Pub Date : 2026-01-22DOI: 10.1038/s41564-025-02237-8
Chuankai Cheng, Brittany D. Bennett, Pratixa Savalia, Hasti Asrari, Carmen Biel, Kate A. Evans, Rui Tang, J. Cameron Thrash
Genome streamlining is hypothesized to occur in bacteria as an adaptation to resource-limited environments but can result in gene losses affecting fundamental aspects of cellular physiology. The most abundant marine microorganisms, SAR11 (order Pelagibacterales), exhibit canonical genome streamlining, but the consequences of this genotype on core cellular processes such as cell division remain unexplored. Here, analysis of 470 SAR11 genomes revealed widespread absence of key cell cycle control genes. Growth experiments demonstrated that although SAR11 bacteria maintain a normal cell cycle under oligotrophic conditions, they exhibit growth inhibition and aneuploidy when exposed to nutrient enrichment, carbon source shifts or temperature stress. Detailed growth measurements and antibiotic inhibition experiments showed that these phenotypes resulted from cell division disruption with continuing DNA replication, leading to heterogeneous subpopulations of normal and polyploid cells. This vulnerability raises questions about microbial genome evolution and the evolutionary trade-offs between adaptation to stable nutrient-limited conditions and physiological resilience. Without key cell cycle control genes, SAR11 cells experience aneuploidy and growth inhibition when exposed to changes in nutrients, carbon sources or temperature stress, a vulnerability that may represent an evolutionary trade-off for adaptation to oligotrophic environments.
{"title":"Cell cycle dysregulation of globally important SAR11 bacteria resulting from environmental perturbation","authors":"Chuankai Cheng, Brittany D. Bennett, Pratixa Savalia, Hasti Asrari, Carmen Biel, Kate A. Evans, Rui Tang, J. Cameron Thrash","doi":"10.1038/s41564-025-02237-8","DOIUrl":"10.1038/s41564-025-02237-8","url":null,"abstract":"Genome streamlining is hypothesized to occur in bacteria as an adaptation to resource-limited environments but can result in gene losses affecting fundamental aspects of cellular physiology. The most abundant marine microorganisms, SAR11 (order Pelagibacterales), exhibit canonical genome streamlining, but the consequences of this genotype on core cellular processes such as cell division remain unexplored. Here, analysis of 470 SAR11 genomes revealed widespread absence of key cell cycle control genes. Growth experiments demonstrated that although SAR11 bacteria maintain a normal cell cycle under oligotrophic conditions, they exhibit growth inhibition and aneuploidy when exposed to nutrient enrichment, carbon source shifts or temperature stress. Detailed growth measurements and antibiotic inhibition experiments showed that these phenotypes resulted from cell division disruption with continuing DNA replication, leading to heterogeneous subpopulations of normal and polyploid cells. This vulnerability raises questions about microbial genome evolution and the evolutionary trade-offs between adaptation to stable nutrient-limited conditions and physiological resilience. Without key cell cycle control genes, SAR11 cells experience aneuploidy and growth inhibition when exposed to changes in nutrients, carbon sources or temperature stress, a vulnerability that may represent an evolutionary trade-off for adaptation to oligotrophic environments.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"551-565"},"PeriodicalIF":19.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030469","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 : 2026-01-22DOI: 10.1038/s41564-025-02240-z
Yi Xu, Bowei Gu, Huiying Yao, Mikkel Schultz-Johansen, Isabella Wilkie, Leesa Jane Klau, Yuerong Chen, Luis H. Orellana, Finn Lillelund Aachmann, Mahum Farhan, Greta Reintjes, Silvia Vidal-Melgosa, Dairong Qiao, Yi Cao, Jan-Hendrik Hehemann
Brown algae and diatoms convert carbon dioxide into the polysaccharide fucoidan, which sequesters carbon in the ocean despite the prevalence of marine bacterial fucoidanase genes. Bacteria with fucoidanase genes also have high-affinity phosphate transporters, suggesting that phosphate could impact fucoidan degradation and subsequent carbon sequestration. Here, to test this hypothesis, we assembled a system consisting of a microalga that produces and a bacterium that degrades fucoidan. The fixation of carbon dioxide into fucoidan by the microalga Glossomastix sp. PLY432 occurred independent of the phosphate concentration. In contrast, the fucoidan-degrading Verrucomicrobiaceae bacterium 227 was inhibited by a lack of phosphate. Degradation of the structurally simpler polysaccharide laminarin was less affected by the phosphate concentration. Phosphate deprivation enabled the fixation of carbon dioxide in fucoidan and disabled its degradation. These conclusions suggest that phosphate deprivation could be a potential strategy to promote the fixation and sequestration of carbon dioxide as fucoidan. Limiting phosphate concentrations could be a strategy to protect and sequester carbon dioxide as fucoidan, a polysaccharide produced by marine algae.
{"title":"Phosphate deprivation restricts bacterial degradation of the marine polysaccharide fucoidan","authors":"Yi Xu, Bowei Gu, Huiying Yao, Mikkel Schultz-Johansen, Isabella Wilkie, Leesa Jane Klau, Yuerong Chen, Luis H. Orellana, Finn Lillelund Aachmann, Mahum Farhan, Greta Reintjes, Silvia Vidal-Melgosa, Dairong Qiao, Yi Cao, Jan-Hendrik Hehemann","doi":"10.1038/s41564-025-02240-z","DOIUrl":"10.1038/s41564-025-02240-z","url":null,"abstract":"Brown algae and diatoms convert carbon dioxide into the polysaccharide fucoidan, which sequesters carbon in the ocean despite the prevalence of marine bacterial fucoidanase genes. Bacteria with fucoidanase genes also have high-affinity phosphate transporters, suggesting that phosphate could impact fucoidan degradation and subsequent carbon sequestration. Here, to test this hypothesis, we assembled a system consisting of a microalga that produces and a bacterium that degrades fucoidan. The fixation of carbon dioxide into fucoidan by the microalga Glossomastix sp. PLY432 occurred independent of the phosphate concentration. In contrast, the fucoidan-degrading Verrucomicrobiaceae bacterium 227 was inhibited by a lack of phosphate. Degradation of the structurally simpler polysaccharide laminarin was less affected by the phosphate concentration. Phosphate deprivation enabled the fixation of carbon dioxide in fucoidan and disabled its degradation. These conclusions suggest that phosphate deprivation could be a potential strategy to promote the fixation and sequestration of carbon dioxide as fucoidan. Limiting phosphate concentrations could be a strategy to protect and sequester carbon dioxide as fucoidan, a polysaccharide produced by marine algae.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"391-405"},"PeriodicalIF":19.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02240-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021585","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 : 2026-01-22DOI: 10.1038/s41564-025-02252-9
Benjamin N. Granzow
Bacterial degradation of extracellular fucoidan is resource-intensive and, therefore, limited by low-phosphate concentrations. This mechanism provides a competitive advantage to fucoidan-producing microalgae and enhances carbon sequestration.
{"title":"Phosphate availability stabilizes fucoidan produced by marine microalgae","authors":"Benjamin N. Granzow","doi":"10.1038/s41564-025-02252-9","DOIUrl":"10.1038/s41564-025-02252-9","url":null,"abstract":"Bacterial degradation of extracellular fucoidan is resource-intensive and, therefore, limited by low-phosphate concentrations. This mechanism provides a competitive advantage to fucoidan-producing microalgae and enhances carbon sequestration.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"343-344"},"PeriodicalIF":19.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021745","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 : 2026-01-21DOI: 10.1038/s41564-025-02247-6
Robert J. Fillinger, Abhishek Mishra, Liza Loza, Shabnam Sircaik, Cristobal Carrera Carriel, Anna I. Mackey, Travis D. Stratton, Scott G. Filler, Anna M. Selmecki, Richard J. Bennett, Matthew Z. Anderson
Candida albicans is a major human fungal pathogen that reproduces by mitotic growth of diploid cells but can also undergo a parasexual cycle. The latter involves an uncoordinated process of ploidy reduction via aberrant mitotic divisions following the fusion of opposite- or same-sex cells. The ability of parasex to recapitulate the genome plasticity of meiosis remains largely unclear. Here we induced parasexual crosses between genetically distinct strains and analysed the genotypic make-up of parasexual progeny following whole-genome sequencing or selective genotyping to determine the genomic landscape generated by the parasexual cycle. Our results show that C. albicans parasex leads to high levels of recombination and chromosome shuffling as observed in a conventional meiosis. Parasexual progeny also showed diversity in the pathogenesis-related phenotypes of filamentation, drug response and in vivo fitness that was associated with variation in inherited, recombinant genotypes. We propose that the parasexual cycle in non-meiotic eukaryotes can enable escape from a purely asexual mode of reproduction and confer the ability to rapidly adapt to new or changing host niches among commensal and pathogenic species. An alternative mating system, termed parasex, produces progeny with high levels of genotypic diversity and is able to fulfil the roles of meiosis when it is absent in the fungal pathobiont Candida albicans.
{"title":"Parasex generates highly recombinant progeny in Candida albicans with increased virulence","authors":"Robert J. Fillinger, Abhishek Mishra, Liza Loza, Shabnam Sircaik, Cristobal Carrera Carriel, Anna I. Mackey, Travis D. Stratton, Scott G. Filler, Anna M. Selmecki, Richard J. Bennett, Matthew Z. Anderson","doi":"10.1038/s41564-025-02247-6","DOIUrl":"10.1038/s41564-025-02247-6","url":null,"abstract":"Candida albicans is a major human fungal pathogen that reproduces by mitotic growth of diploid cells but can also undergo a parasexual cycle. The latter involves an uncoordinated process of ploidy reduction via aberrant mitotic divisions following the fusion of opposite- or same-sex cells. The ability of parasex to recapitulate the genome plasticity of meiosis remains largely unclear. Here we induced parasexual crosses between genetically distinct strains and analysed the genotypic make-up of parasexual progeny following whole-genome sequencing or selective genotyping to determine the genomic landscape generated by the parasexual cycle. Our results show that C. albicans parasex leads to high levels of recombination and chromosome shuffling as observed in a conventional meiosis. Parasexual progeny also showed diversity in the pathogenesis-related phenotypes of filamentation, drug response and in vivo fitness that was associated with variation in inherited, recombinant genotypes. We propose that the parasexual cycle in non-meiotic eukaryotes can enable escape from a purely asexual mode of reproduction and confer the ability to rapidly adapt to new or changing host niches among commensal and pathogenic species. An alternative mating system, termed parasex, produces progeny with high levels of genotypic diversity and is able to fulfil the roles of meiosis when it is absent in the fungal pathobiont Candida albicans.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"522-534"},"PeriodicalIF":19.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02247-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146006265","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 : 2026-01-19DOI: 10.1038/s41564-025-02219-w
Phionah Tushabe, Manasi Majumdar, Sarah Carlyle, Lester Shulman, Alfred Ssekagiri, Marie-Line Joffret, Dimitra Klapsa, Jeroen Cremer, Kafayat O. Arowolo, Erika Bujaki, Henry Bukenya, EPI Laboratory team, Mary Bridget Nanteza, Irene Turyahabwe, Prossy Namuwulya, Molly Birungi, James Peter Eliku, Francis Aine, Mayi Tibanagwa, Lucy Nakabazzi, Joseph Gaizi, Arnold Mugagga Ssebuuma, Rajab Dhatemwa, Charles Okia, Mary Nyachwo, Mary Bridget Nanteza, Irene Turyahabwe, Prossy Namuwulya, Molly Birungi, James Peter Eliku, Francis Aine, Mayi Tibanagwa, Lucy Nakabazzi, Joseph Gaizi, Arnold Mugagga Ssebuuma, Rajab Dhatemwa, Charles Okia, Mary Nyachwo, Kaija M. Hawes, Barnabas Bakamutumaho, Erwin Duizer, Mael Bessaud, Ananda S. Bandyopadhyay, Andrew Macadam, Charles R. Byabamazima, Javier Martin, Josephine Bwogi
The novel oral poliovirus vaccine type 2 (nOPV2) was developed to reduce the risk of circulating vaccine-derived poliovirus outbreaks by incorporating genetic modifications to enhance genetic stability and reduce reversion to virulence while retaining protection. Here we report the characterization of 231 nOPV2 isolates from Uganda during a 1-year period following nOPV2 use. Whole-genome sequencing revealed that most isolates retained nOPV2’s genetic modifications, with limited mutations in the VP1 region indicating no relevant virus transmission. However, a double recombinant strain identified in a sewage sample lost all key nOPV2 modifications through recombination with enterovirus C strains upstream and downstream of the capsid coding region. This resulted in high neurovirulence comparable to that of wild-type 2 poliovirus. Despite this, the strain did not spread widely, probably due to high vaccination coverage. These findings underscore the enhanced genetic stability of nOPV2 and its reduced risk of reversion compared with Sabin monovalent OPV2 (mOPV2), while highlighting the importance of surveillance to detect rare recombination events. Continued use of nOPV2 and inactivated polio vaccine, combined with robust immunization and monitoring, remains essential for achieving and sustaining global polio eradication. Whole-genome sequencing of polioviruses in Uganda following nOPV2 use showed high genetic stability and no sustained transmission, even though a rare double recombinant strain regained virulence, but did not spread due to high vaccination coverage.
{"title":"Higher stability of novel live-attenuated oral poliovirus type 2 (nOPV2) despite the emergence of a neurovirulent double recombinant strain in Uganda","authors":"Phionah Tushabe, Manasi Majumdar, Sarah Carlyle, Lester Shulman, Alfred Ssekagiri, Marie-Line Joffret, Dimitra Klapsa, Jeroen Cremer, Kafayat O. Arowolo, Erika Bujaki, Henry Bukenya, EPI Laboratory team, Mary Bridget Nanteza, Irene Turyahabwe, Prossy Namuwulya, Molly Birungi, James Peter Eliku, Francis Aine, Mayi Tibanagwa, Lucy Nakabazzi, Joseph Gaizi, Arnold Mugagga Ssebuuma, Rajab Dhatemwa, Charles Okia, Mary Nyachwo, Mary Bridget Nanteza, Irene Turyahabwe, Prossy Namuwulya, Molly Birungi, James Peter Eliku, Francis Aine, Mayi Tibanagwa, Lucy Nakabazzi, Joseph Gaizi, Arnold Mugagga Ssebuuma, Rajab Dhatemwa, Charles Okia, Mary Nyachwo, Kaija M. Hawes, Barnabas Bakamutumaho, Erwin Duizer, Mael Bessaud, Ananda S. Bandyopadhyay, Andrew Macadam, Charles R. Byabamazima, Javier Martin, Josephine Bwogi","doi":"10.1038/s41564-025-02219-w","DOIUrl":"10.1038/s41564-025-02219-w","url":null,"abstract":"The novel oral poliovirus vaccine type 2 (nOPV2) was developed to reduce the risk of circulating vaccine-derived poliovirus outbreaks by incorporating genetic modifications to enhance genetic stability and reduce reversion to virulence while retaining protection. Here we report the characterization of 231 nOPV2 isolates from Uganda during a 1-year period following nOPV2 use. Whole-genome sequencing revealed that most isolates retained nOPV2’s genetic modifications, with limited mutations in the VP1 region indicating no relevant virus transmission. However, a double recombinant strain identified in a sewage sample lost all key nOPV2 modifications through recombination with enterovirus C strains upstream and downstream of the capsid coding region. This resulted in high neurovirulence comparable to that of wild-type 2 poliovirus. Despite this, the strain did not spread widely, probably due to high vaccination coverage. These findings underscore the enhanced genetic stability of nOPV2 and its reduced risk of reversion compared with Sabin monovalent OPV2 (mOPV2), while highlighting the importance of surveillance to detect rare recombination events. Continued use of nOPV2 and inactivated polio vaccine, combined with robust immunization and monitoring, remains essential for achieving and sustaining global polio eradication. Whole-genome sequencing of polioviruses in Uganda following nOPV2 use showed high genetic stability and no sustained transmission, even though a rare double recombinant strain regained virulence, but did not spread due to high vaccination coverage.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"406-414"},"PeriodicalIF":19.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02219-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003893","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 : 2026-01-19DOI: 10.1038/s41564-025-02228-9
Bruce R. Thorley
The release of a more genetically stable form of a live, attenuated oral polio vaccine, nOPV2, was heralded as a major advance towards global polio eradication. Virus recombination events can undo all the hard work.
{"title":"Double recombinant nOPV2 vaccine","authors":"Bruce R. Thorley","doi":"10.1038/s41564-025-02228-9","DOIUrl":"10.1038/s41564-025-02228-9","url":null,"abstract":"The release of a more genetically stable form of a live, attenuated oral polio vaccine, nOPV2, was heralded as a major advance towards global polio eradication. Virus recombination events can undo all the hard work.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"345-347"},"PeriodicalIF":19.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003823","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 : 2026-01-16DOI: 10.1038/s41564-025-02239-6
Toni A. Nagy, Gina W. Gersabeck, Amy N. Conte, Aaron T. Whiteley
Bacteria have evolved sophisticated antiphage systems that halt phage replication upon detecting specific phage triggers. Identifying phage triggers is crucial to our understanding of immune signalling; however, they are challenging to predict. Here we used a plasmid library that expressed over 400 phage protein-coding genes from 6 phages to identify triggers of known and undiscovered antiphage systems. We transformed our library into 39 diverse strains of E. coli. Each strain natively harbours a different suite of antiphage systems whose activation typically inhibits growth. By tracking plasmids that were selectively depleted, we identified over 100 candidate phage trigger–E. coli pairs. Two phage proteins were further investigated, revealing that T7 gp17 and additional tail fibre proteins activated the undescribed antiphage system PD-T2-1 and identifying that λ gpE major capsid protein activated the antiphage system Avs8. These experiments provide a unique dataset for the continued definition of the molecular mechanisms underlying the bacterial immune system. A library of 400 phage protein-coding genes is used to find a trove of antiphage systems, revealing systems that target tail fibre and major capsid proteins.
{"title":"A phage protein screen identifies triggers of the bacterial innate immune system","authors":"Toni A. Nagy, Gina W. Gersabeck, Amy N. Conte, Aaron T. Whiteley","doi":"10.1038/s41564-025-02239-6","DOIUrl":"10.1038/s41564-025-02239-6","url":null,"abstract":"Bacteria have evolved sophisticated antiphage systems that halt phage replication upon detecting specific phage triggers. Identifying phage triggers is crucial to our understanding of immune signalling; however, they are challenging to predict. Here we used a plasmid library that expressed over 400 phage protein-coding genes from 6 phages to identify triggers of known and undiscovered antiphage systems. We transformed our library into 39 diverse strains of E. coli. Each strain natively harbours a different suite of antiphage systems whose activation typically inhibits growth. By tracking plasmids that were selectively depleted, we identified over 100 candidate phage trigger–E. coli pairs. Two phage proteins were further investigated, revealing that T7 gp17 and additional tail fibre proteins activated the undescribed antiphage system PD-T2-1 and identifying that λ gpE major capsid protein activated the antiphage system Avs8. These experiments provide a unique dataset for the continued definition of the molecular mechanisms underlying the bacterial immune system. A library of 400 phage protein-coding genes is used to find a trove of antiphage systems, revealing systems that target tail fibre and major capsid proteins.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"597-609"},"PeriodicalIF":19.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986516","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}
Elevated levels of serum branched-chain amino acids (BCAA) are linked to various metabolic disorders such as obesity, insulin resistance and type 2 diabetes. Although gut microbiota can regulate circulating BCAA levels via direct transformation, here we uncover an indirect mechanism that influences host BCAA metabolism. Comparisons between the metabolome and gut microbiota of germ-free and wild-type mice and pigs revealed Lactobacillus reuteri and its metabolite l-theanine to be associated with increased BCAA catabolism. This effect was reproduced by monocolonization of the animals with Lactobacillus reuteri or treatment with l-theanine. Experiments with pig cell lines showed that l-theanine enhanced the expression of branched-chain aminotransferases (BCATs), host enzymes involved in BCAA catabolism. Specifically, l-theanine promoted the expression of BCAT2 mRNA by suppressing its histone methylation and stabilizing the BCAT2 protein by inhibiting ubiquitination of specific lysine residues. Our findings provide a potential avenue for development of therapies against disorders associated with elevated BCAA levels. Experiments in mice and pigs revealed that l-theanine produced by Lactobacillus reuteri acts on host cells to increase the catabolism of branched-chain amino acids by stabilizing the expression of branched-chain amino acid transferases.
{"title":"Gut microbiota-derived l-theanine promotes host branched-chain amino acid catabolism","authors":"Youxia Wang, Bingnan Liu, Ziyi Han, Peng Bin, Wenjie Tang, Jian Fu, Ifen Hung, Chunxue Liu, Hong Wei, Liangpeng Ge, Wenkai Ren","doi":"10.1038/s41564-025-02236-9","DOIUrl":"10.1038/s41564-025-02236-9","url":null,"abstract":"Elevated levels of serum branched-chain amino acids (BCAA) are linked to various metabolic disorders such as obesity, insulin resistance and type 2 diabetes. Although gut microbiota can regulate circulating BCAA levels via direct transformation, here we uncover an indirect mechanism that influences host BCAA metabolism. Comparisons between the metabolome and gut microbiota of germ-free and wild-type mice and pigs revealed Lactobacillus reuteri and its metabolite l-theanine to be associated with increased BCAA catabolism. This effect was reproduced by monocolonization of the animals with Lactobacillus reuteri or treatment with l-theanine. Experiments with pig cell lines showed that l-theanine enhanced the expression of branched-chain aminotransferases (BCATs), host enzymes involved in BCAA catabolism. Specifically, l-theanine promoted the expression of BCAT2 mRNA by suppressing its histone methylation and stabilizing the BCAT2 protein by inhibiting ubiquitination of specific lysine residues. Our findings provide a potential avenue for development of therapies against disorders associated with elevated BCAA levels. Experiments in mice and pigs revealed that l-theanine produced by Lactobacillus reuteri acts on host cells to increase the catabolism of branched-chain amino acids by stabilizing the expression of branched-chain amino acid transferases.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"507-521"},"PeriodicalIF":19.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968533","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 : 2026-01-12DOI: 10.1038/s41564-025-02250-x
In 22 patients with auto-brewery syndrome, we found enrichment of gut bacterial genes in metabolic pathways associated with ethanol production. Treatment with faecal microbiota transplantation in one patient led to improvement in symptoms that correlated with changes in gut microbiota composition and improved metabolic function.
{"title":"Microbial ethanol production in patients with auto-brewery syndrome","authors":"","doi":"10.1038/s41564-025-02250-x","DOIUrl":"10.1038/s41564-025-02250-x","url":null,"abstract":"In 22 patients with auto-brewery syndrome, we found enrichment of gut bacterial genes in metabolic pathways associated with ethanol production. Treatment with faecal microbiota transplantation in one patient led to improvement in symptoms that correlated with changes in gut microbiota composition and improved metabolic function.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"348-349"},"PeriodicalIF":19.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956195","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 : 2026-01-12DOI: 10.1038/s41564-025-02246-7
Rebecca A. Drummond
A mouse commensal fungus, Kazachstania pintolopesii, secretes a protein, Ygp1, that promotes epithelial cell regeneration and healing in mouse models of intestinal injury, renewing the interest in probiotic activities of commensal fungi.
{"title":"Commensal fungus to the rescue of gut injury","authors":"Rebecca A. Drummond","doi":"10.1038/s41564-025-02246-7","DOIUrl":"10.1038/s41564-025-02246-7","url":null,"abstract":"A mouse commensal fungus, Kazachstania pintolopesii, secretes a protein, Ygp1, that promotes epithelial cell regeneration and healing in mouse models of intestinal injury, renewing the interest in probiotic activities of commensal fungi.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"339-340"},"PeriodicalIF":19.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956194","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}
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