Jing Xu , Haoming Xu , Jianhong Li , Wenqi Huang , Yingfei Li , Xue Guo , Minzheng Zhu , Yao Peng , Youlian Zhou , Yuqiang Nie
{"title":"Clostridium butyricum-induced balance in colonic retinol metabolism and short-chain fatty acid levels inhibit IgA-related mucosal immunity and relieve colitis developments","authors":"Jing Xu , Haoming Xu , Jianhong Li , Wenqi Huang , Yingfei Li , Xue Guo , Minzheng Zhu , Yao Peng , Youlian Zhou , Yuqiang Nie","doi":"10.1016/j.micres.2025.128203","DOIUrl":"10.1016/j.micres.2025.128203","url":null,"abstract":"<div><div>Gut microbiota and their metabolites play a significant role in inflammatory bowel disease. Here, we attempted to determine the anti-inflammatory role of the probiotic <em>Clostridium. butyricum</em> (CB) in inflammatory bowel disease and identify the exact immune mechanism. The clinical significance of Clostridiales and CB was explored in patients with ulcerative colitis. The inflammation-suppressive role of CB was evaluated in mice with DSS-induced colitis. 16S rRNA sequencing was performed to assess changes in the gut microbiota. Altered transcription levels were detected by RNA sequencing. Flow cytometry was performed to assess the frequency of IgA responses to gut microbiota. Clostridiales and CB were depleted in ulcerative colitis. Oral gavage with CB significantly suppressed weight loss and colon shortening in the dextran sulfate sodium-induced colitis mouse model. Intestinal barrier injury was reversed and the gut microbiota was restored upon treatment with CB administration. The mucosal immune response to gut microbiota was reversed upon treatment with CB. CB conditional medium was more effective than heat-killed CB in alleviating inflammation. Mechanistically, retinol metabolism and retinoic acid levels were higher in groups treated with CB and butyrate. CB and the metabolite butyrate exerted a suppressive role on the abundance of Immunoglobulin A-coated gut microbiota by inhibiting retinoic acid synthesis. In summary, CB protects against inflammation and intestinal barrier injury by producing anti-inflammatory metabolites that can regulate the mucosal immune response to gut microbiota by increasing retinoic acid levels in the colon.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"298 ","pages":"Article 128203"},"PeriodicalIF":6.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian Wang , Ruiying Liu , Yuanyuan Niu , Yuchen Wang , Jingling Qin , Yu Huang , Jiamin Qian , Xiaoyu Zheng , Meng Wang , Di Huang , Yutao Liu
{"title":"Regulatory mechanisms of two-component systems in Vibrio cholerae: Enhancing pathogenicity and environmental adaptation","authors":"Qian Wang , Ruiying Liu , Yuanyuan Niu , Yuchen Wang , Jingling Qin , Yu Huang , Jiamin Qian , Xiaoyu Zheng , Meng Wang , Di Huang , Yutao Liu","doi":"10.1016/j.micres.2025.128198","DOIUrl":"10.1016/j.micres.2025.128198","url":null,"abstract":"<div><div>Cholera, which is caused by the bacterium <em>Vibrio cholerae</em>, is a highly dangerous disease characterized by severe symptoms such as watery diarrhea, dehydration, and even death. <em>V. cholerae</em> can both colonize the host intestine and survive in environmental reservoirs. Two-component systems (TCSs) are essential regulatory mechanisms that allow bacteria to adapt to changing environments. This review focuses on the regulatory mechanisms of TCS-mediated gene expression in <em>V. cholerae</em>. We first summarize the composition and classification of TCSs in <em>V. cholerae</em> N16961. We then discuss the roles of TCSs in facilitating adaptation to diverse environmental stimuli and increasing pathogenicity. Furthermore, we analyze the distribution of TCSs in pandemic and nonpandemic-<em>V. cholerae</em> strains, demonstrating their indispensable role in promoting virulence and facilitating the widespread dissemination of pandemic strains. Elucidation of these mechanisms is crucial for devising new strategies to combat cholera and prevent future outbreaks, ultimately contributing to improved public health outcomes.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"298 ","pages":"Article 128198"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiayang Jiang , Juanjuan Li , Haoyu Dong , Xinping Chen , Yanqiong Tang , Xiang Ma , Hong Li , Xue Chi , Xianwen Yang , Zhu Liu
{"title":"Xanthocillin X combats Burkholderia pseudomallei by targeting UDP-N-acetylglucosamine acyltransferase","authors":"Jiayang Jiang , Juanjuan Li , Haoyu Dong , Xinping Chen , Yanqiong Tang , Xiang Ma , Hong Li , Xue Chi , Xianwen Yang , Zhu Liu","doi":"10.1016/j.micres.2025.128195","DOIUrl":"10.1016/j.micres.2025.128195","url":null,"abstract":"<div><div>Drug-resistance in <em>Burkholderia pseudomallei</em> (<em>B. pseudomallei</em>) and the limited ability of antibiotics to eradicate biofilms underscore the urgent need for alternative therapeutic options. New drugs which suppress the biofilm formation without emergence of antimicrobial resistance have clearly attracted global attention. We report a deep-sea-derived natural product xanthocillin X (Xan) for the therapeutic of <em>B. pseudomallei</em> 1 induced infections. Xan possesses superior antibacterial ability over commercial ceftazidime even at an ultralow concentration of 62.5 ng/mL, and can inhibit the formation of biofilm with high efficiency without drug resistance. Specially, Xan demonstrates stable binding ability with LpxA which is responsible for lipopolysaccharide synthesis, and thus disrupting the formation of biofilm. In two murine models, Xan exhibits therapeutic potency for combating <em>B. pseudomallei</em> 1 induced infections. Taken together, Xan that specifically interacts with LpxA impairs the formation of biofilm without drug resistance, endowing the compound with dominant antibacterial activity and accelerating tissue repair after infection.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"298 ","pages":"Article 128195"},"PeriodicalIF":6.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyu Guo , Yuzhen Yang , Yanqiu Li , Bin Chen , Huajun Li , Chen Zhang , Jiping Ma , Mingwen Zhao , Jing Zhu
{"title":"Nitrogen-dependent regulation of extracellular and intracellular polysaccharide content in Ganoderma lucidum via the transcription factor AreA","authors":"Xiaoyu Guo , Yuzhen Yang , Yanqiu Li , Bin Chen , Huajun Li , Chen Zhang , Jiping Ma , Mingwen Zhao , Jing Zhu","doi":"10.1016/j.micres.2025.128197","DOIUrl":"10.1016/j.micres.2025.128197","url":null,"abstract":"<div><div>Fungal polysaccharides serve as vital components and hold significant value in food and medicinal applications. Nitrogen plays a crucial role in the biosynthesis of fungal polysaccharides, yet our comprehension of its specific influence on fungal polysaccharides biosynthesis remains limited. In this study, we analyzed the transcriptomic profiles of <em>Ganoderma lucidum</em> cultured under ammonium or nitrate sources, revealing an enrichment of the polysaccharide synthesis pathway. Further studies revealed that ammonium nitrogen promotes the synthesis of extracellular polysaccharides (EPS), while nitrate enhances that of intracellular polysaccharides (IPS). Subsequently, the role of AreA, a key transcription factor in nitrogen metabolism, in polysaccharide synthesis was investigated. Under nitrate conditions, compared to the wild-type (WT), EPS content increased by approximately 33 %, whereas IPS, chitin, and β-1,3-glucan content in the <em>areA</em>-silenced strains were significantly reduced by 24 %, 20 %, and 20 %-25 %, respectively. Changes in the content of chitin and β-1,3-glucan affect the cell wall's structure and integrity. Compared to ammonium conditions, under nitrate conditions, the cell wall thinned by approximately 23 % following <em>areA</em> silencing, and sensitivity to cell wall perturbing agents increased by approximately 20 %-30 %. In summary, this study elucidates the impact of nitrogen sources on polysaccharide synthesis, providing valuable insights into strategies for enhancing polysaccharide content in <em>G.lucidum</em>.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128197"},"PeriodicalIF":6.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shengnan Jiang , Marta Matuszewska , Mengzhen Chen , Yueqin Hong , Yiyi Chen , Zhengan Wang , Hemu Zhuang , Lu Sun , Feiteng Zhu , Haiping Wang , Xueqing Wu , Shujuan Ji , Mark A. Holmes , Xiaoliang Ba , Yan Chen , Yunsong Yu
{"title":"Emergence and spread of ST5 methicillin-resistant Staphylococcus aureus with accessory gene regulator dysfunction: genomic insights and antibiotic resistance","authors":"Shengnan Jiang , Marta Matuszewska , Mengzhen Chen , Yueqin Hong , Yiyi Chen , Zhengan Wang , Hemu Zhuang , Lu Sun , Feiteng Zhu , Haiping Wang , Xueqing Wu , Shujuan Ji , Mark A. Holmes , Xiaoliang Ba , Yan Chen , Yunsong Yu","doi":"10.1016/j.micres.2025.128196","DOIUrl":"10.1016/j.micres.2025.128196","url":null,"abstract":"<div><div>The globally disseminated <em>Staphylococcus aureus</em> ST5 clone poses a major public health threat due to its multidrug resistance and virulence. Here, we identified an <em>agr</em>-dysfunctional (<em>agrA</em>-I238K) ST5 MRSA clone that has spread across East and Southeast Asia, with recent increases in China since its emergence in the 1970s. Comparative genomic analyses identified distinct single-nucleotide polymorphisms and mobile genetic elements linked to enhanced resistance and virulence. This clone exhibits resistance to seven antimicrobial classes, including third-generation tetracyclines and fusidic acid, and shares phenotypic and genetic similarities with the vancomycin-intermediate <em>S. aureus</em> Mu50 strain, including reduced susceptibility to vancomycin, teicoplanin, and daptomycin. The <em>agrA</em>-I238K mutation attenuates hemolytic activity, increases biofilm formation, and reduces daptomycin susceptibility, suggesting a key role in the clone’s success. Our results demonstrate the important role of <em>agrA</em>-I238K mutation in the widespread distribution of <em>agr</em>-dysfunctional MRSA and highlight the importance of genomic surveillance in tracking the spread of <em>agr</em>-dysfunctional ST5 MRSA.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128196"},"PeriodicalIF":6.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaofan Xie , Andéole Niyongabo Turatsinze , Yang Liu , Gaofeng Chen , Liang Yue , Ailing Ye , Qin Zhou , Zongyu Zhang , Yun Wang , Yubao Zhang , Weijie Jin , Zhongping Li , Angela Sessitsch , Günter Brader , Ruoyu Wang
{"title":"Bioinoculant substitution enhances rhizosphere soil quality and maize growth by modulating microbial communities and host gene expression in alkaline soils","authors":"Xiaofan Xie , Andéole Niyongabo Turatsinze , Yang Liu , Gaofeng Chen , Liang Yue , Ailing Ye , Qin Zhou , Zongyu Zhang , Yun Wang , Yubao Zhang , Weijie Jin , Zhongping Li , Angela Sessitsch , Günter Brader , Ruoyu Wang","doi":"10.1016/j.micres.2025.128194","DOIUrl":"10.1016/j.micres.2025.128194","url":null,"abstract":"<div><div>The application of plant growth-promoting bacteria (PGPB) as bioinoculants is widely recognized for improving crop yields and soil fertility. However, the precise mechanisms underlying their impact on rhizosphere soil quality and crop productivity remain insufficiently understood. This study elucidates how a solid bioinoculant, comprising <em>Bacillus velezensis</em> FZB42 and attapulgite clay, enhances rhizosphere soil quality and maize (<em>Zea mays</em>) growth in nutrient-deficient alkaline calcareous soils. Pot experiments reveal that bioinoculant application promotes extensive root colonization under nitrogen-deficient conditions, with significantly higher colonization rates observed in the half-nitrogen (HN) and zero-nitrogen (ZN) treatments compared to full-nitrogen conditions. Notably, bioinoculant application in ZN and HN significantly increases phosphorus availability and soil quality in the rhizosphere. Furthermore, maize growth parameters, including plant height, stem diameter, and kernel yield, are markedly enhanced, with optimal biomass accumulation achieved under HN conditions. High-throughput sequencing of rhizosphere microbiomes uncovers significant shifts in microbial community composition, with enrichment of key taxa involved in nutrient cycling and plant-microbe interactions. Transcriptomic analysis of maize tissues demonstrates the upregulation of genes associated with nutrient transport, photosynthesis, fatty acid biosynthesis, and kernel development, with a pronounced enrichment in metabolic pathways linked to growth and productivity. Structural equation modeling indicates that increased microbial diversity and gene expression collectively account for 69 % of the variance in the soil quality index and 45 % of the variance in maize yield. These findings provide critical mechanistic insights into the role of solid bioinoculant in enhancing soil fertility and crop performance, highlighting their potential as a sustainable agricultural strategy for improving productivity in low-fertility alkaline soils.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128194"},"PeriodicalIF":6.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DBP degradation and PGPR-mediated enhancement: Mechanisms of Enterobacter sp. X1 revealed by maize (Zea mays L.) transcriptome and rhizosphere microbiome analysis","authors":"Xiaoge Zhang, Lihua Qi, Wenqing Zhou, Jingjing Yang, Yalan Zhu, Zhiman Li, Fenyan Chen, Chunfeng Guan","doi":"10.1016/j.micres.2025.128193","DOIUrl":"10.1016/j.micres.2025.128193","url":null,"abstract":"<div><div>Dibutyl phthalate (DBP), a common plasticizer in industrial production, is often detected in agricultural fields and exhibits significant endocrine disrupting effects on humans. Recently, plant growth promoting rhizobacteria (PGPR) have received considerable attention for their application in enhancing phytoremediation of soil organic pollutants. However, few studies have revealed the underlying mechanisms of gene expression changes in the PGPR-assisted phytoremediation process through plant transcriptome and rhizome microbiome analyses. Therefore, a DBP-degrading bacterium with multiple PGP traits was isolated, characterized and named strain X1. The effects of strain X1 inoculation on the promotion of maize (<em>Zea mays</em> L.) to remediate DBP-contaminated soil were then evaluated. The results showed that, compared to the DBP group, the soil DBP removal efficiency in the DBP + X1 treatment group increased 29.3 % (<em>P</em> < 0.05), accompanied by a significant reduction in DBP accumulation in maize (14.5 %) (<em>P</em> < 0.05). On one hand, transcriptome analysis further revealed that gene expression of detoxifying enzymes and antioxidants in plant tissues was up-regulated after inoculation with strain X1, which could prevent the excessive DBP accumulation in maize. Additionally, strain X1 could improve maize photosynthesis by inducing the expression of genes encoding proteins involved in the photosynthetic signaling pathway. On the other hand, the introduction of strain X1 greatly adjusted the diversity of the soil microbial community, enriched the abundance of DBP-degrading bacteria and improved soil enzyme activities in DBP-contaminated soil. In particular, this study also found that the expression of some plant genes was closely related to the relative abundance of rhizosphere microorganisms, such as <em>Massilia</em> and <em>Devosia</em> were associated with up-regulation of the expression of genes involved in the synthesis of alkaline phosphatase, which was of great importance in further exploration of microbial-plant interaction mechanisms. Consequently, this study investigated the role of PGPR on plant growth and the remediation of DBP-contaminated soil during phytoremediation through plant transcriptome and rhizosphere microbiome analysis, which provided a new perspective for future mechanism research on the remediation of contaminated farmland.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128193"},"PeriodicalIF":6.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zibo Yin , Diandian Huang , Elian M.A. Kuhn , T. Fintan Moriarty , Guofeng Li , Xing Wang
{"title":"Unraveling persistent bacteria: Formation, niches, and eradication strategies","authors":"Zibo Yin , Diandian Huang , Elian M.A. Kuhn , T. Fintan Moriarty , Guofeng Li , Xing Wang","doi":"10.1016/j.micres.2025.128189","DOIUrl":"10.1016/j.micres.2025.128189","url":null,"abstract":"<div><div>Persistent bacteria (persisters) are phenotypic variants that emerge either randomly or in response to a range of adverse environmental conditions. Persistence represents a state whereby a subpopulation of microorganisms can spontaneously enter a \"dormant\" state in response to environmental factors, while simultaneously exhibiting elevated tolerance to antimicrobial agents. This review provides the current definition of bacterial persistence and summarizes the mechanisms of persisters formation as well as the various niches of bacterial persistence encountered in clinical practice. Strategies targeting persisters are outlined, including but not limited to direct killing, awakening of persistent bacteria, combined clearance, and inhibition of persistence formation, and we conclude by proposing challenges and solutions for addressing bacterial persistence in current clinical practice.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128189"},"PeriodicalIF":6.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Boosting Rhizobium-legume symbiosis: The role of nodule non-rhizobial bacteria in hormonal and nutritional regulation under stress","authors":"Hassan Etesami , Gustavo Santoyo","doi":"10.1016/j.micres.2025.128192","DOIUrl":"10.1016/j.micres.2025.128192","url":null,"abstract":"<div><div>Legumes are vital for sustainable agriculture due to their unique ability to fix atmospheric nitrogen through symbiosis with rhizobia. Recent research has highlighted the significant role of non-rhizobial bacteria (NRB) within root nodules in enhancing this symbiotic relationship, particularly under stress conditions. These NRB exhibit plant growth-promoting (PGP) metabolites by modulating phytohormones and enhancing nutrient availability, thereby improving nodule development and function. Bacteria produce essential hormones, such as auxin (indole-3-acetic acid), cytokinins, gibberellic acids abscisic acid, jasmonic acid, and salicylic acid, and enzymes like 1-aminocyclopropane-1-carboxylate deaminase, which mitigate ethylene's inhibitory effects on nodulation. Furthermore, NRB contribute to nutrient cycling by solubilizing minerals like phosphate, potassium, silicate, zinc, and iron, essential for effective nitrogen fixation. The co-inoculation of legumes with both rhizobia and NRB with multiple PGP metabolites has shown synergistic effects on plant growth, yield, and resilience against environmental stresses. This review emphasizes the need to further explore the diversity and functional roles of nodule-associated non-rhizobial endophytes, aiming to optimize legume productivity through improved nutrient and hormonal management. Understanding these interactions is crucial for developing sustainable agricultural practices that enhance the efficiency of legume-rhizobia symbiosis, ultimately contributing to food security and ecosystem health.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128192"},"PeriodicalIF":6.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhi Liu , Hong Zhang , Jingjing Wang , Yutong Yao , Xiaoyi Wang , Yang Liu , Weijia Fang , Xingyin Liu , Yi Zheng
{"title":"Clca1 deficiency exacerbates colitis susceptibility via impairment of mucus barrier integrity and gut microbiota homeostasis","authors":"Zhi Liu , Hong Zhang , Jingjing Wang , Yutong Yao , Xiaoyi Wang , Yang Liu , Weijia Fang , Xingyin Liu , Yi Zheng","doi":"10.1016/j.micres.2025.128191","DOIUrl":"10.1016/j.micres.2025.128191","url":null,"abstract":"<div><div>The intestinal mucus barrier has emerged as a promising therapeutic target for inflammatory bowel disease. Understanding its regulatory mechanisms is critical for elucidating ulcerative colitis (UC) pathogenesis, improving diagnostics, guiding treatments, and preventing relapse. Chloride Channel Accessory 1 (<em>Clca1</em>), a constituent of the mucus layer, remains understudied in colitis. Here, we investigated <em>Clca1</em>’s role in mucosal immunity and intestinal homeostasis using experimental colitis models. <em>Clca1</em>-deficient (<em>Clca1</em><sup>−/−</sup>) mice displayed compromised mucus layer integrity, reduced neutrophil infiltration, and gut microbiota dysbiosis. Notably, <em>Clca1</em><sup>−/−</sup> mice exhibited exacerbated colitis severity following dextran sulfate sodium (DSS) challenge, accompanied by a diminished goblet cell populations. Fecal microbiota transplantation (FMT) studies revealed that gut microbiota critically modulates divergent phenotypic outcomes between genotypes. Our findings establish <em>Clca1</em> as a multifunctional regulator of mucus barrier integrity through mechanisms involving goblet cell maintenance, neutrophil-mediated immunity, and host-microbiota crosstalk. These results advance the understanding of UC pathogenesis and identify <em>Clca1</em>-associated pathways as potential targets for barrier restoration therapies.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128191"},"PeriodicalIF":6.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}