Pub Date : 2026-02-19DOI: 10.1016/j.chom.2026.01.018
Rosalind J. Xu, Hao Zhang, Paolo Cadinu, Phillip B. Nicol, Uli S. Herrmann, Tyrone Lee, Ludwig Geistlinger, Rafael A. Irizarry, Jeffrey R. Moffitt
The gastrointestinal environment is home to a massive diversity of diet-, host-, and microbiota-derived small molecules, collectively sensed by a remarkable variety of cells. To explore the cellular and spatial organization of sensation, we use MERFISH to profile receptor expression across 2.1 million cells in multiple regions of the murine gut under specific-pathogen-free (SPF) and germ-free (GF) conditions. This atlas reveals expected and previously unidentified cell types—including a candidate murine homolog of human BEST4⁺ enterocytes—demonstrates cell-type regional specialization, discovers extensive location-dependent spatial fine-tuning in mucosal cell expression, and suggests cell-type-specific mediators of the effects of microbiota-derived small molecules. Additionally, this atlas reveals that, aside from immune cell abundance, many aspects of the murine gut are host-intrinsic and modified only modestly in the absence of a microbiota. Collectively, this atlas provides a valuable resource for understanding the cellular and spatial organization underlying small-molecule sensation in the gut.
{"title":"An image-based transcriptomics atlas reveals the regional and microbiota-dependent molecular, cellular, and spatial structure of the murine gut","authors":"Rosalind J. Xu, Hao Zhang, Paolo Cadinu, Phillip B. Nicol, Uli S. Herrmann, Tyrone Lee, Ludwig Geistlinger, Rafael A. Irizarry, Jeffrey R. Moffitt","doi":"10.1016/j.chom.2026.01.018","DOIUrl":"https://doi.org/10.1016/j.chom.2026.01.018","url":null,"abstract":"The gastrointestinal environment is home to a massive diversity of diet-, host-, and microbiota-derived small molecules, collectively sensed by a remarkable variety of cells. To explore the cellular and spatial organization of sensation, we use MERFISH to profile receptor expression across 2.1 million cells in multiple regions of the murine gut under specific-pathogen-free (SPF) and germ-free (GF) conditions. This atlas reveals expected and previously unidentified cell types—including a candidate murine homolog of human BEST4⁺ enterocytes—demonstrates cell-type regional specialization, discovers extensive location-dependent spatial fine-tuning in mucosal cell expression, and suggests cell-type-specific mediators of the effects of microbiota-derived small molecules. Additionally, this atlas reveals that, aside from immune cell abundance, many aspects of the murine gut are host-intrinsic and modified only modestly in the absence of a microbiota. Collectively, this atlas provides a valuable resource for understanding the cellular and spatial organization underlying small-molecule sensation in the gut.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"37 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223317","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 : 2026-02-11DOI: 10.1016/j.chom.2026.01.009
Usman Hussain, Marine C. Cambon, Bridget Crampton, Sunitha Subramaniam, Anparasy Kajamuhan, Alejandra Ordoñez, Jim Downie, Jasen Finch, Manfred Beckmann, Nathan Brown, Amy Elison, Carrie Brady, Elena Vanguelova, Sandra Denman, James E. McDonald
{"title":"Microbial communities in semi-mature oak trees are resilient to drought, nutrient limitation, and pathogen challenge","authors":"Usman Hussain, Marine C. Cambon, Bridget Crampton, Sunitha Subramaniam, Anparasy Kajamuhan, Alejandra Ordoñez, Jim Downie, Jasen Finch, Manfred Beckmann, Nathan Brown, Amy Elison, Carrie Brady, Elena Vanguelova, Sandra Denman, James E. McDonald","doi":"10.1016/j.chom.2026.01.009","DOIUrl":"https://doi.org/10.1016/j.chom.2026.01.009","url":null,"abstract":"","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"60 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146160732","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 : 2026-02-09DOI: 10.1016/j.chom.2026.01.016
Weijie Wen, Runping Su, Yunyun Liu, Zhiyang Feng, Yancai Li, Jieli Li, Ziyu Huang, Fen Zhang, Shanshan Gao, Yingfei Ma, Qinghua Zhou, Emad M. El-Omar, Jeremy J. Barr, Tao Zuo
The human gut harbors a diverse virome, believed to play a crucial role in maintaining intestinal homeostasis. However, the magnitude of heterogeneity of the gut mucosal virome, and how it differentially regulates host inflammation phenotypes, such as those observed in Crohn’s disease (CD), remains unclear. Here, we identify two mucosal DNA virome enterotypes (E1 and E2) in humans, with E2 subjects exhibiting higher virome diversity and nuanced bacteriophage-bacteria correlations. Moreover, E2-enterotyped CD patients exhibited higher Wulfhauvirus abundance than healthy controls. The E2 virome is causally more proinflammatory in inducing intestinal inflammation in mice. Mechanistically, the novel E2-virome-enriched phage øBTZT001P (belonging to Wulfhauvirus) lysogenically infects Bacteroides thetaiotaomicron, increasing sphingosine production. Downstream, sphingosine suppresses the commensal bacterium Blautia obeum in the gut, leading to worsened intestinal inflammation. Our findings reveal that configurational differences in the gut virome may dictate disease outcome through a phage-bacteria-metabolite-intestine axis, highlighting the importance of gut phage-bacteria crosstalk in health.
{"title":"Gut DNA virome enterotype dictates inflammation heterogeneity through tuning the phage-bacteria-sphingosine-intestine axis in Crohn's disease","authors":"Weijie Wen, Runping Su, Yunyun Liu, Zhiyang Feng, Yancai Li, Jieli Li, Ziyu Huang, Fen Zhang, Shanshan Gao, Yingfei Ma, Qinghua Zhou, Emad M. El-Omar, Jeremy J. Barr, Tao Zuo","doi":"10.1016/j.chom.2026.01.016","DOIUrl":"https://doi.org/10.1016/j.chom.2026.01.016","url":null,"abstract":"The human gut harbors a diverse virome, believed to play a crucial role in maintaining intestinal homeostasis. However, the magnitude of heterogeneity of the gut mucosal virome, and how it differentially regulates host inflammation phenotypes, such as those observed in Crohn’s disease (CD), remains unclear. Here, we identify two mucosal DNA virome enterotypes (E1 and E2) in humans, with E2 subjects exhibiting higher virome diversity and nuanced bacteriophage-bacteria correlations. Moreover, E2-enterotyped CD patients exhibited higher <ce:italic>Wulfhauvirus</ce:italic> abundance than healthy controls. The E2 virome is causally more proinflammatory in inducing intestinal inflammation in mice. Mechanistically, the novel E2-virome-enriched phage øBTZT001P (belonging to <ce:italic>Wulfhauvirus</ce:italic>) lysogenically infects <ce:italic>Bacteroides thetaiotaomicron</ce:italic>, increasing sphingosine production. Downstream, sphingosine suppresses the commensal bacterium <ce:italic>Blautia obeum</ce:italic> in the gut, leading to worsened intestinal inflammation. Our findings reveal that configurational differences in the gut virome may dictate disease outcome through a phage-bacteria-metabolite-intestine axis, highlighting the importance of gut phage-bacteria crosstalk in health.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"16 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146660","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 : 2026-02-09DOI: 10.1016/j.chom.2026.01.013
Ana C. da Silva, Jacob Lapkin, Qi Yin, Efrat Muller, Alexandre Almeida
{"title":"Meta-analysis of the uncultured gut microbiome across 11,115 global metagenomes reveals a candidate signature of health","authors":"Ana C. da Silva, Jacob Lapkin, Qi Yin, Efrat Muller, Alexandre Almeida","doi":"10.1016/j.chom.2026.01.013","DOIUrl":"https://doi.org/10.1016/j.chom.2026.01.013","url":null,"abstract":"","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"9 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152834","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 : 2026-02-03DOI: 10.1016/j.chom.2026.01.008
Anne-Marie C. Overstreet, McKenzie Burge, Brady Anderson, Xiaorong Zhu, Yun Tao, Candace M. Cham, Brenna Michaud, Soyar Horam, Naseer Sangwan, Mohammed Dwidar, Xuefeng Liu, Akeem Santos, Vartika Srivastava, Chelsea Finney, Christopher M. Goins, Zhanghan Dai, B. Ben Koff, Shaun R. Stauffer, Vanessa A. Leone, Jeannette S. Messer
{"title":"HMGB1 functions as a critical mediator of host defense at the gut mucosal barrier","authors":"Anne-Marie C. Overstreet, McKenzie Burge, Brady Anderson, Xiaorong Zhu, Yun Tao, Candace M. Cham, Brenna Michaud, Soyar Horam, Naseer Sangwan, Mohammed Dwidar, Xuefeng Liu, Akeem Santos, Vartika Srivastava, Chelsea Finney, Christopher M. Goins, Zhanghan Dai, B. Ben Koff, Shaun R. Stauffer, Vanessa A. Leone, Jeannette S. Messer","doi":"10.1016/j.chom.2026.01.008","DOIUrl":"https://doi.org/10.1016/j.chom.2026.01.008","url":null,"abstract":"","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"43 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146110542","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}