iMeta最新文献

筛选
英文 中文
Nano-plastics disrupt systemic metabolism by remodeling the bile acid–microbiota axis and driving hepatic–intestinal dysfunction 纳米塑料通过重塑胆汁酸-微生物群轴和驱动肝肠功能障碍来破坏全身代谢
IF 23.7
iMeta Pub Date : 2026-03-20 Epub Date: 2025-12-31 DOI: 10.1002/imt2.70103
Yi Zhang, Zheng Lin, Runtong Huang, Yang Zhang, Lei Wang, Zan Fu, Chao Wang, Shuai Xiao, Heru Pramono, Kui Xu, Zhimin Xu, Yulong Yin
{"title":"Nano-plastics disrupt systemic metabolism by remodeling the bile acid–microbiota axis and driving hepatic–intestinal dysfunction","authors":"Yi Zhang,&nbsp;Zheng Lin,&nbsp;Runtong Huang,&nbsp;Yang Zhang,&nbsp;Lei Wang,&nbsp;Zan Fu,&nbsp;Chao Wang,&nbsp;Shuai Xiao,&nbsp;Heru Pramono,&nbsp;Kui Xu,&nbsp;Zhimin Xu,&nbsp;Yulong Yin","doi":"10.1002/imt2.70103","DOIUrl":"https://doi.org/10.1002/imt2.70103","url":null,"abstract":"<p>The pervasiveness of microplastic pollution poses a growing health risk, yet its long-term metabolic consequences remain poorly defined. Here, we exposed mice to polyethylene terephthalate nanoparticle (NP) and combined histopathology, biochemistry, metabolomics, and metagenomics to resolve their interactions. NP ingestion induced a severe systemic phenotype characterized by weight loss, organ atrophy, dyslipidemia, and gut barrier collapse. Mechanistically, NPs disrupted bile acid (BA) homeostasis by hyperactivating hepatic synthesis pathways while suppressing microbial 7α-dehydroxylation. This accumulation of cytotoxic BAs drove hepatic lipogenesis and aggravated mucosal inflammation. Crucially, metagenomics uncovered significant gut microbiota dysbiosis, where the enrichment of bile salt hydrolase-encoding taxa and depletion of 7α-dehydroxylating clades reinforced this BA imbalance. Furthermore, the microbiota exhibited functional deterioration, shifting toward glycan degradation with a concurrent loss of antibiotic resistance genes, signaling reduced ecological resilience. These findings identify BA dysregulation and specific microbiota functional losses as primary drivers of NP-induced systemic metabolic collapse.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"5 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147570294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CAT-BLAST: Engineered bacteria for robust targeting and elimination of cancer-associated fibroblasts CAT-BLAST:用于强大靶向和消除癌症相关成纤维细胞的工程细菌
IF 23.7
iMeta Pub Date : 2026-03-20 Epub Date: 2026-01-05 DOI: 10.1002/imt2.70102
Mengdi Xu, Ehsan Hashemi, Hui Gao, Qumar Zaman, Yi Ma, Jufang Wang, Wenjun Mao, Zhuobin Liang
{"title":"CAT-BLAST: Engineered bacteria for robust targeting and elimination of cancer-associated fibroblasts","authors":"Mengdi Xu,&nbsp;Ehsan Hashemi,&nbsp;Hui Gao,&nbsp;Qumar Zaman,&nbsp;Yi Ma,&nbsp;Jufang Wang,&nbsp;Wenjun Mao,&nbsp;Zhuobin Liang","doi":"10.1002/imt2.70102","DOIUrl":"https://doi.org/10.1002/imt2.70102","url":null,"abstract":"<p>Cancer-associated fibroblasts (CAFs) construct a protective stromal barrier that promotes tumor growth and resistance to therapy. To dismantle this, we developed CAT-BLAST, an engineered bacterial platform designed to potently eliminate these cells. We engineered a safe, high-expression <i>E. coli</i> chassis, arming it with a FAP-specific synthetic adhesin for precise CAF targeting and the ability to secrete the ClyA cytotoxin to induce apoptosis in both CAFs and adjacent tumor cells. This platform demonstrated robust, FAP-specific targeting across diverse human tumor xenograft models and achieved significant tumor suppression in both murine colorectal cancer and melanoma.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"5 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147563329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microbial metabolites in tumor epigenetic regulation 微生物代谢物在肿瘤表观遗传调控中的作用
IF 23.7
iMeta Pub Date : 2026-03-20 Epub Date: 2026-03-13 DOI: 10.1002/imt2.70115
Wangzheqi Zhang, Haoling Zhang, Yan Liao, Shuya Jiang, Haolong Zhang, Chenwei Huang, Zhijing Song, Rui Zhao, Ping Lu, Xiaohong Kang, Eryan Kong, Yalin Zhu, Wei Wang, Xuesong Liu, Yisheng Chen, Zhiwen Luo, Zhaoyu Li, Di Wang, Na Xing, Yadong Guo, Jingjing Zhang, Xiaojing Wang, Wenyi Wang, Mowaffaq Adam, Bakiah Shaharuddin, Muhamad Yusri Musa, Doblin Sandai, Chenglong Zhu, Aimin Jiang, Peng Luo, Zhijie Zhao, Zui Zou
{"title":"Microbial metabolites in tumor epigenetic regulation","authors":"Wangzheqi Zhang,&nbsp;Haoling Zhang,&nbsp;Yan Liao,&nbsp;Shuya Jiang,&nbsp;Haolong Zhang,&nbsp;Chenwei Huang,&nbsp;Zhijing Song,&nbsp;Rui Zhao,&nbsp;Ping Lu,&nbsp;Xiaohong Kang,&nbsp;Eryan Kong,&nbsp;Yalin Zhu,&nbsp;Wei Wang,&nbsp;Xuesong Liu,&nbsp;Yisheng Chen,&nbsp;Zhiwen Luo,&nbsp;Zhaoyu Li,&nbsp;Di Wang,&nbsp;Na Xing,&nbsp;Yadong Guo,&nbsp;Jingjing Zhang,&nbsp;Xiaojing Wang,&nbsp;Wenyi Wang,&nbsp;Mowaffaq Adam,&nbsp;Bakiah Shaharuddin,&nbsp;Muhamad Yusri Musa,&nbsp;Doblin Sandai,&nbsp;Chenglong Zhu,&nbsp;Aimin Jiang,&nbsp;Peng Luo,&nbsp;Zhijie Zhao,&nbsp;Zui Zou","doi":"10.1002/imt2.70115","DOIUrl":"https://doi.org/10.1002/imt2.70115","url":null,"abstract":"<p>With an increasing global cancer burden, the regulatory function of the human microbiome and its metabolites in tumor epigenetics has garnered significant interest. Microbial metabolites are not merely passive byproducts but serve as signaling molecules and epigenetic modulators, contributing to tumor progression through multiple overlapping pathways. Short-chain fatty acids (SCFAs) such as butyrate directly inhibit histone deacetylases to reactivate tumor suppressor genes, while secondary bile acids (BAs) induce gene silencing via DNA methylation remodeling by altering the FXR/TGR5 signaling pathway. Folate and vitamin B12 serve as substrates for DNA and histone methylation through one-carbon metabolism. A complex bidirectional feedback loop exists between microbial metabolism and tumor epigenetics: reprogramming driven by hypoxia or oncogenes alters metabolite flux, generating molecules such as lactate and succinate that not only remodel chromatin and the tumor microenvironment (TME) but also selectively promote the growth of metabolically adapted microbial species, thereby reinforcing epigenetic dysregulation. Despite growing mechanistic insights, establishing causality and correlating spatiotemporal dynamics and dose responses within the highly heterogeneous TME remain major challenges. Data integration across multi-omics remains limited by methodological and computational constraints. Resolving these issues will be critical for understanding the microbe–metabolite–epigenetic axis and advancing personalized precision oncology.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"5 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of the gut microbiome in the regulation of high-altitude adaptation 肠道微生物群在高原适应调节中的作用
IF 23.7
iMeta Pub Date : 2026-03-20 Epub Date: 2026-01-19 DOI: 10.1002/imt2.70104
Xinyu Zhang, Senlin Zhu, Michael Kreuzer, Shoukun Ji, Wei Wang, Yanliang Bi, Shengli Li
{"title":"The role of the gut microbiome in the regulation of high-altitude adaptation","authors":"Xinyu Zhang,&nbsp;Senlin Zhu,&nbsp;Michael Kreuzer,&nbsp;Shoukun Ji,&nbsp;Wei Wang,&nbsp;Yanliang Bi,&nbsp;Shengli Li","doi":"10.1002/imt2.70104","DOIUrl":"https://doi.org/10.1002/imt2.70104","url":null,"abstract":"<p>Hypoxia and cold temperatures are major limiting factors for animals reared at high altitudes. Previous adaptation studies have primarily focused on genetic and genomic aspects, while the mechanisms by which the gut microbiome contributes to this adaptation are still not fully understood. We used ruminants as both naturally adapted (yaks) and non-adapted (Holstein cows) models to investigate the role of gut microbiome in high-altitude adaptation by applying multi-omics approaches. First, 20 yaks and 20 Holstein cows that had been reared at approximately 4000 m altitude since birth were fed the same diet for 44 days prior to sampling to eliminate the short-term effects of nutrition and altitude adaptation. The yak rumen microbiome showed significant enrichment in carbon metabolism, particularly central carbon metabolism pathways, such as glycolysis/gluconeogenesis, pyruvate metabolism, and the pentose phosphate pathway, whereas that of Holstein cows was enriched in starch, sucrose, pentose, and glucuronate interconversions. Compared with those of Holstein cows kept at high altitudes for their entire life, the yak rumen epithelial cells, as determined by single-nucleus RNA sequencing, exhibited higher elevated scores for ketone body biosynthesis and fatty acid beta-oxidation. Second, mixed rumen fluid was transplanted from 10 yaks to 10 Holstein cows. Holstein cows then showed better milk production performance. A progressive decline in carbon metabolism activity from 6 h to 7 and 28 days post-transplantation was verified. In conclusion, the rumen microbiome and host epithelial function appear to support high-altitude adaptation by improving the energy supply of the host.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"5 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147566938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of ferroptosis by microbiota-derived lithocholic acid underlies the intestinal radioprotection of a host defensin-derived oligopeptide 微生物来源的石胆酸对铁下垂的抑制是宿主防御素来源的寡肽对肠道辐射保护的基础
IF 23.7
iMeta Pub Date : 2026-03-20 Epub Date: 2026-02-19 DOI: 10.1002/imt2.70113
Xue Ouyang, Yingjuan He, Zihao Jin, Shaobo Wang, Gaomei Zhao, Xiaona Su, Jia Du, Yin Chen, Chengzhang Tan, Xin Li, Songling Han, Bin Wang, Jinghong Zhao, Jianqin Niu, Chuan Chen, Junping Wang, Cheng Wang
{"title":"Inhibition of ferroptosis by microbiota-derived lithocholic acid underlies the intestinal radioprotection of a host defensin-derived oligopeptide","authors":"Xue Ouyang,&nbsp;Yingjuan He,&nbsp;Zihao Jin,&nbsp;Shaobo Wang,&nbsp;Gaomei Zhao,&nbsp;Xiaona Su,&nbsp;Jia Du,&nbsp;Yin Chen,&nbsp;Chengzhang Tan,&nbsp;Xin Li,&nbsp;Songling Han,&nbsp;Bin Wang,&nbsp;Jinghong Zhao,&nbsp;Jianqin Niu,&nbsp;Chuan Chen,&nbsp;Junping Wang,&nbsp;Cheng Wang","doi":"10.1002/imt2.70113","DOIUrl":"https://doi.org/10.1002/imt2.70113","url":null,"abstract":"<p>Ionizing radiation-induced intestinal injury (IRIII) reduces survival in nuclear accident victims and compromises the efficacy of abdominal radiotherapy, and current treatment options remain limited. Human defensin 5 (HD5)-derived fragments are endogenous regulators of the gut microbiota, which affects host responses to radiation. However, whether these fragments influence intestinal radiosensitivity or can serve as lead compounds for IRIII therapeutics remains unclear. In this study, we investigated the role of HD5-derived fragments in IRIII and developed AT9(C/G), a potent radioprotective oligopeptide based on the lead fragment AT9. Fecal metagenomic and metabolomic analyses revealed that the oral administration of AT9(C/G) enriches <i>Bifidobacterium pseudolongum</i> and increases lithocholic acid (LCA) levels in the intestine. Both murine and clinical studies demonstrated a negative correlation between IRIII severity and fecal LCA levels. The radioprotective effect of LCA was further validated in both mouse models and human small intestinal organoids. Mechanistically, LCA suppresses ferroptosis in irradiated cells by remodeling lipid metabolism. Specifically, LCA activates Takeda G protein-coupled receptor 5 (TGR5), leading to the upregulation of sterol regulatory element-binding protein 1 (SREBP1), which transcriptionally modulates stearoyl-CoA desaturase 1 (SCD1) to catalyze monounsaturated fatty acid production. Pharmacological inhibition of SCD1 or genetic ablation of G-protein coupled bile acid receptor 1 (<i>Gpbar1</i>, encodes TGR5) attenuates the protective effects of AT9(C/G) in mice. This study establishes that an oligopeptide can modulate gut microbiota-derived LCA to confer intestinal radioprotection, presenting a promising preventive strategy against IRIII.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"5 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147567044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Embracing the Dragon-Horse Spirit: Gratitude and forward momentum 拥抱龙马精神:感恩与前进
IF 23.7
iMeta Pub Date : 2026-03-20 Epub Date: 2026-02-08 DOI: 10.1002/imt2.70110
Yong-Xin Liu, Yunyun Gao, Tong Chen, Danyi Li, Canhui Lan, Chun-Lin Shi, Jingyuan Fu, Shuang-Jiang Liu
{"title":"Embracing the Dragon-Horse Spirit: Gratitude and forward momentum","authors":"Yong-Xin Liu,&nbsp;Yunyun Gao,&nbsp;Tong Chen,&nbsp;Danyi Li,&nbsp;Canhui Lan,&nbsp;Chun-Lin Shi,&nbsp;Jingyuan Fu,&nbsp;Shuang-Jiang Liu","doi":"10.1002/imt2.70110","DOIUrl":"https://doi.org/10.1002/imt2.70110","url":null,"abstract":"<p>Dragon-Horse Spirit: A metaphor for a person's vigorous and enterprising spirit and demeanor. Inspired by this spirit, iMeta and its sister journals have achieved a series of groundbreaking advancements in submission and impact over the past 4 years. As the Chinese Year of the Horse is coming, we extend our gratitude to all the editorial board members, associate editors, youth editors, and reviewers who have contributed to the development of iMeta series.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"5 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147563886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Construction of a clickable probe-based protein chip platform for discovering covalent mIDH1 inhibitors from natural medicinal extracts 构建可点击探针蛋白芯片平台,用于从天然药物提取物中发现共价mIDH1抑制剂
IF 23.7
iMeta Pub Date : 2026-03-20 Epub Date: 2026-02-12 DOI: 10.1002/imt2.70107
Zhao Cui, Jiameng Li, Caifeng Li, Mo Sun, Wei Liu, Xuxia Cao, Shiwen Deng, Junxian Cao, Hongjun Yang, Peng Chen
{"title":"Construction of a clickable probe-based protein chip platform for discovering covalent mIDH1 inhibitors from natural medicinal extracts","authors":"Zhao Cui,&nbsp;Jiameng Li,&nbsp;Caifeng Li,&nbsp;Mo Sun,&nbsp;Wei Liu,&nbsp;Xuxia Cao,&nbsp;Shiwen Deng,&nbsp;Junxian Cao,&nbsp;Hongjun Yang,&nbsp;Peng Chen","doi":"10.1002/imt2.70107","DOIUrl":"https://doi.org/10.1002/imt2.70107","url":null,"abstract":"<p>The early discovery of covalent drugs is frequently inspired by, or derived from, natural sources, with such compounds often showing favorable safety profiles and a comparatively lower risk of clinical failure. However, a straightforward, high-throughput technique for screening covalent-binding molecules directly from complex medicinal plant extracts remains unavailable. In this study, we introduce an integrated strategy that combines protein microarrays with bioorthogonal click chemistry (Ccc-Chip). This platform includes a differential scanning fluorimetry (DSF)-based pre-screening step to enhance efficiency, with the Ccc-Chip serving as the core confirmation tool. It provides simple and intuitive readouts, enabling synchronous, high-throughput screening of covalent ligands targeting multiple proteins through detection of their competitive binding with cysteine-reactive probes. To validate the approach, we constructed a mutant isocitrate dehydrogenase 1 (mIDH1) protein microarray and used the integrated workflow to screen 110 medicinal plants. Our results led to the identification of flavokawain C (Flc), a covalent inhibitor of mIDH1, from <i>Piper methysticum</i> Forst. Subsequent in vivo experiments showed that Flc significantly reduced 2-hydroxyglutarate (2-HG) levels in an mIDH1-driven orthotopic tumor model and enhanced CD8⁺ T cell activity. Notably, when combined with a programmed cell death protein 1 (PD-1) blocking antibody, Flc synergistically augmented antitumor immunity, resulting in suppressed tumor growth. This work not only supports the high-throughput utility of the Ccc-Chip strategy but also provides a practical framework for combining bioorthogonal labeling with protein microarray technology, facilitating the discovery of bioactive covalent molecules from plant sources for challenging therapeutic targets.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"5 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of ferroptosis by microbiota-derived lithocholic acid underlies the intestinal radioprotection of a host defensin-derived oligopeptide 微生物来源的石胆酸对铁下垂的抑制是宿主防御素来源的寡肽对肠道辐射保护的基础
IF 23.7
iMeta Pub Date : 2026-03-20 Epub Date: 2026-02-19 DOI: 10.1002/imt2.70113
Xue Ouyang, Yingjuan He, Zihao Jin, Shaobo Wang, Gaomei Zhao, Xiaona Su, Jia Du, Yin Chen, Chengzhang Tan, Xin Li, Songling Han, Bin Wang, Jinghong Zhao, Jianqin Niu, Chuan Chen, Junping Wang, Cheng Wang
{"title":"Inhibition of ferroptosis by microbiota-derived lithocholic acid underlies the intestinal radioprotection of a host defensin-derived oligopeptide","authors":"Xue Ouyang,&nbsp;Yingjuan He,&nbsp;Zihao Jin,&nbsp;Shaobo Wang,&nbsp;Gaomei Zhao,&nbsp;Xiaona Su,&nbsp;Jia Du,&nbsp;Yin Chen,&nbsp;Chengzhang Tan,&nbsp;Xin Li,&nbsp;Songling Han,&nbsp;Bin Wang,&nbsp;Jinghong Zhao,&nbsp;Jianqin Niu,&nbsp;Chuan Chen,&nbsp;Junping Wang,&nbsp;Cheng Wang","doi":"10.1002/imt2.70113","DOIUrl":"https://doi.org/10.1002/imt2.70113","url":null,"abstract":"<p>Ionizing radiation-induced intestinal injury (IRIII) reduces survival in nuclear accident victims and compromises the efficacy of abdominal radiotherapy, and current treatment options remain limited. Human defensin 5 (HD5)-derived fragments are endogenous regulators of the gut microbiota, which affects host responses to radiation. However, whether these fragments influence intestinal radiosensitivity or can serve as lead compounds for IRIII therapeutics remains unclear. In this study, we investigated the role of HD5-derived fragments in IRIII and developed AT9(C/G), a potent radioprotective oligopeptide based on the lead fragment AT9. Fecal metagenomic and metabolomic analyses revealed that the oral administration of AT9(C/G) enriches <i>Bifidobacterium pseudolongum</i> and increases lithocholic acid (LCA) levels in the intestine. Both murine and clinical studies demonstrated a negative correlation between IRIII severity and fecal LCA levels. The radioprotective effect of LCA was further validated in both mouse models and human small intestinal organoids. Mechanistically, LCA suppresses ferroptosis in irradiated cells by remodeling lipid metabolism. Specifically, LCA activates Takeda G protein-coupled receptor 5 (TGR5), leading to the upregulation of sterol regulatory element-binding protein 1 (SREBP1), which transcriptionally modulates stearoyl-CoA desaturase 1 (SCD1) to catalyze monounsaturated fatty acid production. Pharmacological inhibition of SCD1 or genetic ablation of G-protein coupled bile acid receptor 1 (<i>Gpbar1</i>, encodes TGR5) attenuates the protective effects of AT9(C/G) in mice. This study establishes that an oligopeptide can modulate gut microbiota-derived LCA to confer intestinal radioprotection, presenting a promising preventive strategy against IRIII.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"5 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147567043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Host-driven hepatic conversion of gut microbiota-derived putrescine to spermidine mediates mannose's protective effects against hepatic steatosis in zebrafish 宿主驱动的肠道微生物源腐胺向亚精胺的肝脏转化介导甘露糖对斑马鱼肝脂肪变性的保护作用
IF 23.7
iMeta Pub Date : 2026-03-20 Epub Date: 2025-12-20 DOI: 10.1002/imt2.70101
Delong Meng, Zhen Zhang, Tsegay Teame, Benjamin Earl Niemann, Rui Xia, Shichang Xu, Yajie Zhao, Yalin Yang, Chao Ran, Le Luo Guan, Zhigang Zhou
{"title":"Host-driven hepatic conversion of gut microbiota-derived putrescine to spermidine mediates mannose's protective effects against hepatic steatosis in zebrafish","authors":"Delong Meng,&nbsp;Zhen Zhang,&nbsp;Tsegay Teame,&nbsp;Benjamin Earl Niemann,&nbsp;Rui Xia,&nbsp;Shichang Xu,&nbsp;Yajie Zhao,&nbsp;Yalin Yang,&nbsp;Chao Ran,&nbsp;Le Luo Guan,&nbsp;Zhigang Zhou","doi":"10.1002/imt2.70101","DOIUrl":"https://doi.org/10.1002/imt2.70101","url":null,"abstract":"<p>Evidence for liver metabolism of gut-derived microbial compounds into beneficial secondary metabolites has been lacking. Here, we demonstrate that <i>Cetobacterium somerae</i> (<i>C. somerae</i>), enriched by mannose supplementation under high-fat diet conditions, convert arginine into putrescine. The liver subsequently converts this microbial-derived putrescine to spermidine, which functions as an effector molecule to reduce hepatic lipid accumulation. These findings uncover a novel host-microbiota collaborative mechanism in which the arginine-putrescine-spermidine metabolic pathway is completed through inter-kingdom cooperation to ameliorate hepatic steatosis.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"5 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147567323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Majorbio Cloud 2026 provides comprehensive analysis workflows for microbiome Majorbio Cloud 2026提供全面的微生物组分析工作流程
IF 23.7
iMeta Pub Date : 2026-03-20 Epub Date: 2026-02-05 DOI: 10.1002/imt2.70109
Jianhua Zhao, Linmeng Liu, Jichen Han, Junbiao Zhang, Xiaodan Li, Yan Wang, Qianhui Han, Xue Gong, Linna Zhang, Hao Gao, Bing Yang, Yachen Dong, Huasheng Huang, Xianglin Zhang, Kegang Yu
{"title":"Majorbio Cloud 2026 provides comprehensive analysis workflows for microbiome","authors":"Jianhua Zhao,&nbsp;Linmeng Liu,&nbsp;Jichen Han,&nbsp;Junbiao Zhang,&nbsp;Xiaodan Li,&nbsp;Yan Wang,&nbsp;Qianhui Han,&nbsp;Xue Gong,&nbsp;Linna Zhang,&nbsp;Hao Gao,&nbsp;Bing Yang,&nbsp;Yachen Dong,&nbsp;Huasheng Huang,&nbsp;Xianglin Zhang,&nbsp;Kegang Yu","doi":"10.1002/imt2.70109","DOIUrl":"https://doi.org/10.1002/imt2.70109","url":null,"abstract":"<p>The integrated microbiome data analysis platform on Majorbio Cloud (https://cloud.majorbio.com/) encompasses 26 analytical workflows, with a core architecture of two modules: single-omics workflows and cross-omics integration and correlation workflows. The platform supports multi-scale microbiome research (strain to community levels) and cross-omics analyses spanning DNA, RNA, protein, and metabolite layers. The platform features four key functions: (1) Application guide, streamlines analytical workflows for user convenience; (2) Default analysis parameters and one-click analysis, enables one-step data processing; (3) One-click plot enhancement, optimizes figures to meet academic publication standards; (4) Plot patchwork feature, stores optimized images in my gallery, facilitates the creation of publication-ready image composites, supports composite downloads in PDF/PNG/SVG formats, and allows the preservation of patchwork templates for subsequent applications. By late 2025, the platform has facilitated over 5,050 scientific publications, accelerating microbiome research advances.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"5 1","pages":""},"PeriodicalIF":23.7,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147563192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信
小红书