Pub Date : 2025-12-10DOI: 10.1016/j.chom.2025.11.011
Jack T. Sumner, Stefanie Huttelmaier, Chiagozie I. Pickens, Anahid A. Moghadam, Hiam Abdala-Valencia, Jiaxian Shen
The precise microbial determinants driving clinical outcomes in severe pneumonia are unknown. Competing ecological forces produce dynamic microbiota states in health and disease, and a more thorough understanding of these states has the potential to improve pneumonia therapy. Here, we leverage a large collection of bronchoscopic samples from patients with suspected pneumonia to determine lung microbial ecosystem dynamics throughout the course of pneumonia. We combine 16S rRNA gene, metagenomic, and metatranscriptomic sequencing with bacterial-load quantification to reveal clinically relevant drivers of pneumonia progression. Microbiota states are predictive of pneumonia subtypes and exhibit differential stability and pneumonia therapy response. Disruptive forces, such as aspiration, are associated with cohesive changes in gene expression and microbial community structure. In summary, we show that host and microbiota landscapes change in unison with clinical phenotypes and that microbiota state dynamics reflect pneumonia progression. We suggest that distinct pathways of lung microbial community succession mediate pneumonia progression.
{"title":"Transitions in lung microbiota landscape associate with distinct patterns of pneumonia progression","authors":"Jack T. Sumner, Stefanie Huttelmaier, Chiagozie I. Pickens, Anahid A. Moghadam, Hiam Abdala-Valencia, Jiaxian Shen","doi":"10.1016/j.chom.2025.11.011","DOIUrl":"https://doi.org/10.1016/j.chom.2025.11.011","url":null,"abstract":"The precise microbial determinants driving clinical outcomes in severe pneumonia are unknown. Competing ecological forces produce dynamic microbiota states in health and disease, and a more thorough understanding of these states has the potential to improve pneumonia therapy. Here, we leverage a large collection of bronchoscopic samples from patients with suspected pneumonia to determine lung microbial ecosystem dynamics throughout the course of pneumonia. We combine 16S rRNA gene, metagenomic, and metatranscriptomic sequencing with bacterial-load quantification to reveal clinically relevant drivers of pneumonia progression. Microbiota states are predictive of pneumonia subtypes and exhibit differential stability and pneumonia therapy response. Disruptive forces, such as aspiration, are associated with cohesive changes in gene expression and microbial community structure. In summary, we show that host and microbiota landscapes change in unison with clinical phenotypes and that microbiota state dynamics reflect pneumonia progression. We suggest that distinct pathways of lung microbial community succession mediate pneumonia progression.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"55 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710999","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 : 2025-12-10DOI: 10.1016/j.chom.2025.11.010
Anne E. D’Armond, Jay K. Kolls
In this issue of Cell Host & Microbe, Sumner et al. utilize a multi-omics approach to delineate various “pneumotypes,” or distinct microbial states, in the lungs of patients with pneumonia. These pneumotypes have potential predictive value for clinical outcomes and therapeutic success.
{"title":"Segregating pneumonia into pneumotypes","authors":"Anne E. D’Armond, Jay K. Kolls","doi":"10.1016/j.chom.2025.11.010","DOIUrl":"https://doi.org/10.1016/j.chom.2025.11.010","url":null,"abstract":"In this issue of <em>Cell Host & Microbe</em>, Sumner et al. utilize a multi-omics approach to delineate various “pneumotypes,” or distinct microbial states, in the lungs of patients with pneumonia. These pneumotypes have potential predictive value for clinical outcomes and therapeutic success.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"13 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711060","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 : 2025-12-10DOI: 10.1016/j.chom.2025.11.013
Jessica C. Hargarten, Amariliz Rivera
In this issue of Cell Host & Microbe, Reyes et al.1 uncovered that delayed microglial activation provides Cryptococcus a temporal advantage in establishing central nervous system infections in a CD4+ T cell-competent setting. This delay carries implications for the development of severe cryptococcal meningoencephalitis and post-infection syndrome in humans.
{"title":"Hide and seek: Cryptococcus evasion of microglial sensing enables meningitis","authors":"Jessica C. Hargarten, Amariliz Rivera","doi":"10.1016/j.chom.2025.11.013","DOIUrl":"https://doi.org/10.1016/j.chom.2025.11.013","url":null,"abstract":"In this issue of Cell Host & Microbe, Reyes et al.1 uncovered that delayed microglial activation provides Cryptococcus a temporal advantage in establishing central nervous system infections in a CD4+ T cell-competent setting. This delay carries implications for the development of severe cryptococcal meningoencephalitis and post-infection syndrome in humans.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"233 1","pages":"2007-2009"},"PeriodicalIF":30.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731088","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 : 2025-12-10DOI: 10.1016/j.chom.2025.11.006
Daniela Ramírez-Sánchez, Detlef Weigel
In this issue of Cell Host & Microbe, Xu and colleagues investigate host pH modulation as a microbiome-mediated defense mechanism. Pseudomonas strains can protect wheat against the pathogenic fungus Fusarium graminearum by counteracting alkalinization of the host environment by the fungus, although other Pseudomonas strains support the fungus by further alkalinization.
{"title":"Pseudomonas can make or break a happy phyllosphere microbiota","authors":"Daniela Ramírez-Sánchez, Detlef Weigel","doi":"10.1016/j.chom.2025.11.006","DOIUrl":"https://doi.org/10.1016/j.chom.2025.11.006","url":null,"abstract":"In this issue of Cell Host & Microbe, Xu and colleagues investigate host pH modulation as a microbiome-mediated defense mechanism. Pseudomonas strains can protect wheat against the pathogenic fungus Fusarium graminearum by counteracting alkalinization of the host environment by the fungus, although other Pseudomonas strains support the fungus by further alkalinization.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"11 1","pages":"2004-2007"},"PeriodicalIF":30.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732380","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 : 2025-12-10DOI: 10.1016/j.chom.2025.11.003
Maren Ziegler, Claudia Pogoreutz
Microbial symbioses enable animals to colonize the most extreme habitats on Earth. The study by Wei et al.1 in this issue of Cell Host & Microbe elucidates how intricate molecular adaptations of a coral host and its newly discovered microbial symbionts underpin their entwined lives in the deep sea.
{"title":"Microbes help corals conquer the deep sea","authors":"Maren Ziegler, Claudia Pogoreutz","doi":"10.1016/j.chom.2025.11.003","DOIUrl":"https://doi.org/10.1016/j.chom.2025.11.003","url":null,"abstract":"Microbial symbioses enable animals to colonize the most extreme habitats on Earth. The study by Wei et al.<span><span><sup>1</sup></span></span> in this issue of <em>Cell Host & Microbe</em> elucidates how intricate molecular adaptations of a coral host and its newly discovered microbial symbionts underpin their entwined lives in the deep sea.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"148 1","pages":"2001-2002"},"PeriodicalIF":30.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728740","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 : 2025-12-10DOI: 10.1016/j.chom.2025.10.017
Richard A. Insel, John B. Jarman, Pedro J. Torres, Stephen Van Dien, Stephanie J. Culler, Willem M. de Vos
An early-life microbiota with increased Bifidobacterium and human milk oligosaccharide (HMO) utilization genes has been linked to decreased risk of childhood allergic disease. As infant microbiomes increasingly have reduced Bifidobacterium, we examine early-life dysbiosis and interventions that potentially prevent or reverse this dysbiotic state, thus mitigating noncommunicable diseases.
{"title":"Restoring a gut Bifidobacterium community in early infancy","authors":"Richard A. Insel, John B. Jarman, Pedro J. Torres, Stephen Van Dien, Stephanie J. Culler, Willem M. de Vos","doi":"10.1016/j.chom.2025.10.017","DOIUrl":"https://doi.org/10.1016/j.chom.2025.10.017","url":null,"abstract":"An early-life microbiota with increased <em>Bifidobacterium</em> and human milk oligosaccharide (HMO) utilization genes has been linked to decreased risk of childhood allergic disease. As infant microbiomes increasingly have reduced <em>Bifidobacterium</em>, we examine early-life dysbiosis and interventions that potentially prevent or reverse this dysbiotic state, thus mitigating noncommunicable diseases.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"37 1","pages":"2012-2016"},"PeriodicalIF":30.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728785","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 : 2025-12-10DOI: 10.1016/j.chom.2025.11.012
Chrishan M. Fernando, Nicole D. Marino
Across all domains of life, immune systems rely on nucleotide-based signaling molecules to activate defense responses. In a recent Cell Host & Microbe study, Doherty, Nomburg, and colleagues identify and characterize diverse families of viral two-histidine phosphodiesterase enzymes that degrade these immune signals, each with distinct substrate specificities.
{"title":"Viral enzymes degrade to evade","authors":"Chrishan M. Fernando, Nicole D. Marino","doi":"10.1016/j.chom.2025.11.012","DOIUrl":"https://doi.org/10.1016/j.chom.2025.11.012","url":null,"abstract":"Across all domains of life, immune systems rely on nucleotide-based signaling molecules to activate defense responses. In a recent <em>Cell Host & Microbe</em> study, Doherty, Nomburg, and colleagues identify and characterize diverse families of viral two-histidine phosphodiesterase enzymes that degrade these immune signals, each with distinct substrate specificities.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"16 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710970","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 : 2025-12-10DOI: 10.1016/j.chom.2025.11.005
Frances Pitsillides, Hassan Salem
In a recent publication in Science, Nishino et al.1 reveal the evolutionary co-option of an auditory structure into a newly identified type of symbiotic organ. This organ, found on the hindlegs of female stinkbugs, houses fungi that act as defensive symbionts by protecting eggs from parasitism by wasps.
{"title":"An earful of fungi: Hearing organ repurposed for symbiosis","authors":"Frances Pitsillides, Hassan Salem","doi":"10.1016/j.chom.2025.11.005","DOIUrl":"https://doi.org/10.1016/j.chom.2025.11.005","url":null,"abstract":"In a recent publication in <em>Science</em>, Nishino et al.<span><span><sup>1</sup></span></span> reveal the evolutionary co-option of an auditory structure into a newly identified type of symbiotic organ. This organ, found on the hindlegs of female stinkbugs, houses fungi that act as defensive symbionts by protecting eggs from parasitism by wasps.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"34 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711059","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 : 2025-12-01DOI: 10.1016/j.chom.2025.11.009
Anna P. Zagieboylo, Ran Mo, Bentley Lim, Andrew L. Goodman
The gut microbiome, comprising hundreds of individual species, is a complex and dynamic host-associated microbial community. However, how microbes interact within populations of the same species is largely unexplored. Using single-cell approaches, we discover that the human gut microbe Bacteroides thetaiotaomicron forms distinct sub-populations in the gut environment, which can be distinguished using N-hydroxysuccinimide (NHS) ester probes. This heterogeneity results from a locus encoding two secreted effector proteins and a cognate immunity factor. At the population level, this locus is among the most significantly upregulated across the B. thetaiotaomicron transcriptome in response to gut colonization; at the single-cell level, its variable expression leads to heterogeneity within the population. Sub-populations form in response to these effectors, exhibit distinct gene expression programs, and remain stable over time. Together, these findings demonstrate that prominent gut commensals establish population heterogeneity by producing and responding to secreted effector proteins.
{"title":"A commensal bacterium secretes effector proteins to establish population heterogeneity in the gut","authors":"Anna P. Zagieboylo, Ran Mo, Bentley Lim, Andrew L. Goodman","doi":"10.1016/j.chom.2025.11.009","DOIUrl":"https://doi.org/10.1016/j.chom.2025.11.009","url":null,"abstract":"The gut microbiome, comprising hundreds of individual species, is a complex and dynamic host-associated microbial community. However, how microbes interact within populations of the same species is largely unexplored. Using single-cell approaches, we discover that the human gut microbe <em>Bacteroides thetaiotaomicron</em> forms distinct sub-populations in the gut environment, which can be distinguished using <em>N</em>-hydroxysuccinimide (NHS) ester probes. This heterogeneity results from a locus encoding two secreted effector proteins and a cognate immunity factor. At the population level, this locus is among the most significantly upregulated across the <em>B. thetaiotaomicron</em> transcriptome in response to gut colonization; at the single-cell level, its variable expression leads to heterogeneity within the population. Sub-populations form in response to these effectors, exhibit distinct gene expression programs, and remain stable over time. Together, these findings demonstrate that prominent gut commensals establish population heterogeneity by producing and responding to secreted effector proteins.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"25 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651405","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 : 2025-12-01DOI: 10.1016/j.chom.2025.11.008
Estefany Y. Reyes, Jae Yong, Devon T. DiPalma, Jonathan L. Messerschmidt, Miranda Lumbreras, Hana H. Hendi, Danira R. Mukhamedyarova, Emily C. Troutman, Emily J. Wert, Mari L. Shinohara
Cryptococcus, a neurotropic fungus classified as a critical-priority pathogen by the World Health Organization (WHO), causes cryptococcal meningoencephalitis (CM), the second leading cause of death in HIV/AIDS patients. Despite its clinical importance, host brain responses during CM remain poorly understood. In a mouse systemic infection model, Cryptococcus infiltrates the brain within a day. However, full activation of microglia and recruitment of leukocytes takes 14 days, a delay not observed in brain infections caused by Candida albicans. Microglia exhibit limited ability to directly detect Cryptococcus, and their activation depends on interferon (IFN)-γ from Th1 cells. Therefore, adaptive immunity (Th1 responses) precedes innate immune responses (microglial activation) in the brain during CM. Moreover, microglia-derived osteopontin (OPN/Spp1) exacerbates CM by altering peripheral immunity and increasing fungal loads in peripheral organs. These findings reveal a uniquely slow host cellular response to Cryptococcus brain infiltration, allowing the fungus an extended window to establish the infection.
{"title":"Cryptococcus exploits delayed microglial activation, and microglial osteopontin/Spp1 impairs peripheral host control","authors":"Estefany Y. Reyes, Jae Yong, Devon T. DiPalma, Jonathan L. Messerschmidt, Miranda Lumbreras, Hana H. Hendi, Danira R. Mukhamedyarova, Emily C. Troutman, Emily J. Wert, Mari L. Shinohara","doi":"10.1016/j.chom.2025.11.008","DOIUrl":"https://doi.org/10.1016/j.chom.2025.11.008","url":null,"abstract":"<em>Cryptococcus</em>, a neurotropic fungus classified as a critical-priority pathogen by the World Health Organization (WHO), causes cryptococcal meningoencephalitis (CM), the second leading cause of death in HIV/AIDS patients. Despite its clinical importance, host brain responses during CM remain poorly understood. In a mouse systemic infection model, <em>Cryptococcus</em> infiltrates the brain within a day. However, full activation of microglia and recruitment of leukocytes takes 14 days, a delay not observed in brain infections caused by <em>Candida albicans</em>. Microglia exhibit limited ability to directly detect <em>Cryptococcus</em>, and their activation depends on interferon (IFN)-γ from Th1 cells. Therefore, adaptive immunity (Th1 responses) precedes innate immune responses (microglial activation) in the brain during CM. Moreover, microglia-derived osteopontin (OPN/<em>Spp1</em>) exacerbates CM by altering peripheral immunity and increasing fungal loads in peripheral organs. These findings reveal a uniquely slow host cellular response to <em>Cryptococcus</em> brain infiltration, allowing the fungus an extended window to establish the infection.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"1 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651400","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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