Quinn T Easter, Zabdiel Alvarado-Martinez, Meik Kunz, Bruno F Matuck, Brittany T Rupp, Theresa Weaver, Zhi Ren, Aleksandra Tata, Juan Caballero-Perez, Nick Oscarson, Akira Hasuike, Ameer N Ghodke, Adam J Kimple, Purushothama R Tata, Scott H Randell, Hyun Koo, Kang I Ko, Kevin M Byrd
{"title":"Polybacterial intracellular macromolecules shape single-cell inflammatory profiles in upper airway epithelia.","authors":"Quinn T Easter, Zabdiel Alvarado-Martinez, Meik Kunz, Bruno F Matuck, Brittany T Rupp, Theresa Weaver, Zhi Ren, Aleksandra Tata, Juan Caballero-Perez, Nick Oscarson, Akira Hasuike, Ameer N Ghodke, Adam J Kimple, Purushothama R Tata, Scott H Randell, Hyun Koo, Kang I Ko, Kevin M Byrd","doi":"10.1038/s41522-025-00735-5","DOIUrl":"10.1038/s41522-025-00735-5","url":null,"abstract":"<p><p>Mucosal epithelial cells of the upper airways are continuously exposed to microbes throughout life. Specialized niches such as the anterior nares and the tooth are especially susceptible to dysbiosis and chronic inflammatory diseases. Here, we reanalyzed our v1-Human Periodontal Atlas, identifying polybacterial signatures (20% Gram-positive; 80% Gram-negative) and distinct responses of bacterial-associated epithelia. Fluorescence microscopy detected numerous persistent polybacterial intracellular macromolecules (PIMs) within human oral keratinocytes (HOKs), including bacterial rRNA, mRNA, and glycolipids. PIM levels directly correlated with enhanced receptor-ligand signaling in vivo. Inflammatory \"keratokines\" targeting immune cells were synergistically upregulated in lipopolysaccharide-challenged HOKs, while endogenous lipoteichoic acid (LTA) correlated with CXCL1/8 expression in vitro and in vivo. Application of Drug2Cell suggested altered drug efficacy predictions based on PIM detection-agnostic of disease state. CXCL1/8 expression again correlated with LTA in epithelial cells of the nasal cavity, oropharynx, and trachea. Thus, PIMs shape epithelial single-cell profiles across upper airway mucosae.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"100"},"PeriodicalIF":7.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266917","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}
Binu Kundukad, Scott A Rice, Patrick S Doyle, Staffan Kjelleberg
{"title":"Alginate exopolymer significantly modulates the viscoelastic properties and resilience of bacterial biofilms.","authors":"Binu Kundukad, Scott A Rice, Patrick S Doyle, Staffan Kjelleberg","doi":"10.1038/s41522-025-00718-6","DOIUrl":"10.1038/s41522-025-00718-6","url":null,"abstract":"<p><p>Biofilms are viscoelastic gels with a cross-linked network of biopolymers forming an extracellular matrix that protects bacteria from most antimicrobial treatments. This study examines the physical role of the matrix in preventing recolonisation using a mucoid Pseudomonas aeruginosa (P. aeruginosa ΔmucA) and isogenic wild-type Pseudomonas aeruginosa PAO1. We investigated the recolonisation of pre-formed live biofilms and the residual matrix left behind after bacterial eradication with N-acetyl cysteine (NAC). P. aeruginosa ΔmucA, which overproduces alginate, prevented recolonisation through swelling and increased elastic modulus. In contrast, the wild-type P. aeruginosa biofilm matrix exhibited minimal swelling and decreased elasticity, suggesting crosslink breakage. These observations align with polymer physics theories where alginate's polyelectrolyte nature drives swelling through the Donnan effect, enhancing matrix stability. Meanwhile, the Psl-rich wild-type matrix limited swelling but showed reduced mechanical stability. This study underscores the critical role of matrix composition in biofilm mechanics, influencing bacterial protection regardless of viability.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"98"},"PeriodicalIF":7.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258628","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}
Chonghui Zhao, Yehua Peng, Wenfeng Li, Muhammad Fahad Raza, Wenbo Wang, Yi Zhang, Yanping Chen, Jun Guo, Shaokang Huang, Richou Han
{"title":"The role of gut microbiota-gonadal axis in ovary activation of Asian honey bee (Apis cerana) queens.","authors":"Chonghui Zhao, Yehua Peng, Wenfeng Li, Muhammad Fahad Raza, Wenbo Wang, Yi Zhang, Yanping Chen, Jun Guo, Shaokang Huang, Richou Han","doi":"10.1038/s41522-025-00723-9","DOIUrl":"10.1038/s41522-025-00723-9","url":null,"abstract":"<p><p>The gut microbiota-gonadal axis is increasingly recognized, but its reproductive roles remain unclear. Here, we used the Asian honey bee Apis cerana queens as a model to investigate the role of the gut microbiota-gonadal axis on ovary activation. By artificially caging and releasing the mated queens for a short or long period and monitoring the morphological changes of their ovaries, we confirmed that the activation and suppression of the queen ovary could be switched quickly. We found that the ovary weight was positively correlated with the body weight. 16S rRNA sequencing showed ovarian deactivation reduced gut Lactobacillus abundance. Untargeted metabolomics identified purine metabolism as the dominant ovarian pathway, while correlation analyses implicated Lactobacillus in modulating ovarian morphology through purine signaling. This study elucidates microbiota-gonadal crosstalk governing reproduction, providing mechanistic insights with translational potential for reproductive health management.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"97"},"PeriodicalIF":7.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248956","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}
Julia Leeflang, Josephine A Wright, Daniel L Worthley, M Omar Din, Susan L Woods
{"title":"Evolutionary adaptation of probiotics in the gut: selection pressures, optimization strategies, and regulatory challenges.","authors":"Julia Leeflang, Josephine A Wright, Daniel L Worthley, M Omar Din, Susan L Woods","doi":"10.1038/s41522-025-00734-6","DOIUrl":"10.1038/s41522-025-00734-6","url":null,"abstract":"<p><p>Probiotics and live bacterial therapeutics are garnering increased attention for use in human health and have the potential to revolutionise the treatment of gastrointestinal diseases. However, a pervasive feature of bacteria that must be considered in the design of safe and effective probiotics and live bacterial therapeutics is their capacity for rapid evolution, both at the individual (epi)genetic level and in terms of population dynamics. Here we summarise gastrointestinal-specific evolution of bacteria, focussing on genetic and population levels of adaptation to factors such as carbon source availability, environmental stressors, and interactions with the native microbiome. We also address regulatory and safety considerations for the development of probiotics and live biotherapeutics from an evolutionary perspective, with a discussion of methods that utilise evolution to improve probiotic safety and efficacy via directed evolution, in comparison to another popular approach, genetic engineering.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"96"},"PeriodicalIF":7.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248955","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}
Ofri Bar, Stylianos Vagios, Omer Barkai, Joseph Elshirbini, Irene Souter, Jiawu Xu, Kaitlyn James, Charles Bormann, Makiko Mitsunami, Jorge E Chavarro, Philipp Foessleitner, Douglas S Kwon, Moran Yassour, Caroline Mitchell
{"title":"Harnessing vaginal inflammation and microbiome: a machine learning model for predicting IVF success.","authors":"Ofri Bar, Stylianos Vagios, Omer Barkai, Joseph Elshirbini, Irene Souter, Jiawu Xu, Kaitlyn James, Charles Bormann, Makiko Mitsunami, Jorge E Chavarro, Philipp Foessleitner, Douglas S Kwon, Moran Yassour, Caroline Mitchell","doi":"10.1038/s41522-025-00732-8","DOIUrl":"10.1038/s41522-025-00732-8","url":null,"abstract":"<p><p>Humans are the only species with a commensal Lactobacillus-dominant vaginal microbiota. Reproductive tract microbes have been linked to fertility outcomes, as has intrauterine inflammation, suggesting immune response may mediate adverse outcomes. In this pilot study, we compared vaginal microbiota composition and immune marker concentrations between patients with unexplained or male factor infertility (MFI), as a control. We applied a supervised machine learning algorithm that integrated microbiome and inflammation data to predict pregnancy outcomes.Twenty-eight participants provided vaginal swabs at three IVF cycle time points; 18 achieved pregnancy. Pregnant participants had lower microbial diversity and inflammation. Among them, MFI cases had higher diversity but lower inflammation than those with unexplained infertility. Our model showed the highest prediction accuracy at time point 2 of the IVF cycle. These findings suggest that vaginal microbiota and inflammation jointly impact fertility and can inform predictive tools in reproductive medicine.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"95"},"PeriodicalIF":7.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234670","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}
Manisha Behera, Priyanka Singh, Anita Kamra Verma, Sachinandan De, Soma M Ghorai
{"title":"Activity of GS-linked chimeric endolysin CHAPk-SH3bk against methicillin-resistant Staphylococcus aureus biofilms: an in-vitro, ex-vivo and in-vivo study.","authors":"Manisha Behera, Priyanka Singh, Anita Kamra Verma, Sachinandan De, Soma M Ghorai","doi":"10.1038/s41522-025-00728-4","DOIUrl":"10.1038/s41522-025-00728-4","url":null,"abstract":"<p><p>The evolution of antibiotic resistance and the propensity of methicillin-resistant Staphylococcus aureus to form biofilms impedes antibiotic therapy, which enkindles the rummage for novel therapeutic agents like bacteriophage endolysins. This study investigates the biofilm degradation activity of novel chimeric endolysin CHAPk-SH3bk compared to single domain construct CHAPk. The in-vitro biofilm degradation assay displayed higher antibiofilm activity of CHAPk-SH3bk compared to CHAPk on glass and steel surfaces. Treatment of CHAPk-SH3bk effectively inhibited biofilm formation of hospital-associated and bovine-origin MRSA. The in-vivo results displayed a higher reduction of 24 h MRSA-biofilm using CHAPk-SH3bk compared to CHAPk in mice skin infection model. Further, confocal laser scanning microscopy, scanning electron microscopy, and immunohistochemistry confirmed the in-vivo results. The study indicated that attachment of SH3b using glycine-serine linker to CHAPk increased the catalytic domains biofilm reduction ability. The study demonstrates that construction of novel chimeric endolysins by shuffling parental endolysin domains may increase their antibiofilm activity.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"94"},"PeriodicalIF":7.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216420","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":"TSP50 deficiency in neural stem cells aggravates colitis in mice by altering intestinal microbiome.","authors":"Xiaoli Li, Rong Jin, Zhaoxia Wang, Chunxue Niu, Zhenbo Song, Xiaoling Liu, Jian Huang, Huan Zhang, Xia Qian, Feng Gao, Shuyue Wang, Chunlei Yu, Luguo Sun, Yanxin Huang, Lihua Zheng, Guannan Wang, Ying Sun, Xiaoguang Yang, Yongli Bao, Jiawei Li","doi":"10.1038/s41522-025-00737-3","DOIUrl":"10.1038/s41522-025-00737-3","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a complex disease characterized by persistent chronic inflammation of the gastrointestinal tract and periodic episodes. Despite the increasing number of related studies, the detailed pathogenesis of IBD has not been elucidated. In recent years, host-microbiota interactions in the pathogenesis of IBD have received extensive attention. Testes-specific protease 50 (TSP50) is a potential risk gene for IBD, but whether it can affect the susceptibility of colitis by regulating the gut microbiome is still unclear. Here, we showed that TSP50 deficiency in neural stem cells (NSCs) aggravated colitis in mice by altering intestinal microbiome. Mechanistically, TSP50 maintained the level of neurotransmitter acetylcholine (ACh) by degrading acetylcholinesterase (AChE), thereby maintaining intestinal mucosa and intestinal microecological homeostasis and reducing the susceptibility to colitis. These findings provide a new perspective on the interaction between host and commensal microbiota, which may be beneficial for developing potential therapeutic strategies for IBD.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"93"},"PeriodicalIF":7.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216421","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":"Metagenomic analysis reveals the novel role of vaginal Lactobacillus iners in Chinese healthy pregnant women.","authors":"Xudong Wang, Qingru Jiang, Xiaohui Tian, Wei Chen, Junrui Mai, Gan Lin, Yingfang Huo, Haiyang Zheng, Dandan Yan, Xiaohong Wang, Tian Li, Yu Gao, Xiangyu Mou, Wenjing Zhao","doi":"10.1038/s41522-025-00731-9","DOIUrl":"10.1038/s41522-025-00731-9","url":null,"abstract":"<p><p>This study investigated the relationship between vaginal microbiota and women's health conditions in 95 Chinese pregnant women in their third trimester. We conducted vaginal metagenomic analysis, examining species, functional pathways, and genes, and utilized correlation and LEfSe analyses to link microbiota to health conditions. Results revealed that healthy participants exhibited higher levels of Lactobacillus iners, with its abundance associated with tetrahydrofolate biosynthesis pathways. They also possessed more glycosyltransferase and ErmB antibiotic resistance genes compared to women with diagnosed conditions. Comparative genomics demonstrated that L. iners strains linked to bacterial vaginosis (BV) possessed more genes encoding biofilm-associated YhgE/Pip domain-containing proteins than healthy-associated strains. Notably, three BV-associated L. iners strains exhibited stronger biofilm formation abilities than four healthy-associated strains isolated in this study. Also, four out of seven L. iners strains inhibited the growth of Gardnerella vaginalis. Overall, L. iners may help maintain vaginal ecosystem stability in Chinese pregnant women.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"92"},"PeriodicalIF":7.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187390","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}
Hoon Je Seong, Yoon Mee Park, Bong-Soo Kim, Hyun Ju Yoo, Taeyune Kim, Sun Mi Yoon, Jeong-Hyun Kim, So-Yeon Lee, Yun Kyung Lee, Dong-Woo Lee, Myung Hee Nam, Soo-Jong Hong
{"title":"Integrated multi-omics reveals different host crosstalk of atopic dermatitis-enriched Bifidobacterium longum Strains.","authors":"Hoon Je Seong, Yoon Mee Park, Bong-Soo Kim, Hyun Ju Yoo, Taeyune Kim, Sun Mi Yoon, Jeong-Hyun Kim, So-Yeon Lee, Yun Kyung Lee, Dong-Woo Lee, Myung Hee Nam, Soo-Jong Hong","doi":"10.1038/s41522-025-00714-w","DOIUrl":"10.1038/s41522-025-00714-w","url":null,"abstract":"<p><p>The infant gut microbiome is essential for long-term health and is linked to atopic dermatitis (AD), although the underlying mechanisms are not fully understood. This study investigated gut microbiome-host interactions in 31 infants with AD and 29 healthy controls using multi-omics approaches, including metagenomic, host transcriptomic, and metabolomic analyses. Microbial diversity was significantly altered in AD, with Bifidobacterium longum and Clostridium innocuum associated with these changes. At the strain-level, only B. longum differed significantly between groups, with pangenome analyses identifying genetic variations potentially affecting amino acid and lipid metabolites. Notably, B. longum subclade I, which was more prevalent in healthy controls, correlated with host transcriptomic pathways involved in phosphatidylinositol 3-kinase-AKT signaling and neuroactive ligand-receptor pathways, as well as specific metabolites, including tetrahydrocortisol and ornithine. These findings highlight the role of B. longum strain-level variation in infants, offering new insights into microbiome-host interactions related to AD.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"91"},"PeriodicalIF":7.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182932","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":"Mediation effect and metabolic pathways of gut microbiota in the associations between lifestyles and dyslipidemia.","authors":"Lijun Zeng, Bin Yu, Peibin Zeng, Zhuoma Duoji, Haojiang Zuo, Jian Lian, Tingting Yang, Yingxue Dai, Yuemei Feng, Peng Yu, Jiqi Yang, Shujuan Yang, Qingyu Dou","doi":"10.1038/s41522-025-00721-x","DOIUrl":"10.1038/s41522-025-00721-x","url":null,"abstract":"<p><p>Whether the role of gut microbial features lies in the pathways from lifestyles to dyslipidemia remains unclear. In this cross-sectional study, we conducted a metagenome-wide association analysis and fecal metabolomic profiling in 994 adults from the China Multi-Ethnic cohort. A total of 26 microbial species were identified as mediators between lifestyle factors and risk for dyslipidemia. Specifically, the abundance of [Ruminococcus] gnavus mediated the associations between lifestyles and risks for dyslipidemia, elevated low-density lipoprotein cholesterol, elevated total cholesterol, and elevated triglycerides. [Ruminococcus] gnavus, Alistipes shahii, and Lachnospira eligens were replicated to be associated with dyslipidemia in an external validation cohort. The potential metabolic pathways included arachidonic acid, bile acid, and aromatic amino-acid metabolism.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"90"},"PeriodicalIF":7.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174007","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}
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