Pub Date : 2025-04-18DOI: 10.1016/j.chom.2025.03.015
Yupeng Feng, Sanne E. de Jong, Ana Paula B.N. Oliveira, Hady Samaha, Fan Yang, Mengyun Hu, Yanli Wang, Nour Beydoun, Xia Xie, Haibo Zhang, Dmitri Kazmin, Zhuoqing Fang, Jun Zou, Andrew T. Gewirtz, Scott D. Boyd, Thomas Hagan, Nadine Rouphael, Bali Pulendran
The gut microbiome plays a crucial role in modulating human immunity. Previously, we reported that antibiotic-induced microbiome perturbation affects influenza vaccine responses, depending on pre-existing immunity levels. Here, we employed a systems biology approach to analyze the impact of antibiotic administration on both primary and secondary immune responses to the rabies vaccine in humans. Antibiotic administration reduced the gut bacterial load, with a long-lasting reduction in commensal diversity. This alteration was associated with reduced rabies-specific humoral responses. Multi-omics profiling revealed that antibiotic administration induced (1) an enhanced pro-inflammatory signature early after vaccination, (2) a shift in the balance of vaccine-specific T-helper 1 (Th1) to T-follicular-helper response toward Th1 phenotype, and (3) profound alterations in metabolites, particularly in secondary bile acids in the blood. By integrating multi-omics datasets, we generated a multiscale, multi-response network that revealed key regulatory nodes, including the microbiota, secondary bile acids, and humoral immunity to vaccination.
{"title":"Antibiotic-induced gut microbiome perturbation alters the immune responses to the rabies vaccine","authors":"Yupeng Feng, Sanne E. de Jong, Ana Paula B.N. Oliveira, Hady Samaha, Fan Yang, Mengyun Hu, Yanli Wang, Nour Beydoun, Xia Xie, Haibo Zhang, Dmitri Kazmin, Zhuoqing Fang, Jun Zou, Andrew T. Gewirtz, Scott D. Boyd, Thomas Hagan, Nadine Rouphael, Bali Pulendran","doi":"10.1016/j.chom.2025.03.015","DOIUrl":"https://doi.org/10.1016/j.chom.2025.03.015","url":null,"abstract":"The gut microbiome plays a crucial role in modulating human immunity. Previously, we reported that antibiotic-induced microbiome perturbation affects influenza vaccine responses, depending on pre-existing immunity levels. Here, we employed a systems biology approach to analyze the impact of antibiotic administration on both primary and secondary immune responses to the rabies vaccine in humans. Antibiotic administration reduced the gut bacterial load, with a long-lasting reduction in commensal diversity. This alteration was associated with reduced rabies-specific humoral responses. Multi-omics profiling revealed that antibiotic administration induced (1) an enhanced pro-inflammatory signature early after vaccination, (2) a shift in the balance of vaccine-specific T-helper 1 (Th1) to T-follicular-helper response toward Th1 phenotype, and (3) profound alterations in metabolites, particularly in secondary bile acids in the blood. By integrating multi-omics datasets, we generated a multiscale, multi-response network that revealed key regulatory nodes, including the microbiota, secondary bile acids, and humoral immunity to vaccination.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"9 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846642","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 : 2025-04-15DOI: 10.1016/j.chom.2025.04.008
Pingmei Huang, Fenfen Ji, Alvin Ho-Kwan Cheung, Kaili Fu, Qiming Zhou, Xiao Ding, Danyu Chen, Yufeng Lin, Luyao Wang, Ying Jiao, Eagle S.H. Chu, Wei Kang, Ka Fai To, Jun Yu, Chi Chun Wong
No Abstract
{"title":"Peptostreptococcus stomatis promotes colonic tumorigenesis and receptor tyrosine kinase inhibitor resistance by activating ERBB2-MAPK","authors":"Pingmei Huang, Fenfen Ji, Alvin Ho-Kwan Cheung, Kaili Fu, Qiming Zhou, Xiao Ding, Danyu Chen, Yufeng Lin, Luyao Wang, Ying Jiao, Eagle S.H. Chu, Wei Kang, Ka Fai To, Jun Yu, Chi Chun Wong","doi":"10.1016/j.chom.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.chom.2025.04.008","url":null,"abstract":"No Abstract","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"60 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832151","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 : 2025-04-09DOI: 10.1016/j.chom.2025.03.007
Justin A. Boddey, Friedrich Frischknecht
Plasmodium liver infection is limited by type I interferons (IFN-I) but the mechanisms remain unknown. In this issue of Cell Host & Microbe, Marques-da-Silva et al. reveal two IFN-I-induced pathways that trigger the fusion of lysosomes with, and the disruption of, the membranes surrounding the parasites, leading to their clearance.
{"title":"Interferoning with Plasmodium development in the liver","authors":"Justin A. Boddey, Friedrich Frischknecht","doi":"10.1016/j.chom.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.chom.2025.03.007","url":null,"abstract":"<em>Plasmodium</em> liver infection is limited by type I interferons (IFN-I) but the mechanisms remain unknown. In this issue of <em>Cell Host & Microbe</em>, Marques-da-Silva et al. reveal two IFN-I-induced pathways that trigger the fusion of lysosomes with, and the disruption of, the membranes surrounding the parasites, leading to their clearance.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"14 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806338","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 : 2025-04-09DOI: 10.1016/j.chom.2025.03.012
Yufeng Lin, Harry Cheuk-Hay Lau, Chuanfa Liu, Xiao Ding, Yang Sun, Jiamei Rong, Xiang Zhang, Luyao Wang, Kai Yuan, Yinglei Miao, William Ka-Kei Wu, Sunny Hei Wong, Joseph Jao-Yiu Sung, Jun Yu
Microbial alterations in different tumor locations of colorectal cancer (CRC) remain unclear. Here, 1,375 fecal metagenomes from six in-house and published datasets were analyzed, including 128 right-sided CRC (rCRC), 168 left-sided CRC (lCRC), 250 rectal cancer (RC), and 829 controls. Firmicutes progressively increase from rCRC, lCRC, to RC, in contrast to the gradual decrease of Bacteroidetes. Tumor location-associated fecal microbes are identified, including Veillonella parvula for rCRC, Streptococcus angionosus for lCRC, and Peptostreptococcus anaerobius for RC, while Fusobacterium nucleatum is enriched in all tumor locations. Tumor location-associated bacteria correlate with patient survival. Clinically, we establish a microbial biomarker panel for each tumor location that accurately diagnoses rCRC (area under the receiver operating characteristic curve [AUC] = 91.59%), lCRC (AUC = 91.69%), or RC (AUC = 90.53%) from controls. Tumor location-specific biomarkers also have higher diagnostic accuracy (AUC = 91.38%) than location-non-specific biomarkers (AUC = 82.92%). Overall, we characterize fecal microbes associated with different CRC tumor locations, highlighting that tumor location should be considered in non-invasive diagnosis.
{"title":"Multi-cohort analysis reveals colorectal cancer tumor location-associated fecal microbiota and their clinical impact","authors":"Yufeng Lin, Harry Cheuk-Hay Lau, Chuanfa Liu, Xiao Ding, Yang Sun, Jiamei Rong, Xiang Zhang, Luyao Wang, Kai Yuan, Yinglei Miao, William Ka-Kei Wu, Sunny Hei Wong, Joseph Jao-Yiu Sung, Jun Yu","doi":"10.1016/j.chom.2025.03.012","DOIUrl":"https://doi.org/10.1016/j.chom.2025.03.012","url":null,"abstract":"Microbial alterations in different tumor locations of colorectal cancer (CRC) remain unclear. Here, 1,375 fecal metagenomes from six in-house and published datasets were analyzed, including 128 right-sided CRC (rCRC), 168 left-sided CRC (lCRC), 250 rectal cancer (RC), and 829 controls. Firmicutes progressively increase from rCRC, lCRC, to RC, in contrast to the gradual decrease of Bacteroidetes. Tumor location-associated fecal microbes are identified, including <em>Veillonella parvula</em> for rCRC, <em>Streptococcus angionosus</em> for lCRC, and <em>Peptostreptococcus anaerobius</em> for RC, while <em>Fusobacterium nucleatum</em> is enriched in all tumor locations. Tumor location-associated bacteria correlate with patient survival. Clinically, we establish a microbial biomarker panel for each tumor location that accurately diagnoses rCRC (area under the receiver operating characteristic curve [AUC] = 91.59%), lCRC (AUC = 91.69%), or RC (AUC = 90.53%) from controls. Tumor location-specific biomarkers also have higher diagnostic accuracy (AUC = 91.38%) than location-non-specific biomarkers (AUC = 82.92%). Overall, we characterize fecal microbes associated with different CRC tumor locations, highlighting that tumor location should be considered in non-invasive diagnosis.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"1 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806107","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 : 2025-04-09DOI: 10.1016/j.chom.2025.03.009
Laura D. Schell, Rachel N. Carmody
Early-life antibiotic (ELA) exposure has garnered attention for its potential role in modulating obesity risk, although outcomes from mouse experiments and human epidemiological studies often vary based on dosage and sex. Low-dose (subtherapeutic) antibiotics can enhance energy availability through moderate alterations in gut microbiome profile, while high-dose (therapeutic) antibiotics substantially deplete the gut microbiota, thereby contributing to short-term negative energy balance. In this perspective, we propose a framework to understand how these distinct impacts of antibiotics on the gut microbiome during critical developmental windows shape long-term obesity risk through their influence on host energy balance. Using this framework, we then propose several hypotheses to explain variation in ELA-induced obesity outcomes across males and females. We conclude by discussing the evolutionary implications of ELAs, positing that the response of the gut microbiome to ELAs may signal energy availability and environmental volatility, influencing metabolic programming and adaptive traits across generations.
{"title":"An energetic framework for gut microbiome-mediated obesity induced by early-life exposure to antibiotics","authors":"Laura D. Schell, Rachel N. Carmody","doi":"10.1016/j.chom.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.chom.2025.03.009","url":null,"abstract":"Early-life antibiotic (ELA) exposure has garnered attention for its potential role in modulating obesity risk, although outcomes from mouse experiments and human epidemiological studies often vary based on dosage and sex. Low-dose (subtherapeutic) antibiotics can enhance energy availability through moderate alterations in gut microbiome profile, while high-dose (therapeutic) antibiotics substantially deplete the gut microbiota, thereby contributing to short-term negative energy balance. In this perspective, we propose a framework to understand how these distinct impacts of antibiotics on the gut microbiome during critical developmental windows shape long-term obesity risk through their influence on host energy balance. Using this framework, we then propose several hypotheses to explain variation in ELA-induced obesity outcomes across males and females. We conclude by discussing the evolutionary implications of ELAs, positing that the response of the gut microbiome to ELAs may signal energy availability and environmental volatility, influencing metabolic programming and adaptive traits across generations.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"39 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806106","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 : 2025-04-09DOI: 10.1016/j.chom.2025.03.002
Yanan Wang, Min Li
Staphylococcus aureus is a major pathogen with rising antibiotic resistance. In this issue of Cell Host & Microbe, Shekhar et al. find that quinoxalinediones reduce S. aureus lung infections through α-hemolysin inhibition, offering a therapeutic strategy for S. aureus pneumonia.
{"title":"QDS pathoblockers target and lock α-hemolysin","authors":"Yanan Wang, Min Li","doi":"10.1016/j.chom.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.chom.2025.03.002","url":null,"abstract":"<em>Staphylococcus aureus</em> is a major pathogen with rising antibiotic resistance. In this issue of <em>Cell Host & Microbe</em>, Shekhar et al. find that quinoxalinediones reduce <em>S. aureus</em> lung infections through α-hemolysin inhibition, offering a therapeutic strategy for <em>S. aureus</em> pneumonia.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"65 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806286","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 : 2025-04-09DOI: 10.1016/j.chom.2025.03.011
Mengning Luo, Xinyang Song
Plant phenolic glycosides are thought to be beneficial for human health. In a recent issue of Cell, Kuziel et al. identified that Bacteroides species, the dominant symbiotic bacteria in the gut, harbor a unique multi-enzyme system that processes dietary plant glycosides into various aglycone metabolites with antimicrobial or immunomodulatory activities.
{"title":"Phyto-metabolites on guard: Role of gut microbial deglycosylation","authors":"Mengning Luo, Xinyang Song","doi":"10.1016/j.chom.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.chom.2025.03.011","url":null,"abstract":"Plant phenolic glycosides are thought to be beneficial for human health. In a recent issue of <em>Cell</em>, Kuziel et al. identified that <em>Bacteroides</em> species, the dominant symbiotic bacteria in the gut, harbor a unique multi-enzyme system that processes dietary plant glycosides into various aglycone metabolites with antimicrobial or immunomodulatory activities.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"34 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806103","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 : 2025-04-09DOI: 10.1016/j.chom.2025.03.013
Jarel Elgin Tolentino, Spyros Lytras, Jumpei Ito, Kei Sato
Three studies recently published in Cell reveal distinct ACE2 binding interactions across the merbecoviruses, uncovering how HKU5 can use ACE2s of many non-human hosts and identifying a novel HKU5 lineage capable of using human ACE2. These findings highlight merbecovirus receptor plasticity and caution for preparedness against potential merbecovirus threats.
{"title":"Beyond MERS: Merbecovirus receptor plasticity calls for emergence preparedness","authors":"Jarel Elgin Tolentino, Spyros Lytras, Jumpei Ito, Kei Sato","doi":"10.1016/j.chom.2025.03.013","DOIUrl":"https://doi.org/10.1016/j.chom.2025.03.013","url":null,"abstract":"Three studies recently published in <em>Cell</em> reveal distinct ACE2 binding interactions across the merbecoviruses, uncovering how HKU5 can use ACE2s of many non-human hosts and identifying a novel HKU5 lineage capable of using human ACE2. These findings highlight merbecovirus receptor plasticity and caution for preparedness against potential merbecovirus threats.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"25 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806104","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 : 2025-04-09DOI: 10.1016/j.chom.2025.03.003
Zeyu Duan, Xiao Liu
In this issue of Cell Host & Microbe, Honda et al. identify an antiviral defense system in fungi. Mycoviruses trigger the expression of RNA-editing enzymes, which catalyze the editing of mRNAs encoding zinc finger transcription factors. This system differs from the RNA interference and is conserved in filamentous fungi.
{"title":"Emerging antiviral defense systems in fungi","authors":"Zeyu Duan, Xiao Liu","doi":"10.1016/j.chom.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.chom.2025.03.003","url":null,"abstract":"In this issue of <em>Cell Host & Microbe</em>, Honda et al. identify an antiviral defense system in fungi. Mycoviruses trigger the expression of RNA-editing enzymes, which catalyze the editing of mRNAs encoding zinc finger transcription factors. This system differs from the RNA interference and is conserved in filamentous fungi.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"21 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806339","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 : 2025-04-09DOI: 10.1016/j.chom.2025.02.009
Tim Rollenske
Immunoglobulin A (IgA) antibodies maintain homeostasis between the host and its microbiota, by exerting luminal control over fungi and bacteria. In this issue of Cell Host & Microbe, Lisicka et al. show that IgA antibodies also control the population of specific members of our virome.
{"title":"Mucosal stargazing: IgA keeps astrovirus in check","authors":"Tim Rollenske","doi":"10.1016/j.chom.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.chom.2025.02.009","url":null,"abstract":"Immunoglobulin A (IgA) antibodies maintain homeostasis between the host and its microbiota, by exerting luminal control over fungi and bacteria. In this issue of <em>Cell Host & Microbe</em>, Lisicka et al. show that IgA antibodies also control the population of specific members of our virome.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"1 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806105","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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