Xingzhen Yang, Jiale Wang, Xinyu Qi, Menglong Hou, Mengkuan Liu, Yang Xiao, Siqi Liu, Jinfeng Zhou, Jingsu Yu, Yang Wang, Guo Chen, Lin Yu, Khongorzul Batchuluun, Batbold Batsaikhan, Turtushikh Damba, Yuehui Liang, Xue Liang, Jie Ma, Yunxiao Liang, Yixing Li, Lei Zhou
{"title":"HLF and PPARα axis regulates metabolic-associated fatty liver disease through extracellular vesicles derived from the intestinal microbiota","authors":"Xingzhen Yang, Jiale Wang, Xinyu Qi, Menglong Hou, Mengkuan Liu, Yang Xiao, Siqi Liu, Jinfeng Zhou, Jingsu Yu, Yang Wang, Guo Chen, Lin Yu, Khongorzul Batchuluun, Batbold Batsaikhan, Turtushikh Damba, Yuehui Liang, Xue Liang, Jie Ma, Yunxiao Liang, Yixing Li, Lei Zhou","doi":"10.1002/imt2.70022","DOIUrl":"https://doi.org/10.1002/imt2.70022","url":null,"abstract":"<p>Metabolic-associated fatty liver disease (MAFLD) has become increasingly widespread. The intestine is the primary site of lipid absorption and is important for the homeostasis of lipid metabolism. However, the mechanism underlying the participation of the intestinal tract in the development of MAFLD requires additional investigation. In this study, analysis of the single-cell transcriptome of intestinal tissue from cynomolgus monkeys found that hepatic leukemia factor (HLF) participated in the genetic regulation of intestinal lipid absorption. Results obtained from normal and intestine-specific <i>Hlf</i>-knockout mice confirmed that HLF alleviated intestinal barrier disorders by inhibiting peroxisome proliferator-activated receptor alpha (PPARα) expression. The HLF/PPARα axis alleviated MAFLD by mediating gut microbiota-derived extracellular vesicles (fEVs), thereby inhibiting hepatocyte ferroptosis. Lipidomics and functional experiments verified that taurochenodeoxycholic acid (TCDCA), a conjugated bile acid contained in the fEVs, had a key role in the process. In conclusion, intestinal HLF activity was mediated by fEVs and identified as a novel therapeutic target for MAFLD.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 2","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826653","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}
Wencheng Zong, Li Chen, Dongjie Zhang, Yuebo Zhang, Jinbu Wang, Xinhua Hou, Jie Chai, Yalong An, Ming Tian, Xinmiao He, Chengyi Song, Jun He, Xin Liu, Ligang Wang, Enrico D'Alessandro, Lixian Wang, Yulong Yin, Mingzhou Li, Di Liu, Jinyong Wang, Longchao Zhang
{"title":"Two telomere-to-telomere pig genome assemblies and pan-genome analyses provide insights into genomic structural landscape and genetic adaptations","authors":"Wencheng Zong, Li Chen, Dongjie Zhang, Yuebo Zhang, Jinbu Wang, Xinhua Hou, Jie Chai, Yalong An, Ming Tian, Xinmiao He, Chengyi Song, Jun He, Xin Liu, Ligang Wang, Enrico D'Alessandro, Lixian Wang, Yulong Yin, Mingzhou Li, Di Liu, Jinyong Wang, Longchao Zhang","doi":"10.1002/imt2.70013","DOIUrl":"https://doi.org/10.1002/imt2.70013","url":null,"abstract":"<p>This study presented two high-precision telomere-to-telomere genome assemblies for Min and Rongchang pigs, including a detailed exploration of the telomeric and centromeric regions. By integrating pan-genome and multi-omics analyses, structural variations linked to genetic adaptation were identified, providing a valuable resource for advancing pig breeding and genetic improvement.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 2","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826854","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}
Jialu Shi, Wenjun Mao, Yuqing Song, Yuxin Wang, Lili Zhang, Yan Xu, Huiwen Gu, Siyu Yao, Yuanhang Yao, Zhifeng Liu, Vijaya Raghavan, Jin Wang
{"title":"Butyrate alleviates food allergy by improving intestinal barrier integrity through suppressing oxidative stress-mediated Notch signaling","authors":"Jialu Shi, Wenjun Mao, Yuqing Song, Yuxin Wang, Lili Zhang, Yan Xu, Huiwen Gu, Siyu Yao, Yuanhang Yao, Zhifeng Liu, Vijaya Raghavan, Jin Wang","doi":"10.1002/imt2.70024","DOIUrl":"https://doi.org/10.1002/imt2.70024","url":null,"abstract":"<p>Food allergy (FA) has received increased attention in recent years. Multiple studies have highlighted the crucial role of short-chain fatty acids (SCFAs) in the development of IgE-mediated FA. Here, a case-control approach was employed to analyze SCFAs profiles in children with FA, while an ovalbumin (OVA)-sensitized mouse model was utilized to explore the underlying mechanism by which SCFAs mitigate FA. Children with food-sensitized tolerance (FST) (<i>n</i> = 20) or FA (<i>n</i> = 20), and healthy controls (HC) (<i>n</i> = 20) were recruited to analyze SCFAs profiles. The HC group exhibited higher SCFAs levels in fecal samples than the FST, FA, and FST + FA groups. Data from an OVA-sensitized mouse model showed that butyrate exhibited a more significant effect on reducing allergic reactions compared to other SCFAs. Compared to the negative control group, OVA-induced oxidative stress (OS) triggered excessive Notch signaling activation, which subsequently impaired both tight junctions integrity and mucosal barrier function in murine intestinal epithelial cells (IECs). Gut dysbiosis induced mucus layer erosion, thereby elevating IECs exposure to food antigens and OS, which potentiated Notch signaling activation. However, butyrate counteracted this loop by restoring microbiota structure and suppressing reactive oxygen species (ROS)/Notch cascades. Strikingly, low-dose butyrate (0.25–1 mM) protected rat small intestine crypt epithelial cells (IEC-6) by inhibiting ROS, whereas high-dose (2–5 mM) exacerbated oxidative injury and triggered activation of Notch signaling. Our study revealed the potential molecular mechanisms through which butyrate alleviates food allergy, providing a potential therapeutic strategy for its management.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 3","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197137","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}
{"title":"The impact of school heavy metal exposure on children's gut microbiota: The mediating role of environmental microorganisms","authors":"Yuchen Zou, Menglong Li, Tuerxunayi Abudumijiti, Huiming He, Mengying Guan, Yeerlin Asihaer, Miao Li, Nourhan M. Khattab, Mushui Shu, Yifei Hu","doi":"10.1002/imt2.70021","DOIUrl":"https://doi.org/10.1002/imt2.70021","url":null,"abstract":"<p>Heavy metals are toxic and harmful pollutants that can affect the school environment and the exposed children's health. This study collected dust samples and children's fecal specimens, and performed gene sequencing. We used eXtreme Gradient Boosting to determine the impact of heavy metals on environmental microorganisms and gut microbiota, while using the relative length of the quadrant and Fourth-corner analysis to explore the relationship among the three components. We found heavy metal pollution existed in the classroom environment, with lead and copper significantly affecting environmental microorganisms' community structure. Although nonsignificant associations were observed between heavy metals and gut microbiota, Fourth-corner analysis revealed the associations were significantly mediated by environmental microorganisms. Both heavy metals and microorganisms in the environment can disrupt the microbial community structure in the intestines of exposed children.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 2","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826972","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}
{"title":"MDIPID: Microbiota-drug interaction and disease phenotype interrelation database","authors":"Jiayi Yin, Hui Ma, Yuting Qi, Qingwei Zhao, Su Zeng, Fengcheng Li, Feng Zhu","doi":"10.1002/imt2.70019","DOIUrl":"https://doi.org/10.1002/imt2.70019","url":null,"abstract":"<p>The intricate bidirectional relationships among microbiota, microbial proteins, drugs, and diseases are essential for advancing precision medicine and minimizing adverse drug reactions. However, there are currently no data resources that comprehensively describe these valuable interactions. Therefore, the Microbiota-Drug Interaction and Disease Phenotype Interrelation Database (MDIPID) database was developed in this study. MDIPID is distinctive in its ability to elucidate the complex interactions among microbiota, microbial proteins, drugs/substances, and disease phenotypes, thereby providing a comprehensive interconnected network that facilitates the identification of microbial therapy targets and advances personalized medicine. This comprehensive resource is expected to become a popular repository for researchers aiming to identify microbial therapeutic targets, predict drug efficacy, and develop new therapies, thereby facilitating the advancement of personalized medicine. MDIPID can be accessed free without any login requirement at: https://idrblab.org/mdipid/.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 2","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826742","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}
{"title":"New insights into genome assembly at the chromosome-level of Prunus tomentosa in evolution and cold tolerance","authors":"Songtao Jiu, Muhammad Aamir Manzoor, Zhengxin Lv, Baozheng Chen, Shaoqin Shen, Yan Xu, Moyang Liu, Chengwei Li, Xunju Liu, Yanhong Fu, Qijing Zhang, Ruie Liu, Xinyu Zhang, Shiping Wang, Xiaoming Song, Yang Dong, Caixi Zhang","doi":"10.1002/imt2.70016","DOIUrl":"https://doi.org/10.1002/imt2.70016","url":null,"abstract":"<p>This study assembled a high-quality chromosome-level genome of <i>Prunus tomentosa</i>, offering a vital resource for elucidating its genetic architecture, evolutionary relationships, and facilitating genome-assisted breeding efforts. Multi-omics integration revealed <i>PtIMP3</i> and <i>PtMIOX1L</i> as key factors in cold tolerance of <i>P. tomentosa</i>. <i>PtIMP3</i> drives the conversion of glucose-6-phosphate to <i>myo</i>-inositol, while <i>PtMIOX1L</i> catalyzes <i>myo</i>-inositol to <span>d</span>-glucuronic acid. Specifically, the high expression abundance of <i>PtIMP3</i> and low expression abundance of <i>PtMIOX1L</i> resulted in high endogenous inositol levels in <i>P. tomentosa</i>. The application of <i>myo</i>-inositol enhanced the cold tolerance of cherry rootstocks by modulating reactive oxygen species concentrations and maintaining a stable relative water content. This finding supports the superior performance of <i>P. tomentosa</i> in adapting to extreme low-temperatures environmental conditions. These insights advance strategies for improving cold tolerance in horticultural crops, bridging fundamental research with practical applications in developing climate-resilient crops.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 2","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826710","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}
{"title":"Gut microbiota in cancer: From molecular mechanisms to precision medicine applications","authors":"Weihua Xiao, Qiong Chen, Chunjiao Liu, Yueer Yu, Tianliang Liu, Yang Jin, Haifen Ma, Shifu Chen, Chao Jiang","doi":"10.1002/imt2.70017","DOIUrl":"https://doi.org/10.1002/imt2.70017","url":null,"abstract":"<p>The gut microbiota–cancer interaction functions through multi-level biological mechanisms, forming the basis for both diagnostic and therapeutic applications. Current technical and biological challenges drive the field toward precision medicine approaches, aiming to integrate multi-dimensional data for optimized, personalized cancer treatments.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 2","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827051","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}
{"title":"Tidyplots empowers life scientists with easy code-based data visualization","authors":"Jan Broder Engler","doi":"10.1002/imt2.70018","DOIUrl":"https://doi.org/10.1002/imt2.70018","url":null,"abstract":"<p>Code-based data visualization is a crucial tool for understanding and communicating experimental findings while ensuring scalability and reproducibility. However, complex programming interfaces pose a significant barrier for life scientists. To address this challenge, tidyplots provides a user-friendly code-based interface for creating customizable and insightful plots. With its consistent and intuitive syntax, tidyplots empowers researchers to leverage automated data visualization pipelines while minimizing required programming skills.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 2","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827053","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}
{"title":"Preconception maternal gut dysbiosis affects enteric nervous system development and disease susceptibility in offspring via the GPR41–GDNF/RET/SOX10 signaling pathway","authors":"Cunzheng Zhang, Yuzhu Chen, Ruqiao Duan, Yiming Zhang, Haonan Zheng, Jindong Zhang, Tao Zhang, Jingxian Xu, Kailong Li, Fei Pei, Liping Duan","doi":"10.1002/imt2.70012","DOIUrl":"https://doi.org/10.1002/imt2.70012","url":null,"abstract":"<p>Maternal health, specifically changes in the gut microbiota, can profoundly impact offspring health; however, our understanding of how gut microbiota alterations during the preconception period influence the offspring remains limited. In this study, we investigated the impact and mechanisms of preconception maternal gut dysbiosis on the development of the enteric nervous system (ENS) in mice. We found that preconception maternal exposure to antibiotics led to the abnormal development of the ENS in offspring, increasing their susceptibility to water avoidance stress at the adult stage. Metagenomic, targeted metabolomic, and transcriptomic analyses revealed that preconception antibiotic exposure disrupted the expression of genes crucial for embryonic ENS development by altering maternal gut microbiota composition. Multi-omics analysis combined with <i>Limosilactobacillus reuteri</i> and propionate gestational supplementation demonstrated that the maternal gut microbiota and metabolites may influence embryonic ENS development via the GPR41–GDNF/RET/SOX10 signaling pathway. Our findings highlight the critical importance of maintaining a healthy maternal gut microbiota before conception to support normal ENS development in offspring.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":"4 2","pages":""},"PeriodicalIF":23.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827048","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}