The gut microbiota acts as a crucial mediator in the interaction between the diet components and the host metabolism. However, the molecular mechanism by which the gut microbiota adapts to dietary components and subsequently regulates host physiological responses remains unclear.
Objectives
This study aimed to investigate the response of gut microbiota to a plant-based protein diet (soybean meal, SM) and the effects of gut microbiota on host intestinal barrier function, along with the underlying mechanisms in a fish model.
Methods
Histopathological examination, and transepithelial electrical resistance test were used to evaluate the effects of Cetobacterium somerae on intestinal barrier function. Potential molecular mechanisms were validated by integrating whole-genome sequencing, microbiota composition sequencing, transcriptomics, and metabolomics, and utilizing in vitro cell models and mouse-derived organoid models.
Results
The results revealed that the SM diet significantly increased the abundance of Cetobacterium somerae in fish. Administration of C.somerae ZNN-1, a dominant strain isolated from the intestine of fish fed with the SM diet, enhanced the intestinal barrier function, particularly increasing the number of goblet cells in the intestine. Whole genome analysis of C. somerae ZNN-1 showed carbohydrate metabolism-associated genes were the most abundant in its metabolic modules. C.somerae ZNN-1 supplementation significantly inhibited the Notch signaling pathway in fish intestine. Metabolomics analysis revealed that administration of C.somerae ZNN-1 increased the glutamine level in fish gut. In vitro experiments demonstrated that glutamine regulated the differentiation of goblet cell by inhibiting the Notch signaling pathway in both human intestinal epithelial cell model and mouse intestinal organoid model.
Conclusion
C. somerae served as a key bacterium adapted to soybean meal-derived carbohydrates, and it promoted goblet cell differentiation by inhibiting the Notch pathway. This study provides a new perspective for unraveling the interaction mechanisms among diet components, intestinal microbiota and host health.
{"title":"Cetobacterium somerae ZNN-1 promotes goblet cell differentiation through glutamine-mediated Notch signaling suppression","authors":"Nan-Nan Zhou, Jun-Xi Liu, Tong Wang, , Lu-Kuan Li, Fang Qiao, Zhen-Yu Du, Mei-Ling Zhang","doi":"10.1016/j.jare.2025.12.046","DOIUrl":"https://doi.org/10.1016/j.jare.2025.12.046","url":null,"abstract":"<h3>Introduction</h3>The gut microbiota acts as a crucial mediator in the interaction between the diet components and the host metabolism. However, the molecular mechanism by which the gut microbiota adapts to dietary components and subsequently regulates host physiological responses remains unclear.<h3>Objectives</h3>This study aimed to investigate the response of gut microbiota to a plant-based protein diet (soybean meal, SM) and the effects of gut microbiota on host intestinal barrier function, along with the underlying mechanisms in a fish model.<h3>Methods</h3>Histopathological examination, and transepithelial electrical resistance test were used to evaluate the effects of <em>Cetobacterium somerae</em> on intestinal barrier function. Potential molecular mechanisms were validated by integrating whole-genome sequencing, microbiota composition sequencing, transcriptomics, and metabolomics, and utilizing <em>in vitro</em> cell models and mouse-derived organoid models.<h3>Results</h3>The results revealed that the SM diet significantly increased the abundance of <em>Cetobacterium somerae</em> in fish. Administration of <em>C.somerae</em> ZNN-1, a dominant strain isolated from the intestine of fish fed with the SM diet, enhanced the intestinal barrier function, particularly increasing the number of goblet cells in the intestine. Whole genome analysis of <em>C. somerae</em> ZNN-1 showed carbohydrate metabolism-associated genes were the most abundant in its metabolic modules. <em>C.somerae</em> ZNN-1 supplementation significantly inhibited the Notch signaling pathway in fish intestine. Metabolomics analysis revealed that administration of <em>C.somerae</em> ZNN-1 increased the glutamine level in fish gut. In <em>vitro</em> experiments demonstrated that glutamine regulated the differentiation of goblet cell by inhibiting the Notch signaling pathway in both human intestinal epithelial cell model and mouse intestinal organoid model.<h3>Conclusion</h3><em>C. somerae</em> served as a key bacterium adapted to soybean meal-derived carbohydrates, and it promoted goblet cell differentiation by inhibiting the Notch pathway. This study provides a new perspective for unraveling the interaction mechanisms among diet components, intestinal microbiota and host health.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"169 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-28DOI: 10.1016/j.jare.2025.12.044
Zijian Kang, Jianzheng Zhang, Chen Zhu, Edward CH Lau, Ying Zhu, Ping Li, Kai Li, Qiang Tong, Sheng-Ming Dai
{"title":"Plasma proteomics mediate the association between degenerative joint diseases and dementia risk","authors":"Zijian Kang, Jianzheng Zhang, Chen Zhu, Edward CH Lau, Ying Zhu, Ping Li, Kai Li, Qiang Tong, Sheng-Ming Dai","doi":"10.1016/j.jare.2025.12.044","DOIUrl":"https://doi.org/10.1016/j.jare.2025.12.044","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-27DOI: 10.1016/j.jare.2025.12.032
Chunying Sun, Jingwen Zhu, Xueyuan Sun, Zhidong Zhang, Yantong Sun, Yan Jin, Tao Wu
{"title":"Targeting the human gut microbiome: a comparative review of probiotics, prebiotics, synbiotics, and postbiotics","authors":"Chunying Sun, Jingwen Zhu, Xueyuan Sun, Zhidong Zhang, Yantong Sun, Yan Jin, Tao Wu","doi":"10.1016/j.jare.2025.12.032","DOIUrl":"https://doi.org/10.1016/j.jare.2025.12.032","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"22 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-27DOI: 10.1016/j.jare.2025.12.037
Ruomeng Li, Xueyin Wu, Jing Yao, Jiawen Chen, Xindong Shui, Xiaoqing Zheng, Wujin Tian, Long Wang, Ying Zhou, Tao Zhang, Dongmei Chen, Yang Liu, Tae Ho Lee
{"title":"Selective degradation of DAPK1 via a novel hydrophobic tagging attenuates tau pathology in Alzheimer’s disease","authors":"Ruomeng Li, Xueyin Wu, Jing Yao, Jiawen Chen, Xindong Shui, Xiaoqing Zheng, Wujin Tian, Long Wang, Ying Zhou, Tao Zhang, Dongmei Chen, Yang Liu, Tae Ho Lee","doi":"10.1016/j.jare.2025.12.037","DOIUrl":"https://doi.org/10.1016/j.jare.2025.12.037","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"30 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-27DOI: 10.1016/j.jare.2025.12.035
Cunhu Wang, Di Li, Hao Mei, Xu Zhao, Lin Wang, Xiao Xu, Zhongwei Li, Xinghua Zhang, Hong Liao, Yongjia Zhong
Microbiota-mediated nutrient turnover in the rhizosphere determines nutrient bioavailability, thereby enhancing nutrient uptake, utilization, and ultimately crop productivity. Consequently, elucidating the functional core microbiota in rhizosphere nutrient turnover is of critical importance. In this study, we leveraged soybean germplasm core collections to investigate the tripartite relationship among host genotype, core microbiota and nutrient availability, with a focus on delineating the pivotal role of core microbiota in nutrient turnover. Our results suggest that phylogenetic variation significantly shape root-associated microbial communities and rhizosphere nutrient availability, explaining 11.75 % and 2.07 % of total variances, respectively. Core microbiota analysis identified 29 phylogenetic conserved core amplicon sequence variants (ASVs), the majority of which exhibited significant correlated with nutrient availability. Notably, three key core ASVs—ASV13, ASV14 and ASV12, positively correlated with alkali-hydrolyzed nitrogen, available phosphorus, and soil organic matter, respectively. These taxa were subsequently incorporated into a Bradyrhizobium-based synthetic bacterial community (SynCom) to validate their functional roles. Further experiments confirmed that core microbiota-driven nutrient turnover directly facilitates host plant, as evidenced by SynCom inoculation assays. Collectively, this study establishes that phylogenetically conserved core microbiota critically regulate nutrient turnover and acquisition efficiency in the rhizosphere. These insights advance our understanding the ecological function of core microbiota in the rhizosphere and provide a framework for harnessing the beneficial traits in sustainable agriculture.
{"title":"The genotypically conserved core microbiota modulates nutrient turnover in soybean rhizosphere","authors":"Cunhu Wang, Di Li, Hao Mei, Xu Zhao, Lin Wang, Xiao Xu, Zhongwei Li, Xinghua Zhang, Hong Liao, Yongjia Zhong","doi":"10.1016/j.jare.2025.12.035","DOIUrl":"https://doi.org/10.1016/j.jare.2025.12.035","url":null,"abstract":"Microbiota-mediated nutrient turnover in the rhizosphere determines nutrient bioavailability, thereby enhancing nutrient uptake, utilization, and ultimately crop productivity. Consequently, elucidating the functional core microbiota in rhizosphere nutrient turnover is of critical importance. In this study, we leveraged soybean germplasm core collections to investigate the tripartite relationship among host genotype, core microbiota and nutrient availability, with a focus on delineating the pivotal role of core microbiota in nutrient turnover. Our results suggest that phylogenetic variation significantly shape root-associated microbial communities and rhizosphere nutrient availability, explaining 11.75 % and 2.07 % of total variances, respectively. Core microbiota analysis identified 29 phylogenetic conserved core amplicon sequence variants (ASVs), the majority of which exhibited significant correlated with nutrient availability. Notably, three key core ASVs—ASV13, ASV14 and ASV12, positively correlated with alkali-hydrolyzed nitrogen, available phosphorus, and soil organic matter, respectively. These taxa were subsequently incorporated into a <em>Bradyrhizobium</em>-based synthetic bacterial community (SynCom) to validate their functional roles. Further experiments confirmed that core microbiota-driven nutrient turnover directly facilitates host plant, as evidenced by SynCom inoculation assays. Collectively, this study establishes that phylogenetically conserved core microbiota critically regulate nutrient turnover and acquisition efficiency in the rhizosphere. These insights advance our understanding the ecological function of core microbiota in the rhizosphere and provide a framework for harnessing the beneficial traits in sustainable agriculture.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"127 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-26DOI: 10.1016/j.jare.2025.12.033
Ming Lu, ZhaoHong Miao, YunWei Niu, ZuoBing Xiao, Di Zhao
{"title":"Application of γ-cyclodextrin encapsulation of eugenol and isoeugenol: characterization, stability, and taste impact","authors":"Ming Lu, ZhaoHong Miao, YunWei Niu, ZuoBing Xiao, Di Zhao","doi":"10.1016/j.jare.2025.12.033","DOIUrl":"https://doi.org/10.1016/j.jare.2025.12.033","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"12 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-26DOI: 10.1016/j.jare.2025.12.039
Yu Wang, Pu Chen, Shiqian Huang, Lin Chen, Yangyang Ge, Heng Gu, Yangqi Chu, Yiyi Yang, Yun Lin, Shanglong Yao
Introduction
Lung ischemia–reperfusion injury (LIRI)—a fatal complication following major surgery, trauma, or shock— is characterized by pulmonary endothelial barrier (PEB) dysfunction. Although thioredoxin domain-containing protein 5 (TXNDC5) regulates endothelial homeostasis, its role in LIRI pathogenesis remains unknown.
Objectives
In the present study, we investigate the role of TXNDC5 in LIRI-induced PEB disruption and explore its underlying mechanisms and therapeutic potential.
Methods
We established LIRI models in rats (left pulmonary hilum occlusion) and human umbilical vein endothelial cells (oxygen-glucose deprivation/reperfusion). TXNDC5 expression was modulated via AAV-shRNA knockdown, whereas endoplasmic reticulum (ER) stress was inhibited pharmacologically (4-PBA and Ceapin-A7). Structural and functional changes of the PEB, including HSP90/eNOS complex stability, were examined. Mechanistic studies included ChIP-seq identified ATF6 binding to the TXNDC5 promoter, followed by rescue experiments with ATF6 inhibition and TXNDC5 overexpression. Clinical validation was performed using plasma proteomics in patients with LIRI. A TXNDC5-based nomogram model for LIRI early-warning was constructed and internally validated. Incremental prediction value of TXNDC5 was evaluated using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).
Results
Single-cell RNA sequencing revealed TXNDC5 upregulation in pulmonary endothelial cells during LIRI, correlating with PEB disruption, apoptosis, ER stress, and NF-κB activation. TXNDC5 knockdown restored HSP90/eNOS stability and improved endothelial integrity in vitro/vivo. Ceapin-A7, or 4-PBA, attenuated TXNDC5-driven PEB injury, and TXNDC5 overexpression confirmed the causal role of the ATF6-TXNDC5 axis. Mechanistically, ER stress promoted TXNDC5 transcription via ATF6 binding to its promoter. Clinically, elevated plasma TXNDC5 levels predicted LIRI and correlated with the severity of the condition. Incorporating the TXNDC5 index into the clinical predictors model enhanced the forecast of LIRI, as demonstrated by the NRI and IDI.
Conclusion
Our findings demonstrate that ER stress-induced TXNDC5 upregulation exacerbates LIRI by impairing HSP90/eNOS-dependent endothelial function. ER stress-TXNDC5 signaling is a mechanistically distinct and potential target in LIRI.
{"title":"Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced pulmonary endothelial barrier dysfunction by activating TXNDC5","authors":"Yu Wang, Pu Chen, Shiqian Huang, Lin Chen, Yangyang Ge, Heng Gu, Yangqi Chu, Yiyi Yang, Yun Lin, Shanglong Yao","doi":"10.1016/j.jare.2025.12.039","DOIUrl":"https://doi.org/10.1016/j.jare.2025.12.039","url":null,"abstract":"<h3>Introduction</h3>Lung ischemia–reperfusion injury (LIRI)—a fatal complication following major surgery, trauma, or shock— is characterized by pulmonary endothelial barrier (PEB) dysfunction. Although thioredoxin domain-containing protein 5 (TXNDC5) regulates endothelial homeostasis, its role in LIRI pathogenesis remains unknown.<h3>Objectives</h3>In the present study, we investigate the role of TXNDC5 in LIRI-induced PEB disruption and explore its underlying mechanisms and therapeutic potential.<h3>Methods</h3>We established LIRI models in rats (left pulmonary hilum occlusion) and human umbilical vein endothelial cells (oxygen-glucose deprivation/reperfusion). TXNDC5 expression was modulated via AAV-shRNA knockdown, whereas endoplasmic reticulum (ER) stress was inhibited pharmacologically (4-PBA and Ceapin-A7). Structural and functional changes of the PEB, including HSP90/eNOS complex stability, were examined. Mechanistic studies included ChIP-seq identified ATF6 binding to the TXNDC5 promoter, followed by rescue experiments with ATF6 inhibition and TXNDC5 overexpression. Clinical validation was performed using plasma proteomics in patients with LIRI. A TXNDC5-based nomogram model for LIRI early-warning was constructed and internally validated. Incremental prediction value of TXNDC5 was evaluated using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).<h3>Results</h3>Single-cell RNA sequencing revealed TXNDC5 upregulation in pulmonary endothelial cells during LIRI, correlating with PEB disruption, apoptosis, ER stress, and NF-κB activation. TXNDC5 knockdown restored HSP90/eNOS stability and improved endothelial integrity <em>in vitro</em>/<em>vivo</em>. Ceapin-A7, or 4-PBA, attenuated TXNDC5-driven PEB injury, and TXNDC5 overexpression confirmed the causal role of the ATF6-TXNDC5 axis. Mechanistically, ER stress promoted TXNDC5 transcription via ATF6 binding to its promoter. Clinically, elevated plasma TXNDC5 levels predicted LIRI and correlated with the severity of the condition. Incorporating the TXNDC5 index into the clinical predictors model enhanced the forecast of LIRI, as demonstrated by the NRI and IDI.<h3>Conclusion</h3>Our findings demonstrate that ER stress-induced TXNDC5 upregulation exacerbates LIRI by impairing HSP90/eNOS-dependent endothelial function. ER stress-TXNDC5 signaling is a mechanistically distinct and potential target in LIRI.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"9 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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