mSystems最新文献

{"title":"A call for healing and unity.","authors":"Patrick D Schloss","doi":"10.1128/msystems.00266-25","DOIUrl":"https://doi.org/10.1128/msystems.00266-25","url":null,"abstract":"","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0026625"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515768","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":"Comparative metagenome-associated analysis of gut microbiota and antibiotic resistance genes in acute gastrointestinal injury patients with the risk of in-hospital mortality.","authors":"Yunpeng Bai, Yali Hu, Xiangyin Chen, Linhui Hu, Kunyong Wu, Silin Liang, Jinshui Zheng, Michael G Gänzle, Chunbo Chen","doi":"10.1128/msystems.01444-24","DOIUrl":"https://doi.org/10.1128/msystems.01444-24","url":null,"abstract":"<p><p>Acute gastrointestinal injury (AGI) is known for its poor long-term prognosis and the associated increase in mortality among intensive care unit (ICU) patients. As the role of the gut microbiome and resistome in AGI remains unclear, the present study aimed to explore the possible associations between dysbacteriosis and in-hospital mortality in ICU patients with gastrointestinal dysfunction. Fecal samples were collected from a prospective cohort of 210 ICU patients with AGI, and shotgun metagenomic sequencing was used to determine the taxonomic composition of gut microbiota and the differences of antibiotic resistance genes (ARGs) between the Death and Survival groups. Compared to the Survival group, patients in the Death group shifted from strict anaerobes to facultative anaerobes in the fecal microbial community, with more <i>Klebsiella</i> but less <i>Prevotella</i>. The co-occurrence patterns revealed that more ARG subtypes were enriched in microbial taxa in the Death group, especially for <i>Clostridium</i> and <i>Methanobrevibacter</i>. Furthermore, the ARG type had large area under the curve (AUCs) in receiver operating characteristic for predicting the disease severity, and a combined gut microbiota-ARG subtype classifiers showed better performance than either of them. Thus, comparative metagenome-associated analysis can help to obtain valuable information about gut microbiota and gene coding for antibiotic resistance in AGI patients.</p><p><strong>Importance: </strong>A metagenomic-related strategy was conducted to obtain a highly valuable resource to improve understanding of intestinal microbiota dysbiosis and antibiotic resistance genes (ARGs) profiles. The results indicate that intestinal microbiota, including <i>Klebsiella</i> and <i>Prevotella</i>, changed dramatically in intensive care unit (ICU) patients with acute gastrointestinal injury (AGI). Due to longer ICU stays and receiving more antibiotic treatment, the types and correlations of ARGs in the Death group were significantly higher than those in the Survival group. The findings of this study are expected to expand our knowledge of gut microbiota and resistome profiles reflecting gastrointestinal status, accelerate the identification of disease biomarkers, and provide new insights into the prevention and treatment of AGI-related diseases.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0144424"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515972","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":"Fecal bacterial biomarkers and blood biochemical indicators as potential key factors in the development of colorectal cancer.","authors":"Ping Cai, Qingzhen Yang, Jiaqi Lu, Xiaoyu Dai, Jinbo Xiong","doi":"10.1128/msystems.00043-25","DOIUrl":"https://doi.org/10.1128/msystems.00043-25","url":null,"abstract":"<p><p>The incidence of colorectal cancer (CRC) has been increasing in recent decades. Current methods for CRC screening have their own drawbacks, thus there is an urgent need to identify the key microbes that drive the development of CRC for wider application in the early detection and prevention of CRC. To address this issue, we performed fecal microbiome analysis by high-throughput sequencing of 16S rRNA gene combined with blood biochemical indicators in patients with CRC stages I, II, III, and IV, healthy people, and patients with polyps. Fecal microbiota of patients with CRC was disturbed, as evidenced by significantly reduced α-diversity in patients with CRC stage IV and markedly different β-diversity. The random forest model identified the top 25 genera from 174 training data, resulting in a diagnostic accuracy of 87.95%. Further, by combining with differential genera analysis, we screened out 11 biomarkers that significantly changed in different groups. <i>Peptostreptococcus</i>, <i>Parvimonas</i>, <i>Shewanella</i>, <i>Oscillibacter</i>, <i>Eggerthella</i>, and <i>Gemella</i> associated with the development of CRC were significantly enriched, while <i>Fenollaria</i>, <i>Staphylococcus</i>, <i>Ezakiella</i>, <i>Finegoldia,</i> and <i>Neisseria</i> associated with the remission of CRC were significantly suppressed in patients with CRC. Importantly, carcinoembryonic antigen (CEA) was significantly correlated with these 11 microbial biomarkers, and carbohydrate antigen 19-9 (CA 19-9) was markedly correlated with <i>Oscillibacter</i>. Notably, co-occurrence network analysis at the genus level exhibited that the microbial co-occurrence network of CRC IV was the most complex and stable. These results suggested that CEA, CA 19-9 and 11 microbial biomarkers may be co-biomarkers for the disease occurrence and development, and non-invasive diagnosis of CRC.</p><p><strong>Importance: </strong>Identifying the key microbes that drive the development of colorectal cancer (CRC) has been important in this field. We delved into the research on the association between CRC and fecal microbiota in this study, providing a detailed analysis of the characteristics of fecal microbiota during the transition from normal intestine to polyps to cancer. Fecal bacterial biomarkers and blood biochemical indicators may be co-biomarkers in the development of CRC.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0004325"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516081","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":"Dual RNA-seq reveals the complement protein C3-mediated host-pathogen interaction in the brain abscess caused by <i>Staphylococcus aureus</i>.","authors":"Qiyuan Jin, Yaxuan Zhai, Rui Qiang, Xin Ma, Chenhao Zhao, Jinqi Zhong, Jijie Li, Qi Chen, Mingxiao Han, Hong Du, Qifei Cong, Haifang Zhang","doi":"10.1128/msystems.01540-24","DOIUrl":"https://doi.org/10.1128/msystems.01540-24","url":null,"abstract":"<p><p>This study aimed to elucidate the complement protein C3-mediated host-pathogen interaction in the brain abscess caused by <i>Staphylococcus aureus</i> infection. Dual RNA-seq was employed to analyze the transcriptomic differences between C3 deficiency and wild-type mice of <i>S. aureus-</i>induced brain abscess model, and then we investigated the potential regulatory pathways of <i>S. aureus-</i>host interaction mediated by C3 and <i>S. aureus</i> genes associated with the pathogenesis of brain abscess. Finally, C3 deficient-mice and <i>hla</i> mutants of <i>S. aureus</i> were used to verify the specific pathogen-host interaction. In the <i>S. aureus-</i>induced brain abscess mouse model, the transcriptomic analysis revealed significant changes in bacterial virulence factors, such as hemolysin. Based on these data, we predicted a regulatory network formed by genes like <i>hrcA</i> and <i>dnaK</i>, which represent a possible regulation mechanism of <i>S. aureus</i> responding to the host. Furthermore, we identified that <i>hla</i> was the C3 response gene in <i>S. aureus</i>. From the host perspective, we observed that the absence of C3 significantly impacted the host's inflammatory response, primarily by altering the gene expression of several key immune and inflammatory pathways. These findings suggest that C3 deficiency may impair the host's ability to recognize and respond to external pathogens. To the best of our knowledge, this study proposed that <i>S. aureus</i> may affect host immune response through C3, and C3 plays a critical role in regulating inflammation and immune signaling pathways in the brain abscess caused by <i>S. aureus</i> infection.IMPORTANCEIn this work, we employed immunofluorescence and Western blot analysis to reveal a significant upregulation of microglia-derived C3 in the brain abscess mice model caused by <i>S. aureus</i> infection. By integrating the individual RNA sequencing data of <i>S. aureus</i> and the dual RNA-seq data of <i>S. aureus</i> infection brain abscess mice model, the potential regulatory pathways between <i>S. aureus</i> and host were identified, and host C3 not only affects the immune response but also mediates the regulation network of <i>S. aureus</i>. This study provided the potential novel targets for therapeutic strategies in mitigating the effects of <i>S. aureus</i> infections and improving treatment outcomes.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0154024"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502687","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":"Context matters: assessing the impacts of genomic background and ecology on microbial biosynthetic gene cluster evolution.","authors":"Rauf Salamzade, Lindsay R Kalan","doi":"10.1128/msystems.01538-24","DOIUrl":"https://doi.org/10.1128/msystems.01538-24","url":null,"abstract":"<p><p>Encoded within many microbial genomes, biosynthetic gene clusters (BGCs) underlie the synthesis of various secondary metabolites that often mediate ecologically important functions. Several studies and bioinformatics methods developed over the past decade have advanced our understanding of both microbial pangenomes and BGC evolution. In this minireview, we first highlight challenges in broad evolutionary analysis of BGCs, including delineation of BGC boundaries and clustering of BGCs across genomes. We further summarize key findings from microbial comparative genomics studies on BGC conservation across taxa and habitats and discuss the potential fitness effects of BGCs in different settings. Afterward, recent research showing the importance of genomic context on the production of secondary metabolites and the evolution of BGCs is highlighted. These studies draw parallels to recent, broader, investigations on gene-to-gene associations within microbial pangenomes. Finally, we describe mechanisms by which microbial pangenomes and BGCs evolve, ranging from the acquisition or origination of entire BGCs to micro-evolutionary trends of individual biosynthetic genes. An outlook on how expansions in the biosynthetic capabilities of some taxa might support theories that open pangenomes are the result of adaptive evolution is also discussed. We conclude with remarks about how future work leveraging longitudinal metagenomics across diverse ecosystems is likely to significantly improve our understanding on the evolution of microbial genomes and BGCs.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0153824"},"PeriodicalIF":5.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483667","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":"Rationally minimizing natural product libraries using mass spectrometry.","authors":"Monica Ness, Thilini Peramuna, Karen L Wendt, Jennifer E Collins, Jarrod B King, Raphaella Paes, Natalia Mojica Santos, Crystal Okeke, Cameron R Miller, Debopam Chakrabarti, Robert H Cichewicz, Laura-Isobel McCall","doi":"10.1128/msystems.00844-24","DOIUrl":"10.1128/msystems.00844-24","url":null,"abstract":"<p><p>Natural products are a critical source of novel chemotypes for drug discovery. However, the implementation of natural product extract libraries in high throughput screening is hampered by natural product structural redundancy and potential for bioactive re-discovery. This challenge and large library sizes drastically increase the time and cost during initial high throughput screens. To address these limitations, we developed a method that leverages liquid chromatography-tandem mass spectrometry spectral similarity to dramatically reduce natural product library size, with minimal bioactive loss, and applied this to a collection of fungal extracts. Importantly, this method also afforded increased bioassay hit rates against microbial targets, with broad applicability across assays and natural product sources. Thus, this method offers a broadly applicable strategy for accelerated and cost-effective natural product drug discovery.</p><p><strong>Importance: </strong>Natural product libraries are large collections of extracts derived from fungi, plants, bacteria, or any other natural sources. These libraries play an important role in the initial phases of drug discovery, providing the basis for bioassays against a target of interest. However, these collections often comprise thousands of extracts with sometimes overlapping chemical structures, which can result in a bottleneck in both time and costs for the initial phases of drug discovery. Here, we have developed a method that uses mass spectrometry to dramatically reduce the size of these libraries, with minimal tradeoffs and improved success rates in bioassays. Ultimately, this will speed up the process of bioactive candidate identification and isolation, and drug development overall.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0084424"},"PeriodicalIF":5.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483672","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":"Environmental matrix and moisture influence soil microbial phenotypes in a simplified porous media incubation.","authors":"Josué Rodríguez-Ramos, Natalie Sadler, Elias K Zegeye, Yuliya Farris, Samuel Purvine, Sneha Couvillion, William C Nelson, Kirsten S Hofmockel","doi":"10.1128/msystems.01616-24","DOIUrl":"https://doi.org/10.1128/msystems.01616-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Soil moisture and porosity regulate microbial metabolism by influencing factors, such as system chemistry, substrate availability, and soil connectivity. However, accurately representing the soil environment and establishing a tractable microbial community that limits confounding variables is difficult. Here, we use a reduced-complexity microbial consortium grown in a glass bead porous media amended with chitin to test the effects of moisture and a structural matrix on microbial phenotypes. Leveraging metagenomes, metatranscriptomes, metaproteomes, and metabolomes, we saw that our porous media system significantly altered microbial phenotypes compared with the liquid incubations, denoting the importance of incorporating pores and surfaces for understanding microbial phenotypes in soils. These phenotypic shifts were mainly driven by differences in expression of &lt;i&gt;Streptomyces&lt;/i&gt; and &lt;i&gt;Ensifer&lt;/i&gt;, which included a significant decrease in overall chitin degradation between porous media and liquid. Our findings suggest that the success of &lt;i&gt;Ensifer&lt;/i&gt; in porous media is likely related to its ability to repurpose carbon via the glyoxylate shunt amidst a lack of chitin degradation byproducts while potentially using polyhydroxyalkanoate granules as a C source. We also identified traits expressed by &lt;i&gt;Ensifer&lt;/i&gt; and others, including motility, stress resistance, and carbon conservation, that likely influence the metabolic profiles observed across treatments. Together, these results demonstrate that porous media incubations promote structure-induced microbial phenotypes and are likely a better proxy for soil conditions than liquid culture systems. Furthermore, they emphasize that microbial phenotypes encompass not only the multi-enzyme pathways involved in metabolism but also include the complex interactions with the environment and other community members.IMPORTANCESoil moisture and porosity are critical in shaping microbial metabolism. However, accurately representing the soil environment in tractable laboratory experiments remains a challenging frontier. Through our reduced complexity microbial consortium experiment in porous media, we reveal that predicting microbial metabolism from gene-based pathways alone often falls short of capturing the intricate phenotypes driven by cellular interactions. Our findings highlight that porosity and moisture significantly affect chitin decomposition, with environmental matrix (i.e., glass beads) shifting community metabolism towards stress tolerance, reduced resource acquisition, and increased carbon conservation, ultimately invoking unique microbial strategies not evident in liquid cultures. Moreover, we find evidence that changes in moisture relate to community shifts regarding motility, transporters, and biofilm formation, which likely influence chitin degradation. Ultimately, our incubations showcase how reduced complexity communities can be informative of microbial metabolism and present a useful","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0161624"},"PeriodicalIF":5.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483669","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":"Plasmid-borne <i>mcr-1</i> and replicative transposition of episomal and chromosomal <i>bla</i>_NDM-1, <i>bla</i>_OXA-69, and <i>bla</i>_OXA-23 carbapenemases in a clinical <i>Acinetobacter baumannii</i> isolate.","authors":"Masego Mmatli, Nontombi Marylucy Mbelle, John Osei Sekyere","doi":"10.1128/msystems.01683-24","DOIUrl":"https://doi.org/10.1128/msystems.01683-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;A multidrug-resistant clinical &lt;i&gt;Acinetobacter baumannii&lt;/i&gt; isolate with resistance to most antibiotics was isolated from a patient at an intensive care unit. The genetic environment, transcriptome, mobile, and resistome were characterized. The MicroScan system, disc diffusion, and broth microdilution were used to determine the resistance profile of the isolate. A multiplex PCR assay was also used to screen for carbapenemases and &lt;i&gt;mcr&lt;/i&gt;-1 to -5 resistance genes. Efflux-pump inhibitors were used to evaluate efflux activity. The resistome, mobilome, epigenome, and transcriptome were characterized. There was phenotypic resistance to 22 of the 25 antibiotics tested, intermediate resistance to levofloxacin and nalidixic acid, and susceptibility to tigecycline, which corresponded to the 27 resistance genes found in the genome, most of which occurred in multiple copies through replicative transposition. A plasmid-borne (pR-B2.MM_C3) &lt;i&gt;mcr-&lt;/i&gt;1 and chromosomal &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;PER-7&lt;/sub&gt;&lt;i&gt;, bla&lt;/i&gt;&lt;sub&gt;OXA-69&lt;/sub&gt;&lt;i&gt;, bla&lt;/i&gt;&lt;sub&gt;OXA-23&lt;/sub&gt; (three copies), &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;ADC-25&lt;/sub&gt;, &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;TEM-1B&lt;/sub&gt;, and &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;NDM-1&lt;/sub&gt; were found within composite transposons, ISs, and/or class 1 and 2 integrons on genomic islands. Types I and II methylases and restriction endonucleases were in close synteny to these resistance genes within the genomic islands; chromosomal genomic islands aligned with known plasmids. There was a closer evolutionary relationship between the strain and global strains but not local or regional strains; the resistomes also differed. Significantly expressed/repressed genes (6.2%) included resistance genes, hypothetical proteins, mobile elements, methyltransferases, transcription factors, and membrane and efflux proteins. The genomic evolution observed in this strain explains its adaptability and pandrug resistance and shows its genomic plasticity on exposure to antibiotics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;A pandrug-resistant pathogen that was susceptible to only a single antibiotic, tigecycline, was isolated from a middle-aged patient in an ICU. This pathogen contained two plasmids and had a chromosome that contained portions that were integrated externally from plasmids. These genomic islands were rich with resistance genes, mobile genetic elements, and restriction-modification systems that protected the pathogen and facilitated gene regulation. The strain contained 35 resistance genes and 12 virulence genes. The strain was of closer evolutionary distance to several international strains suggesting that it was imported into South Africa. However, its resistome was unique, suggesting an independent evolution on exposure to antibiotic therapy mediated by epigenomic factors and MGE transposition events. The varied mechanisms available to this strain to overcome antibiotic resistance and spread to other areas and/or transfer its resistance determinants are worrying. This is ultimately a risk to public ","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0168324"},"PeriodicalIF":5.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483670","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":"Gut microbiota development in very preterm infants following fortification of human milk.","authors":"Lin Yang, Yan Hui, Per Torp Sangild, Witold Piotr Kot, Lise Aunsholt, Gitte Zachariassen, Ping-Ping Jiang, Dennis Sandris Nielsen","doi":"10.1128/msystems.00916-24","DOIUrl":"https://doi.org/10.1128/msystems.00916-24","url":null,"abstract":"<p><p>Very preterm infants (VPIs) are born with an immature gut and predisposed to gut microbiota dysbiosis-related diseases, for example, necrotizing enterocolitis. Although fortification of human milk is required for these infants, the optimal fortifier remains uncertain. Bovine colostrum (BC), rich in protein and bioactive components, could serve as an alternative to conventional fortifiers (CF). The gut microbiota (GM) of 225 VPIs fed human milk fortified with either BC or CF (FortiColos study, NCT03537365) was profiled by 16S rRNA gene amplicon sequencing of fecal samples collected before, and after 1 and 2 weeks of fortification. Birth mode exhibited transient effects on the microbial community structure shortly after birth, with cesarean section-born VPIs dominated by <i>Firmicutes</i>, whereas vaginally born VPIs were dominated by <i>Proteobacteria</i>. This birth mode-derived difference diminished with age and disappeared around 1 month after birth. Fortifier type affected the microbial community structure to a modest extent, but no specific taxa significantly differed between the BC and CF groups. Fecal pH, increased by BC, was positively correlated with <i>Staphylococcus</i> and <i>Corynebacterium</i> and negatively with <i>Bifidobacterium</i> abundance. Change in the relative abundance of <i>Staphylococcus</i> was negatively correlated with body weight gain. Collectively, fortification of human milk with BC or CF does influence the GM of VPIs but only to a modest extent during early life. Birth mode appears to have a significant, but temporary influence on the GM during this period.IMPORTANCEEarly life is a key period for gut microbiota (GM) establishment, where enteral feeding plays a significant role. This is also the case for infants born preterm, who, due to their immature gut, are at a high risk of developing GM dysbiosis-related diseases. Human milk is the optimal feed for preterm infants, but it requires fortification to reach adequate levels of especially protein. Only a few studies have investigated the impact of fortifiers on GM development in preterm infants. Here, we demonstrate that two different bovine milk-based fortifiers, bovine colostrum and a conventional fortifier based on mature bovine milk, exhibit limited effects on the microbial community structure of very preterm infants. These findings suggest that although great care in terms of optimally maturing the preterm infant GM should be taken, the choice of fortifier only has limited impact. In clinical practice, the choice of fortifier can thus be fully focussed on optimizing preterm infant nutrition.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT03537365.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0091624"},"PeriodicalIF":5.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468500","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":"Integrating sequence composition information into microbial diversity analyses with k-mer frequency counting.","authors":"Nicholas A Bokulich","doi":"10.1128/msystems.01550-24","DOIUrl":"https://doi.org/10.1128/msystems.01550-24","url":null,"abstract":"<p><p>k-mer frequency information in biological sequences is used for a wide range of applications, including taxonomy classification, sequence similarity estimation, and supervised learning. However, in spite of its widespread utility, k-mer counting has been largely neglected for diversity estimation. This work examines the application of k-mer counting for alpha and beta diversity as well as supervised classification from microbiome marker-gene sequencing data sets (16S rRNA gene and full-length fungal internal transcribed spacer [ITS] sequences). Results demonstrate a close correspondence with phylogenetically aware diversity metrics, and advantages for using k-mer-based metrics for measuring microbial biodiversity in microbiome sequencing surveys. k-mer counting appears to be a suitable and efficient strategy for feature processing prior to diversity estimation as well as supervised learning in microbiome surveys. This allows the incorporation of subsequence-level information into diversity estimation without the computational cost of pairwise sequence alignment. k-mer counting is proposed as a complementary approach for feature processing prior to diversity estimation and supervised learning analyses, enabling large-scale reference-free profiling of microbiomes in biogeography, ecology, and biomedical data. A method for k-mer counting from marker-gene sequence data is implemented in the QIIME 2 plugin q2-kmerizer (https://github.com/bokulich-lab/q2-kmerizer).</p><p><strong>Importance: </strong>k-mers are all of the subsequences of length k that comprise a sequence. Comparing the frequency of k-mers in DNA sequences yields valuable information about the composition of these sequences and their similarity. This work demonstrates that k-mer frequencies from marker-gene sequence surveys can be used to inform diversity estimates and machine learning predictions that incorporate sequence composition information. Alpha and beta diversity estimates based on k-mer frequencies closely correspond to phylogenetically aware diversity metrics, suggesting that k-mer-based diversity estimates are useful proxy measurements especially when reliable phylogenies are not available, as is often the case for some DNA sequence targets such as for internal transcribed spacer sequences.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0155024"},"PeriodicalIF":5.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458633","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}