Markus Lakemeyer, Rocco Latorre, Kristyna Blazkova, Hannah M. Wood, Dane D. Jensen, Nayab Shakil, Scott C. Thomas, Deepak Saxena, Yatendra Mulpuri, David Poolman, Paz Duran, Laura J. Keller, David E. Reed, Brian L. Schmidt, Néstor N. Jiménez-Vargas, Fangxi Xu, Alan E. Lomax, Nigel W. Bunnett, Matthew Bogyo
{"title":"A Bacteroides fragilis protease activates host PAR2 to induce intestinal pain and inflammation","authors":"Markus Lakemeyer, Rocco Latorre, Kristyna Blazkova, Hannah M. Wood, Dane D. Jensen, Nayab Shakil, Scott C. Thomas, Deepak Saxena, Yatendra Mulpuri, David Poolman, Paz Duran, Laura J. Keller, David E. Reed, Brian L. Schmidt, Néstor N. Jiménez-Vargas, Fangxi Xu, Alan E. Lomax, Nigel W. Bunnett, Matthew Bogyo","doi":"10.1016/j.chom.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.chom.2025.09.010","url":null,"abstract":"Protease-activated receptor 2 (PAR<sub>2</sub>) is a central regulator of intestinal barrier function, inflammation, and pain. Upregulated intestinal proteolysis and PAR<sub>2</sub> signaling are implicated in inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS), conditions often associated with gut microbiome alterations. To identify potential bacterial regulators of PAR<sub>2</sub> activity, we developed a functional assay for PAR<sub>2</sub> processing to screen a library of diverse gut microbes. We identify multiple bacteria that secrete proteases capable of cleaving host PAR<sub>2</sub>. Using chemoproteomic profiling with a covalent irreversible inhibitor, we uncovered a previously uncharacterized <em>Bacteroides fragilis</em> serine protease 1 (Bfp1) and show that it cleaves and activates PAR<sub>2</sub> in multicellular and murine models. PAR<sub>2</sub> cleavage by Bfp1 disrupts the intestinal barrier, sensitizes nociceptors, and triggers colonic inflammation and abdominal pain. Collectively, our findings uncover Bfp1-mediated PAR<sub>2</sub> processing as an axis of host-commensal interaction in the gut that has the potential to be targeted for therapeutic intervention in IBD or IBS.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"100 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140954","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}
Sarah K. Munyoki, Julie P. Goff, Amanda Reshke, Erin Wilderoter, Nyasha Mafarachisi, Antonija Kolobaric, Yi Sheng, Steven J. Mullett, Gabrielle E. King, Jacob D. DeSchepper, Richard J. Bookser, Carlos A. Castro, Stacy L. Gelhaus, Mayara Grizotte-Lake, Kathleen E. Morrison, Anthony J. Zeleznik, Timothy W. Hand, Miguel A. Brieño-Enriquez, Eldin Jašarević
{"title":"The microbiota extends the reproductive lifespan of mice by safeguarding the ovarian reserve","authors":"Sarah K. Munyoki, Julie P. Goff, Amanda Reshke, Erin Wilderoter, Nyasha Mafarachisi, Antonija Kolobaric, Yi Sheng, Steven J. Mullett, Gabrielle E. King, Jacob D. DeSchepper, Richard J. Bookser, Carlos A. Castro, Stacy L. Gelhaus, Mayara Grizotte-Lake, Kathleen E. Morrison, Anthony J. Zeleznik, Timothy W. Hand, Miguel A. Brieño-Enriquez, Eldin Jašarević","doi":"10.1016/j.chom.2025.09.006","DOIUrl":"https://doi.org/10.1016/j.chom.2025.09.006","url":null,"abstract":"Infertility affects one in six people, but the underlying mechanisms remain unclear. We show that the microbiota governs female reproductive longevity in mice. Germ-free mice have fewer primordial follicles, increased atresia, and ovarian fibrosis, leading to smaller litters, fewer offspring, and a shorter reproductive lifespan. Germ-free mice are born with a similar ovarian reserve but display excessive activation, impaired progression, and increased atresia during post-natal development. Microbiome colonization during a critical post-natal window rescues premature ovarian reserve loss by normalizing follicle kinetics and gene expression patterns. These changes parallel increased short-chain fatty acids (SCFAs), and SCFA administration mitigates ovarian dysfunction in germ-free mice. Similar oocyte dysfunction occurred in conventionally raised mice fed a high-fat diet, but additional dietary fiber helped preserve oocyte quality and embryo competence. Thus, host-microbe interactions shape female fertility, and microbiota-targeted interventions may offer strategies to address reproductive disorders.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"99 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134464","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}
Aleksander Czauderna, Grishma Kulkarni, Niccolò Bianchi, Liqing Cheng, Marissa Sim, Nicola R. Realini, Joanna Gach, Aurelie Caillon, Joachim Kloehn, Gérard Lambeau, Annika Hausmann, Stefano Serra, Matthew T. Sorbara, Simone Becattini
{"title":"Long-chain unsaturated fatty acids released during immune responses stimulate host-microbe trans-kingdom communication","authors":"Aleksander Czauderna, Grishma Kulkarni, Niccolò Bianchi, Liqing Cheng, Marissa Sim, Nicola R. Realini, Joanna Gach, Aurelie Caillon, Joachim Kloehn, Gérard Lambeau, Annika Hausmann, Stefano Serra, Matthew T. Sorbara, Simone Becattini","doi":"10.1016/j.chom.2025.08.011","DOIUrl":"https://doi.org/10.1016/j.chom.2025.08.011","url":null,"abstract":"Immune responses can significantly alter the structure and function of the gut microbiota, leading to rapid transcriptional and metabolic shifts in commensal microbes. However, the host mediators involved in this process and their effects on bacteria remain poorly elucidated. Here, using a flagellin injection model to induce immune activation, we identified unsaturated long-chain fatty acids (uLCFAs) as broad modulators that are released into the gut lumen and alter bacterial gene expression. Luminal release of uLCFAs is partially mediated by host phospholipases, including PLA2G5. In response to uLCFAs, commensals such as <em>Blautia</em> trigger the expression of <em>ohyA</em>, encoding oleate hydratase, which converts toxic uLCFAs to non-toxic hydroxy fatty acids with immunomodulatory properties. Remarkably, oral administration of uLCFAs to mice replicates many of the bacterial transcriptional changes induced by flagellin. This molecular loop underscores the sophisticated interactions between host and microbiota and sheds light on how immune responses affect gut commensal functions.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"68 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078378","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}
Qian Zhang, Wenyue Zheng, Haoxiang Huang, Shuchen Wang, Sizhe Li, Kaixiang Wang, Haixia You, Hao Gong, Xiayan Pan, Zhongqiang Qi, Yan Du, Junjie Yu, Mina Yu, Huijuan Cao, Rongsheng Zhang, Yuanchao Wang, Daolong Dou, Zhenchuan Ma, Yongfeng Liu, Tianqiao Song
{"title":"Fungal resistance in rice is restored by interfamily transfer of an evolutionarily lost co-receptor","authors":"Qian Zhang, Wenyue Zheng, Haoxiang Huang, Shuchen Wang, Sizhe Li, Kaixiang Wang, Haixia You, Hao Gong, Xiayan Pan, Zhongqiang Qi, Yan Du, Junjie Yu, Mina Yu, Huijuan Cao, Rongsheng Zhang, Yuanchao Wang, Daolong Dou, Zhenchuan Ma, Yongfeng Liu, Tianqiao Song","doi":"10.1016/j.chom.2025.08.015","DOIUrl":"https://doi.org/10.1016/j.chom.2025.08.015","url":null,"abstract":"The interfamily transfer of pattern-recognition receptors (PRRs) offers a promising strategy to enhance plant immunity; however, factors causing functional limitations across species remain unknown. Here, we identify secreted TOM20 domain-containing protein (STOM), a previously uncharacterized fungal microbe-associated molecular pattern (MAMP) that triggers immunity in <em>Nicotiana benthamiana</em> but not in rice (<em>Oryza sativa</em>). We identify NbSTOMR as the receptor that recognizes and binds STOM, and NbSTOMRh as the co-receptor that, despite lacking ligand-binding ability, is essential through its extracellular interaction with NbSTOMR. Transferring NbSTOMR to rice fails to confer resistance, but NbSTOMRh alone enhances resistance to false smut and blast disease. Evolutionary analyses reveal that while STOMR is conserved, monocots have lost STOMRh due to transposon-mediated chromosomal separation of its extracellular domain. Although OsSTOMR binds STOM, OsSTOMRh is non-functional; however, NbSTOMRh promotes OsSTOMR-dependent STOM recognition. These findings highlight the critical role of co-receptors in overcoming taxonomic barriers and provide a strategy for reconstituting PRR-mediated immunity in monocot crops.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"52 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072169","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}
Xianhong Zhang, Xue Jin, Jiawei Li, Francisco Dini-Andreote, Hongyu Li, Muhammad Khashi u Rahman, Minmin Du, Fengzhi Wu, Zhong Wei, Xingang Zhou, Marcel G.A. van der Heijden, Matthias C. Rillig
{"title":"Common mycorrhizal networks facilitate plant disease resistance by altering rhizosphere microbiome assembly","authors":"Xianhong Zhang, Xue Jin, Jiawei Li, Francisco Dini-Andreote, Hongyu Li, Muhammad Khashi u Rahman, Minmin Du, Fengzhi Wu, Zhong Wei, Xingang Zhou, Marcel G.A. van der Heijden, Matthias C. Rillig","doi":"10.1016/j.chom.2025.08.016","DOIUrl":"https://doi.org/10.1016/j.chom.2025.08.016","url":null,"abstract":"Arbuscular mycorrhizal fungi can interconnect the roots of individual plants by forming common mycorrhizal networks (CMNs). These symbiotic structures can act as conduits for interplant communication. Despite their importance, the mechanisms of signal transfer via CMNs and their implications for plant community performance remain unknown. Here, we demonstrate that CMNs act as a pathway to elicit defense responses in healthy receiver plants connected to pathogen-infected donors. Specifically, we show that donor plants infected by the phytopathogen <em>Botrytis cinerea</em> transfer jasmonic acid via CMNs, which then act as a chemical signal in receiver plants. This signal transfer to receiver plants induces shifts in root exudates, promoting the recruitment of specific microbial taxa (<em>Streptomyces</em> and <em>Actinoplanes</em>) that are directly linked to the suppression of <em>B. cinerea</em> infection. Collectively, our study reveals that CMNs act as interplant chemical communication conduits, transferring signals that contribute to plant disease resistance via modulation of the rhizosphere microbiota.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"19 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068042","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}
Amanda M. Brandow, Samantha N. Atkinson, Zulmary Manjarres, Vanessa L. Ehlers, McKenna L. Pratt, Iti Mehta, Sruthi Mudunuri, Aishwarya Kappagantu, Stephanie I. Shiers, Khadijah Mazhar, Mackenzie A. Simms, Sahar Alhendi, Anagha Sheshadri, Anna M. Cervantes, Jeffrey C. Reese, Diana Tavares-Ferreira, Ishwarya Sankaranarayanan, Mandee K. Schaub, Tyler B. Waltz, Michael Hayward, Katelyn E. Sadler
{"title":"Gut microbiota and metabolites drive chronic sickle cell disease pain in mice","authors":"Amanda M. Brandow, Samantha N. Atkinson, Zulmary Manjarres, Vanessa L. Ehlers, McKenna L. Pratt, Iti Mehta, Sruthi Mudunuri, Aishwarya Kappagantu, Stephanie I. Shiers, Khadijah Mazhar, Mackenzie A. Simms, Sahar Alhendi, Anagha Sheshadri, Anna M. Cervantes, Jeffrey C. Reese, Diana Tavares-Ferreira, Ishwarya Sankaranarayanan, Mandee K. Schaub, Tyler B. Waltz, Michael Hayward, Katelyn E. Sadler","doi":"10.1016/j.chom.2025.08.012","DOIUrl":"https://doi.org/10.1016/j.chom.2025.08.012","url":null,"abstract":"Individuals with sickle cell disease (SCD) suffer from debilitating chronic pain that does not have a clear etiology. Recent 16S ribosomal RNA gene sequencing studies revealed gut dysbiosis in individuals with SCD. It is unclear, however, whether these intestinal microbial changes contribute to chronic SCD pain. Using transgenic SCD mice, we determined that chronic SCD pain is alleviated following fecal microbiota transplantation from healthy controls, specifically by increasing the relative abundance of probiotic <em>Akkermansia muciniphila</em>. Reciprocally, transplantation of the SCD gut microbiome induced persistent pain in wild-type recipients via bilirubin-vagus nerve TRPM2 signaling. Biospecimens from individuals with SCD and spatial transcriptomic analysis of human nodose ganglia tissue identified additional bacterial species and neuronally expressed transcripts that should be explored as novel SCD analgesic targets.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"35 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068044","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}
{"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}
{"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}
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
{"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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
