Pub Date : 2024-11-13DOI: 10.1016/j.chom.2024.10.009
Charlie Y. Mo
Bacteriophages have evolved numerous mechanisms to evade targeting by CRISPR-Cas defense systems. However, the evolutionary origin of these so-called “anti-CRISPRs” remains poorly understood. In a recent issue of Nature, Katz et al.1 provide evidence that some anti-CRISPRs were derived from genes of the CRISPR-Cas systems themselves.
{"title":"If you can’t beat them, join them: Anti-CRISPR proteins derived from CRISPR-associated genes","authors":"Charlie Y. Mo","doi":"10.1016/j.chom.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.009","url":null,"abstract":"Bacteriophages have evolved numerous mechanisms to evade targeting by CRISPR-Cas defense systems. However, the evolutionary origin of these so-called “anti-CRISPRs” remains poorly understood. In a recent issue of <em>Nature</em>, Katz et al.<span><span><sup>1</sup></span></span> provide evidence that some anti-CRISPRs were derived from genes of the CRISPR-Cas systems themselves.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"2 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601043","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 : 2024-11-13DOI: 10.1016/j.chom.2024.10.014
Xiaonan Han, Qingrui Huang, Jinghua Yan
In recent work, Mucker et al.1 demonstrated that mRNA-1769 outperforms modified vaccinia Ankara (MVA), which has been deployed against recent mpox virus (MPXV) outbreaks, in reducing clinical symptoms and controlling viral replication, highlighting its potential as a scalable, safe, and effective next-generation platform for orthopoxvirus vaccination.
{"title":"mRNA vaccines: A promising platform for safer, more effective next-generation Orthopoxvirus immunization","authors":"Xiaonan Han, Qingrui Huang, Jinghua Yan","doi":"10.1016/j.chom.2024.10.014","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.014","url":null,"abstract":"In recent work, Mucker et al.<span><span><sup>1</sup></span></span> demonstrated that mRNA-1769 outperforms modified vaccinia Ankara (MVA), which has been deployed against recent mpox virus (MPXV) outbreaks, in reducing clinical symptoms and controlling viral replication, highlighting its potential as a scalable, safe, and effective next-generation platform for orthopoxvirus vaccination.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"35 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601050","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}
Hyperplasia of mesenteric tissues in Crohn’s disease, called creeping fat (CrF), is associated with surgical recurrence. Although microbiota translocation and colonization have been found in CrF, convincing mouse phenotypes and the underlying mechanisms of CrF formation remain unclear. Utilizing single-nucleus RNA (snRNA) sequencing of CrF and different mouse models, we demonstrate that the commensal Achromobacter pulmonis induces mesenteric adipogenesis through macrophage alteration. Targeted metabolome analysis reveals that L-kynurenine is the most enriched metabolite in CrF. Upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) enhances kynurenine metabolism and drives mesenteric adipogenesis. Leveraging single-cell RNA (scRNA) sequencing of mouse mesenteric tissues and macrophage-specific IDO1 knockout mice, we verify the role of macrophage-sourced L-kynurenine in mesenteric adipogenesis. Mechanistically, L-kynurenine-induced adipogenesis is mediated by the aryl hydrocarbon receptors in adipocytes. Administration of an IDO1 inhibitor or bacteria engineered to degrade L-kynurenine alleviates mesenteric adipogenesis in mice. Collectively, our study demonstrates that microbiota-induced modulation of macrophage metabolism potentiates CrF formation.
{"title":"Microbiota-induced alteration of kynurenine metabolism in macrophages drives formation of creeping fat in Crohn’s disease","authors":"Jinjie Wu, Wanyi Zeng, Hongyu Xie, Mujia Cao, Jingyi Yang, Yanchun Xie, Zhanhao Luo, Zongjin Zhang, Haoyang Xu, Weidong Huang, Tingyue Zhou, Jinyu Tan, Xiaomin Wu, Zihuan Yang, Shu Zhu, Ren Mao, Zhen He, Ping Lan","doi":"10.1016/j.chom.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.008","url":null,"abstract":"Hyperplasia of mesenteric tissues in Crohn’s disease, called creeping fat (CrF), is associated with surgical recurrence. Although microbiota translocation and colonization have been found in CrF, convincing mouse phenotypes and the underlying mechanisms of CrF formation remain unclear. Utilizing single-nucleus RNA (snRNA) sequencing of CrF and different mouse models, we demonstrate that the commensal <em>Achromobacter pulmonis</em> induces mesenteric adipogenesis through macrophage alteration. Targeted metabolome analysis reveals that L-kynurenine is the most enriched metabolite in CrF. Upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) enhances kynurenine metabolism and drives mesenteric adipogenesis. Leveraging single-cell RNA (scRNA) sequencing of mouse mesenteric tissues and macrophage-specific IDO1 knockout mice, we verify the role of macrophage-sourced L-kynurenine in mesenteric adipogenesis. Mechanistically, L-kynurenine-induced adipogenesis is mediated by the aryl hydrocarbon receptors in adipocytes. Administration of an IDO1 inhibitor or bacteria engineered to degrade L-kynurenine alleviates mesenteric adipogenesis in mice. Collectively, our study demonstrates that microbiota-induced modulation of macrophage metabolism potentiates CrF formation.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"7 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601051","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 : 2024-11-13DOI: 10.1016/j.chom.2024.10.013
Huihui Sun, Guan-Hong Wang
In this issue of Cell Host & Microbe, Zhong et al.1 uncover gut microbiota-host connections that promote cognitive function in honeybees. They discover the role of the microbiota in lipid metabolism and the synthesis of lipid-derived neurotransmitters, which modulate the endocannabinoid system.
{"title":"Microbial alchemists unlock honeybee cognition","authors":"Huihui Sun, Guan-Hong Wang","doi":"10.1016/j.chom.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.013","url":null,"abstract":"In this issue of <em>Cell Host & Microbe</em>, Zhong et al.<span><span><sup>1</sup></span></span> uncover gut microbiota-host connections that promote cognitive function in honeybees. They discover the role of the microbiota in lipid metabolism and the synthesis of lipid-derived neurotransmitters, which modulate the endocannabinoid system.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"36 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601047","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 : 2024-11-13DOI: 10.1016/j.chom.2024.10.005
Cancan Qi, Ri-hua Xie, Yan He, Muxuan Chen
Vaginal lactobacilli are key regulators of host inflammation, yet the mechanisms remain understudied. In this issue of Cell Host & Microbe, Glick et al. identify a family of beta-carbolines as anti-inflammatory effectors produced by vaginal Lactobacillus species, highlighting their potential as therapeutics for vaginal inflammatory disorders.
{"title":"Beta-carbolines suppress vaginal inflammation","authors":"Cancan Qi, Ri-hua Xie, Yan He, Muxuan Chen","doi":"10.1016/j.chom.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.005","url":null,"abstract":"Vaginal lactobacilli are key regulators of host inflammation, yet the mechanisms remain understudied. In this issue of <em>Cell Host & Microbe</em>, Glick et al. identify a family of beta-carbolines as anti-inflammatory effectors produced by vaginal <em>Lactobacillus</em> species, highlighting their potential as therapeutics for vaginal inflammatory disorders.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"95 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601045","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 : 2024-11-07DOI: 10.1016/j.chom.2024.10.012
Molly R. Sargen, Sophie Helaine
Most bacteria are polylysogens that carry multiple prophages integrated into the chromosome. These prophages confer advantages to their bacterial host, yet also pose a lethal threat as they can reactivate and enter a lytic cycle. DNA damage of the bacterial host is a common trigger of prophage lytic cycles. Because DNA damage is frequently experienced by bacterial pathogens exposed to host immune defenses, prophage activation may be common during infection. Investigating the consequences of prophage induction in Salmonella, we discover a prophage competition element in the Gifsy-1 prophage that we name ribonuclease effector module with ATPase, inhibitor, and nuclease (RemAIN) because it blocks the lytic cycles and release of viral particles of co-resident prophages. Intramacrophage Salmonella persisters, a subpopulation that incurs DNA damage, experience prophage reactivation and subsequent RemAIN activation, which influences Salmonella persisters and macrophage response to infection. Our findings reveal a multi-layered host-pathogen arms race in which prophage-prophage competition influences bacterial persistence and the mammalian immune response.
大多数细菌都是多聚原生体，其染色体上集成有多个噬菌体。这些噬菌体给细菌宿主带来优势，但也构成致命威胁，因为它们可以重新激活并进入溶菌循环。细菌宿主的 DNA 受损是噬菌体溶菌循环的常见触发因素。由于细菌病原体经常受到宿主免疫防御系统的 DNA 损伤，因此噬菌体在感染过程中可能会被激活。在研究沙门氏菌噬菌体诱导的后果时，我们在 Gifsy-1 噬菌体中发现了一种噬菌体竞争元件，我们将其命名为具有 ATP 酶、抑制剂和核酸酶的核糖核酸酶效应模块（REMAIN），因为它能阻止共驻噬菌体的溶解循环和病毒颗粒的释放。巨噬细胞内的沙门氏菌宿主是造成 DNA 损伤的亚群，它们会经历噬菌体再激活和随后的 RemAIN 激活，这影响了沙门氏菌宿主和巨噬细胞对感染的反应。我们的研究结果揭示了宿主与病原体之间的多层次军备竞赛，其中噬菌体与巨噬细胞之间的竞争影响了细菌的持久性和哺乳动物的免疫反应。
{"title":"A prophage competition element protects Salmonella from lysis","authors":"Molly R. Sargen, Sophie Helaine","doi":"10.1016/j.chom.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.012","url":null,"abstract":"Most bacteria are polylysogens that carry multiple prophages integrated into the chromosome. These prophages confer advantages to their bacterial host, yet also pose a lethal threat as they can reactivate and enter a lytic cycle. DNA damage of the bacterial host is a common trigger of prophage lytic cycles. Because DNA damage is frequently experienced by bacterial pathogens exposed to host immune defenses, prophage activation may be common during infection. Investigating the consequences of prophage induction in <em>Salmonella</em>, we discover a prophage competition element in the Gifsy-1 prophage that we name ribonuclease effector module with ATPase, inhibitor, and nuclease (RemAIN) because it blocks the lytic cycles and release of viral particles of co-resident prophages. Intramacrophage <em>Salmonella</em> persisters, a subpopulation that incurs DNA damage, experience prophage reactivation and subsequent RemAIN activation, which influences <em>Salmonella</em> persisters and macrophage response to infection. Our findings reveal a multi-layered host-pathogen arms race in which prophage-prophage competition influences bacterial persistence and the mammalian immune response.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"64 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594575","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 : 2024-10-30DOI: 10.1016/j.chom.2024.10.006
Angeli D.G. Macandog, Carlotta Catozzi, Mariaelena Capone, Amir Nabinejad, Padma P. Nanaware, Shujing Liu, Smita Vinjamuri, Johanna A. Stunnenberg, Serena Galiè, Maria Giovanna Jodice, Francesca Montani, Federica Armanini, Ester Cassano, Gabriele Madonna, Domenico Mallardo, Benedetta Mazzi, Salvatore Pece, Maria Tagliamonte, Vito Vanella, Massimo Barberis, Luigi Nezi
Immune checkpoint inhibitors (ICIs) improve outcomes in advanced melanoma, but many patients are refractory or experience relapse. The gut microbiota modulates antitumor responses. However, inconsistent baseline predictors point to heterogeneity in responses and inadequacy of cross-sectional data. We followed patients with unresectable melanoma from baseline and during anti-PD-1 therapy, collecting fecal and blood samples that were surveyed for changes in the gut microbiota and immune markers. Varying patient responses were linked to different gut microbiota dynamics during ICI treatment. We select complete responders by their stable microbiota functions and validate them using multiple external cohorts and experimentally. We identify major histocompatibility complex class I (MHC class I)-restricted peptides derived from flagellin-related genes of Lachnospiraceae (FLach) as structural homologs of tumor-associated antigens, detect FLach-reactive CD8+ T cells in complete responders before ICI therapy, and demonstrate that FLach peptides improve antitumor immunity. These findings highlight the prognostic value of microbial functions and therapeutic potential of tumor-mimicking microbial peptides.
免疫检查点抑制剂（ICIs）可改善晚期黑色素瘤的治疗效果，但许多患者会出现难治性或复发。肠道微生物群调节抗肿瘤反应。然而，不一致的基线预测因素导致了反应的异质性和横断面数据的不足。我们对无法切除的黑色素瘤患者进行了基线和抗PD-1治疗期间的随访，收集粪便和血液样本，调查肠道微生物群和免疫标记物的变化。在 ICI 治疗期间，患者不同的反应与不同的肠道微生物群动态有关。我们通过稳定的微生物群功能筛选出完全应答者，并通过多个外部队列和实验进行验证。我们确定了主要组织相容性复合体 I 类（MHC I 类）限制肽，这些肽来源于拉赫诺斯皮拉科（Lachnospiraceae）鞭毛蛋白相关基因（FLach），是肿瘤相关抗原的结构同源物，在 ICI 治疗前检测到完全应答者中的 FLach 反应性 CD8+ T 细胞，并证明 FLach 肽能提高抗肿瘤免疫力。这些发现凸显了微生物功能的预后价值和仿肿瘤微生物肽的治疗潜力。
{"title":"Longitudinal analysis of the gut microbiota during anti-PD-1 therapy reveals stable microbial features of response in melanoma patients","authors":"Angeli D.G. Macandog, Carlotta Catozzi, Mariaelena Capone, Amir Nabinejad, Padma P. Nanaware, Shujing Liu, Smita Vinjamuri, Johanna A. Stunnenberg, Serena Galiè, Maria Giovanna Jodice, Francesca Montani, Federica Armanini, Ester Cassano, Gabriele Madonna, Domenico Mallardo, Benedetta Mazzi, Salvatore Pece, Maria Tagliamonte, Vito Vanella, Massimo Barberis, Luigi Nezi","doi":"10.1016/j.chom.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.006","url":null,"abstract":"Immune checkpoint inhibitors (ICIs) improve outcomes in advanced melanoma, but many patients are refractory or experience relapse. The gut microbiota modulates antitumor responses. However, inconsistent baseline predictors point to heterogeneity in responses and inadequacy of cross-sectional data. We followed patients with unresectable melanoma from baseline and during anti-PD-1 therapy, collecting fecal and blood samples that were surveyed for changes in the gut microbiota and immune markers. Varying patient responses were linked to different gut microbiota dynamics during ICI treatment. We select complete responders by their stable microbiota functions and validate them using multiple external cohorts and experimentally. We identify major histocompatibility complex class I (MHC class I)-restricted peptides derived from flagellin-related genes of <em>Lachnospiraceae</em> (<em>FLach</em>) as structural homologs of tumor-associated antigens, detect <em>FLach</em>-reactive CD8<sup>+</sup> T cells in complete responders before ICI therapy, and demonstrate that <em>FLach</em> peptides improve antitumor immunity. These findings highlight the prognostic value of microbial functions and therapeutic potential of tumor-mimicking microbial peptides.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"62 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541485","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}
Tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), is a significant health problem worldwide. Here, we developed a method to detect large insertions and deletions (indels), which have been generally understudied. Leveraging this framework, we performed a comprehensive analysis of single nucleotide variants and small and large indels across 1,960 Mtb clinical isolates. Comparing the distribution of variants demonstrated that gene disruptive variants are underrepresented in genes essential for bacterial survival. An evolutionary analysis revealed that Mtb genomes are enriched in partially deleterious mutations. Genome-wide association studies identified small and large deletions in eccB2 significantly associated with patient prognosis. Additionally, we unveil significant associations with antibiotic resistance in 23 non-canonical genes. Among these, large indels are primarily found in genetic regions of Rv1216c, Rv1217c, fadD11, and ctpD. This study provides a comprehensive catalog of genetic variations and highlights their potential impact for the future treatment and risk prediction of tuberculosis.
{"title":"Comprehensive analysis of Mycobacterium tuberculosis genomes reveals genetic variations in bacterial virulence","authors":"Wittawin Worakitchanon, Hideki Yanai, Pundharika Piboonsiri, Reiko Miyahara, Supalert Nedsuwan, Worarat Imsanguan, Boonchai Chaiyasirinroje, Waritta Sawaengdee, Sukanya Wattanapokayakit, Nuanjan Wichukchinda, Yosuke Omae, Prasit Palittapongarnpim, Katsushi Tokunaga, Surakameth Mahasirimongkol, Akihiro Fujimoto","doi":"10.1016/j.chom.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.004","url":null,"abstract":"Tuberculosis, a disease caused by <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>), is a significant health problem worldwide. Here, we developed a method to detect large insertions and deletions (indels), which have been generally understudied. Leveraging this framework, we performed a comprehensive analysis of single nucleotide variants and small and large indels across 1,960 <em>Mtb</em> clinical isolates. Comparing the distribution of variants demonstrated that gene disruptive variants are underrepresented in genes essential for bacterial survival. An evolutionary analysis revealed that <em>Mtb</em> genomes are enriched in partially deleterious mutations. Genome-wide association studies identified small and large deletions in <em>eccB2</em> significantly associated with patient prognosis. Additionally, we unveil significant associations with antibiotic resistance in 23 non-canonical genes. Among these, large indels are primarily found in genetic regions of <em>Rv1216c</em>, <em>Rv1217c</em>, <em>fadD11</em>, and <em>ctpD</em>. This study provides a comprehensive catalog of genetic variations and highlights their potential impact for the future treatment and risk prediction of tuberculosis.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"35 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519560","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 : 2024-10-28DOI: 10.1016/j.chom.2024.10.002
Minwoo Bae, Chi Le, Raaj S. Mehta, Xueyang Dong, Lindsey M. Pieper, Lorenzo Ramirez, Margaret Alexander, Sina Kiamehr, Peter J. Turnbaugh, Curtis Huttenhower, Andrew T. Chan, Emily P. Balskus
Gut microbial catechol dehydroxylases are a largely uncharacterized family of metalloenzymes that potentially impact human health by metabolizing dietary polyphenols. Here, we use metatranscriptomics (MTX) to identify highly transcribed catechol-dehydroxylase-encoding genes in human gut microbiomes. We discover a prevalent, previously uncharacterized catechol dehydroxylase (Gp Hcdh) from Gordonibacter pamelaeae that dehydroxylates hydrocaffeic acid (HCA), an anti-inflammatory gut microbial metabolite derived from plant-based foods. Further analyses suggest that the activity of Gp Hcdh may reduce anti-inflammatory benefits of polyphenol-rich foods. Together, these results show the utility of combining MTX analysis and biochemical characterization for gut microbial enzyme discovery and reveal a potential link between host inflammation and a specific polyphenol-metabolizing gut microbial enzyme.
{"title":"Metatranscriptomics-guided discovery and characterization of a polyphenol-metabolizing gut microbial enzyme","authors":"Minwoo Bae, Chi Le, Raaj S. Mehta, Xueyang Dong, Lindsey M. Pieper, Lorenzo Ramirez, Margaret Alexander, Sina Kiamehr, Peter J. Turnbaugh, Curtis Huttenhower, Andrew T. Chan, Emily P. Balskus","doi":"10.1016/j.chom.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.002","url":null,"abstract":"Gut microbial catechol dehydroxylases are a largely uncharacterized family of metalloenzymes that potentially impact human health by metabolizing dietary polyphenols. Here, we use metatranscriptomics (MTX) to identify highly transcribed catechol-dehydroxylase-encoding genes in human gut microbiomes. We discover a prevalent, previously uncharacterized catechol dehydroxylase (<em>Gp</em> Hcdh) from <em>Gordonibacter pamelaeae</em> that dehydroxylates hydrocaffeic acid (HCA), an anti-inflammatory gut microbial metabolite derived from plant-based foods. Further analyses suggest that the activity of <em>Gp</em> Hcdh may reduce anti-inflammatory benefits of polyphenol-rich foods. Together, these results show the utility of combining MTX analysis and biochemical characterization for gut microbial enzyme discovery and reveal a potential link between host inflammation and a specific polyphenol-metabolizing gut microbial enzyme.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"33 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519563","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 : 2024-10-25DOI: 10.1016/j.chom.2024.10.001
Deborah Häcker, Kolja Siebert, Byron J. Smith, Nikolai Köhler, Alessandra Riva, Aritra Mahapatra, Helena Heimes, Jiatong Nie, Amira Metwaly, Hannes Hölz, Quirin Manz, Federica De Zen, Jeannine Heetmeyer, Katharina Socas, Giang Le Thi, Chen Meng, Karin Kleigrewe, Josch K. Pauling, Klaus Neuhaus, Markus List, Dirk Haller
Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn’s disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with Lachnospiraceae and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free Il10-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles.
纯肠内营养（EEN）是治疗小儿克罗恩病（CD）的一线疗法，但其保护机制尚不清楚。我们建立了一个前瞻性儿科队列，以描述对 EEN（德国临床试验 DRKS00013306）无效的 CD 患者粪便微生物群的功能和代谢物变化。综合多组学分析从个体可变的微生物组图谱中发现了网络集群，Lachnospiraceae 和中链脂肪酸是保护性特征。生物正交非规范氨基酸标记可选择性地识别对中链脂肪酸有反应的细菌物种。元基因组分析确定了对 EEN 反应的高菌株动态。通过肠道恒温培养和将微生物群转移到无菌的Il10缺陷小鼠体内，进一步验证了饮食暴露粪便微生物群的功能变化。饮食模型条件诱导了患者特异性菌株特征，以预防或导致非生物小鼠发生类似炎症性肠病（IBD）的炎症。因此，我们提供的证据表明，EEN疗法是通过明确改变时间和个体可变的微生物组特征来发挥作用的。
{"title":"Exclusive enteral nutrition initiates individual protective microbiome changes to induce remission in pediatric Crohn’s disease","authors":"Deborah Häcker, Kolja Siebert, Byron J. Smith, Nikolai Köhler, Alessandra Riva, Aritra Mahapatra, Helena Heimes, Jiatong Nie, Amira Metwaly, Hannes Hölz, Quirin Manz, Federica De Zen, Jeannine Heetmeyer, Katharina Socas, Giang Le Thi, Chen Meng, Karin Kleigrewe, Josch K. Pauling, Klaus Neuhaus, Markus List, Dirk Haller","doi":"10.1016/j.chom.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.001","url":null,"abstract":"Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn’s disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with <em>Lachnospiraceae</em> and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free <em>Il10</em>-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"97 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489634","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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