Travis E. Gibson, Younhun Kim, Sawal Acharya, David E. Kaplan, Nicholas DiBenedetto, Richard Lavin, Bonnie Berger, Jessica R. Allegretti, Lynn Bry, Georg K. Gerber
{"title":"Learning ecosystem-scale dynamics from microbiome data with MDSINE2","authors":"Travis E. Gibson, Younhun Kim, Sawal Acharya, David E. Kaplan, Nicholas DiBenedetto, Richard Lavin, Bonnie Berger, Jessica R. Allegretti, Lynn Bry, Georg K. Gerber","doi":"10.1038/s41564-025-02112-6","DOIUrl":"10.1038/s41564-025-02112-6","url":null,"abstract":"Although dynamical systems models are a powerful tool for analysing microbial ecosystems, challenges in learning these models from complex microbiome datasets and interpreting their outputs limit use. We introduce the Microbial Dynamical Systems Inference Engine 2 (MDSINE2), a Bayesian method that learns compact and interpretable ecosystems-scale dynamical systems models from microbiome timeseries data. Microbial dynamics are modelled as stochastic processes driven by interaction modules, or groups of microbes with similar interaction structure and responses to perturbations, and additionally, noise characteristics of data are modelled. Our open-source software package provides multiple tools for interpreting learned models, including phylogeny/taxonomy of modules, and stability, interaction topology and keystoneness. To benchmark MDSINE2, we generated microbiome timeseries data from two murine cohorts that received faecal transplants from human donors and were then subjected to dietary and antibiotic perturbations. MDSINE2 outperforms state-of-the-art methods and identifies interaction modules that provide insights into ecosystems-scale interactions in the gut microbiome. This Bayesian statistical method uses timeseries microbiome data to infer interaction modules and is tested using a faecal transplant experiment in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2550-2564"},"PeriodicalIF":19.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02112-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anders B. Dohlman, Xiangyu Pan, Laurence Zitvogel, Iliyan D. Iliev
{"title":"The multi-kingdom cancer microbiome","authors":"Anders B. Dohlman, Xiangyu Pan, Laurence Zitvogel, Iliyan D. Iliev","doi":"10.1038/s41564-025-02103-7","DOIUrl":"10.1038/s41564-025-02103-7","url":null,"abstract":"Microbial influence on cancer development and therapeutic response is a growing area of cancer research. Although it is known that microorganisms can colonize certain tissues and contribute to tumour initiation, the use of deep sequencing technologies and computational pipelines has led to reports of multi-kingdom microbial communities in a growing list of cancer types. This has prompted discussions on the role and scope of microbial presence in cancer, while raising the possibility of microbiome-based diagnostic, prognostic and therapeutic tools. However, additional investigation and thorough validation of cancer microbiome findings are required before this translational potential can be realized. Here we provide historical context and a conceptual framework for the so-called cancer microbiome and summarize experimental studies into tumour-associated bacteria, fungi and other microorganisms. We also discuss the current evidence for microbial colonization of tumours and their varied influence on the disease, including recent debates. Finally, we consider outstanding questions and discuss our outlook for the field. This Review discusses what comprises the ‘cancer microbiome’, summarizing the studies on tumour-associated microbes, examining the evidence and assessing their impact on the disease.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2369-2383"},"PeriodicalIF":19.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinwei Zhang, Yan Li, Yang Qin, Zhangdi Liao, Chaoqiong Deng, Yangchun Chen, Yan Li, Hongyan Qian, Yan He, Shiju Chen, Guixiu Shi, Yuan Liu
{"title":"Vientovirus capsid protein mimics autoantigens and contributes to autoimmunity in Sjögren’s disease","authors":"Xinwei Zhang, Yan Li, Yang Qin, Zhangdi Liao, Chaoqiong Deng, Yangchun Chen, Yan Li, Hongyan Qian, Yan He, Shiju Chen, Guixiu Shi, Yuan Liu","doi":"10.1038/s41564-025-02115-3","DOIUrl":"10.1038/s41564-025-02115-3","url":null,"abstract":"Viral infections are implicated in the pathogenesis of autoimmune diseases, including Sjögren’s disease (SjD), but the mechanisms linking viral antigens to disease development remain poorly understood. To address this, we conducted shotgun metagenomic sequencing of saliva samples from 35 patients with SjD and 25 healthy controls. The salivary virome of the patients with SjD, particularly those with high disease activity, had an expansion of Siphoviridae bacteriophages and increased eukaryotic viral sequences, including Vientovirus. This virus was associated with lacrimal gland dysfunction and elevated anti-SSA/Ro52 autoantibody levels. Alignment analysis and cross-blocking assay identified molecular mimicry between the Vientovirus capsid protein and the autoantigen SSA/Ro52. Mice immunized with a Vientovirus capsid peptide developed anti-SSA/Ro52 antibodies and showed immunological features resembling those of patients with SjD. These findings highlight distinct virome profiles in SjD and provide mechanistic evidence supporting the role of Vientovirus in triggering autoimmunity through molecular mimicry. Salivary virome profiling revealed distinct virome profiles in Sjögren’s disease and a role for Vientovirus in triggering autoimmunity through molecular mimicry.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2591-2602"},"PeriodicalIF":19.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
François Ribalet, Stephanie Dutkiewicz, Erwan Monier, E. Virginia Armbrust
{"title":"Future ocean warming may cause large reductions in Prochlorococcus biomass and productivity","authors":"François Ribalet, Stephanie Dutkiewicz, Erwan Monier, E. Virginia Armbrust","doi":"10.1038/s41564-025-02106-4","DOIUrl":"10.1038/s41564-025-02106-4","url":null,"abstract":"The cyanobacterium Prochlorococcus is Earth’s most abundant photosynthetic organism and crucial to oceanic ecosystems. However, its sensitivity to a changing climate remains unclear. Here we analysed decade-long field measurements using continuous-flow cytometry from our SeaFlow instrument, collecting per-cell chlorophyll fluorescence and size data for ~800 billion phytoplankton cells across the tropical and subtropical Pacific Ocean to quantify the temperature dependence of cell division. Prochlorococcus division rates appear primarily determined by temperature, increasing exponentially to 28 °C, then sharply declining. Regional surface water temperatures may exceed this range by the end of the century under both moderate and high warming scenarios. Under these future conditions, our global ocean ecosystem model suggests a possible 17–51% reduction in Prochlorococcus production in tropical oceans. Even with the inclusion of hypothetical warm-adapted strains, models show significant production declines in the warmest regions, suggesting that thermal adaptation may not prevent negative impacts. These results highlight the potential vulnerability of Prochlorococcus-dependent marine ecosystems to future warming. Decade-long field measurements and modelling show that projected ocean temperatures could restrict cell division rates of an important marine cyanobacterium.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2441-2453"},"PeriodicalIF":19.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02106-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Esther Shmidov, Alexis Villani, Senén D. Mendoza, Ellay Avihu, Ilana Lebenthal-Loinger, Sarit Karako-Lampert, Sivan Shoshani, Chang Ye, Yiding Wang, Hao Yan, Weixin Tang, Joseph Bondy-Denomy, Ehud Banin
{"title":"Multigenerational proteolytic inactivation of restriction upon subtle genomic hypomethylation in Pseudomonas aeruginosa","authors":"Esther Shmidov, Alexis Villani, Senén D. Mendoza, Ellay Avihu, Ilana Lebenthal-Loinger, Sarit Karako-Lampert, Sivan Shoshani, Chang Ye, Yiding Wang, Hao Yan, Weixin Tang, Joseph Bondy-Denomy, Ehud Banin","doi":"10.1038/s41564-025-02088-3","DOIUrl":"10.1038/s41564-025-02088-3","url":null,"abstract":"Restriction-modification (R-M) systems protect against phage infection by detecting and degrading invading foreign DNA. However, like many prokaryotic anti-phage defences, R-M systems pose a major risk of autoimmunity, exacerbated by the presence of hundreds to thousands of potential cleavage sites in the bacterial genome. Pseudomonas aeruginosa strains experience the temporary inactivation of restriction endonucleases following growth at high temperatures, but the reason and mechanisms for this phenomenon are unknown. Here we report that P. aeruginosa type I restriction endonuclease is degraded and the methyltransferase is partially degraded, by two Lon-like proteases when replicating at >41 °C. This post-translational regulation prevents self-DNA targeting, which is a risk due to stable genomic hypomethylation, as demonstrated by single-molecule, real-time sequencing and TadA-assisted N6-methyladenosine sequencing. When cells grown at >41 °C are returned to 37 °C, full genomic methylation does not fully recover for up to 60 bacterial generations, and thus restriction activity remains off for the duration. Our findings demonstrate that type I R-M is tightly regulated post-translationally with a long memory effect that ensures genomic stability and mitigates autotoxicity. Elevated temperatures inactivate a type I restriction endonuclease in P. aeruginosa for ~60 generations via proteolytic degradation triggered by DNA hypomodification, preventing self-targeting and enabling recovery of restriction activity.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2498-2510"},"PeriodicalIF":19.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wesley B. Burford, Hrag Dilabazian, Laura T. Alto, Duo Ma, Angela B. Mobley, Arun Radhakrishnan, J. David Farrar, Neal M. Alto
{"title":"Single-cell analysis of genetically minimized Salmonella reveals effector gene cooperation in vivo","authors":"Wesley B. Burford, Hrag Dilabazian, Laura T. Alto, Duo Ma, Angela B. Mobley, Arun Radhakrishnan, J. David Farrar, Neal M. Alto","doi":"10.1038/s41564-025-02099-0","DOIUrl":"10.1038/s41564-025-02099-0","url":null,"abstract":"Bacterial pathogens such as Salmonella Typhimurium (S.Tm) can deliver large repertoires of effector proteins directly into host cells. Due to the genetic and functional redundancies found in these systems, it has been difficult to determine how individual effector proteins cooperate with one another to elicit pathogenic phenotypes in vivo. To overcome this challenge, targeted genome minimization has been used to identify small effector protein networks sufficient for S.Tm colonization of complex tissues. Here we used mass cytometry to generate a comprehensive map of minimal effector network functions at single-cell resolution. This approach revealed the temporal progression of S.Tm transmission and uncovered a CD62L+ monocyte population as a major bottleneck to cell-to-cell dissemination in the spleen. We further show how cooperation between two effector gene networks acquired during distinct episodes of bacterial evolution has shaped the cellular and tissue tropism of non-typhoidal Salmonella species. A minimal effector subset enables Salmonella Typhimurium to overcome bottlenecks regulated by the early innate immune response and establish infection within a CD62L+ monocyte niche in the spleen.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2565-2578"},"PeriodicalIF":19.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
William C. Schmidt, Calvin K. Lee, Xuhui Zheng, Jonathan W. Chen, Kirsten L. Fetah, James R. Popoli, Yun Su Choi, Thomas D. Young, Paul S. Weiss, Andrea M. Kasko, George A. O’Toole, Matthew R. Parsek, Gerard C. L. Wong
{"title":"Pseudomonas aeruginosa senses exopolysaccharide trails using type IV pili and adhesins during biofilm formation","authors":"William C. Schmidt, Calvin K. Lee, Xuhui Zheng, Jonathan W. Chen, Kirsten L. Fetah, James R. Popoli, Yun Su Choi, Thomas D. Young, Paul S. Weiss, Andrea M. Kasko, George A. O’Toole, Matthew R. Parsek, Gerard C. L. Wong","doi":"10.1038/s41564-025-02087-4","DOIUrl":"10.1038/s41564-025-02087-4","url":null,"abstract":"During early stages of biofilm formation, Pseudomonas aeruginosa (Pa) PAO1 can sense exopolysaccharide (EPS) trails of Psl deposited on a surface by previous Pa cells to detect trajectories of other cells and to orchestrate motility. This sensory signal is transduced into cyclic diGMP second messengers, but no known Psl receptors and adhesins participate in signal transduction. Here, using bacteria-secreted Psl trails, glycopolymer-patterned surfaces, longitudinal cell tracking, second messenger dual reporters and genetic mutations targeting EPS binding and surface twitching, we find that Pa is capable of sensing EPS directly through mutually constitutive interactions between type IV pili (T4P)-powered twitching and specific adhesin–EPS bonds. This unanticipated mechanochemical surveillance of the Pa environment, where T4P pull against cell-body localized adhesins interacting with EPS trails, such as mannose-binding CdrA, generates a hybrid, transitional planktonic-to-biofilm population with elevated cyclic diGMP and elevated cyclic AMP, as well as increased motility capable of following EPS trails. These results show a generalizable mechanism of surface chemosensing through mechanosensitive appendages. Opposing forces generated by exopolysaccharide trail binding versus type IV pilus retraction generate a high cyclic diGMP–high cyclic AMP state in Pseudomonas aeruginosa that promotes social motility.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2511-2520"},"PeriodicalIF":19.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Udita Chandola, Eric Manirakiza, Margaux Maillard, Louis Josselin Lavier Aydat, Alicia Camuel, Camille Trottier, Atsuko Tanaka, Timothée Chaumier, Eric Giraud, Leïla Tirichine
{"title":"A Bradyrhizobium isolate from a marine diatom induces nitrogen-fixing nodules in a terrestrial legume","authors":"Udita Chandola, Eric Manirakiza, Margaux Maillard, Louis Josselin Lavier Aydat, Alicia Camuel, Camille Trottier, Atsuko Tanaka, Timothée Chaumier, Eric Giraud, Leïla Tirichine","doi":"10.1038/s41564-025-02105-5","DOIUrl":"10.1038/s41564-025-02105-5","url":null,"abstract":"Biological nitrogen fixation converts atmospheric nitrogen into ammonia, essential to the global nitrogen cycle. While cyanobacterial diazotrophs are well characterized, recent studies have revealed a broad distribution of non-cyanobacterial diazotrophs (NCDs) in marine environments, although their study is limited by poor cultivability. Here we report a previously uncharacterized Bradyrhizobium isolated from the marine diatom Phaeodactylum tricornutum. Phylogenomic analysis places the strain within photosynthetic Bradyrhizobium, suggesting evolutionary adaptations to marine and terrestrial niches. Average nucleotide identity supports its classification as a previously undescribed species. Remarkably, inoculation experiments showed that the isolate induced nitrogen-fixing nodules in the Aeschynomene indica legume, pointing to symbiotic capabilities across ecological boundaries. Pangenome analysis and metabolic predictions indicate that this isolate shares more features with terrestrial photosynthetic Bradyrhizobium than with marine NCDs. Overall, these findings suggest that symbiotic interactions could evolve across different ecological niches, and raise questions about the evolution of nitrogen fixation and microbe–host interactions. A non-cyanobacterial diazotroph previously isolated from a marine eukaryotic phytoplankton triggers formation of nitrogen-fixing root nodules when inoculated onto a terrestrial legume.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2486-2497"},"PeriodicalIF":19.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Carotenoids bind rhodopsins and act as photocycle-accelerating pigments in marine Bacteroidota","authors":"Takayoshi Fujiwara, Toshiaki Hosaka, Masumi Hasegawa-Takano, Yosuke Nishimura, Kento Tominaga, Kaho Mori, Satoshi Nishino, Yuno Takahashi, Tomomi Uchikubo-Kamo, Kazuharu Hanada, Takashi Maoka, Shinichi Takaichi, Keiichi Inoue, Mikako Shirouzu, Susumu Yoshizawa","doi":"10.1038/s41564-025-02109-1","DOIUrl":"10.1038/s41564-025-02109-1","url":null,"abstract":"Microbial rhodopsins are photoreceptor proteins widely distributed in marine microorganisms that harness light energy and support marine ecosystems. While retinal is typically the sole chromophore in microbial rhodopsins, some proteorhodopsins, which are proton-pumping rhodopsins abundant in the ocean, use carotenoid antennae to transfer light energy to retinal. However, the mechanism by which carotenoids enhance rhodopsin functions remains unclear. Here, using the marine Bacteroidota isolate Nonlabens marinus S1-08T, we reconstituted complexes of rhodopsins with the carotenoid myxol and detected energy transfer to retinal in both proteorhodopsin and chloride ion-pumping rhodopsin. Carotenoid binding facilitated light harvesting and accelerated the photocycle, thereby improving the light utilization efficiency of proteorhodopsin. Cryogenic electron microscopy structural analysis further revealed the molecular architecture of the carotenoid–rhodopsin complexes. The ability to bind carotenoids is conserved in rhodopsins of the marine-dominant phylum Bacteroidota, which are widely transcribed in the photic zone. These findings reveal how carotenoids enhance rhodopsin functions in marine Bacteroidota. In marine bacteria, carotenoids enhance rhodopsin function by acting as light-harvesting antennae and photocycle-accelerating pigments, a dual mechanism that enhances light energy capture and expands the known strategies of microbial phototrophy.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2603-2615"},"PeriodicalIF":19.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microbes on the menu","authors":"","doi":"10.1038/s41564-025-02117-1","DOIUrl":"10.1038/s41564-025-02117-1","url":null,"abstract":"Bacteria and fungi can augment the flavour, composition and sustainability of foods, but more research is needed to push microbial foods — and consumer palates — to new heights.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2095-2096"},"PeriodicalIF":19.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02117-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}