Heart failure (HF) is highly prevalent in chronic kidney disease (CKD) and associates with alterations in gut microbiota, although the underlying mechanisms remain unclear, complicating diagnosis and treatment. In this study, we identify indoxyl sulfate (IS), produced by E. coli through the tryptophanase (TnaA) pathway, as a key metabolite involved in CKD-related HF. Mechanistically, IS disrupts cardiac mitochondrial function and induces myocardial apoptosis via the AHR-CYP1B1 axis, driving HF progression. To target this gut-microbiota-IS axis for clinical improvement of CKD-related HF, we applied probiotics to reduce E. coli abundance and IS levels, resulting in improved cardiac outcomes in rats and CKD patients. This study was registered at the Chinese Clinical Trial Register (https://www.chictr.org.cn: ChiCTR2500098366 and ChiCTR2500100588). Furthermore, E. coli abundance shows diagnostic potential for early prediction of HF onset within 6 months in a prospective CKD cohort study. These findings underscore the critical role of gut microbiota in CKD-related HF and suggest a microbiota-targeted therapeutic and diagnostic strategy for clinical intervention.
{"title":"Gut-microbiota-derived indole sulfate promotes heart failure in chronic kidney disease","authors":"Yun Zhang, Xuejie Han, Tao Feng, Zewen Li, Hui Yu, Ye Chen, Yunlong Gao, Qianhui Gao, Linwei Zhang, Shanshan Li, Ling Shi, Xiru Zhang, Zhuang Li, Yue Li, Hongwei Zhou","doi":"10.1016/j.chom.2025.08.014","DOIUrl":"https://doi.org/10.1016/j.chom.2025.08.014","url":null,"abstract":"Heart failure (HF) is highly prevalent in chronic kidney disease (CKD) and associates with alterations in gut microbiota, although the underlying mechanisms remain unclear, complicating diagnosis and treatment. In this study, we identify indoxyl sulfate (IS), produced by <em>E. coli</em> through the tryptophanase (TnaA) pathway, as a key metabolite involved in CKD-related HF. Mechanistically, IS disrupts cardiac mitochondrial function and induces myocardial apoptosis via the AHR-CYP1B1 axis, driving HF progression. To target this gut-microbiota-IS axis for clinical improvement of CKD-related HF, we applied probiotics to reduce <em>E. coli</em> abundance and IS levels, resulting in improved cardiac outcomes in rats and CKD patients. This study was registered at the Chinese Clinical Trial Register (<span><span>https://www.chictr.org.cn</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>: ChiCTR2500098366 and ChiCTR2500100588). Furthermore, <em>E. coli</em> abundance shows diagnostic potential for early prediction of HF onset within 6 months in a prospective CKD cohort study. These findings underscore the critical role of gut microbiota in CKD-related HF and suggest a microbiota-targeted therapeutic and diagnostic strategy for clinical intervention.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"15 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-02DOI: 10.1016/j.chom.2025.08.006
Molly R. Sargen, Sophie Helaine
Bacteria counter bacteriophage threats using diverse anti-phage systems often encoded on prophages within hotspots for accessory genes. These prophages must ensure that encoded defense systems do not inhibit their spread. Here, we discover two anti-phage defense elements, RemS and PokE, encoded within the Gifsy-3 prophage of Salmonella enterica Typhimurium 14028 that restrict phage infection without affecting the lytic cycle of Gifsy-3. RemS, an ATPase, is expressed from a hotspot for accessory genes in lambdoid phages. PokE is a small membrane-depolarizing protein/peptide encoded within the Gifsy-3 lysis cassette. During infection by phage BTP1, pokE transcription is specifically driven by the Q antiterminator of BTP1, as the infecting phage prepares to express its lysis genes. PokE then disrupts the BTP1 lytic cycle through abortive infection. Altogether, this work uncovers how a prophage repurposes an essential feature of phage lytic cycles to both detect and respond to a phage-specific essential pathogenic activity.
{"title":"A prophage intercepts pathogenic activity of infecting phage for defense","authors":"Molly R. Sargen, Sophie Helaine","doi":"10.1016/j.chom.2025.08.006","DOIUrl":"https://doi.org/10.1016/j.chom.2025.08.006","url":null,"abstract":"Bacteria counter bacteriophage threats using diverse anti-phage systems often encoded on prophages within hotspots for accessory genes. These prophages must ensure that encoded defense systems do not inhibit their spread. Here, we discover two anti-phage defense elements, RemS and PokE, encoded within the Gifsy-3 prophage of <em>Salmonella enterica</em> Typhimurium 14028 that restrict phage infection without affecting the lytic cycle of Gifsy-3. RemS, an ATPase, is expressed from a hotspot for accessory genes in lambdoid phages. PokE is a small membrane-depolarizing protein/peptide encoded within the Gifsy-3 lysis cassette. During infection by phage BTP1, <em>pokE</em> transcription is specifically driven by the Q antiterminator of BTP1, as the infecting phage prepares to express its lysis genes. PokE then disrupts the BTP1 lytic cycle through abortive infection. Altogether, this work uncovers how a prophage repurposes an essential feature of phage lytic cycles to both detect and respond to a phage-specific essential pathogenic activity.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"28 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-02DOI: 10.1016/j.chom.2025.08.005
Thomas E. Barton, Angharad E. Green, Kate C. Mellor, Abigail E. McKnight, Katharina Bacher, Sumit Kumar, Kyle Newbold, Oliver Lorenz, Elizabeth Pohler, Manal S. Monshi, Adam Bryson, Felix Dube, Heather J. Zar, Mark P. Nicol, Stephen D. Bentley, Markus Hilty, Jason W. Rosch, Stephanie Lo, Daniel R. Neill
Streptococcus pneumoniae colonizes human airways, where it acquires sugars from glycosylated mucins using glycoside hydrolases and sugar transport systems. This study identifies widespread nucleotide sequence variation in the promoter of a pneumococcal operon encoding a glycan scavenging system. We identify 78 promoter sequence patterns across 21,155 genomes, with variation clustered within a stretch of adenines, where mutations accumulate via strand slippage during DNA replication. Promoter mutations influence operon transcription, and multiple promoter patterns are co-identified during single-carriage episodes, suggesting that heterogeneous gene expression provides population-level benefits. In a mouse nasopharyngeal colonization model, promoter mutations arise and undergo selection, with nucleotide insertion promoting gene expression and prolonging carriage longevity. Pre-existing immunity confers resistance to colonization by strains carrying single promoter patterns but does not protect against mixed infections with otherwise isogenic strains differing in promoter sequence. Promoter region sequence variation offers an evolutionary strategy for exploration of phenotypic space to maximize fitness within-host.
{"title":"Naturally acquired promoter variation influences Streptococcus pneumoniae infection outcomes","authors":"Thomas E. Barton, Angharad E. Green, Kate C. Mellor, Abigail E. McKnight, Katharina Bacher, Sumit Kumar, Kyle Newbold, Oliver Lorenz, Elizabeth Pohler, Manal S. Monshi, Adam Bryson, Felix Dube, Heather J. Zar, Mark P. Nicol, Stephen D. Bentley, Markus Hilty, Jason W. Rosch, Stephanie Lo, Daniel R. Neill","doi":"10.1016/j.chom.2025.08.005","DOIUrl":"https://doi.org/10.1016/j.chom.2025.08.005","url":null,"abstract":"<em>Streptococcus pneumoniae</em> colonizes human airways, where it acquires sugars from glycosylated mucins using glycoside hydrolases and sugar transport systems. This study identifies widespread nucleotide sequence variation in the promoter of a pneumococcal operon encoding a glycan scavenging system. We identify 78 promoter sequence patterns across 21,155 genomes, with variation clustered within a stretch of adenines, where mutations accumulate via strand slippage during DNA replication. Promoter mutations influence operon transcription, and multiple promoter patterns are co-identified during single-carriage episodes, suggesting that heterogeneous gene expression provides population-level benefits. In a mouse nasopharyngeal colonization model, promoter mutations arise and undergo selection, with nucleotide insertion promoting gene expression and prolonging carriage longevity. Pre-existing immunity confers resistance to colonization by strains carrying single promoter patterns but does not protect against mixed infections with otherwise isogenic strains differing in promoter sequence. Promoter region sequence variation offers an evolutionary strategy for exploration of phenotypic space to maximize fitness within-host.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"29 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-02DOI: 10.1016/j.chom.2025.08.007
Pengtao Liu, Zhao Zhao, Yaqi Tang, Yangyang Zhou, Jie Liu, Kaiqi Xu, Yaxin Chen, Xiaoting Li, Yaru Tang, Li Yang
Light is essential for plant development, but its influence on pathogen virulence and immunity remains poorly understood. Here, we found that the Pseudomonas syringae DC3000 type III effector, AvrPtoB, exhibits virulence exclusively upon light exposure. This light-dependent regulation is controlled by the Arabidopsis transcription factor ELONGATED HYPOCOTYL 5 (HY5), a central regulator of photomorphogenesis. AvrPtoB targets HY5 in the nucleus, facilitating its ubiquitination and degradation. Genetic disruption of HY5 eliminates susceptibility to AvrPtoB and compromises plant immunity upon light exposure. HY5 enhances immunity by binding promoters of defense-related genes, activating their expression, and stabilizing the transcriptional coregulator NONEXPRESSOR OF PATHOGENESIS-RELATED (PR) GENES 1 (NPR1) by inhibiting its negative regulators NPR3/4. Both HY5-mediated immunity and light-dependent AvrPtoB virulence require NPR1. By contrast, during darkness, CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1)-mediated HY5 degradation suppresses AvrPtoB virulence and HY5-enhanced immunity. These findings elucidate a mechanism in which light modulates bacterial virulence and plant immunity via an HY5-NPR1 module, advancing our understanding of light-pathogen-host interactions.
光对植物发育至关重要，但其对病原体毒力和免疫的影响尚不清楚。在这里，我们发现丁香假单胞菌DC3000 III型效应物AvrPtoB仅在光照下表现出毒力。这种光依赖性调节是由拟南芥转录因子伸长下胚轴5 （HY5）控制的，这是光形态发生的中心调节因子。AvrPtoB靶向细胞核中的HY5，促进其泛素化和降解。HY5的遗传破坏消除了对AvrPtoB的易感性，并损害了植物在光照下的免疫力。HY5通过结合防御相关基因的启动子，激活其表达，并通过抑制其负调控子NPR3/4来稳定转录共调控子NONEXPRESSOR of PATHOGENESIS-RELATED (PR) genes 1 (NPR1)，从而增强免疫。hy5介导的免疫和光依赖性AvrPtoB毒力都需要NPR1。相反，在黑暗中，COP1介导的HY5降解抑制了AvrPtoB的毒力和HY5增强的免疫力。这些发现阐明了光通过HY5-NPR1模块调节细菌毒力和植物免疫的机制，促进了我们对光-病原体-宿主相互作用的理解。
{"title":"The HY5-NPR1 module governs light-dependent virulence of a plant bacterial pathogen","authors":"Pengtao Liu, Zhao Zhao, Yaqi Tang, Yangyang Zhou, Jie Liu, Kaiqi Xu, Yaxin Chen, Xiaoting Li, Yaru Tang, Li Yang","doi":"10.1016/j.chom.2025.08.007","DOIUrl":"https://doi.org/10.1016/j.chom.2025.08.007","url":null,"abstract":"Light is essential for plant development, but its influence on pathogen virulence and immunity remains poorly understood. Here, we found that the <em>Pseudomonas syringae</em> DC3000 type III effector, AvrPtoB, exhibits virulence exclusively upon light exposure. This light-dependent regulation is controlled by the <em>Arabidopsis</em> transcription factor ELONGATED HYPOCOTYL 5 (HY5), a central regulator of photomorphogenesis. AvrPtoB targets HY5 in the nucleus, facilitating its ubiquitination and degradation. Genetic disruption of <em>HY5</em> eliminates susceptibility to AvrPtoB and compromises plant immunity upon light exposure. HY5 enhances immunity by binding promoters of defense-related genes, activating their expression, and stabilizing the transcriptional coregulator NONEXPRESSOR OF PATHOGENESIS-RELATED (PR) GENES 1 (NPR1) by inhibiting its negative regulators NPR3/4. Both HY5-mediated immunity and light-dependent AvrPtoB virulence require NPR1. By contrast, during darkness, CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1)-mediated HY5 degradation suppresses AvrPtoB virulence and HY5-enhanced immunity. These findings elucidate a mechanism in which light modulates bacterial virulence and plant immunity via an HY5-NPR1 module, advancing our understanding of light-pathogen-host interactions.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"50 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.chom.2025.07.020
Michael Katz, Hadas Cohen-Dvashi, Sarah Borni, John Ruedas, Greg Henkel, Ken McCormack, Ron Diskin
Lassa virus (LASV) is a devastating human pathogen with no vaccines and limited therapeutics. The LASV class-I spike complex engages target cells via binding its primary host receptor, matriglycan, followed by macropinocytosis and binding of its secondary receptor, lysosomal-associated membrane protein 1 (LAMP1), to trigger virus fusion. This process occurs across multiple pH-dependent steps, but the molecular events remain largely unknown. Through high-resolution structures, we study the pH-induced conformational changes of the spike preceding membrane fusion. We reveal pH-sensitive metal coordination sites that control the integrity of the spike's native state, elucidate a reorganization of the spike's transmembrane region, and provide a mechanism for dissociation from its primary receptor. Using the entry inhibitor ARN-75039, we validate our findings and establish the molecular basis for the binding and function of this investigational drug. These data define the molecular basis for the cell entry of LASV and will promote efforts in combating this virus and potentially related viral pathogens.
{"title":"pH-induced conformational changes and inhibition of the Lassa virus spike complex","authors":"Michael Katz, Hadas Cohen-Dvashi, Sarah Borni, John Ruedas, Greg Henkel, Ken McCormack, Ron Diskin","doi":"10.1016/j.chom.2025.07.020","DOIUrl":"https://doi.org/10.1016/j.chom.2025.07.020","url":null,"abstract":"Lassa virus (LASV) is a devastating human pathogen with no vaccines and limited therapeutics. The LASV class-I spike complex engages target cells via binding its primary host receptor, matriglycan, followed by macropinocytosis and binding of its secondary receptor, lysosomal-associated membrane protein 1 (LAMP1), to trigger virus fusion. This process occurs across multiple pH-dependent steps, but the molecular events remain largely unknown. Through high-resolution structures, we study the pH-induced conformational changes of the spike preceding membrane fusion. We reveal pH-sensitive metal coordination sites that control the integrity of the spike's native state, elucidate a reorganization of the spike's transmembrane region, and provide a mechanism for dissociation from its primary receptor. Using the entry inhibitor ARN-75039, we validate our findings and establish the molecular basis for the binding and function of this investigational drug. These data define the molecular basis for the cell entry of LASV and will promote efforts in combating this virus and potentially related viral pathogens.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"91 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144924413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-29DOI: 10.1016/j.chom.2025.08.001
Kevin D. Eislmayr, Charlotte A. Nichols, Fitty L. Liu, Sudyut Yuvaraj, Janet Peace Babirye, Justin L. Roncaioli, Jenna Vickery, Gregory M. Barton, Cammie F. Lesser, Russell E. Vance
Bacteria of the genus Shigella replicate in intestinal epithelial cells and cause shigellosis, a severe diarrheal disease that resolves spontaneously in most healthy individuals. During shigellosis, neutrophils are abundantly recruited to the gut and have long been thought to be central to Shigella control and pathogenesis. However, how shigellosis resolves remains poorly understood due to the longstanding lack of a tractable and physiological animal model. Here, using our newly developed Nlrc4–/–Casp11–/– mouse model of shigellosis, we unexpectedly find no major role for neutrophils in limiting Shigella or in disease pathogenesis. Instead, we uncover an essential role for macrophages in the host control of Shigella. Macrophages respond to Shigella via Toll-like receptors (TLRs) to produce IL-12, which then induces IFN-γ, a cytokine that is essential to control Shigella replication in intestinal epithelial cells. Collectively, our findings reshape our understanding of the innate immune response to Shigella.
{"title":"Macrophages orchestrate elimination of Shigella from the intestinal epithelial cell niche via TLR-induced IL-12 and IFN-γ","authors":"Kevin D. Eislmayr, Charlotte A. Nichols, Fitty L. Liu, Sudyut Yuvaraj, Janet Peace Babirye, Justin L. Roncaioli, Jenna Vickery, Gregory M. Barton, Cammie F. Lesser, Russell E. Vance","doi":"10.1016/j.chom.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.chom.2025.08.001","url":null,"abstract":"Bacteria of the genus <em>Shigella</em> replicate in intestinal epithelial cells and cause shigellosis, a severe diarrheal disease that resolves spontaneously in most healthy individuals. During shigellosis, neutrophils are abundantly recruited to the gut and have long been thought to be central to <em>Shigella</em> control and pathogenesis. However, how shigellosis resolves remains poorly understood due to the longstanding lack of a tractable and physiological animal model. Here, using our newly developed <em>Nlrc4</em><sup>–/–</sup><em>Casp11</em><sup>–/–</sup> mouse model of shigellosis, we unexpectedly find no major role for neutrophils in limiting <em>Shigella</em> or in disease pathogenesis. Instead, we uncover an essential role for macrophages in the host control of <em>Shigella</em>. Macrophages respond to <em>Shigella</em> via Toll-like receptors (TLRs) to produce IL-12, which then induces IFN-γ, a cytokine that is essential to control <em>Shigella</em> replication in intestinal epithelial cells. Collectively, our findings reshape our understanding of the innate immune response to <em>Shigella</em>.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"37 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-27DOI: 10.1016/j.chom.2025.07.024
Wanyi Huang, Rui Xu, Abigail Kimball, William H. Witola, Megan T. Baldridge, Yaoyu Feng, Lihua Xiao, L. David Sibley
Cryptosporidium parvum subtypes differ in pathogenicity, but the underlying factors are largely unknown. We show that two genetically similar C. parvum isolates grow equally well in vitro but differ in pathogenicity in immunocompromised mice. Reduced oocyst shedding of the avirulent strain was restored by antibiotic treatment, suggesting susceptibility to colonization resistance imparted by the microbiota. This resistance was associated with a gene encoding a parasite ABC transporter and enhanced infectivity. Molecular analyses indicate that the ABC transporter belongs to a multidrug resistance protein (MRP) family. CpMRP1 binds bacterial metabolites, notably deoxycholic acid (DCA) that inhibits C. parvum growth. CpMRP1 is exported from small granules to the parasite-host interface, potentially mediating the export of xenobiotics. Loss of CpMRP1 reduces infectivity and DCA resistance in mice, and CpMRP1 polymorphisms across isolates determine susceptibility to DCA. These results define CpMRP1 as a determinant of C. parvum sensitivity to microbiome-mediated inhibition, thereby influencing infectivity.
{"title":"Cryptosporidium parvum multidrug resistance protein confers resistance to toxic gut microbial metabolite","authors":"Wanyi Huang, Rui Xu, Abigail Kimball, William H. Witola, Megan T. Baldridge, Yaoyu Feng, Lihua Xiao, L. David Sibley","doi":"10.1016/j.chom.2025.07.024","DOIUrl":"https://doi.org/10.1016/j.chom.2025.07.024","url":null,"abstract":"<em>Cryptosporidium parvum</em> subtypes differ in pathogenicity, but the underlying factors are largely unknown. We show that two genetically similar <em>C. parvum</em> isolates grow equally well <em>in vitro</em> but differ in pathogenicity in immunocompromised mice. Reduced oocyst shedding of the avirulent strain was restored by antibiotic treatment, suggesting susceptibility to colonization resistance imparted by the microbiota. This resistance was associated with a gene encoding a parasite ABC transporter and enhanced infectivity. Molecular analyses indicate that the ABC transporter belongs to a multidrug resistance protein (MRP) family. CpMRP1 binds bacterial metabolites, notably deoxycholic acid (DCA) that inhibits <em>C. parvum</em> growth. CpMRP1 is exported from small granules to the parasite-host interface, potentially mediating the export of xenobiotics. Loss of CpMRP1 reduces infectivity and DCA resistance in mice, and CpMRP1 polymorphisms across isolates determine susceptibility to DCA. These results define CpMRP1 as a determinant of <em>C. parvum</em> sensitivity to microbiome-mediated inhibition, thereby influencing infectivity.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"23 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-22DOI: 10.1016/j.chom.2025.07.019
Ziyu Yang, Jilin Wang, Yifan Chen, Tianchi Chen, Zhen Shen, Yanan Wang, Ying Jian, Guoxiu Xiang, Xiaowei Ma, Na Zhao, Yan Song, Bisheng Shi, Juanxiu Qin, Qian Liu, Zhijun Cao, Michael Otto, Min Li
Crohn’s disease is a severe inflammatory disorder of the intestine for which there is no cure. Individuals suffering from Crohn’s disease are at an increased risk of developing Clostridioides difficile infection (CDI), which considerably exacerbates symptoms. Using a prospective observational clinical study combined with animal models of intestinal inflammation, we show that intestinal colonization by Veillonella, an oral commensal, promotes CDI in Crohn’s disease. In mice, Veillonella parvula suppresses expression of the main bile acid transporter, ASBT, thus preventing bile acid reabsorption. Similarly, Veillonella abundance is associated with increased bile acid metabolism in Crohn’s disease patients. This increase in bile acid availability within the intestinal lumen triggers C. difficile germination. V. parvula expresses a highly pro-inflammatory lipopolysaccharide that triggers the transcription factors c-Jun and c-Fos regulating ASBT expression. These findings highlight that oral commensals can exacerbate intestinal disease, providing pathways to design therapeutics to treat CDI in Crohn’s disease patients.
{"title":"Veillonella intestinal colonization promotes C. difficile infection in Crohn’s disease","authors":"Ziyu Yang, Jilin Wang, Yifan Chen, Tianchi Chen, Zhen Shen, Yanan Wang, Ying Jian, Guoxiu Xiang, Xiaowei Ma, Na Zhao, Yan Song, Bisheng Shi, Juanxiu Qin, Qian Liu, Zhijun Cao, Michael Otto, Min Li","doi":"10.1016/j.chom.2025.07.019","DOIUrl":"https://doi.org/10.1016/j.chom.2025.07.019","url":null,"abstract":"Crohn’s disease is a severe inflammatory disorder of the intestine for which there is no cure. Individuals suffering from Crohn’s disease are at an increased risk of developing <ce:italic>Clostridioides difficile</ce:italic> infection (CDI), which considerably exacerbates symptoms. Using a prospective observational clinical study combined with animal models of intestinal inflammation, we show that intestinal colonization by <ce:italic>Veillonella</ce:italic>, an oral commensal, promotes CDI in Crohn’s disease. In mice, <ce:italic>Veillonella parvula</ce:italic> suppresses expression of the main bile acid transporter, ASBT, thus preventing bile acid reabsorption. Similarly, <ce:italic>Veillonella</ce:italic> abundance is associated with increased bile acid metabolism in Crohn’s disease patients. This increase in bile acid availability within the intestinal lumen triggers <ce:italic>C. difficile</ce:italic> germination. <ce:italic>V. parvula</ce:italic> expresses a highly pro-inflammatory lipopolysaccharide that triggers the transcription factors c-Jun and c-Fos regulating ASBT expression. These findings highlight that oral commensals can exacerbate intestinal disease, providing pathways to design therapeutics to treat CDI in Crohn’s disease patients.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"52 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-13DOI: 10.1016/j.chom.2025.06.017
Dario X. Ramirez-Villacis, Antonio Leon-Reyes, Corné M.J. Pieterse, Jos M. Raaijmakers
Plant domestication is a coevolutionary process shaped by human selection, favoring traits supporting modern-day agriculture. This process has reduced genetic diversity and fixed alleles for desirable traits, coinciding with changes in agricultural practices, particularly soil tilling, crop monocultures, and the (over)use of fertilizers and pesticides. The combined effects—collectively termed “domestication syndrome”—have contributed to the homogenization of soil and plant-associated microbial communities, reducing diversity and disrupting beneficial plant-microbiome alliances. Microbiome rewilding has uncovered ecological, genetic, and molecular principles underlying these depleted plant-microbiome partnerships. Studies have revealed ancestral microbial taxa enriched in wild crop relatives, plant genes, and metabolites critical for microbial recruitment, as well as the potential of reintroducing microbes to enhance nutrient uptake, pathogen resistance, and stress tolerance. These findings offer models for restoring such interactions in modern crops. We review the current state of crop microbiome rewilding and highlight how these discoveries are instrumental for designing resilient crop systems.
{"title":"Born to rewild: Reconnecting beneficial plant-microbiome alliances for resilient future crops","authors":"Dario X. Ramirez-Villacis, Antonio Leon-Reyes, Corné M.J. Pieterse, Jos M. Raaijmakers","doi":"10.1016/j.chom.2025.06.017","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.017","url":null,"abstract":"Plant domestication is a coevolutionary process shaped by human selection, favoring traits supporting modern-day agriculture. This process has reduced genetic diversity and fixed alleles for desirable traits, coinciding with changes in agricultural practices, particularly soil tilling, crop monocultures, and the (over)use of fertilizers and pesticides. The combined effects—collectively termed “domestication syndrome”—have contributed to the homogenization of soil and plant-associated microbial communities, reducing diversity and disrupting beneficial plant-microbiome alliances. Microbiome rewilding has uncovered ecological, genetic, and molecular principles underlying these depleted plant-microbiome partnerships. Studies have revealed ancestral microbial taxa enriched in wild crop relatives, plant genes, and metabolites critical for microbial recruitment, as well as the potential of reintroducing microbes to enhance nutrient uptake, pathogen resistance, and stress tolerance. These findings offer models for restoring such interactions in modern crops. We review the current state of crop microbiome rewilding and highlight how these discoveries are instrumental for designing resilient crop systems.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"37 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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