Pub Date : 2026-01-14DOI: 10.1016/j.chom.2025.12.007
Christa I. DeVette, Marisol Castillo-Castrejon, Jacob E. Friedman
Maternal immune tolerance of the fetus is critical to a successful pregnancy. In this month’s issue of Cell, Brown et al. showed that the maternal microbiota, specifically tryptophan derivatives produced by commensal bacteria, promote maternal tolerance of the fetus to improve pregnancy outcomes.
{"title":"Bacteria’s babysitter role: Indole-driven immune truce in the womb","authors":"Christa I. DeVette, Marisol Castillo-Castrejon, Jacob E. Friedman","doi":"10.1016/j.chom.2025.12.007","DOIUrl":"https://doi.org/10.1016/j.chom.2025.12.007","url":null,"abstract":"Maternal immune tolerance of the fetus is critical to a successful pregnancy. In this month’s issue of <em>Cell</em>, Brown et al. showed that the maternal microbiota, specifically tryptophan derivatives produced by commensal bacteria, promote maternal tolerance of the fetus to improve pregnancy outcomes.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"179 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962082","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 : 2026-01-14DOI: 10.1016/j.chom.2025.12.006
Miruna E. Rosu, Kim B. Westgeest, Miranda de Graaf, Blake M. Hauser, Sina Tureli, Sarah James, Felisita F. Sinartio, Theo M. Bestebroer, Pascal Lexmond, Mark R. Pronk, Stefan van der Vliet, Eugene Skepner, Monique I.J. Spronken, Barbara Mühlemann, Mathilde Richard, Terry C. Jones, Derek J. Smith, Sander Herfst, Ron A.M. Fouchier
Human influenza A viruses escape antibody-mediated immunity through changes in the hemagglutinin (HA) and neuraminidase (NA) glycoproteins. HA antigenic evolution has been studied extensively, with more recent interest in NA due to its importance in influenza vaccine efficacy. Here, the antigenic properties of the NA of more than 300 A(H3N2) and A(H2N2) viruses isolated since 1957 were quantified with a NA inhibition enzyme-linked lectin assay and visualized using antigenic cartography, with follow-up molecular studies using recombinant viruses. The antigenic evolution of N2 NA was more gradual than that described for H3 HA, and antigenic changes in NA and HA were discordant. Multiple substitutions around the NA active site and tetramer lateral side that alter the charge, volume, or hydropathy of amino acids collectively determined antigenic properties. These data facilitate sequence-based genomic surveillance and inference of antigenic phenotypes from genotypes and offer opportunities to improve influenza vaccine effectiveness through increased focus on NA.
{"title":"Molecular basis of 60 years of antigenic evolution of human influenza A(H3N2) virus neuraminidase","authors":"Miruna E. Rosu, Kim B. Westgeest, Miranda de Graaf, Blake M. Hauser, Sina Tureli, Sarah James, Felisita F. Sinartio, Theo M. Bestebroer, Pascal Lexmond, Mark R. Pronk, Stefan van der Vliet, Eugene Skepner, Monique I.J. Spronken, Barbara Mühlemann, Mathilde Richard, Terry C. Jones, Derek J. Smith, Sander Herfst, Ron A.M. Fouchier","doi":"10.1016/j.chom.2025.12.006","DOIUrl":"https://doi.org/10.1016/j.chom.2025.12.006","url":null,"abstract":"Human influenza A viruses escape antibody-mediated immunity through changes in the hemagglutinin (HA) and neuraminidase (NA) glycoproteins. HA antigenic evolution has been studied extensively, with more recent interest in NA due to its importance in influenza vaccine efficacy. Here, the antigenic properties of the NA of more than 300 A(H3N2) and A(H2N2) viruses isolated since 1957 were quantified with a NA inhibition enzyme-linked lectin assay and visualized using antigenic cartography, with follow-up molecular studies using recombinant viruses. The antigenic evolution of N2 NA was more gradual than that described for H3 HA, and antigenic changes in NA and HA were discordant. Multiple substitutions around the NA active site and tetramer lateral side that alter the charge, volume, or hydropathy of amino acids collectively determined antigenic properties. These data facilitate sequence-based genomic surveillance and inference of antigenic phenotypes from genotypes and offer opportunities to improve influenza vaccine effectiveness through increased focus on NA.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"40 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968583","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 : 2026-01-14DOI: 10.1016/j.chom.2025.12.013
Ashwin Balagopal, Andrea L. Cox
Chronic hepatitis B virus (HBV) affects ∼250 million people worldwide. Functional cure is difficult to achieve with existing medications. In this issue, Fernandes et al. developed a double-humanized chronic HBV murine model to test the capsid assembly modulator GLP-26. GLP-26 reduced blood HBV DNA and surface antigen and induced immunomodulation.
{"title":"A small molecule with larger-than-expected effects on hepatitis B virus","authors":"Ashwin Balagopal, Andrea L. Cox","doi":"10.1016/j.chom.2025.12.013","DOIUrl":"https://doi.org/10.1016/j.chom.2025.12.013","url":null,"abstract":"Chronic hepatitis B virus (HBV) affects ∼250 million people worldwide. Functional cure is difficult to achieve with existing medications. In this issue, Fernandes et al. developed a double-humanized chronic HBV murine model to test the capsid assembly modulator GLP-26. GLP-26 reduced blood HBV DNA and surface antigen and induced immunomodulation.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"147 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972546","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 : 2026-01-02DOI: 10.1016/j.chom.2025.12.005
Jianchun Zhou, Cheng Lu, Shijie Tang, Yi Lai, Chuan Li, Dawei Liu, Zhanjie Hou, Yuanyuan Zhou, Lei Ran, Yusong Ge, Xin Li, Hongfei Jiang, Jincheng Jian, Jinzhi Mo, Bishao Sun, Bo Tang, Shiming Yang
Exposure to high altitude (HA) is linked to male spermatogenesis impairment and microbial imbalance; however, the association and underlying mechanisms remain unexplored. Herein, we demonstrate that HA-induced gut microbiota changes in humans and mice lead to reduced sperm quality. Specifically, we observe an increase in intestinal Clostridium symbiosum colonization in HA human populations and mice exposed to HA-mimicking conditions. Furthermore, C. symbiosum causes a decline in sperm quality through succinic acid (su) production. Mechanistically, su targets G-protein-coupled receptor 91(GPR91) to activate the TRPV4/Ca2+ signaling pathway in testicular macrophages (TMs), driving their polarization into inflammatory CD68+CD163− subsets, and ultimately promoting TM-mediated apoptosis of spermatogenic cells. Notably, the influence of C. symbiosum or su on sperm quality is dependent on TRPV4 signaling. Our study reveals a disrupted microbiota-immune axis within the testis under HA exposure, offering potential therapeutic avenues for HA-induced sperm impairment based on gut microbiota manipulation.
{"title":"Gut-derived succinic acid potentiates high-altitude-related spermatogenesis dysfunction","authors":"Jianchun Zhou, Cheng Lu, Shijie Tang, Yi Lai, Chuan Li, Dawei Liu, Zhanjie Hou, Yuanyuan Zhou, Lei Ran, Yusong Ge, Xin Li, Hongfei Jiang, Jincheng Jian, Jinzhi Mo, Bishao Sun, Bo Tang, Shiming Yang","doi":"10.1016/j.chom.2025.12.005","DOIUrl":"https://doi.org/10.1016/j.chom.2025.12.005","url":null,"abstract":"Exposure to high altitude (HA) is linked to male spermatogenesis impairment and microbial imbalance; however, the association and underlying mechanisms remain unexplored. Herein, we demonstrate that HA-induced gut microbiota changes in humans and mice lead to reduced sperm quality. Specifically, we observe an increase in intestinal <em>Clostridium symbiosum</em> colonization in HA human populations and mice exposed to HA-mimicking conditions. Furthermore, <em>C. symbiosum</em> causes a decline in sperm quality through succinic acid (su) production. Mechanistically, su targets G-protein-coupled receptor 91(GPR91) to activate the TRPV4/Ca<sup>2+</sup> signaling pathway in testicular macrophages (TMs), driving their polarization into inflammatory CD68<sup>+</sup>CD163<sup>−</sup> subsets, and ultimately promoting TM-mediated apoptosis of spermatogenic cells. Notably, the influence of <em>C. symbiosum</em> or su on sperm quality is dependent on TRPV4 signaling. Our study reveals a disrupted microbiota-immune axis within the testis under HA exposure, offering potential therapeutic avenues for HA-induced sperm impairment based on gut microbiota manipulation.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"36 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145894379","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 : 2026-01-02DOI: 10.1016/j.chom.2025.12.003
Shanshan Qiao, Ting-Ting Li, Mingeum Jeong, Chuanfa Liu, Sayaka Mizutani, Sung-Min Hwang, Yaxin Li, Mengze Lyu, Kazuhiro Nishiyama, Yu-Ang Tang, Huiqing Shi, Yuelin Angelina Tang, Seong-Ji Han, Jeremy Goc, Chris Parkhurst, Wen-Bing Jin, Xiaoyu Yang, He S. Yang, Mohammad Arifuzzaman, Gregory F. Sonnenberg, Juan R. Cubillos-Ruiz, Jun Yu, Nicholas Collins, David Artis, Chun-Jun Guo
The human microbiota modulates cancer progression through largely unexplored mechanisms. Defining causal pathways is essential for monitoring and fine-tuning the microbiota to improve cancer treatment. Given that amino acid (aa) metabolism is often dysregulated in cancer, we assessed the role of microbiota pathways that modulate intestinal aa levels on colorectal tumor progression in mice. We found that the Bacteroides gene bo-ansB affects tumor responses to dietary asparagine (Asn) by reducing intestinal Asn levels. In mice receiving dietary Asn, bo-ansB promotes tumor progression by altering tumor-infiltrating CD8+ T cells. Mechanistically, bo-ansB depletes Asn in the tumor microenvironment (TME), suppressing the expression of an Asn transporter (SLC1A5) in CD8+ T cells and impairing their stem-like properties and effector functions. In humans, microbiota-encoded genes contributing to aa depletion are associated with colorectal cancer progression. Collectively, these findings reveal nutrient-dependent modulation of anticancer immunity by the gut microbiota and identify diet-microbiota-cancer crosstalk as a potential therapeutic target.
{"title":"Microbiota utilization of intestinal amino acids modulates cancer progression and anticancer immunity","authors":"Shanshan Qiao, Ting-Ting Li, Mingeum Jeong, Chuanfa Liu, Sayaka Mizutani, Sung-Min Hwang, Yaxin Li, Mengze Lyu, Kazuhiro Nishiyama, Yu-Ang Tang, Huiqing Shi, Yuelin Angelina Tang, Seong-Ji Han, Jeremy Goc, Chris Parkhurst, Wen-Bing Jin, Xiaoyu Yang, He S. Yang, Mohammad Arifuzzaman, Gregory F. Sonnenberg, Juan R. Cubillos-Ruiz, Jun Yu, Nicholas Collins, David Artis, Chun-Jun Guo","doi":"10.1016/j.chom.2025.12.003","DOIUrl":"https://doi.org/10.1016/j.chom.2025.12.003","url":null,"abstract":"The human microbiota modulates cancer progression through largely unexplored mechanisms. Defining causal pathways is essential for monitoring and fine-tuning the microbiota to improve cancer treatment. Given that amino acid (aa) metabolism is often dysregulated in cancer, we assessed the role of microbiota pathways that modulate intestinal aa levels on colorectal tumor progression in mice. We found that the Bacteroides gene bo-ansB affects tumor responses to dietary asparagine (Asn) by reducing intestinal Asn levels. In mice receiving dietary Asn, bo-ansB promotes tumor progression by altering tumor-infiltrating CD8+ T cells. Mechanistically, bo-ansB depletes Asn in the tumor microenvironment (TME), suppressing the expression of an Asn transporter (SLC1A5) in CD8+ T cells and impairing their stem-like properties and effector functions. In humans, microbiota-encoded genes contributing to aa depletion are associated with colorectal cancer progression. Collectively, these findings reveal nutrient-dependent modulation of anticancer immunity by the gut microbiota and identify diet-microbiota-cancer crosstalk as a potential therapeutic target.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"89 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145894378","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.2025.11.011
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}
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