and bacterial coinfection on the proteome. The TA signature of vLRTI was characterized by 200 DE proteins (P_adj <0.05) with upregulation of interferons and T cell responses and downregulation of inflammation-modulating proteins including FABP and MIP-5. A nine-protein TA classifier achieved an area under the receiver operator curve (AUC) of 0.96 (95% CI: 0.90-1.00) for identifying vLRTI. In plasma, the host response to vLRTI was more muted with 56 DE proteins. Correlation between TA and plasma was limited, although ISG15 was elevated in both compartments. In bacterial coinfection, we observed increases in the TNF-stimulated protein TSG-6, as well as CRP, and interferon-related proteins. Viral load correlated positively with interferon signaling and negatively with neutrophil-activation pathways. Taken together, our study provides fresh insights into the lower airway and systemic proteome of severe pediatric vLRTI and identifies novel protein biomarkers with diagnostic potential.IMPORTANCEWe describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated a positive correlation with interferon-related protein expression and a negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insights into the lower airway and systemic proteome of severe pediatric vLRTI.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0133524"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between oral microbiome and gastric precancerous lesions.","authors":"Yifei Chen, Lei Lei, Mengying Xia, Ran Cheng, He Cai, Tao Hu","doi":"10.1128/msystems.01322-24","DOIUrl":"10.1128/msystems.01322-24","url":null,"abstract":"<p><p>Gastric precancerous lesions are thought to be precursors in the occurrence and development of gastric cancer through Correa's cascade. Recent studies have investigated the association between the oral microbiome and gastric precancerous lesions. However, there has yet to be a comprehensive synthesis review of the existing literature on the relationship between oral microbiome and gastric precancerous lesions. A systematic review was conducted to characterize the literature on the association between oral microbiome and gastric precancerous lesions. The studies show that oral microbiome is dynamic in individuals with gastric precancerous lesions. Oral-derived microorganisms were colonized in the gastric precancerous lesions. Interactions between oral and gastric microbiomes affect the response of the host immunity. The abnormal proliferation of oral-associated microorganisms may be linked to the reduction of gastric acid. The present review supports the potential association between oral microbiome and gastric precancerous lesions. However, the interactions are complex and multifaceted, which require further investigation.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0132224"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of intratumoral microbiome diversity with hepatocellular carcinoma prognosis.","authors":"Fengle Jiang, Yuan Dang, Zheting Zhang, Yanan Yan, Yingchao Wang, Yi Chen, Lihong Chen, Jialiang Zhang, Jingfeng Liu, Jianmin Wang","doi":"10.1128/msystems.00765-24","DOIUrl":"10.1128/msystems.00765-24","url":null,"abstract":"<p><p>The evidence that intratumoral microbiomes, as a rising hallmark of cancer, have a profound impact on cancer phenotypes is increasingly compelling. However, the impact of the composition and diversity of the intratumoral microbiome on the prognosis of patients undergoing surgical resection for hepatocellular carcinoma (HCC) remains incompletely understood. In this study, we revealed a high abundance of bacteria in the neoplastic tissues. The presence of bacterial lipopolysaccharide and lipoteichoic acid was detected alongside tumor-associated immune cells. By utilizing 16S rRNA gene sequencing, we identified a specific intratumoral microbiome signature that was highly predictive of the prognosis for HCC patients who underwent surgical resection. Specifically, the presence of Intestinimonas, Brachybacterium, and Rothia were identified as independent risk factors for the overall survival of HCC patients who underwent surgical resection.IMPORTANCEAlthough some studies have shown an abundance of bacteria in hepatocellular carcinoma (HCC), there is still limited understanding of the composition and diversity of the intratumoral microbiome that is favorable or adverse to the prognosis of HCC patients. Our results indicated that a greater abundance of bacteria could be observed in the neoplastic tissues than in nonneoplastic tissues. Bacterial cell wall components largely coincided with tumor-associated immune cells. The bacteria in the long overall survival (LOS) group were associated with metabolism and cytokine‒cytokine receptor interaction pathways, while bacteria in the short overall survival (SOS) group were associated with proinflammatory and cell proliferation pathways. Notably, specific taxa could independently predict HCC prognosis. Based on these findings, intratumoral microbiomes facilitate the use of precision medicine in clinical practice.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0076524"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}