{"title":"A clinic-responder-derived defined microbial consortium enhances anti-PD-1 immunotherapy efficacy in mice","authors":"Haiyan Zhou, Ruiming Sun, Xiaoqun Nie, Liliang Xia, Hui Dong, Yujie Liu, Shurui Hou, Wenyue Dong, Xiaokuan Zhu, Yaxian Yao, Guo-Ping Zhao, Shun Lu, Ying Wang, Chen Yang","doi":"10.1038/s41564-026-02279-6","DOIUrl":"10.1038/s41564-026-02279-6","url":null,"abstract":"Targeting the gut microbiota is a promising strategy to enhance the efficiency of cancer immunotherapy; however, success has been limited. Here we combined metagenomic analysis and in silico prediction to identify bacterial species associated with immunotherapy response in patients with non-small-cell lung cancer. We constructed a defined consortium (RCom) of 15 bacterial species, most of which were isolated from responder patient faeces, associated with improved clinical response to anti-programmed cell death protein 1 (PD-1) treatment. Metabolic models and in vitro experiments revealed that RCom is a stable and cooperative community, and in vivo experiments showed that RCom engrafts and produces immunomodulatory metabolites. Oral administration of RCom improved the anti-tumour activity of anti-PD-1 by increasing the intratumoural infiltration and cytotoxic function of CD8+ T cells in syngeneic tumour models and across mice with heterogeneity in baseline gut microbiota composition. RCom supplementation also limited anti-PD-1 resistance in mice conferred by faecal microbiota transplantation from individual non-responsive patients. These findings suggest that RCom is a potential adjuvant to improve responsiveness to anti-PD-1 therapy in cancer. A rationally designed 15-member bacterial community engrafts and promotes T cell responses and anti-PD-1 therapy across heterogeneous baseline microbiotas to promote cancer control in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 4","pages":"993-1007"},"PeriodicalIF":19.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381199","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}
Ioannis Ntekas,Lena Takayasu,David W McKellar,Benjamin Grodner,Chase Holdener,Peter Schweitzer,Young Seo Park,Maya Sauthoff,Qiaojuan Shi,Ilana L Brito,Iwijn De Vlaminck
{"title":"Spatial transcriptomics maps host-gut microbiome biogeography at high resolution.","authors":"Ioannis Ntekas,Lena Takayasu,David W McKellar,Benjamin Grodner,Chase Holdener,Peter Schweitzer,Young Seo Park,Maya Sauthoff,Qiaojuan Shi,Ilana L Brito,Iwijn De Vlaminck","doi":"10.1038/s41564-026-02286-7","DOIUrl":"https://doi.org/10.1038/s41564-026-02286-7","url":null,"abstract":"Intermicrobial and host-microbial interactions are critical for the functioning of the gut microbiome, but few tools are available to measure these interactions in situ. Here we report a method for broad spatial sampling of microbiome-host interactions in the gut at high resolution (1 µm). This method combines enzymatic in situ polyadenylation of both bacterial and host RNA with spatial RNA sequencing to increase bacterial RNA recovery and enable transcriptomic analysis of low-abundance and spatially restricted microbial taxa. We benchmark the method against existing spatial transcriptomic workflows, demonstrating improved sensitivity and resolution. Application of this method in a mouse model of intestinal neoplasia revealed the biogeography of the mouse gut microbiome as function of location in the intestine, frequent strong intermicrobial interactions at short length scales and tumour-associated changes in the architecture of the host-microbiome interface. This method is compatible with widely available commercial platforms for spatial RNA sequencing and can therefore be readily adopted to study the role of short-range, bidirectional host-microbe interactions in microbiome health and disease.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"45 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368449","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}
Stephan Köstlbacher, Jolien J. E. van Hooff, Kassiani Panagiotou, Daniel Tamarit, Valerie De Anda, Kathryn E. Appler, Brett J. Baker, Thijs J. G. Ettema
{"title":"Prediction of eukaryotic cellular complexity in Asgard archaea using structural modelling","authors":"Stephan Köstlbacher, Jolien J. E. van Hooff, Kassiani Panagiotou, Daniel Tamarit, Valerie De Anda, Kathryn E. Appler, Brett J. Baker, Thijs J. G. Ettema","doi":"10.1038/s41564-026-02273-y","DOIUrl":"10.1038/s41564-026-02273-y","url":null,"abstract":"Asgard archaea played a key role in the origin of the eukaryotic cell, with extant genomes encoding relatives of diverse eukaryotic signature proteins (ESPs) involved in cellular organization. However, their often punctuated distribution and the absence of detectable homologues for many eukaryotic proteins limit our ability to reconstruct the cellular complexity of the Asgard archaeal ancestor of eukaryotes. Here we used de novo protein structure modelling and sequence similarity detection across an expanded Asgard archaeal genomic dataset to build a structural catalogue of the Asgard archaeal pangenome. We identified 908 ‘isomorphic’ ESPs—Asgard archaeal proteins with statistically enriched structural matches to eukaryotic proteins, often bridging deep sequence divergence. These isomorphic ESPs are enriched in information storage and processing roles and contain key components of the eukaryotic Vault (MVP) and Commander (COMMD) complexes, with potential roles in cellular compartmentalization and endosomal processing. These findings expand the repertoire of eukaryotic-like proteins in Asgard archaea and suggest a higher degree of eukaryote-like cellular complexity in the archaeal ancestor of eukaryotes. A structural catalogue of the Asgard archaeal pangenome reveals hundreds of eukaryotic-like proteins that suggest a higher degree of cellular complexity in the archaeal ancestor of eukaryotes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"747-758"},"PeriodicalIF":19.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02273-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350673","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}
{"title":"Navigating the promise and pitfalls of artificial intelligence","authors":"","doi":"10.1038/s41564-026-02300-y","DOIUrl":"10.1038/s41564-026-02300-y","url":null,"abstract":"Artificial intelligence stands like a new dawn on the horizon. It carries the promise of effortless collaboration between mind and machine, where tedious tasks melt away and creativity is given room to bloom. With tireless precision, AI sifts through oceans of information, uncovering hidden patterns like constellations in a night sky, guiding us toward wiser decisions and deeper understanding.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"613-614"},"PeriodicalIF":19.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02300-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147352900","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}
Wenjun Xia, Youxiang Mao, Ziyan Xia, Jie Cheng, Peng Jiang
{"title":"Retraction Note: Metabolic remodelling produces fumarate via the aspartate–argininosuccinate shunt in macrophages as an antiviral defence","authors":"Wenjun Xia, Youxiang Mao, Ziyan Xia, Jie Cheng, Peng Jiang","doi":"10.1038/s41564-026-02307-5","DOIUrl":"10.1038/s41564-026-02307-5","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 4","pages":"1133-1133"},"PeriodicalIF":19.4,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02307-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355980","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}
Andrei S. Steindorff, Feng M. Cai, Mingyue Ding, Siqi Jiang, Lea Atanasova, Scott E. Baker, Jomal Rodrigues Barbosa-Filho, Gunseli Bayram Akcapinar, Daren W. Brown, Priscila Chaverri, Peijie Chen, Komal Chenthamara, Chris Daum, Elodie Drula, Mukesh Dubey, Mikael Brandström Durling, Daniel Flatschacher, Thomas Ebner, Tamás Emri, Renwei Gao, Raphaela Castro Georg, Bernard Henrissat, Rosa Hermosa, Alfredo Herrera-Estrella, Wolfgang Hinterdobler, Philipp Kainz, Magnus Karlsson, László Kredics, Christian P. Kubicek, Alan Kuo, Kurt LaButti, Anna Lipzen, Matteo Lorito, Robert L. Mach, Gelsomina Manganiello, Tamás Marik, Natalia Martinez-Reyes, Michael Mayrhofer-Reinhartshuber, Márton Miskei, Marie-Claude Moisan, Stephen Mondo, Enrique Monte, Vivian Ng, Guan Pang, Jasmyn Pangilinan, Mao Peng, Edoardo Piombo, István Pócsi, Mohammad Javad Rahimi, Sumitha K. Reddy, Robert Riley, Sabrina Sarrocco, Matthias Schmal, Monika Schmoll, Attila Szűcs, Sheridan L. Woo, Oded Yarden, Susanne Zeilinger, Christian Zimmermann, Ekaterina Shelest, Adrian Tsang, Randy Berka, Ronald P. de Vries, Igor V. Grigoriev, Irina S. Druzhinina
{"title":"Phenogenomics reveals the ecology and evolution of Trichoderma fungi for sustainable agriculture","authors":"Andrei S. Steindorff, Feng M. Cai, Mingyue Ding, Siqi Jiang, Lea Atanasova, Scott E. Baker, Jomal Rodrigues Barbosa-Filho, Gunseli Bayram Akcapinar, Daren W. Brown, Priscila Chaverri, Peijie Chen, Komal Chenthamara, Chris Daum, Elodie Drula, Mukesh Dubey, Mikael Brandström Durling, Daniel Flatschacher, Thomas Ebner, Tamás Emri, Renwei Gao, Raphaela Castro Georg, Bernard Henrissat, Rosa Hermosa, Alfredo Herrera-Estrella, Wolfgang Hinterdobler, Philipp Kainz, Magnus Karlsson, László Kredics, Christian P. Kubicek, Alan Kuo, Kurt LaButti, Anna Lipzen, Matteo Lorito, Robert L. Mach, Gelsomina Manganiello, Tamás Marik, Natalia Martinez-Reyes, Michael Mayrhofer-Reinhartshuber, Márton Miskei, Marie-Claude Moisan, Stephen Mondo, Enrique Monte, Vivian Ng, Guan Pang, Jasmyn Pangilinan, Mao Peng, Edoardo Piombo, István Pócsi, Mohammad Javad Rahimi, Sumitha K. Reddy, Robert Riley, Sabrina Sarrocco, Matthias Schmal, Monika Schmoll, Attila Szűcs, Sheridan L. Woo, Oded Yarden, Susanne Zeilinger, Christian Zimmermann, Ekaterina Shelest, Adrian Tsang, Randy Berka, Ronald P. de Vries, Igor V. Grigoriev, Irina S. Druzhinina","doi":"10.1038/s41564-026-02260-3","DOIUrl":"10.1038/s41564-026-02260-3","url":null,"abstract":"Trichoderma fungi support sustainable agriculture by suppressing plant diseases and improving crop performance. However, emerging pathogenicity of Trichoderma warrants further ecological and genetic characterization. Here we used machine learning to correlate genomic data from 37 Trichoderma strains with over 140 phenotypic traits, spanning metabolic versatility, biotic interactions, stress tolerance and reproductive strategies. We determined Trichoderma to be an ancient, genetically cohesive and physiologically diverse genus with spores capable of germination in water and dispersal via air and water droplets. Metabolic preferences indicate universal adaptation to mycoparasitism and to niches like arboreal microbial mats, alongside broader saprotrophic versatility. Our analyses are consistent with character displacement among close relatives and convergent evolution in distant lineages, with both processes shaping ecological plasticity and traits including dispersal modes, terrestrialization or endophytism. Our findings reveal that while some Trichoderma species show traits of biosafety concern, its vast ecophysiological diversity enables the development of safe, targeted bioeffectors. Analysis of 37 genomes together with more than 140 phenotypic traits links genomic features to ecological fitness and lifestyle diversity in Trichoderma fungi.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"815-831"},"PeriodicalIF":19.4,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02260-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346264","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}
Maria Sindhura John, Mahendran Chinnappan, Camille I. Sturges, Methinee Artami, Mohini Bhattacharya, Rebecca A. Keogh, Jeffrey S. Kavanaugh, Shivani Jain, Hanna Gedamu, Jessica Komarovsky, Mauricio Velasquez, Tripti Sharma, Jeffrey G. McDonald, Alexander R. Horswill, Tamia A. Harris-Tryon
{"title":"Skin androgens regulate Staphylococcus aureus pathogenicity via quorum sensing","authors":"Maria Sindhura John, Mahendran Chinnappan, Camille I. Sturges, Methinee Artami, Mohini Bhattacharya, Rebecca A. Keogh, Jeffrey S. Kavanaugh, Shivani Jain, Hanna Gedamu, Jessica Komarovsky, Mauricio Velasquez, Tripti Sharma, Jeffrey G. McDonald, Alexander R. Horswill, Tamia A. Harris-Tryon","doi":"10.1038/s41564-026-02261-2","DOIUrl":"10.1038/s41564-026-02261-2","url":null,"abstract":"Skin cells secrete testosterone, with greater amounts secreted at the skin surface of males compared with females. Males are also more susceptible to skin infections than females. Here we report that mice engineered with testosterone-deficient skin are resistant to methicillin-resistant Staphylococcus aureus infections. Testosterone promoted the expression of S. aureus cytotoxic virulence factors by activating the accessory gene regulator (agr) quorum-sensing pathway in a concentration-dependent manner and independent of quorum-sensing-activating auto-inducing peptides. Mutational analysis revealed that a functional histidine kinase AgrC in S. aureus was required for testosterone to exert its effect, with in silico evidence indicating a direct interaction between testosterone and AgrC. An isomer of testosterone, enantiomer-testosterone, that blocked bacterial quorum sensing, inhibited S. aureus-induced cytotoxicity of human cells. These findings advance our understanding of how the skin regulates bacterial virulence and reveals a potential therapeutic strategy for the management of infections. Testosterone produced by skin cells enhances Staphylococcus aureus pathogenicity by activating quorum sensing, and a stereoisomer of testosterone that blocks this interaction inhibits bacterial cytotoxicity towards human cells.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"704-717"},"PeriodicalIF":19.4,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02261-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317299","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}
{"title":"Tryptophanase disruption promotes insect–bacterium mutualism","authors":"Yayun Wang, Minoru Moriyama, Ryuichi Koga, Kohei Oguchi, Takahiro Hosokawa, Hiroki Takai, Shuji Shigenobu, Naruo Nikoh, Takema Fukatsu","doi":"10.1038/s41564-026-02264-z","DOIUrl":"10.1038/s41564-026-02264-z","url":null,"abstract":"Animal–microorganism symbioses are omnipresent, with both partners often gaining benefits as mutualists. A single mutation in the carbon catabolite repression system in Escherichia coli enables mutualism with the stinkbug Plautia stali. Here we find that this mutation is not present in natural symbioses. Given that the carbon catabolite repression pathway affects the expression of >500 downstream genes, we investigated their role in mutualisms. We find that disruption of a single gene, tnaA, encoding tryptophanase makes E. coli mutualistic to P. stali, resulting in the accumulation of tryptophan and the reduction of toxic indole. A survey of wild populations of P. stali and other stinkbug species revealed that their typical microbial symbionts, Pantoea, consistently lack the tnaA gene. Some Pantoea species such as Pantoea ananatis retain the tnaA gene and cannot establish symbiosis with P. stali, but tnaA-disrupted P. ananatis partially restored the symbiotic capability. When a natural Pantoea mutualist of P. stali was transformed with a functional tna operon, its symbiotic capability reduced significantly. Our finding suggests that tryptophanase disruption may have facilitated the evolution of gut bacterial mutualists in insects. Disruption of a single gene encoding tryptophanase makes Escherichia coli mutualistic in a stinkbug model owing to the accumulation of tryptophan and a reduction in toxic indole. This gene is typically lacking in symbionts of wild stinkbugs.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"759-769"},"PeriodicalIF":19.4,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02264-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317409","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}
{"title":"Skin androgens affect virulence of Staphylococcus aureus","authors":"René M. Roy, Juliane Bubeck Wardenburg","doi":"10.1038/s41564-026-02281-y","DOIUrl":"10.1038/s41564-026-02281-y","url":null,"abstract":"Sex-specific differences in susceptibility to skin infections with Staphylococcus aureus are well described. Testosterone now emerges as a direct modulator of the accessory gene regulator quorum sensing system, increasing S. aureus virulence, which both explains sex-specific differences and informs treatment strategies.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"615-616"},"PeriodicalIF":19.4,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317211","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":"Gut bacteria ammonia production restores acetylcholine neurotransmission and bowel motility","authors":"","doi":"10.1038/s41564-026-02292-9","DOIUrl":"10.1038/s41564-026-02292-9","url":null,"abstract":"Acetylcholine levels are reduced in gut dysmotility conditions. We find that gut acetylcholine levels induce a compensatory increase in gut microbiota urease activity and ammonia production. By upregulating presynaptic Cav2.1 calcium channels in enteric neurons, ammonia enhances calcium influx and restores acetylcholine release neurotransmission, revealing a microbiota-driven mechanism that preserves gut motility.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 4","pages":"849-850"},"PeriodicalIF":19.4,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147307934","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}