Pub Date : 2026-01-05DOI: 10.1038/s41564-025-02222-1
Erica T. Grant, Elena Monzel, Mahesh S. Desai
Akkermansia muciniphila is a prominent member of the intestinal microbiota that has the unique ability to subsist on the mucin O-glycans that form a protective barrier between the host and the gut microbiome. Numerous studies highlight its positive role in metabolic regulation and mucosal barrier maintenance, leading to propositions that A. muciniphila could be used as a next-generation probiotic. However, other work indicates that the effects of A. muciniphila vary depending on nutrition, host genetics and the interaction with surrounding microbes. Furthermore, strain-specific differences in the ability to modulate intestinal barrier function and antimicrobial resistance profiles remain underexplored. Here, by focusing on potential sources of this variation, we provide a nuanced discussion on the complex role of A. muciniphila in human health. With A. muciniphila as an example, we argue that a microbe’s specific environment must be considered to enable critical evaluation of next-generation probiotics. This Review discusses the complex role of the gut microbe Akkermansia muciniphila in human health.
{"title":"Navigating the duality of Akkermansia muciniphila","authors":"Erica T. Grant, Elena Monzel, Mahesh S. Desai","doi":"10.1038/s41564-025-02222-1","DOIUrl":"10.1038/s41564-025-02222-1","url":null,"abstract":"Akkermansia muciniphila is a prominent member of the intestinal microbiota that has the unique ability to subsist on the mucin O-glycans that form a protective barrier between the host and the gut microbiome. Numerous studies highlight its positive role in metabolic regulation and mucosal barrier maintenance, leading to propositions that A. muciniphila could be used as a next-generation probiotic. However, other work indicates that the effects of A. muciniphila vary depending on nutrition, host genetics and the interaction with surrounding microbes. Furthermore, strain-specific differences in the ability to modulate intestinal barrier function and antimicrobial resistance profiles remain underexplored. Here, by focusing on potential sources of this variation, we provide a nuanced discussion on the complex role of A. muciniphila in human health. With A. muciniphila as an example, we argue that a microbe’s specific environment must be considered to enable critical evaluation of next-generation probiotics. This Review discusses the complex role of the gut microbe Akkermansia muciniphila in human health.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"20-30"},"PeriodicalIF":19.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898621","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}
Pub Date : 2026-01-05DOI: 10.1038/s41564-025-02226-x
Christine Elizabeth Cerson, Alexander Pierre Hynes
If only temperate bacteriophages should be able to lie dormant in bacterial cells, why have two independent groups found thousands of virulent phages hiding in bacterial sequencing data?
{"title":"Perfect predators persist","authors":"Christine Elizabeth Cerson, Alexander Pierre Hynes","doi":"10.1038/s41564-025-02226-x","DOIUrl":"10.1038/s41564-025-02226-x","url":null,"abstract":"If only temperate bacteriophages should be able to lie dormant in bacterial cells, why have two independent groups found thousands of virulent phages hiding in bacterial sequencing data?","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"12-13"},"PeriodicalIF":19.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898636","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}
Pub Date : 2026-01-05DOI: 10.1038/s41564-025-02220-3
A comprehensive assessment of how transformation of dietary nutrients by the gut microbiota influences host health is needed. Systematic integration of 5,554 global gut metagenomes and various biochemical databases reveals how dietary phytonutrients are biotransformed by the gut microbiota and their enzymes, and how these biotransformations relate to human health.
{"title":"Gut microbial enzymes shape the health benefits of dietary phytonutrients","authors":"","doi":"10.1038/s41564-025-02220-3","DOIUrl":"10.1038/s41564-025-02220-3","url":null,"abstract":"A comprehensive assessment of how transformation of dietary nutrients by the gut microbiota influences host health is needed. Systematic integration of 5,554 global gut metagenomes and various biochemical databases reveals how dietary phytonutrients are biotransformed by the gut microbiota and their enzymes, and how these biotransformations relate to human health.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"18-19"},"PeriodicalIF":19.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898627","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}
Pub Date : 2026-01-05DOI: 10.1038/s41564-025-02229-8
Andrew Jermy, Heidi Burdett, Michael C. Chao, Nonia Pariente, Claudio Nunes-Alves, Agustina Taglialegna, Susan Jones
For the celebration of our tenth anniversary, Nature Microbiology asks the former editors to reflect on their time at the journal.
为了庆祝我们的十周年纪念，《自然微生物学》邀请前编辑们回顾他们在该杂志的时光。
{"title":"Voices of our past editors","authors":"Andrew Jermy, Heidi Burdett, Michael C. Chao, Nonia Pariente, Claudio Nunes-Alves, Agustina Taglialegna, Susan Jones","doi":"10.1038/s41564-025-02229-8","DOIUrl":"10.1038/s41564-025-02229-8","url":null,"abstract":"For the celebration of our tenth anniversary, Nature Microbiology asks the former editors to reflect on their time at the journal.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"7-10"},"PeriodicalIF":19.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898607","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}
Pub Date : 2026-01-05DOI: 10.1038/s41564-025-02245-8
Our January 2026 special issue commemorates the tenth anniversary of the journal and celebrates researchers, peer reviewers and readers from the microbiology community and beyond.
{"title":"Celebrating 10 years of Nature Microbiology","authors":"","doi":"10.1038/s41564-025-02245-8","DOIUrl":"10.1038/s41564-025-02245-8","url":null,"abstract":"Our January 2026 special issue commemorates the tenth anniversary of the journal and celebrates researchers, peer reviewers and readers from the microbiology community and beyond.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"1-1"},"PeriodicalIF":19.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02245-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898589","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}
Pub Date : 2026-01-05DOI: 10.1038/s41564-025-02216-z
A zoonotic Streptococcus species achieves massive proliferation in the brain, leading to potentially lethal meningitis and severe brain injury. This robust growth depends on a species-specific promoter that induces constitutive transcription of a phosphotransferase system that facilitates carbohydrate uptake and prevents the bacterial stringent response in the low-glucose environment of the cerebrospinal fluid.
{"title":"A phosphotransferase system promotes growth of zoonotic Streptococcus species in the brain","authors":"","doi":"10.1038/s41564-025-02216-z","DOIUrl":"10.1038/s41564-025-02216-z","url":null,"abstract":"A zoonotic Streptococcus species achieves massive proliferation in the brain, leading to potentially lethal meningitis and severe brain injury. This robust growth depends on a species-specific promoter that induces constitutive transcription of a phosphotransferase system that facilitates carbohydrate uptake and prevents the bacterial stringent response in the low-glucose environment of the cerebrospinal fluid.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"16-17"},"PeriodicalIF":19.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898616","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}
Pub Date : 2026-01-05DOI: 10.1038/s41564-025-02218-x
Jacob Smith
Jacob Smith interviews microbiologists from around the world for their insights about what’s next for the field. Despite numerous challenges, optimism and creativity are poised to usher in an exciting new era of microbiology.
{"title":"The future of microbiology","authors":"Jacob Smith","doi":"10.1038/s41564-025-02218-x","DOIUrl":"10.1038/s41564-025-02218-x","url":null,"abstract":"Jacob Smith interviews microbiologists from around the world for their insights about what’s next for the field. Despite numerous challenges, optimism and creativity are poised to usher in an exciting new era of microbiology.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"4-6"},"PeriodicalIF":19.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898615","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}
Pub Date : 2026-01-02DOI: 10.1038/s41564-025-02224-z
Zhipeng Wang, Yujue Wang, Hui Gao, Jiani Dai, Na Tang, Yannan Wang, Quanjiang Ji
The evolutionary competition within phage–host systems led to the emergence of CRISPR–Cas defence mechanisms in bacteria and anti-CRISPR elements in bacteriophages. Although anti-CRISPR elements are well characterized, the role of bacterial factors that influence CRISPR–Cas efficacy has been comparatively overlooked. Type V CRISPR–Cas12 systems display striking functional and mechanistic diversity for nucleic acid targeting. Here we use a bioinformatic approach to identify Cas12p, a phage-associated nuclease that forms complexes with the bacterial thioredoxin protein TrxA to enable target DNA degradation. This represents an unexpected phage–bacteria interaction, in which the bacteriophage co-opts a bacterial factor to augment its own genome degradation machinery, potentially against competing phages. Biochemical characterization, cryo-EM-based structural analysis of the Cas12p–TrxA–sgRNA–dsDNA complex at 2.67 Å and bacterial defence assays reveal that TrxA directly binds and activates Cas12p, enabling its nuclease activity and subsequent CRISPR immunity. These findings expand our understanding of the multilayered intricacies of phage–bacteria molecular interactions. In an unexpected interaction, infecting phages co-opt a bacterial protein to potentially facilitate genome degradation of competing phages.
{"title":"Phage-associated Cas12p nucleases require binding to bacterial thioredoxin for activation and cleavage of target DNA","authors":"Zhipeng Wang, Yujue Wang, Hui Gao, Jiani Dai, Na Tang, Yannan Wang, Quanjiang Ji","doi":"10.1038/s41564-025-02224-z","DOIUrl":"10.1038/s41564-025-02224-z","url":null,"abstract":"The evolutionary competition within phage–host systems led to the emergence of CRISPR–Cas defence mechanisms in bacteria and anti-CRISPR elements in bacteriophages. Although anti-CRISPR elements are well characterized, the role of bacterial factors that influence CRISPR–Cas efficacy has been comparatively overlooked. Type V CRISPR–Cas12 systems display striking functional and mechanistic diversity for nucleic acid targeting. Here we use a bioinformatic approach to identify Cas12p, a phage-associated nuclease that forms complexes with the bacterial thioredoxin protein TrxA to enable target DNA degradation. This represents an unexpected phage–bacteria interaction, in which the bacteriophage co-opts a bacterial factor to augment its own genome degradation machinery, potentially against competing phages. Biochemical characterization, cryo-EM-based structural analysis of the Cas12p–TrxA–sgRNA–dsDNA complex at 2.67 Å and bacterial defence assays reveal that TrxA directly binds and activates Cas12p, enabling its nuclease activity and subsequent CRISPR immunity. These findings expand our understanding of the multilayered intricacies of phage–bacteria molecular interactions. In an unexpected interaction, infecting phages co-opt a bacterial protein to potentially facilitate genome degradation of competing phages.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"81-93"},"PeriodicalIF":19.4,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145894377","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}
Pub Date : 2025-12-29DOI: 10.1038/s41564-025-02207-0
Peter Erdmann Dougherty, Charles Bernard, Alexander Byth Carstens, Emmanuel Bumunang, Milan Gerovac, Mathias Müsken, Kim Stanford, Tim A. McAllister, Eduardo P. C. Rocha, Lars Hestbjerg Hansen
Virulent phages, characterized by an obligatory lytic cycle resulting in the death of their bacterial hosts, are assumed to lack the ability to persist within bacterial colonies. Consequently, when bacterial isolates are sequenced, the resulting assemblies are not expected to contain virulent phage genomes. Here we test this assumption at scale by analysing over 267,000 publicly available Escherichia assemblies. Surprisingly, we identified 373 virulent phage genomes within these assemblies. Such viral genomes are associated with specific phage taxa and especially with very large (jumbo) phages such as the phage nucleus-forming family Chimalliviridae. Multiple lines of evidence from culture experiments and bioinformatic analyses suggest that these virulent phage genomes arise from persistent infections without substantial host mortality. We also identified 285 related phage genomes in bacterial taxa beyond Escherichia, highlighting the frequency of as-yet-uncharacterized persistent phages. Our findings challenge the traditional virulent–temperate dichotomy and point to the prevalence of non-canonical phage lifestyles. The long-term existence of diverse virulent phages within cultures of Escherichia coli and others challenges the virulent–temperate dichotomy and points to non-canonical phage lifestyles.
{"title":"Persistent virulent phages exist across bacterial isolates","authors":"Peter Erdmann Dougherty, Charles Bernard, Alexander Byth Carstens, Emmanuel Bumunang, Milan Gerovac, Mathias Müsken, Kim Stanford, Tim A. McAllister, Eduardo P. C. Rocha, Lars Hestbjerg Hansen","doi":"10.1038/s41564-025-02207-0","DOIUrl":"10.1038/s41564-025-02207-0","url":null,"abstract":"Virulent phages, characterized by an obligatory lytic cycle resulting in the death of their bacterial hosts, are assumed to lack the ability to persist within bacterial colonies. Consequently, when bacterial isolates are sequenced, the resulting assemblies are not expected to contain virulent phage genomes. Here we test this assumption at scale by analysing over 267,000 publicly available Escherichia assemblies. Surprisingly, we identified 373 virulent phage genomes within these assemblies. Such viral genomes are associated with specific phage taxa and especially with very large (jumbo) phages such as the phage nucleus-forming family Chimalliviridae. Multiple lines of evidence from culture experiments and bioinformatic analyses suggest that these virulent phage genomes arise from persistent infections without substantial host mortality. We also identified 285 related phage genomes in bacterial taxa beyond Escherichia, highlighting the frequency of as-yet-uncharacterized persistent phages. Our findings challenge the traditional virulent–temperate dichotomy and point to the prevalence of non-canonical phage lifestyles. The long-term existence of diverse virulent phages within cultures of Escherichia coli and others challenges the virulent–temperate dichotomy and points to non-canonical phage lifestyles.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"31-41"},"PeriodicalIF":19.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857385","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}
Microbiome perturbations are associated with advanced chronic liver disease (ACLD), but how microorganisms contribute to disease mechanisms is unclear. Here we analysed metagenomes of paired saliva and faecal samples from an ACLD cohort of 86 individuals, plus 2 control groups of 52 healthy individuals and 14 patients with sepsis. We identified highly similar oral and gut bacterial strains, including Veillonella and Streptococcus spp., which increased in absolute abundance in the gut of patients with ACLD compared with controls. These microbial translocators uniquely share a prtC gene encoding a collagenase-like proteinase, and its faecal abundance was a robust ACLD biomarker (area under precision-recall curve = 0.91). A mouse model of hepatic fibrosis inoculated with Veillonella and Streptococcus prtC-encoding patient isolates showed exacerbation of gut barrier impairment and hepatic fibrosis. Furthermore, faecal collagenase activity was increased in patients with ACLD and experimentally confirmed for the prtC gene of translocating Veillonella parvula. These findings establish mechanistic links between oral–gut translocation and ACLD pathobiology. While oral bacteria rarely colonize the healthy gut, they dominate the gut microbiome of patients with chronic liver disease. Here a bacterial gene encoded by microbial translocators is linked to gut barrier disruption and fibrosis.
{"title":"Microbial collagenase activity is linked to oral–gut translocation in advanced chronic liver disease","authors":"Shen Jin, Aurelie Cenier, Daniela Wetzel, Bethlehem Arefaine, Mar Moreno-Gonzalez, Marilena Stamouli, Merianne Mohamad, Mariia Lupatsii, Emilio Ríos, Sunjae Lee, Ane Zamalloa, Shilpa Chokshi, Adil Mardinoglu, Saeed Shoaie, Naiara Beraza, Vishal C. Patel, Melanie Schirmer","doi":"10.1038/s41564-025-02223-0","DOIUrl":"10.1038/s41564-025-02223-0","url":null,"abstract":"Microbiome perturbations are associated with advanced chronic liver disease (ACLD), but how microorganisms contribute to disease mechanisms is unclear. Here we analysed metagenomes of paired saliva and faecal samples from an ACLD cohort of 86 individuals, plus 2 control groups of 52 healthy individuals and 14 patients with sepsis. We identified highly similar oral and gut bacterial strains, including Veillonella and Streptococcus spp., which increased in absolute abundance in the gut of patients with ACLD compared with controls. These microbial translocators uniquely share a prtC gene encoding a collagenase-like proteinase, and its faecal abundance was a robust ACLD biomarker (area under precision-recall curve = 0.91). A mouse model of hepatic fibrosis inoculated with Veillonella and Streptococcus prtC-encoding patient isolates showed exacerbation of gut barrier impairment and hepatic fibrosis. Furthermore, faecal collagenase activity was increased in patients with ACLD and experimentally confirmed for the prtC gene of translocating Veillonella parvula. These findings establish mechanistic links between oral–gut translocation and ACLD pathobiology. While oral bacteria rarely colonize the healthy gut, they dominate the gut microbiome of patients with chronic liver disease. Here a bacterial gene encoded by microbial translocators is linked to gut barrier disruption and fibrosis.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"211-227"},"PeriodicalIF":19.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02223-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857387","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}
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