ISME JournalPub Date : 2026-10-14DOI: 10.1093/ismejo/wrag268
Marcelo Navarro-Diaz, Kerrin Bertram, Lara Göbel, Laura Camus, Soyoung Ham, Largus T Angenent, Jose Antonio Velazquez Gomez, Simon Heilbronner, Paolo Stincone, Johanna Rapp, Daniel Petras, Hannes Link
{"title":"Community composition drives metabolic competition and Staphylococcus aureus colonization resistance in synthetic nasal communities.","authors":"Marcelo Navarro-Diaz, Kerrin Bertram, Lara Göbel, Laura Camus, Soyoung Ham, Largus T Angenent, Jose Antonio Velazquez Gomez, Simon Heilbronner, Paolo Stincone, Johanna Rapp, Daniel Petras, Hannes Link","doi":"10.1093/ismejo/wrag268","DOIUrl":"https://doi.org/10.1093/ismejo/wrag268","url":null,"abstract":"<p><p>The human nasal microbiome is a low-diversity ecosystem whose assembly principles and mechanisms of colonization resistance remain poorly understood. Staphylococcus aureus is a member of the nasal microbiome of some individuals with variable abundance. We hypothesized that nutritional competition, strain-level diversity, and nutrient availability shape community stability and the ability of commensal species to inhibit S. aureus. To test this, we constructed 50 defined synthetic communities inoculated with 5 to 10 representative human nasal bacterial species differing in strain and species composition and tracked their compositional changes across serial passages, S. aureus growth, metabolic profiles, and nutritional interactions. The resulting consortia, which assembled into communities of up to 6 co-existing species converged in one of three community types. Synthetic communities dominated by specific Corynebacterium propinquum strains showed exclusion of most other community members, including S. aureus. Conversely, communities lacking C. propinquum dominance showed that exclusion of S. aureus was driven primarily by a combination of Staphylococcus epidermidis and Staphylococcus lugdunensis. Growth and coculture assays showed that C. propinquum outcompetes S. aureus in conditions that resemble the nasal environment, whereas S. aureus dominates in nutrient-rich conditions. Metabolomics analyses indicated that nutritional competition, including siderophore utilization and amino acid limitation, likely underlies this colonization resistance. These results establish a reproducible and tractable synthetic community model for the human nasal microbiome and suggest that nutrient-dependent competition and microbial metabolite production are key drivers of community structure and pathogen exclusion.</p>","PeriodicalId":50271,"journal":{"name":"ISME Journal","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ISME JournalPub Date : 2026-10-09DOI: 10.1093/ismejo/wrag259
Jinyeong Choi, Cong Liu, Pradeep Palanichamy, Yumiko Masukagami, Hirotaka Tanaka, Takumasa Kondo, Matthew E Gruwell, Filip Husnik
{"title":"Parallel Evolution of Bacteroidota as Long-Term Endosymbionts of Insects.","authors":"Jinyeong Choi, Cong Liu, Pradeep Palanichamy, Yumiko Masukagami, Hirotaka Tanaka, Takumasa Kondo, Matthew E Gruwell, Filip Husnik","doi":"10.1093/ismejo/wrag259","DOIUrl":"https://doi.org/10.1093/ismejo/wrag259","url":null,"abstract":"<p><p>Symbiotic relationships significantly transform both symbiont and host biology. The most visible changes include a massive reduction of the endosymbiont genome and the development of specialized host organs, cells, and compartments for symbiont housing. However, insect symbiosis studies have often focused on Pseudomonadota or specific symbiosis stages, limiting our understanding of how symbiont diversity arises from particular microbial clades, how the symbiont genomes evolve, and the consequences of symbiosis for diverse host-symbiont pairs. Scale insects, which have experienced repeated gains and losses of nutritional symbionts, provide an ideal evolutionary playground for tracking parallel transitions of insect symbionts originating from the same bacterial phylum. Using extensive genome sampling across the scale insect phylogeny, we recapitulated the path of Bacteroidota transitioning from recently established host-associated bacteria to highly specialized insect endosymbionts with minimal gene sets. Their genomes exhibit strikingly parallel degradation across all gene categories, with some stochastic differences in essential genes for genetic processing and amino acid biosynthesis. Imaging methods further revealed that the symbiotic cells and organs exhibit a trend from more dispersed bacteriocytes to highly compact bacteriomes, closely localized to the host's digestive system. Our results outline a recurrent path by which insect symbioses independently arise, are maintained for up to several hundred million years, and are replaced by new symbionts. The gradual nature of the process implies that the outcomes of symbiosis initially depend on how \"professional\" vs. \"naïve\" the host and symbiont are. Over evolutionary time, compatible host-symbiont lineages emerge from these interactions and become preferred.</p>","PeriodicalId":50271,"journal":{"name":"ISME Journal","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nitrogen-Dependent Regulation of Nitrate Reductase in Coral Symbioses.","authors":"Chloé Stévenne, Christine Ferrier-Pagès, Renaud Grover, Jean-Christophe Plumier, Stéphane Roberty","doi":"10.1093/ismejo/wrag260","DOIUrl":"https://doi.org/10.1093/ismejo/wrag260","url":null,"abstract":"<p><p>The nutritional symbiosis between corals and their photosynthetic dinoflagellate partners underpins the ecological success of reef-building corals in nutrient-poor environments. Although coral holobionts can assimilate the abundant yet highly variable environmental nitrate, direct insight into how nitrate reductase is regulated in these symbiotic algae has been lacking. Here, nitrate reductase protein abundance and gene expression were characterized in cultured Symbiodiniaceae exposed to different nitrogen regimes and light conditions, revealing the multifactorial nature of its regulation. The results indicate that nitrate reductase behaves as a substrate-induced enzyme: nitrate stimulates protein synthesis in nitrogen-starved cultures, whereas ammonium actively suppresses its expression in a concentration-dependent manner. Light availability and photosynthetic electron transport further modulate protein abundance, suggesting that although nitrate reductase synthesis depends on nitrate availability, its stability may rely on photosynthesis. In hospite, nitrate reductase is synthesized within hours of nitrate exposure by symbionts from nitrogen-starved corals, indicating that nitrate reduction can occur within the host environment. However, this response is transient and reduced relative to free-living cells, suggesting that nitrate reduction may function as a facultative pathway activated when preferred nitrogen sources become limited. Finally, gene expression measurements and pharmacological inhibition experiments are consistent with predominant post-transcriptional regulation of nitrate reductase protein expression, enabling rapid and reversible control of nitrate assimilation. Together, these findings describe a tightly regulated and responsive nitrate reduction system in coral symbionts that provides a flexible mechanism contributing to nitrogen homeostasis under fluctuating nutrient regimes.</p>","PeriodicalId":50271,"journal":{"name":"ISME Journal","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ISME JournalPub Date : 2026-09-29DOI: 10.1093/ismejo/wrag245
Sean C Booth, Connor Sharp, Kevin R Foster
{"title":"Similar weapons play different roles in bacterial competition.","authors":"Sean C Booth, Connor Sharp, Kevin R Foster","doi":"10.1093/ismejo/wrag245","DOIUrl":"https://doi.org/10.1093/ismejo/wrag245","url":null,"abstract":"<p><p>Many bacteria are aggressive organisms that inhibit and kill their competitors using a diverse range of molecular weapon systems. Strikingly, strains commonly carry multiple similar weapons that appear to perform the same function. Here we investigate the evolutionary benefits of this apparent functional duplication using the heavily-armed opportunistic pathogen, Pseudomonas aeruginosa as a model species. We first use genomics to ask whether carrying multiple similar bacteriocins (S pyocins) increases the probability of inhibiting other strains. However, simply carrying a single uncommon S pyocin is typically as effective as carrying multiple pyocins. We then combine genome-editing with competition experiments to study the effects of S pyocins alone and in combinations. S pyocins sometimes function better together than alone, which helps to explain their co-carriage. However, we also find evidence of specialisation: pyocin S5 is much more effective than S2 in iron limited conditions, and vice-versa when iron is available. We test the generality of our findings using a second class of weapon carried by P. aeruginosa, contact-dependent inhibition, which again reveals differing effectiveness as conditions change. Our work shows how similar weapons are specialised for combat under different environmental conditions. We argue that functional specialisation is key to understanding why bacteria carry so many weapons.</p>","PeriodicalId":50271,"journal":{"name":"ISME Journal","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ISME JournalPub Date : 2026-09-16DOI: 10.1093/ismejo/wrag235
Subham Mridha, Ove Christopher Mattmann, Sarah-Luise Loose, Saskia Isele, Bernd Roschitzki, Rolf Kümmerli, Simona G Huwiler
{"title":"Outer membrane changes enable evolutionary escape from bacterial predation.","authors":"Subham Mridha, Ove Christopher Mattmann, Sarah-Luise Loose, Saskia Isele, Bernd Roschitzki, Rolf Kümmerli, Simona G Huwiler","doi":"10.1093/ismejo/wrag235","DOIUrl":"https://doi.org/10.1093/ismejo/wrag235","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) is a threat to modern medicine. To combat AMR pathogens, natural predators like bacteriophages and predatory bacteria have gained interest recently. Predatory bacterium Bdellovibrio bacteriovorus is ubiquitous and has a broad prey range. It is particularly potent at killing many AMR Gram-negative bacterial pathogens featured on the WHO priority list. However, it is currently unclear whether prey bacteria can evolve genetically-determined resistance against predation by B. bacteriovorus. Here, we show that the model bacterium Escherichia coli K-12 consistently evolves resistance against B. bacteriovorus during experimental evolution. Selection for resistance scaled positively with predation pressure and was widespread after two cycles of predator exposure. Similar to antibiotics, predation resistance was costly, manifesting in a trade-off between predation resistance and fitness in the absence of predators. Genetic analysis combined with proteomics identified mutations that lead to the down-regulation of the outer membrane porin OmpF as a common resistance mechanism. In addition, a rarer mutation in cell envelope lipopolysaccharide-modifying enzyme WaaF also conferred predation resistance, likely by a pleiotropic effect, which included OmpF down regulation. While our study uncovers evolutionary and mechanistic aspects of prey escape from predation, it also highlights that the high cost of resistance reflects a handicap for the pathogen and can thus be exploited to increase treatment sustainability. Altogether, our work generates essential knowledge in ecologically important predator-prey interactions and can advance predatory bacteria as \"living antibiotics\" to combat AMR.</p>","PeriodicalId":50271,"journal":{"name":"ISME Journal","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ISME JournalPub Date : 2026-09-16DOI: 10.1093/ismejo/wrag244
Yanyan Huang, Xiaoyuan Feng, Xiaoke Hu, Yanyu Sun, Zenglei Song, Mei Xie, Tianhua Liao, Xin Liu, Xin Lv, Ruizhi Liu, Qing Liu, Christian R Voolstra, Haiwei Luo
{"title":"Environmental Gradients as a Dominant Force in the Macroevolution of a Host-Associated Marine Bacterium.","authors":"Yanyan Huang, Xiaoyuan Feng, Xiaoke Hu, Yanyu Sun, Zenglei Song, Mei Xie, Tianhua Liao, Xin Liu, Xin Lv, Ruizhi Liu, Qing Liu, Christian R Voolstra, Haiwei Luo","doi":"10.1093/ismejo/wrag244","DOIUrl":"https://doi.org/10.1093/ismejo/wrag244","url":null,"abstract":"<p><p>Natural selection is imposed by both abiotic environmental filtering and biotic interactions, yet their relative roles in shaping the deep phylogeny of widespread, generalist host-associated bacteria remain unclear. Here, we integrate large-scale phylogenomics, environmental sequencing, functional genomics, and global metagenomic analysis to demonstrate that tidal zonation overrides host association as the dominant macroevolutionary force structuring the marine bacterial genus Ruegeria. Analysis of 533 genomes and 74 global coastal metagenomes reveals that the intertidal-subtidal boundary structures the deepest phylogenetic splits, driving the repeated evolution of distinct ecotypes through independent zonation transitions across global coastlines. These ecotypes possess divergent genomic toolkits: intertidal strains are enriched for genes coding for stress resistance and anaerobic metabolism, whereas subtidal strains specialize in high-affinity nutrient scavenging. Our findings establish that predictable physicochemical gradients act as filters that generate foundational diversity from which specialized host symbionts subsequently emerge, reframing how environmental gradients shape microbial evolution at the eco-evolutionary interface.</p>","PeriodicalId":50271,"journal":{"name":"ISME Journal","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ISME JournalPub Date : 2026-09-15DOI: 10.1093/ismejo/wrag246
Tina Keller-Costa, Romie Tignat-Perrier, Matilde Marques, Christine Ferrier-Pagès, Claudia Pogoreutz
{"title":"Symbiotic interactions and climate change implications of the octocoral microbiome.","authors":"Tina Keller-Costa, Romie Tignat-Perrier, Matilde Marques, Christine Ferrier-Pagès, Claudia Pogoreutz","doi":"10.1093/ismejo/wrag246","DOIUrl":"https://doi.org/10.1093/ismejo/wrag246","url":null,"abstract":"<p><p>Octocorals are vital components of tropical, temperate, and cold-water benthic marine ecosystems. Their associated microbiomes, comprising microeukaryotes, prokaryotes, and viruses, are increasingly recognised as central to host health, nutrient cycling, and chemical defence. Metagenomics and amplicon sequencing have uncovered taxonomic and functional complexity within these microbial communities, revealing patterns of host specificity and health status, along with seasonality and geographic structuring. However, anthropogenic stressors, particularly those associated with global climate change, exert intense pressure on coral-dominated ecosystems, leading to complex and poorly understood local and regional patterns of octocoral expansion and mortality. Microbial interactions may be a main driver of these contrasting outcomes by mediating the ecological resilience of octocorals to environmental stress. We synthesise the current state of research on the diversity, organisation, and function of the octocoral microbiome, and identify critical knowledge gaps on octocoral holobionts relative to scleractinian corals. Our meta-analysis of 79 publicly available bacterial genomes from octocorals reveals group-specific specialisation in denitrification and nitrate assimilation, along with widespread capacities for essential amino acid, cofactor, and vitamin production, suggesting important contributions to nutrient cycling in the holobiont. While sampling efforts between cultured and uncultured lineages are even, our genomic survey reveals strong sampling bias toward the Atlantic Ocean, temperate gorgonians, and healthy host states, whereas bacterial genomes representing the pathobiome, tropical and/or deep-sea regions, and other octocoral taxa remain underrepresented. Accordingly, we propose future research directions to advance understanding of octocoral microbiome ecology and its role in the resilience of tropical, temperate and cold-water coral reefs.</p>","PeriodicalId":50271,"journal":{"name":"ISME Journal","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ISME JournalPub Date : 2026-09-14DOI: 10.1093/ismejo/wrag239
Hyeon Seop Lee, Sumin Choi, Wonsik Mun, Robert J Mitchell
{"title":"Lipopolysaccharide Architecture Dictates Susceptibility to Predation by Bdellovibrio bacteriovorus.","authors":"Hyeon Seop Lee, Sumin Choi, Wonsik Mun, Robert J Mitchell","doi":"10.1093/ismejo/wrag239","DOIUrl":"https://doi.org/10.1093/ismejo/wrag239","url":null,"abstract":"<p><p>Predatory bacteria such as Bdellovibrio bacteriovorus exert strong top-down control on Gram-negative bacterial populations, yet the prey surface determinants governing susceptibility to predation remain incompletely resolved. Lipopolysaccharide (LPS) is a dominant structural component of the Gram-negative outer membrane and has long been implicated in predator attachment and invasion, but how specific features of LPS architecture influence predation efficiency remains unclear. Here, the susceptibility of Escherichia coli K-12 mutants bearing defined truncations in LPS core biosynthesis was systematically examined using B. bacteriovorus 109J and three additional Bdellovibrio, HD100, BD-DH1, and EY2.3. Disruption of inner core biosynthesis genes (waaC, waaD, waaE, and waaF) or the waaG gene significantly delayed predation by all four predators. Reduced susceptibility scaled with the extent of truncation, with the shortest LPS structures conferring the greatest reduced susceptibility although none of the mutants were completely resistant and long-term killing was observed. In contrast, susceptibility to outer core truncations varied among predators, revealing strain-specific predation patterns. Restoration of O-antigen biosynthesis reduced prey susceptibility to some predators, consistent with the possibility that O-antigen sterically masks LPS-associated surface features involved in predation. Beyond its structural role, LPS also modulated predator activity. Whereas exogenous LPS acted as a decoy and delayed predation when added concomitantly with predators, pre-exposures accelerated prey killing, indicating extracellular LPS modulates predation activities and rates. Together, these findings demonstrate that the prey LPS architecture plays an important role in shaping Bdellovibrio predatory activities, with implications for predator-prey dynamics in Gram-negative microbial communities.</p>","PeriodicalId":50271,"journal":{"name":"ISME Journal","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ISME JournalPub Date : 2026-08-26DOI: 10.1093/ismejo/wrag218
Anton E Shikov, Ruslan O Alagov, Maria E Belousova, Anton A Nizhnikov, Kirill S Antonets
{"title":"Site-specific recombination and purifying selection influence Cry toxin formation and specialization.","authors":"Anton E Shikov, Ruslan O Alagov, Maria E Belousova, Anton A Nizhnikov, Kirill S Antonets","doi":"10.1093/ismejo/wrag218","DOIUrl":"https://doi.org/10.1093/ismejo/wrag218","url":null,"abstract":"<p><p>In bacteria, multi-domain toxins represent a universal tool for determining the host range, being a cornerstone for public health and agriculture. Given high host specificity and potency, Cry toxins represent the most widely used bioinsecticides in agriculture. Their worldwide application grows annually; thus, the rational design of bioinsecticides requires a deeper understanding of the processes that orchestrate the origin and evolution of Cry toxins. The accepted views on how Cry toxins exchange domains postulate that homologous recombination sparks domain III swapping, altering host specificity and broadening strains' activities. This perspective, however, stems from laboratory experiments and has never been studied in nature. Here, we leveraged all available Cry sequences and uncovered the mechanism of the evolution of Cry toxins via site-specific recombination guided by XerCD recombinases that target insertions and conserved blocks between domain borders. The emergence of specialists from generalists is sparked by the purifying selection of specialized hybrids. Therefore, our model of domain shuffling caused by site-specific recombination of cry loci, followed by selection-driven specialization, illustrates how multi-domain toxins evolve and attune to specific hosts.</p>","PeriodicalId":50271,"journal":{"name":"ISME Journal","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Model-guided design of defined microbial community reveals interactions underpinning plant growth and stress tolerance.","authors":"Shinichi Yamazaki, Masaru Nakayasu, Keiko Kanai, Rie Mizuno, Rumi Kaida, Sachiko Masuda, Arisa Shibata, Ken Shirasu, Atsushi J Nagano, Yoshiharu Fujii, Akifumi Sugiyama, Yuichi Aoki","doi":"10.1093/ismejo/wrag219","DOIUrl":"https://doi.org/10.1093/ismejo/wrag219","url":null,"abstract":"<p><p>Defined microbial communities (DMCs; also known as SynComs) offer a promising strategy to enhance plant growth and stress tolerance by harnessing beneficial plant-associated microbes. However, the rational design and efficient exploration of complex DMC configurations remain challenging. Here, we present an interpretable model-guided framework that integrates plant phenotyping, microbial genomics, and machine learning to optimize DMC outcomes and identify microbial interactions relevant to plant performance. Using tomato as a model, we evaluated diverse DMC, temperature, and metabolite combinations in growth experiment and used a quality-controlled dataset comprising 301 plants representing 102 DMC compositions for predictive modeling. An Elastic Net regression model trained on plant biomass data and DMC composition features enabled prediction of unseen DMC outcomes, and incorporating genomic features substantially improved predictive performance, supporting the importance of functional potential in modeling community effects. We applied the model to prioritize and design improved DMCs, which were validated in laboratory assays and field trials. One model-guided DMC significantly enhanced plant growth in the field and improved heat stress tolerance under controlled conditions. Model interpretation and multi-omics analyses highlighted specific microbial interactions, including metabolite-associated relationships involving Sphingobium sp. and tomatine, that were linked to host stress-responsive gene expression. Together, our results demonstrate a scalable framework for predicting and prioritizing DMCs and identify candidate metabolite-associated microbial interactions that may contribute to plant growth promotion and abiotic stress tolerance.</p>","PeriodicalId":50271,"journal":{"name":"ISME Journal","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}