{"title":"Gut commensals-derived succinate impels colonic inflammation in ulcerative colitis.","authors":"Rajdeep Dalal, Srikanth Sadhu, Aashima Batra, Sandeep Goswami, Jyotsna Dandotiya, Vinayakadas K V, Rahul Yadav, Virendra Singh, Kartikey Chaturvedi, Rahul Kannan, Shakti Kumar, Yashwant Kumar, Deepak Kumar Rathore, Deepak B Salunke, Vineet Ahuja, Amit Awasthi","doi":"10.1038/s41522-025-00672-3","DOIUrl":"10.1038/s41522-025-00672-3","url":null,"abstract":"<p><p>Gut microbiota-derived metabolites play a crucial role in modulating the inflammatory response in inflammatory bowel disease (IBD). In this study, we identify gut microbiota-derived succinate as a driver of inflammation in ulcerative colitis (UC) by activating succinate-responsive, colitogenic helper T (Th) cells that secrete interleukin (IL)-9. We demonstrate that colitis is associated with an increase in succinate-producing gut bacteria and decrease in succinate-metabolizing gut bacteria. Similarly, UC patients exhibit elevated levels of succinate-producing gut bacteria and luminal succinate. Intestinal colonization by succinate-producing gut bacteria or increased succinate availability, exacerbates colonic inflammation by activating colitogenic Th9 cells. In contrast, intestinal colonization by succinate-metabolizing gut bacteria, blocking succinate receptor signaling with an antagonist, or neutralizing IL-9 with an anti-IL-9 antibody alleviates inflammation by reducing colitogenic Th9 cells. Our findings underscore the role of gut microbiota-derived succinate in driving colitogenic Th9 cells and suggesting its potential as a therapeutic target for treating IBD.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"44"},"PeriodicalIF":7.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut microbiota as a new target for anticancer therapy: from mechanism to means of regulation.","authors":"Jiaao Sun, Shiyan Song, Jiahua Liu, Feng Chen, Xiaorui Li, Guangzhen Wu","doi":"10.1038/s41522-025-00678-x","DOIUrl":"10.1038/s41522-025-00678-x","url":null,"abstract":"<p><p>In order to decipher the relationship between gut microbiota imbalance and cancer, this paper reviewed the role of intestinal microbiota in anticancer therapy and related mechanisms, discussed the current research status of gut microbiota as a biomarker of cancer, and finally summarized the reasonable means of regulating gut microbiota to assist cancer therapy. Overall, our study reveals that the gut microbiota can serve as a potential target for improving cancer management.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"43"},"PeriodicalIF":7.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian Jiang, Mengmeng Xu, Hong Chen, Yao Zhang, Yuting Sun, Li Tao, Zheng Wang, Deqin Yang
{"title":"V-ATPase contributes to the cariogenicity of Candida albicans- Streptococcus mutans biofilm.","authors":"Qian Jiang, Mengmeng Xu, Hong Chen, Yao Zhang, Yuting Sun, Li Tao, Zheng Wang, Deqin Yang","doi":"10.1038/s41522-025-00660-7","DOIUrl":"10.1038/s41522-025-00660-7","url":null,"abstract":"<p><p>The interaction between Candida albicans and Streptococcus mutans plays an important role in the progression of dental caries. The vacuolar proton pump (V-ATPase) is a vital enzyme regulating the growth and virulence of C. albicans, which is a potential target for caries prevention. However, the effect of V-ATPase on the cariogenicity of C. albicans-S. mutans biofilm remains to be explored. In this study, the detection rate of C. albicans in caries-active (group CA) (22.03%) was significantly higher than that in caries-free (group CF) children (8.00%), and the expression of V-ATPase related genes were higher in group CA. Then, the higher expressed V-ATPase coding genes VMA3, VMA4 and VMA11 in CA group were knocked out. Compared with the wild type SC5314, the mutants showed slower growth rate, inhibited hyphal growth, and defective integrity of cell wall. The biofilm biomass and extracellular polysaccharide (EPS) production of dual biofilm were significantly reduced, and the biofilm structure was impacted. Transcriptome analysis indicated that V-ATPase participated in various metabolisms and biosynthesis pathways of C. albicans, and influenced EPS metabolism of S. mutans. Finally, compared with the positive control, the caries severity, the biomass and EPS production of dental plaque were significantly reduced after deletion of VMA3, VMA4 and VMA11 in vivo. This study revealed for the first time the regulating effect of V-ATPase on the cariogenicity of C. albicans-S. mutans biofilm and its potential mechanisms. The results may provide basis for new strategies of ecological prevention and treatment of dental caries.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"41"},"PeriodicalIF":7.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonna E Teikari, David A Russo, Markus Heuser, Otto Baumann, Julie A Z Zedler, Anton Liaimer, Elke Dittmann
{"title":"Competition and interdependence define interactions of Nostoc sp. and Agrobacterium sp. under inorganic carbon limitation.","authors":"Jonna E Teikari, David A Russo, Markus Heuser, Otto Baumann, Julie A Z Zedler, Anton Liaimer, Elke Dittmann","doi":"10.1038/s41522-025-00675-0","DOIUrl":"10.1038/s41522-025-00675-0","url":null,"abstract":"<p><p>Cyanobacteria of the Nostoc genus are capable of forming symbiotic relationships with plants but also serve as a hub for heterotrophic bacteria. By comparing the axenic strain Nostoc punctiforme PCC 73102 and the xenic strains Nostoc sp. KVJ2 and KVJ3, we were able to demonstrate an almost obligate dependence of the cyanobacteria on the heterotrophic partners under carbon-limiting conditions. A detailed analysis of the intimate relationship between N. punctiforme and the isolate Agrobacterium tumefaciens Het4 using shotgun proteomics and microscopy uncovered a complex partnership characterized by competition for iron and facilitation for carbon. The prevalent extracarboxysomal localization of the carbon-fixing enzyme RubisCO suggests that a weak carbon-concentrating mechanism in N. punctiforme enforces a dependence on heterotrophic bacteria. Our study indicates a limited autonomy of symbiotic Nostoc strains, which may also explain its preference for symbiotic interactions.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"42"},"PeriodicalIF":7.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu-Ming Cai, Feng Hong, Amber De Craemer, Jacob George Malone, Aurélie Crabbé, Tom Coenye
{"title":"Echinacoside reduces intracellular c-di-GMP levels and potentiates tobramycin activity against Pseudomonas aeruginosa biofilm aggregates.","authors":"Yu-Ming Cai, Feng Hong, Amber De Craemer, Jacob George Malone, Aurélie Crabbé, Tom Coenye","doi":"10.1038/s41522-025-00673-2","DOIUrl":"10.1038/s41522-025-00673-2","url":null,"abstract":"<p><p>Cyclic diguanylate (c-di-GMP) is a central biofilm regulator in Pseudomonas aeruginosa, where increased intracellular levels promote biofilm formation and antibiotic tolerance. Targeting the c-di-GMP network may be a promising anti-biofilm approach, but most strategies studied so far aimed at eliminating surface-attached biofilms, while in vivo P. aeruginosa biofilms often occur as suspended aggregates. Here, the expression profile of c-di-GMP metabolism-related genes was analysed among 32 P. aeruginosa strains grown as aggregates in synthetic cystic fibrosis sputum. The diguanylate cyclase SiaD proved essential for auto-aggregation under in vivo-like conditions. Virtual screening predicted a high binding affinity of echinacoside towards the active site of SiaD. Echinacoside reduced c-di-GMP levels and aggregate sizes and potentiated tobramycin activity against aggregates in >80% of strains tested. This synergism was also observed in P. aeruginosa-infected 3-D alveolar epithelial cells and murine lungs, demonstrating echinacoside's potential as an adjunctive therapy for recalcitrant P. aeruginosa infections.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"40"},"PeriodicalIF":7.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecules-mediated bidirectional interactions between microbes and human cells.","authors":"Shengbo Wu, Xueying Bu, Danlei Chen, Xueyan Wu, Hao Wu, Qinggele Caiyin, Jianjun Qiao","doi":"10.1038/s41522-025-00657-2","DOIUrl":"10.1038/s41522-025-00657-2","url":null,"abstract":"<p><p>Complex molecules-mediated interactions, which are based on the bidirectional information exchange between microbes and human cells, enable the defense against diseases and health maintenance. Recently, diverse single-direction interactions based on active metabolites, immunity factors, and quorum sensing signals have largely been summarized separately. In this review, according to a simplified timeline, we proposed the framework of Molecules-mediated Bidirectional Interactions (MBI) between microbe and humans to decipher and understand their intricate interactions systematically. About the microbe-derived interactions, we summarized various molecules, such as short-chain fatty acids, bile acids, tryptophan catabolites, and quorum sensing molecules, and their corresponding human receptors. Concerning the human-derived interactions, we reviewed the effect of human molecules, including hormones, cytokines, and other circulatory metabolites on microbial characteristics and phenotypes. Finally, we discussed the challenges and trends for developing and deciphering molecule-mediated bidirectional interactions and their potential applications in the guard of human health.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"38"},"PeriodicalIF":7.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Ding, Lingping Tan, Lingzhi Wu, Jinyu Li, Yong Zhang, Zongshan Shen, Chi Zhang, Chuanjiang Zhao, Li Gao
{"title":"Regulation of tryptophan-indole metabolic pathway in Porphyromonas gingivalis virulence and microbiota dysbiosis in periodontitis.","authors":"Jing Ding, Lingping Tan, Lingzhi Wu, Jinyu Li, Yong Zhang, Zongshan Shen, Chi Zhang, Chuanjiang Zhao, Li Gao","doi":"10.1038/s41522-025-00669-y","DOIUrl":"10.1038/s41522-025-00669-y","url":null,"abstract":"<p><p>Pathogenesis of periodontitis is marked by microbiota dysbiosis and disrupted host responses. Porphyromonas gingivalis is a keystone pathogen of periodontitis which expresses various crucial virulence factors. This study aimed to clarify the role and mechanisms of P. gingivalis tryptophan-indole metabolic pathway in the pathogenesis of periodontitis. This study showed that periodontitis patients exhibited elevated tryptophan metabolism and salivary pathogen abundance. Tryptophanase gene-deficiency altered proteome and metabolome of P. gingivalis, inhibited P. gingivalis virulent factors expression, biofilm growth, hemin utilization, cell adhesion/invasion and pro-inflammation ability. Tryptophan-indole pathway of P. gingivalis stimulated periodontitis biofilm formation and induced oral microbiota dysbiosis. In periodontitis mice, this pathway of P. gingivalis aggravated alveolar bone loss and gingival tissue destruction, causing oral and gut microbiota dysbiosis. This study indicates that the tryptophan-indole pathway serves as a significant regulator of P. gingivalis virulence and oral microbiota dysbiosis, which is also associated with gut dysbiosis.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"37"},"PeriodicalIF":7.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
João Gabriel S Souza, Fabio Azevedo, Maria Helena Rossy Borges, Raphael Cavalcante Costa, Takahiko Shiba, Shlomo Barak, Yaniv Mayer, Luciene Cristina de Figueiredo, Magda Feres, Valentim A R Barão, Jamil A Shibli
{"title":"Microbiome modulation of implant-related infection by a novel miniaturized pulsed electromagnetic field device.","authors":"João Gabriel S Souza, Fabio Azevedo, Maria Helena Rossy Borges, Raphael Cavalcante Costa, Takahiko Shiba, Shlomo Barak, Yaniv Mayer, Luciene Cristina de Figueiredo, Magda Feres, Valentim A R Barão, Jamil A Shibli","doi":"10.1038/s41522-025-00667-0","DOIUrl":"10.1038/s41522-025-00667-0","url":null,"abstract":"<p><p>Dental implant-related infections, which lack effective therapeutic strategies, are considered the primary cause for treatment failure. Pulsed electromagnetic field (PEMF) technology has been introduced as a safe and effective modality for enhancing biological responses. However, the PEMF effect on modulating microbial diversity has not been explored. Thus, we tested a miniaturized PEMF biomedical device as a healing component for dental implants. PEMF activation did not alter the chemical composition, surface roughness, wettability, and electrochemical performance. PEMF effectively controlled chronic in vitro polymicrobial microbial accumulation. The in vivo study where devices were inserted in the patients' oral cavities and 16S RNA sequencing analysis evidenced a fivefold or more reduction in 23 bacterial species for PEMF group and the absence of some species for this group, including pathogens associated with implant-related infections. PEMF altered bacterial interactions and promoted specific bacterial pathways. PEMF has emerged as an effective strategy for controlling implant-related infections.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"36"},"PeriodicalIF":7.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Claudia Siverino, Lena Gens, Tim Buchholz, Caroline Constant, Manuela Ernst, Dominic Gehweiler, Mario Morgenstern, R Geoff Richards, Henning Richter, Niels Vanvelk, Maja Waschk, Markus Windolf, Stephan Zeiter, T Fintan Moriarty
{"title":"Irrigation of the intramedullary channel improves outcome of DAIR in a sheep model.","authors":"Claudia Siverino, Lena Gens, Tim Buchholz, Caroline Constant, Manuela Ernst, Dominic Gehweiler, Mario Morgenstern, R Geoff Richards, Henning Richter, Niels Vanvelk, Maja Waschk, Markus Windolf, Stephan Zeiter, T Fintan Moriarty","doi":"10.1038/s41522-024-00643-0","DOIUrl":"10.1038/s41522-024-00643-0","url":null,"abstract":"<p><p>The management of fracture-related infection (FRI) with Debridement, Antibiotics, Irrigation, and Implant Retention (DAIR) is an appealing option, but its suitability is restricted to a relatively narrow proportion of patients. This study aimed to create a large animal model of DAIR after FRI and to evaluate outcomes after early (2 weeks) and delayed (5 weeks) DAIR. Additionally, intramedullary lavage (IML) of the intramedullary canal (IMC) is introduced as a novel technique to remove infected tissue. Our findings showed that DAIR failed to resolve infections in both early and delayed groups, whilst IML significantly reduced bacterial counts, leading to culture-negative results in the soft tissue and bone marrow. IML did not compromise long-term bone healing as revealed by an implant load sensor on the plate. In conclusion, DAIR was successfully achieved in a new large animal model with minimal losses. The IML method improves treatment efficacy, potentially broadening the range of patients suitable for DAIR.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"35"},"PeriodicalIF":7.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}