Cell host & microbe最新文献

Bacteroides sphingolipids promote anti-inflammatory responses through the mevalonate pathway 鞘脂类拟杆菌通过甲羟戊酸途径促进抗炎反应

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-05-30 DOI: 10.1016/j.chom.2025.05.007

Eric M. Brown, Emily R. Temple, Sarah Jeanfavre, Julian Avila-Pacheco, Noel Taylor, Kai Liu, Phuong N.U. Nguyen, Ahmed M.T. Mohamed, Panhasith Ung, Rebecca A. Walker, Daniel B. Graham, Clary B. Clish, Ramnik J. Xavier

{"title":"Bacteroides sphingolipids promote anti-inflammatory responses through the mevalonate pathway","authors":"Eric M. Brown, Emily R. Temple, Sarah Jeanfavre, Julian Avila-Pacheco, Noel Taylor, Kai Liu, Phuong N.U. Nguyen, Ahmed M.T. Mohamed, Panhasith Ung, Rebecca A. Walker, Daniel B. Graham, Clary B. Clish, Ramnik J. Xavier","doi":"10.1016/j.chom.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.007","url":null,"abstract":"Sphingolipids derived from Bacteroides species are associated with changes in host inflammation and metabolic syndrome; however, the signaling mechanisms within host cells are unknown. We utilize outer membrane vesicles (OMVs) from wild-type and sphingolipid-deficient Bacteroides strains to understand how these lipids modulate host inflammation. Characterization of the lipidome of B. thetaiotaomicron OMVs revealed enrichment of dihydroceramide phosphoethanolamine (CerPE). OMVs deliver bacterial sphingolipids into host dendritic and epithelial cells, where a subset of lipids, including CerPE, stably persist. Similarly, B. thetaiotaomicron colonization results in sphingolipid persistence in murine tissues and host lipidome alterations that are not observed with the sphingolipid-deficient strain. OMVs induce a potent, sphingolipid-dependent interleukin-10 (IL-10) anti-inflammatory response in dendritic cells, which depends on mevalonate pathway activation. Adding a CerPE fraction to sphingolipid-deficient OMVs rescued IL-10 secretion, similarly dependent on mevalonate pathway activation. These data highlight the essential roles of sphingolipids in stimulating anti-inflammatory responses mediated by mevalonate pathway induction.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"36 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176801","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}

引用次数: 0

Single-tooth resolved, whole-mouth prediction of early childhood caries via spatiotemporal variations of plaque microbiota 通过牙菌斑微生物群的时空变化来预测单齿、全口早期儿童龋病

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-05-30 DOI: 10.1016/j.chom.2025.05.006

Fang Yang, Fei Teng, Yufeng Zhang, Yanfei Sun, Jian Xu, Shi Huang

{"title":"Single-tooth resolved, whole-mouth prediction of early childhood caries via spatiotemporal variations of plaque microbiota","authors":"Fang Yang, Fei Teng, Yufeng Zhang, Yanfei Sun, Jian Xu, Shi Huang","doi":"10.1016/j.chom.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.006","url":null,"abstract":"Early childhood caries (ECC) exhibits tooth specificity, highlighting the need for single-tooth-level prevention. We profiled 2,504 dental plaque microbiota samples from 89 preschoolers across two cohorts, tracking compositional changes with imputed functional trends at a single-tooth resolution over 11 months. In healthy children, dental microbiota exhibited an anterior-to-posterior ecological gradient on maxillary teeth and strong bilateral symmetry. These patterns were disrupted in caries-affected children due to caries-driven microbial reorganization. Leveraging tooth-specific disease-associated taxa and spatially related clinical/microbial features, we developed spatial microbial indicators of caries (spatial-MiC or sMiC) using machine-learning techniques. sMiC achieves 98% accuracy in diagnosing ECC at a single-tooth resolution and 93% accuracy in predicting new caries 2 months in advance in perceived-healthy teeth. This high-resolution spatiotemporal microbial atlas of ECC development disentangles the microbial etiology at the single-tooth level, identifies a characteristic microbial signature for each tooth, and provides a foundation for tooth-specific ECC prevention strategies.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"16 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176800","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}

引用次数: 0

Bacteroides fragilis promotes chemoresistance in colorectal cancer, and its elimination by phage VA7 restores chemosensitivity 脆弱拟杆菌促进结直肠癌的化疗耐药，通过噬菌体VA7消除其可恢复化疗敏感性

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-05-29 DOI: 10.1016/j.chom.2025.05.004

Xiao Ding, Nick Lung-Ngai Ting, Chi Chun Wong, Pingmei Huang, Lanping Jiang, Chuanfa Liu, Yufeng Lin, Shiyu Li, Yujie Liu, Mingxu Xie, Weixin Liu, Kai Yuan, Luyao Wang, Xinyue Zhang, Yanqiang Ding, Qing Li, Yang Sun, Yinglei Miao, Lanqing Ma, Xiang Gao, Jun Yu

{"title":"Bacteroides fragilis promotes chemoresistance in colorectal cancer, and its elimination by phage VA7 restores chemosensitivity","authors":"Xiao Ding, Nick Lung-Ngai Ting, Chi Chun Wong, Pingmei Huang, Lanping Jiang, Chuanfa Liu, Yufeng Lin, Shiyu Li, Yujie Liu, Mingxu Xie, Weixin Liu, Kai Yuan, Luyao Wang, Xinyue Zhang, Yanqiang Ding, Qing Li, Yang Sun, Yinglei Miao, Lanqing Ma, Xiang Gao, Jun Yu","doi":"10.1016/j.chom.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.004","url":null,"abstract":"Chemoresistance is a main cause of colorectal cancer (CRC) treatment failure. We identified that Bacteroides fragilis is enriched in patients with CRC resistant to chemotherapy in two independent cohorts, and its abundance is associated with poor survival. Consistently, administration of B. fragilis to CRC xenografts and ApcMin/+- and AOM/DSS-induced CRC mice all significantly attenuated the antitumor efficacy of 5-FU and OXA. Mechanistically, B. fragilis colonized colon tumors and mediated its effect via its surface protein SusD/RagB binding to the Notch1 receptor in CRC cells, leading to activation of the Notch1 signaling pathway and the induction of epithelial-to-mesenchymal transition (EMT)/stemness to suppress chemotherapy-induced apoptosis. Either deletion of SusD/RagB or blockade of Notch1 signaling abrogated B. fragilis-mediated chemoresistance. Finally, B. fragilis-targeting phage VA7 selectively suppressed B. fragilis and restored chemosensitivity in preclinical CRC mouse models. Our findings have offered insights into the potential of precise gut microbiota manipulation for the clinical management of CRC.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"58 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165305","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}

引用次数: 0

Drought-induced plant microbiome and metabolic enrichments improve drought resistance 干旱诱导的植物微生物组和代谢丰富可提高抗旱性

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-05-29 DOI: 10.1016/j.chom.2025.05.002

Jiayu Li, Hongwei Liu, Juntao Wang, Catriona A. Macdonald, Pankaj Singh, Vu Thanh Cong, Marcus Klein, Manuel Delgado-Baquerizo, Brajesh K. Singh

{"title":"Drought-induced plant microbiome and metabolic enrichments improve drought resistance","authors":"Jiayu Li, Hongwei Liu, Juntao Wang, Catriona A. Macdonald, Pankaj Singh, Vu Thanh Cong, Marcus Klein, Manuel Delgado-Baquerizo, Brajesh K. Singh","doi":"10.1016/j.chom.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.002","url":null,"abstract":"Plant-microbiome interactions are crucial in maintaining plant health and productivity under stress; however, little is known about these interactions under drought. Here, using wheat as a model, we combine genomics and culture-dependent methods to investigate the interactions between the soil, root, and rhizosphere microbiomes with rhizosphere metabolomes and plant phenotypes. We find that drought conditions promote microbial colonization in plant microbiomes, enriching Streptomyces coeruleorubidus and Leifsonia shinshuensis, while also increasing 4-oxoproline levels in the rhizosphere, potentially attracting S. coeruleorubidus. Consistently, genes facilitating microbial responses to drought, including the N-terminal acetyltransferase rimJ, are enriched, while S. coeruleorubidus and L. shinshuensis reintroduction promotes host drought resistance. Drought-legacy-effect experiments further support these benefits, with increased plant biomass and yield in the subsequent growth cycle under drought. Collectively, this study informs how drought-induced microbial and metabolite enrichments improve plant adaptation to abiotic stresses, potentially informing development of bio-based tools to mitigate drought effects.<h3>Video abstract</h3><video controls=\"\" crossorigin=\"anonymous\" poster=\"https://ars.els-cdn.com/content/image/1-s2.0-S1931312825001817-mmc5.jpg\" preload=\"auto\" style=\"width:100%\"><source src=\"https://ars.els-cdn.com/content/image/1-s2.0-S1931312825001817-mmc5.mp4\" type=\"video/mp4\"/></video>Download: Download video (4MB)","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"22 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165306","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}

引用次数: 0

Targeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease 靶向抑制病原菌毒力因子可减轻酒精相关性肝病

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-05-28 DOI: 10.1016/j.chom.2025.05.003

Yongqiang Yang, Yi Duan, Sonja Lang, Marcos F. Fondevila, David Schöler, Aenne Harberts, Noemí Cabré, Sainan Chen, Yan Shao, Kevin Vervier, Yukiko Miyamoto, Xinlian Zhang, Huikuan Chu, Ling Yang, Chen Tan, Lars Eckmann, Francisco Bosques-Padilla, Elizabeth C. Verna, Juan G. Abraldes, Robert S. Brown, Bernd Schnabl

{"title":"Targeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease","authors":"Yongqiang Yang, Yi Duan, Sonja Lang, Marcos F. Fondevila, David Schöler, Aenne Harberts, Noemí Cabré, Sainan Chen, Yan Shao, Kevin Vervier, Yukiko Miyamoto, Xinlian Zhang, Huikuan Chu, Ling Yang, Chen Tan, Lars Eckmann, Francisco Bosques-Padilla, Elizabeth C. Verna, Juan G. Abraldes, Robert S. Brown, Bernd Schnabl","doi":"10.1016/j.chom.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.003","url":null,"abstract":"Alcohol-associated liver disease poses a global health burden with high mortality. Imbalances in the gut microbiota are important for disease progression. Using metagenomic sequencing of fecal samples from a multicenter, international cohort of patients with alcohol-associated hepatitis, we found that the presence of virulence factor KpsM, encoded in the genome of Escherichia coli (E. coli), correlated with patient mortality. Functional studies using gnotobiotic mouse models and genetic manipulation of bacteria demonstrated that kpsM-positive E. coli exacerbate ethanol-induced liver disease. The kpsM gene mediates the translocation of capsular polysaccharides to the cell surface. This enables kpsM-positive E. coli to evade phagocytosis by the scavenger receptor Marco on Kupffer cells in the liver, leading to bacterial spread. Importantly, inhibiting kpsM-dependent capsules with the small molecule 2-(4-phenylphenyl)benzo[g]quinoline-4-carboxylic acid (C7) attenuated ethanol-induced liver disease in mice. We show that precision targeting of the virulence factor KpsM is a promising approach to improve outcomes of patients with alcohol-associated hepatitis.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"5 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154231","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}

引用次数: 0

Microbiota-derived urocanic acid triggered bytyrosine kinase inhibitors potentiates cancer immunotherapy efficacy 微生物源性尿尿酸触发的酪氨酸激酶抑制剂增强了癌症免疫治疗的疗效

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-05-28 DOI: 10.1016/j.chom.2025.04.022

Mengying Zhang, Zhonghong Wei, Bin Wei, Changjie Lai, Gangfan Zong, Enxiang Tao, Minmin Fan, Yehua Pan, Bingyan Zhou, Luping Shen, Jingjing Wu, Qingqing Wang, Ying Peng, Le Zhen, Yunhao Wu, Yin Lu, Guangji Wang, Fang Zhou, Yunlong Shan

{"title":"Microbiota-derived urocanic acid triggered bytyrosine kinase inhibitors potentiates cancer immunotherapy efficacy","authors":"Mengying Zhang, Zhonghong Wei, Bin Wei, Changjie Lai, Gangfan Zong, Enxiang Tao, Minmin Fan, Yehua Pan, Bingyan Zhou, Luping Shen, Jingjing Wu, Qingqing Wang, Ying Peng, Le Zhen, Yunhao Wu, Yin Lu, Guangji Wang, Fang Zhou, Yunlong Shan","doi":"10.1016/j.chom.2025.04.022","DOIUrl":"https://doi.org/10.1016/j.chom.2025.04.022","url":null,"abstract":"Interactions between the host and the gut microbiota influence cancer progression and treatment responses. While the combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockade (ICB) has improved outcomes, some cancer patients still have poor responses. The underlying mediators of this heterogeneity remain unclear. Here, we demonstrate that TKIs potentiate the immunotherapy response by increasing the abundance of Muribaculum and its metabolite, urocanic acid (UCA), which reduces myeloid-derived suppressor cell (MDSC) recruitment via the CXCL1-CXCR2 axis by inhibiting p65 in tumor vascular endothelial cells. Mechanistically, UCA selectively binds to the aspartic acid 31 residue of IκBα and suppresses its phosphorylation at serine 32. Compared with non-responders, clinical ICB responders present a higher UCA concentration and a greater level of Muribaculum gordoncarteri in feces, indicating both as potential predictive biomarkers for treatment response. Collectively, our findings reveal and highlight the important role of the gut microbial metabolite UCA in response to ICB.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"3 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154232","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}

引用次数: 0

Gut microbial enzymes and metabolic dysfunction-associated steatohepatitis: Function, mechanism, and therapeutic prospects 肠道微生物酶和代谢功能障碍相关的脂肪性肝炎：功能、机制和治疗前景

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-05-26 DOI: 10.1016/j.chom.2025.04.020

Xi Luo, Kai Wang, Changtao Jiang

{"title":"Gut microbial enzymes and metabolic dysfunction-associated steatohepatitis: Function, mechanism, and therapeutic prospects","authors":"Xi Luo, Kai Wang, Changtao Jiang","doi":"10.1016/j.chom.2025.04.020","DOIUrl":"https://doi.org/10.1016/j.chom.2025.04.020","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide. The liver communicates with the intestine, in large part through the gut microbiota. Microbial enzymes are key mediators that affect the progression of MASLD and the more severe metabolic dysfunction-associated steatohepatitis (MASH). These enzymes contribute to the metabolism or biosynthesis of steroids, fatty acids, amino acids, ethanol, choline, and intestinal hormones that contribute to disease progression. Additionally, dysbiosis and functional alterations in the microbiota compromise the intestinal barrier, increasing its permeability to bacterial metabolites and liver exposure to microbial-associated molecular patterns (MAMPs), thereby exacerbating liver inflammation and fibrosis. Furthermore, functional alterations in the gut microbiota can modulate intestinal signaling pathways through metabolites or gut hormones, subsequently affecting hepatic metabolism. A deeper understanding of the roles of the gut microbiota and microbial enzymes in MASH will facilitate the development of personalized treatments targeting specific gut microbes or functional enzymes.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"33 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137122","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}

引用次数: 0

E. coli prophages encode an arsenal of defense systems to protect against temperate phages 大肠杆菌噬菌体编码了一系列防御系统来抵御温带噬菌体

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-05-22 DOI: 10.1016/j.chom.2025.04.021

Lucas R. Brenes, Michael T. Laub

引用次数: 0

Rhizosphere microbes mitigate the shade avoidance responses in Arabidopsis 根际微生物减轻拟南芥避荫反应

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-05-21 DOI: 10.1016/j.chom.2025.04.019

Huanhuan Lu, Caiyi Lu, Sha Huang, Wenbo Liu, Like Wang, Chuanwei Yang, Ertao Wang, Lin Li

引用次数: 0

Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations 狂犬病糖蛋白的深度突变扫描定义了突变约束和抗体逃逸突变