mSystems最新文献

{"title":"Systematic analyses uncover robust salivary microbial signatures and host-microbiome perturbations in oral squamous cell carcinoma.","authors":"Zewen Han, Yichen Hu, Xin Lin, Hongyu Cheng, Biao Dong, Xuan Liu, Buling Wu, Zhenjiang Zech Xu","doi":"10.1128/msystems.01247-24","DOIUrl":"10.1128/msystems.01247-24","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a prevalent malignancy in the oral-maxillofacial region with a poor prognosis. Oral microbiomes play a potential role in the pathogenesis of this disease. However, findings from individual studies have been inconsistent, and a comprehensive understanding of OSCC-associated microbiome dysbiosis remains elusive. Here, we conducted a large-scale meta-analysis by integrating 11 publicly available data sets comprising salivary microbiome profiles of OSCC patients and healthy controls. After correcting for batch effects, we observed significantly elevated alpha diversity and distinct beta-diversity patterns in the OSCC salivary microbiome compared to healthy controls. Leveraging random effects models, we identified robust microbial signatures associated with OSCC across data sets, including enrichment of taxa such as <i>Streptococcus</i>, <i>Lactobacillus</i>, <i>Prevotella</i>, <i>Bulleidia moorei</i>, and <i>Haemophilus</i> in OSCC samples. The machine learning models constructed from these microbial markers accurately predicted OSCC status, highlighting their potential as non-invasive diagnostic biomarkers. Intriguingly, our analyses revealed that the age- and gender-associated signatures in normal saliva microbiome were disrupted in the OSCC, suggesting perturbations in the intricate host-microbe interactions. Collectively, our findings uncovered complex alterations in the oral microbiome in OSCC, providing novel insights into disease etiology and paving the way for microbiome-based diagnostic and therapeutic strategies. Given that the salivary microbiome can reflect the overall health status of the host and that saliva sampling is a safe, non-invasive approach, it may be worthwhile to conduct broader screening of the salivary microbiome in high-risk OSCC populations as implications for early detection.</p><p><strong>Importance: </strong>The oral cavity hosts a diverse microbial community that plays a crucial role in systemic and oral health. Accumulated research has investigated significant differences in the saliva microbiota associated with oral cancer, suggesting that microbiome dysbiosis may contribute to the pathogenesis of oral squamous cell carcinoma (OSCC). However, the specific microbial alterations linked to OSCC remain controversial. This meta-analysis reveals robust salivary microbiome alterations. Machine learning models using differential operational taxonomic units accurately predicted OSCC status, highlighting the potential of the salivary microbiome as a non-invasive diagnostic biomarker. Interestingly, age- and gender-associated signatures in the normal salivary microbiome were disrupted in OSCC, suggesting perturbations in host-microbe interactions.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0124724"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053076","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":"Deciphering the biosynthetic landscape of biofilms in glacier-fed streams.","authors":"Aileen Ute Geers, Grégoire Michoud, Susheel Bhanu Busi, Hannes Peter, Tyler J Kohler, Leïla Ezzat, Tom J Battin","doi":"10.1128/msystems.01137-24","DOIUrl":"10.1128/msystems.01137-24","url":null,"abstract":"<p><p>Glacier-fed streams are permanently cold, ultra-oligotrophic, and physically unstable environments, yet microbial life thrives in benthic biofilm communities. Within biofilms, microorganisms rely on secondary metabolites for communication and competition. However, the diversity and genetic potential of secondary metabolites in glacier-fed stream biofilms remain poorly understood. In this study, we present the first large-scale exploration of biosynthetic gene clusters (BGCs) from benthic glacier-fed stream biofilms sampled by the <i>Vanishing Glaciers</i> project from the world's major mountain ranges. We found a remarkable diversity of BGCs, with more than 8,000 of them identified within 2,868 prokaryotic metagenome-assembled genomes, some of them potentially conferring ecological advantages, such as UV protection and quorum sensing. The BGCs were distinct from those sourced from other aquatic microbiomes, with over 40% of them being novel. The glacier-fed stream BGCs exhibited the highest similarity to BGCs from glacier microbiomes. BGC composition displayed geographic patterns and correlated with prokaryotic alpha diversity. We also found that BGC diversity was positively associated with benthic chlorophyll <i>a</i> and prokaryotic diversity, indicative of more biotic interactions in more extensive biofilms. Our study provides new insights into a hitherto poorly explored microbial ecosystem, which is now changing at a rapid pace as glaciers are shrinking due to climate change.</p><p><strong>Importance: </strong>Glacier-fed streams are characterized by low temperatures, high turbidity, and high flow. They host a unique microbiome within biofilms, which form the foundation of the food web and contribute significantly to biogeochemical cycles. Our investigation into secondary metabolites, which likely play an important role in these complex ecosystems, found a unique genetic potential distinct from other aquatic environments. We found the potential to synthesize several secondary metabolites, which may confer ecological advantages, such as UV protection and quorum sensing. This biosynthetic diversity was positively associated with the abundance and complexity of the microbial community, as well as concentrations of chlorophyll <i>a</i>. In the face of climate change, our study offers new insights into a vanishing ecosystem.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0113724"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915077","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":"Cooling perspectives on the risk of pathogenic viruses from thawing permafrost.","authors":"Rachel Mackelprang, Robyn A Barbato, Andrew M Ramey, Ursel M E Schütte, Mark P Waldrop","doi":"10.1128/msystems.00042-24","DOIUrl":"10.1128/msystems.00042-24","url":null,"abstract":"<p><p>Climate change is inducing wide-scale permafrost thaw in the Arctic and subarctic, triggering concerns that long-dormant pathogens could reemerge from the thawing ground and initiate epidemics or pandemics. Viruses, as opposed to bacterial pathogens, garner particular interest because outbreaks cannot be controlled with antibiotics, though the effects can be mitigated by vaccines and newer antiviral drugs. To evaluate the potential hazards posed by viral pathogens emerging from thawing permafrost, we review information from a diverse range of disciplines. This includes efforts to recover infectious virus from human remains, studies on disease occurrence in polar animal populations, investigations into viral persistence and infectivity in permafrost, and assessments of human exposure to the enormous viral diversity present in the environment. Based on currently available knowledge, we conclude that the risk posed by viruses from thawing permafrost is no greater than viruses in other environments such as temperate soils and aquatic systems.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0004224"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951951","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":"Biodiversity within phytoplankton-associated microbiomes regulates host physiology, host community ecology, and nutrient cycling.","authors":"Jonathan R Dickey, Nikki M Mercer, Mirte C M Kuijpers, Ruben Props, Sara L Jackrel","doi":"10.1128/msystems.01462-24","DOIUrl":"10.1128/msystems.01462-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Biological diversity is declining across the tree of life, including among prokaryotes. With the increasing awareness of host-associated microbes as potential regulators of eukaryotic host physiology, behavior, and ecology, it is important to understand the implications of declining diversity within host microbiomes on host fitness, ecology, and ecosystem function. We used phytoplankton and their associated environmental microbiomes as model systems to test the independent and interactive effects of declining microbiome diversity with and without other stressors often caused by human activity-elevated temperature and altered nutrient availability. We found effects of low microbiome diversity on host physiology, phytoplankton community dynamics, and nutrient cycling. Low microbiome diversity caused greater host cellular stress, as indicated by elevated δ&lt;sup&gt;13&lt;/sup&gt;C and δ&lt;sup&gt;15&lt;/sup&gt;N. Microbiome diversity also significantly affected host cell morphological metrics, likely as a consequence of this effect on cell stress. Despite causing greater host cellular stress, the effects of low microbiome diversity on host community ecology included elevated phytoplankton community diversity and biomass. The diversity of these host-associated microbes also had cascading implications on ecosystem nutrient cycling, where lower microbiome diversity caused a depletion of total dissolved N and P in the environment. The magnitude of these effects, caused by microbiome diversity, was greatest among nutrient-depleted environments and at elevated temperatures. Our results emphasize the widespread implications of declining host-associated microbial diversity from host cellular physiology to ecosystem nutrient cycling. These demonstrated effects of declining microbiome diversity are likely to be amplified in ecosystems experiencing multiple stressors caused by anthropogenic activities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;As evidence is emerging of the key roles that host-associated microbiomes often play in regulating the physiology, fitness, and ecology of their eukaryotic hosts, human activities are causing declines in biological diversity, including within the microbial world. Here, we use a multifactorial manipulative experiment to test the effects of declining diversity within host microbiomes both alone and in tandem with the effects of emerging global changes, including climate warming and shifts in nutrient bioavailability, which are inflicting increasing abiotic stress on host organisms. Using single-celled eukaryotic phytoplankton that harbor an external microbiome as a model system, we demonstrate that diversity within host-associated microbiomes impacts multiple tiers of biological organization, including host physiology, the host population and community ecology, and ecosystem nutrient cycling. Notably, these microbiome diversity-driven effects became magnified in abiotically stressful environments, suggesting that the importance of microbiome dive","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0146224"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053038","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":"Exploration of the genetic landscape of bacterial dsDNA viruses reveals an ANI gap amid extensive mosaicism.","authors":"Wanangwa Ndovie, Jan Havránek, Jade Leconte, Janusz Koszucki, Leonid Chindelevitch, Evelien M Adriaenssens, Rafal J Mostowy","doi":"10.1128/msystems.01661-24","DOIUrl":"10.1128/msystems.01661-24","url":null,"abstract":"<p><p>Average nucleotide identity (ANI) is a widely used metric to estimate genetic relatedness, especially in microbial species delineation. While ANI calculation has been well optimized for bacteria and closely related viral genomes, accurate estimation of ANI below 80%, particularly in large reference data sets, has been challenging due to a lack of accurate and scalable methods. To bridge this gap, we introduce MANIAC, an efficient computational pipeline optimized for estimating ANI and alignment fraction (AF) in viral genomes with divergence around ANI of 70%. Using a rigorous simulation framework, we demonstrate MANIAC's accuracy and scalability compared to existing approaches, even to data sets of hundreds of thousands of viral genomes. Applying MANIAC to a curated data set of complete bacterial dsDNA viruses revealed a multimodal ANI distribution, with a distinct gap around 80%, akin to the bacterial ANI gap (~90%) but shifted, likely due to viral-specific evolutionary processes such as recombination dynamics and mosaicism. We then evaluated ANI and AF as predictors of genus-level taxonomy using a logistic regression model. We found that this model has strong predictive power (PR-AUC = 0.981), but that it works much better for virulent (PR-AUC = 0.997) than temperate (PR-AUC = 0.847) bacterial viruses. This highlights the complexity of taxonomic classification in temperate phages, known for their extensive mosaicism, and cautions against over-reliance on ANI in such cases. MANIAC can be accessed at https://github.com/bioinf-mcb/MANIAC.IMPORTANCEWe introduce a novel computational pipeline called MANIAC, designed to accurately assess average nucleotide identity (ANI) and alignment fraction (AF) between diverse viral genomes, scalable to data sets of over 100k genomes. Using computer simulations and real data analyses, we show that MANIAC could accurately estimate genetic relatedness between pairs of viral genomes of around 60%-70% ANI. We applied MANIAC to investigate the question of ANI discontinuity in bacterial dsDNA viruses, finding evidence for an ANI gap, akin to the one seen in bacteria but around ANI of 80%. We then assessed the ability of ANI and AF to predict taxonomic genus boundaries, finding its strong predictive power in virulent, but not in temperate phages. Our results suggest that bacterial dsDNA viruses may exhibit an ANI threshold (on average around 80%) above which recombination helps maintain population cohesiveness, as previously argued in bacteria.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0166124"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059760","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":"With a little help from my friends: importance of protist-protist interactions in structuring marine protistan communities in the San Pedro Channel.","authors":"Samantha J Gleich, Lisa Y Mesrop, Jacob A Cram, J L Weissman, Sarah K Hu, Yi-Chun Yeh, Jed A Fuhrman, David A Caron","doi":"10.1128/msystems.01045-24","DOIUrl":"10.1128/msystems.01045-24","url":null,"abstract":"<p><p>Marine protists form complex communities that are shaped by environmental and biological ecosystem properties, as well as ecological interactions between organisms. While all of these factors play a role in shaping protistan communities, the specific ways in which these properties and interactions influence protistan communities remain poorly understood. Fourteen years and 9 months of eukaryotic amplicon (18S-V4 rRNA gene) data collected monthly at the San Pedro Ocean Time-series (SPOT) station were used to evaluate the impacts that environmental and biological factors, and protist-protist interactions had on protistan community composition. Statistical analysis of the amplicon data revealed that seasonal patterns in protistan community composition were apparent, but that the environmental data collected through routine time-series sampling efforts could not explain most of the variability that was evident in the communities. To identify some of the protist-protist interactions that may have played a role in shaping protistan communities, ecological networks were constructed using the amplicon data and the network predictions were compared against a database of confirmed protist-protist interactions. The database comparisons revealed hundreds of established parasitic, predator-prey, photosymbiotic, and mutualistic relationships in the networks. Although many interactions were confirmed using the database, these confirmed interactions constituted only 2% of the interactions identified at the SPOT station, highlighting the need to better characterize protist-protist interactions in marine environments. Finally, the network-predicted interactions that were not found in the database were used to identify putative, novel protist-protist interactions that may have played a role in structuring the protistan communities at the SPOT station.</p><p><strong>Importance: </strong>Network analyses are commonly used to identify some of the ecological interactions that may be occurring between protists in the ocean; however, evaluating predictions obtained from these analyses remains difficult due to the large number of interactions that may be recovered and the limited amount of information available on protist-protist interactions in nature. In this study, ecological network analyses were conducted using data collected at the San Pedro Ocean Time-series (SPOT) station and the network predictions were compared against a database of established protist-protist interactions. These database comparisons revealed hundreds of confirmed protist-protist interactions, and thousands of putative, novel interactions that may be occurring at the SPOT station. The database comparisons carried out in this study provide a new way of evaluating network predictions and highlight the complex, yet critical role that ecological interactions play in shaping protistan community composition in marine ecosystems.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0104524"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059765","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":"<i>Caenorhabditis</i> nematodes influence microbiome and metabolome characteristics of their natural apple substrates over time.","authors":"J Johnke, J Zimmermann, T Stegemann, D Langel, A Franke, L Thingholm, H Schulenburg","doi":"10.1128/msystems.01533-24","DOIUrl":"10.1128/msystems.01533-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The microbiomes of host organisms and their direct source environments are closely linked and key for shaping microbial community dynamics. The relationship between these linked dynamics is largely unexplored because source substrates are usually unavailable. To address this current knowledge gap, we employed bacteriovorous &lt;i&gt;Caenorhabditis&lt;/i&gt; nematodes as a unique model system, for which source substrates like rotting apples can be easily collected. We compared single host microbiomes with their corresponding apple source substrates, as well as nematode-free substrates, over a 2-year sampling period in the botanical garden in Kiel, Germany. We found that single worms have unique microbiomes, which overlap most strongly with nematodes from the same source apple. A comparison to previous, related work revealed that variation in microbiome composition of natural &lt;i&gt;Caenorhabditis&lt;/i&gt; isolates is significantly influenced by the substrate type, from which worms were obtained (e.g., fruits or compost). Our current sampling further showed that microbiome assembly is mostly driven by dispersal limitation. Importantly, two independent analysis approaches consistently suggest that worm microbiomes significantly influence characteristics of the apple microbiomes, possibly indicating niche construction by nematodes. Moreover, combining apple microbiome and metabolome data, we identified individual microbes and specific compounds indicative of fruit ripening that are significantly associated with nematode presence. In conclusion, our study elucidates the complex relationship between host microbiomes and their directly connected substrate microbiomes. Our analyses underscore the significant influence of nematode microbiomes on shaping the apple microbiome and, consequently, the fruit's metabolic capacity, thereby enhancing our general understanding of host-microbiome interactions in their natural habitat.IMPORTANCEAlmost all complex organisms are host to a microbial community, the microbiome. This microbiome can influence diverse host functions, such as food processing, protection against parasites, or development. The relationship between host and microbiome critically depends on the assembly of the microbial community, which may be shaped by microbes in the directly linked environment, the source microbiome. This assembly process is often not well understood because of the unavailability of source substrates. Here, we used &lt;i&gt;Caenorhabditis&lt;/i&gt; nematodes as a model system that facilitates a direct comparison of host and source microbiomes. Based on a 2-year sampling period, we identified (i) a clear link between assembly dynamics of host and source microbiomes, (ii) a significant influence of nematode microbiomes on apple microbiomes, and (iii) specific microbes and compounds that are associated with the presence of nematodes in the sampled substrates. Overall, our study enhances our understanding of microbiome assembly dynamics and resulting functi","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0153324"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951911","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 combination of <i>Clostridium butyricum</i> and <i>Akkermansia muciniphila</i> mitigates DSS-induced colitis and attenuates colitis-associated tumorigenesis by modulating gut microbiota and reducing CD8⁺ T cells in mice.","authors":"Dengxiong Hua, Qin Yang, Xiaowei Li, Xuexue Zhou, Yingqian Kang, Yan Zhao, Daoyan Wu, Zhengrong Zhang, Boyan Li, Xinxin Wang, Xiaolan Qi, Zhenghong Chen, Guzhen Cui, Wei Hong","doi":"10.1128/msystems.01567-24","DOIUrl":"10.1128/msystems.01567-24","url":null,"abstract":"<p><p>The gut microbiota is closely associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). Probiotics such as <i>Clostridium butyricum</i> (CB) or <i>Akkermansia muciniphila</i> (AKK) have the potential to treat inflammatory bowel disease (IBD) or colorectal cancer (CRC). However, research on the combined therapeutic effects and immunomodulatory mechanisms of CB and AKK in treating IBD or CRC has never been studied. This study evaluates the potential of co-administration of CB and AKK in treating DSS/AOM-induced IBD and colitis-associated CRC. Our results indicate that compared to mono-administration, the co-administration of CB and AKK not only significantly alleviates symptoms such as weight loss, colon shortening, and increased Disease Activity Index in IBD mice but also regulates the gut microbiota composition and effectively suppresses colonic inflammatory responses. In the colitis-associated CRC mice model, a combination of CB and AKK significantly alleviates weight loss and markedly reduces inflammatory infiltration of macrophages and cytotoxic T lymphocytes (CTLs) in the colon, thereby regulating anti-tumor immunity and inhibiting the occurrence of inflammation-induced CRC. In addition, we found that the combined probiotic therapy of CB and AKK can enhance the sensitivity of colitis-associated CRC mice to the immune checkpoint inhibitor anti-mouse PD-L1 (aPD-L1), significantly improving the anti-tumor efficacy of immunotherapy and the survival rate of colitis-associated CRC mice. Furthermore, fecal microbiota transplantation therapy showed that transplanting feces from CRC mice treated with the co-administration of CB and AKK into other CRC mice alleviated the tumor loads in the colon and significantly extended their survival rate. Our study suggests that the combined use of two probiotics, CB and AKK, can not only alleviate chronic intestinal inflammation but also inhibit the progression to CRC. This may be a natural and relatively safe method to support the gut microbiota and enhance the host's immunity against cancer.</p><p><strong>Importance: </strong>Our study suggests that the combined administration of CB and AKK probiotics, as opposed to a single probiotic strain, holds considerable promise in preventing the advancement of IBD to CRC. This synergistic effect is attributed to the ability of this probiotic combination to more effectively modulate the gut microbiota, curb inflammatory reactions, bolster the efficacy of immunotherapeutic approaches, and optimize treatment results via fecal microbiota transplantation.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0156724"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008532","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":"Bioenergetic trade-offs can reveal the path to superior microbial CO₂ fixation pathways.","authors":"Ahmed Taha, Mauricio Patón, Jorge Rodríguez","doi":"10.1128/msystems.01274-24","DOIUrl":"10.1128/msystems.01274-24","url":null,"abstract":"<p><p>A comprehensive optimization of known prokaryotic autotrophic carbon dioxide (CO₂) fixation pathways is presented that evaluates all their possible variants under different environmental conditions. This was achieved through a computational methodology recently developed that considers the trade-offs between energy efficiency (yield) and growth rate, allowing us to evaluate candidate metabolic modifications <i>in silico</i> for microbial conversions. The results revealed the superior configurations in terms of both yield (efficiency) and rate (driving force). The pathways from anaerobic organisms appear to fix carbon at lower net ATP cost than those found in aerobic organisms, and the reverse TCA cycle pathway shows the lowest overall energy cost and maximum adaptability across a broad range of CO₂ and electron donor (H₂) concentrations. The reverse tricarboxylic acid cycle and Wood-Ljungdahl pathways appear highly efficient under a broad range of conditions, while the 3-hydroxypropionate 4-hydroxybutyrate cycle and the 3-hydroxypropionate bicycle appear capable of generating large thermodynamic driving forces at only moderate ATP yield losses.IMPORTANCEBiotechnology can lead to cost-effective processes for capturing carbon dioxide using the natural or genetically engineered metabolic capabilities of microorganisms. However, introducing desirable genetic modifications into microbial strains without compromising their fitness (growth yield and rate) during industrial-scale cultivation remains a challenge. The approach and results presented can guide optimal pathway configurations for enhanced prokaryotic carbon fixation through metabolic engineering. By aligning strain modifications with these theoretically revealed near-optimal pathway configurations, we can optimally engineer strains of good fitness under open culture industrial-scale conditions.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0127424"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047273","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":"Allosteric regulation of pyruvate kinase enables efficient and robust gluconeogenesis by preventing metabolic conflicts and carbon overflow.","authors":"Fukang She, Brent W Anderson, Daven B Khana, Shenwei Zhang, Wieland Steinchen, Danny K Fung, Nathalie G Lesser, Lauren N Lucas, David M Stevenson, Theresa J Astmann, Gert Bange, Jan-Peter van Pijkeren, Daniel Amador-Noguez, Jue D Wang","doi":"10.1128/msystems.01131-24","DOIUrl":"10.1128/msystems.01131-24","url":null,"abstract":"<p><p>Gluconeogenesis, the reciprocal pathway of glycolysis, is an energy-consuming process that generates glycolytic intermediates from non-carbohydrate sources. In this study, we demonstrate that robust and efficient gluconeogenesis in bacteria relies on the allosteric inactivation of pyruvate kinase, the enzyme responsible for the irreversible final step of glycolysis. Using the model bacterium <i>Bacillus subtilis</i> as an example, we discovered that pyruvate kinase activity is inhibited during gluconeogenesis via its extra C-terminal domain (ECTD), which is essential for autoinhibition and metabolic regulation. Physiologically, a <i>B. subtilis</i> mutant lacking the ECTD in pyruvate kinase displayed multiple defects under gluconeogenic conditions, including inefficient carbon utilization, slower growth, and decreased resistance to the herbicide glyphosate. These defects were not caused by the phosphoenolpyruvate-pyruvate-oxaloacetate futile cycle. Instead, we identified two major metabolic consequences of pyruvate kinase dysregulation during gluconeogenesis: failure to establish high phosphoenolpyruvate (PEP) concentrations necessary for robust gluconeogenesis and increased carbon overflow into the medium. <i>In silico</i> analysis revealed that, in wild-type cells, an expanded PEP pool enabled by pyruvate kinase inactivation is critical for maintaining the thermodynamic feasibility of gluconeogenesis. Additionally, we discovered that <i>B. subtilis</i> exhibits glyphosate resistance specifically under gluconeogenic conditions, and this resistance depends on the PEP pool expansion resulting from pyruvate kinase inactivation. Our findings underscore the importance of allosteric regulation during gluconeogenesis in coordinating metabolic flux, efficient carbon utilization, and antimicrobial resistance.IMPORTANCEPyruvate kinase catalyzes the final irreversible step in glycolysis and is commonly thought to play a critical role in regulating this pathway. In this study, we identified a constitutively active variant of pyruvate kinase, which did not impact glycolysis but instead led to multiple metabolic defects during gluconeogenesis. Contrary to conventional understanding, these defects were not due to the phosphoenolpyruvate-pyruvate-oxaloacetate futile cycle. Our findings suggest that the defects arose from an insufficient buildup of the phosphoenolpyruvate pool and an increase in carbon overflow metabolism. Overall, this study demonstrates the essential role of pyruvate kinase allosteric regulation during gluconeogenesis in maintaining adequate phosphoenolpyruvate levels, which helps prevent overflow metabolism and enhances the thermodynamic favorability of the pathway. This study also provides a novel link between glyphosate resistance and gluconeogenesis.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0113124"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053063","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}