Pub Date : 2025-12-22DOI: 10.1186/s40168-025-02323-3
Irina Utkina, Yi Fan, Benjamin P Willing, John Parkinson
{"title":"Correction: Metabolic modeling of microbial communities in the chicken ceca reveals a landscape of competition and co-operation.","authors":"Irina Utkina, Yi Fan, Benjamin P Willing, John Parkinson","doi":"10.1186/s40168-025-02323-3","DOIUrl":"10.1186/s40168-025-02323-3","url":null,"abstract":"","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"256"},"PeriodicalIF":12.7,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12720474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810198","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}
Pub Date : 2025-12-22DOI: 10.1186/s40168-025-02316-2
Da Lin, Gong-Yu Lin, Jin-Ting Zheng, Zhi-Hong Qiao, Hua-Yuan Shangguan, Hai-Feng Yao, Tian-Lun Zhang, Jia-Yang Xu, Hongjie Li, Martin F Breed, Xin Sun, Yong-Guan Zhu, Dong Zhu
Background: Biocontrols can be used to manage pests while supporting soil health. However, the effects of the biocontrols such as predatory mites on antibiotic resistance in bacterial communities remains largely unknown. Here, we examined long-term field experiments in tea garden soils, combined with global datasets and soil microcosm experiments, to explore the effects and underlying mechanisms of predatory mite treatment on the abundance of antibiotic resistance genes (ARGs) and virulence factor genes (VFGs).
Results: Predatory mite treatment may intensify the predation pressure exerted by bacterial predators on bacterial communities through trophic cascades. This led to genome streamlining and alterations in microdiversity and functions within the bacterial communities. In this process, members of the phylum Actinobacteriota, especially the family Pseudonocardiaceae, demonstrated greater adaptability, with their relative abundance increasing from 25.0 to 41.8%, due to their higher nucleotide diversity and growth rates compared to other bacterial taxa. These taxa served as the primary hosts for ARGs and VFGs, which were also identified in global datasets, playing a key role in promoting the abundance of ARGs and VFGs in soil ecosystems. The possibility of trophic cascade effects of predatory mites on the dispersal of ARGs and VFGs were further validated through soil microcosm experiments.
Conclusions: These findings advance our understanding of bacterial evolutionary trajectories under biocontrols, which is crucial for slowing the spread of antibiotic resistance and promoting sustainable agriculture. Video Abstract.
{"title":"Effects of predatory mite biocontrols on the dispersal of antibiotic resistomes and virulence factors in tea garden soils.","authors":"Da Lin, Gong-Yu Lin, Jin-Ting Zheng, Zhi-Hong Qiao, Hua-Yuan Shangguan, Hai-Feng Yao, Tian-Lun Zhang, Jia-Yang Xu, Hongjie Li, Martin F Breed, Xin Sun, Yong-Guan Zhu, Dong Zhu","doi":"10.1186/s40168-025-02316-2","DOIUrl":"10.1186/s40168-025-02316-2","url":null,"abstract":"<p><strong>Background: </strong>Biocontrols can be used to manage pests while supporting soil health. However, the effects of the biocontrols such as predatory mites on antibiotic resistance in bacterial communities remains largely unknown. Here, we examined long-term field experiments in tea garden soils, combined with global datasets and soil microcosm experiments, to explore the effects and underlying mechanisms of predatory mite treatment on the abundance of antibiotic resistance genes (ARGs) and virulence factor genes (VFGs).</p><p><strong>Results: </strong>Predatory mite treatment may intensify the predation pressure exerted by bacterial predators on bacterial communities through trophic cascades. This led to genome streamlining and alterations in microdiversity and functions within the bacterial communities. In this process, members of the phylum Actinobacteriota, especially the family Pseudonocardiaceae, demonstrated greater adaptability, with their relative abundance increasing from 25.0 to 41.8%, due to their higher nucleotide diversity and growth rates compared to other bacterial taxa. These taxa served as the primary hosts for ARGs and VFGs, which were also identified in global datasets, playing a key role in promoting the abundance of ARGs and VFGs in soil ecosystems. The possibility of trophic cascade effects of predatory mites on the dispersal of ARGs and VFGs were further validated through soil microcosm experiments.</p><p><strong>Conclusions: </strong>These findings advance our understanding of bacterial evolutionary trajectories under biocontrols, which is crucial for slowing the spread of antibiotic resistance and promoting sustainable agriculture. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":"41"},"PeriodicalIF":12.7,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810281","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}
Pub Date : 2025-12-22DOI: 10.1186/s40168-025-02296-3
Tianyi Dong, Qi Wang, Tengcheng Que, Haorui Si, Jia Su, Ying Chen, Kaixin Yang, Cong Li, Mengjie Qin, Bei Li, Yan Zhu, Shousheng Li, Yingjiao Li, Meihong He, Yanli Zhong, Qingyu Xiao, Ben Hu, Leiping Zeng
Background: Pangolins, the world's most trafficked mammals, have emerged as critical subjects of study due to their potential role as intermediate hosts for zoonotic viruses. While previous studies have primarily focused on diseased pangolins, the virome composition of healthy individuals remains largely unexplored.
Results: To address this knowledge gap, we performed comprehensive metatranscriptomic analysis of 83 healthy pangolins, in comparison with virome data of 52 diseased individuals derived from previously published datasets. We identified 51 viral operational taxonomic units (vOTUs) across six mammalian-associated viral families: Parvoviridae, Picornaviridae, Papillomaviridae, Circoviridae, Flaviviridae, and Paramyxoviridae. Notably, we observed recombination in Morbillivirus canis isolate BJ16B35, Canine distemper virus strain PS, and UN_MBA191024-Paramyxoviridae-1 from pangolins and domestic dogs, suggesting cross-species transmission dynamics. Co-infection analysis revealed a strong positive correlation between Copiparvovirus P171T/pangolin/2018 and Pangolin protoparvovirus, suggesting possible shared transmission pathways. Several viruses, including Orthopneumovirus hominis and Orthorubulavirus mammalis, were exclusively detected in diseased pangolins, implicating their potential role in pathogenesis. Zoonotic risk assessment identified 16 vOTUs with high predicted potential for human infection, including Pangolin pestivirus and Manis javanica papillomavirus 1.
Conclusions: Our findings significantly expand our understanding of viral diversity in healthy pangolins and help distinguish commensal viral communities from potentially pathogenic ones. This research underscores the importance of continued wildlife viral surveillance for both conservation and public health preparedness. Video Abstract.
{"title":"Healthy pangolin virome reveals mammalian viral diversity and zoonotic risk.","authors":"Tianyi Dong, Qi Wang, Tengcheng Que, Haorui Si, Jia Su, Ying Chen, Kaixin Yang, Cong Li, Mengjie Qin, Bei Li, Yan Zhu, Shousheng Li, Yingjiao Li, Meihong He, Yanli Zhong, Qingyu Xiao, Ben Hu, Leiping Zeng","doi":"10.1186/s40168-025-02296-3","DOIUrl":"10.1186/s40168-025-02296-3","url":null,"abstract":"<p><strong>Background: </strong>Pangolins, the world's most trafficked mammals, have emerged as critical subjects of study due to their potential role as intermediate hosts for zoonotic viruses. While previous studies have primarily focused on diseased pangolins, the virome composition of healthy individuals remains largely unexplored.</p><p><strong>Results: </strong>To address this knowledge gap, we performed comprehensive metatranscriptomic analysis of 83 healthy pangolins, in comparison with virome data of 52 diseased individuals derived from previously published datasets. We identified 51 viral operational taxonomic units (vOTUs) across six mammalian-associated viral families: Parvoviridae, Picornaviridae, Papillomaviridae, Circoviridae, Flaviviridae, and Paramyxoviridae. Notably, we observed recombination in Morbillivirus canis isolate BJ16B35, Canine distemper virus strain PS, and UN_MBA191024-Paramyxoviridae-1 from pangolins and domestic dogs, suggesting cross-species transmission dynamics. Co-infection analysis revealed a strong positive correlation between Copiparvovirus P171T/pangolin/2018 and Pangolin protoparvovirus, suggesting possible shared transmission pathways. Several viruses, including Orthopneumovirus hominis and Orthorubulavirus mammalis, were exclusively detected in diseased pangolins, implicating their potential role in pathogenesis. Zoonotic risk assessment identified 16 vOTUs with high predicted potential for human infection, including Pangolin pestivirus and Manis javanica papillomavirus 1.</p><p><strong>Conclusions: </strong>Our findings significantly expand our understanding of viral diversity in healthy pangolins and help distinguish commensal viral communities from potentially pathogenic ones. This research underscores the importance of continued wildlife viral surveillance for both conservation and public health preparedness. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":"42"},"PeriodicalIF":12.7,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810230","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}
Pub Date : 2025-12-18DOI: 10.1186/s40168-025-02239-y
Li Zheng, Xinmin Lv, Anqi Fu, Haojie Fang, Mengbing Li, Shilian Huang, Tom Hsiang
Background: Litchi downy blight (LDB) is a major disease affecting litchi (Litchi chinensis), damaging fruits, inflorescences, and leaves, and significantly hindering the development of the litchi industry in China and globally. Bacillus amyloliquefaciens PP19 has demonstrated significant biocontrol efficacy against LDB, but its mechanism of action remains unclear.
Results: This study used microbiome analysis and bacterial interaction studies to investigate the biocontrol mechanism by which PP19 regulates core microbial communities on litchi exocarps to suppress LDB. First, 16S rRNA diversity analysis revealed that PP19 pretreatment effectively prevented bacterial diversity imbalances caused by Peronophythora litchii infection, maintaining microbial stability by regulating the abundance of specific genera (Actinomycetospora, Paenibacillus, and Spirosoma). Microbial interaction networks and functional prediction revealed that PP19 might modulate bacterial motility pathways, resulting in changes to the abundance of specific microbial communities on litchi exocarps. These changes facilitated the formation of a core microbiome negatively correlated with the abundance of P. litchii. By isolating and genetically identifying 83 cultivable bacterial strains from litchi exocarps and using correlation analysis, 16 candidate strains with potentially significant interactions with PP19 and P. litchii SC18 were identified. Plate antagonism, liquid co-culture, and leaf biocontrol efficacy analyses ultimately identified four representative strains (Sphingomonas sp. F14, Rhizobium sp. F26, Pseudomonas sp. F32, and Enterobacter cloacae F63) with significant interactions with either PP19 or P. litchii. Interaction, motility, and biofilm production analyses showed that PP19 interacted with the four litchi exocarp bacteria to prevent disease through various mechanisms, and enhanced their motility and biofilm production to varying degrees.
Conclusions: PP19 regulates core microbial communities on litchi exocarps, maintaining community stability and enriching interacting strains which together inhibit the growth of P. litchii, thereby achieving biocontrol efficacy. Video Abstract.
{"title":"Bacillus amyloliquefaciens PP19 regulation of microbial communities and suppression of Peronophythora litchii.","authors":"Li Zheng, Xinmin Lv, Anqi Fu, Haojie Fang, Mengbing Li, Shilian Huang, Tom Hsiang","doi":"10.1186/s40168-025-02239-y","DOIUrl":"10.1186/s40168-025-02239-y","url":null,"abstract":"<p><strong>Background: </strong>Litchi downy blight (LDB) is a major disease affecting litchi (Litchi chinensis), damaging fruits, inflorescences, and leaves, and significantly hindering the development of the litchi industry in China and globally. Bacillus amyloliquefaciens PP19 has demonstrated significant biocontrol efficacy against LDB, but its mechanism of action remains unclear.</p><p><strong>Results: </strong>This study used microbiome analysis and bacterial interaction studies to investigate the biocontrol mechanism by which PP19 regulates core microbial communities on litchi exocarps to suppress LDB. First, 16S rRNA diversity analysis revealed that PP19 pretreatment effectively prevented bacterial diversity imbalances caused by Peronophythora litchii infection, maintaining microbial stability by regulating the abundance of specific genera (Actinomycetospora, Paenibacillus, and Spirosoma). Microbial interaction networks and functional prediction revealed that PP19 might modulate bacterial motility pathways, resulting in changes to the abundance of specific microbial communities on litchi exocarps. These changes facilitated the formation of a core microbiome negatively correlated with the abundance of P. litchii. By isolating and genetically identifying 83 cultivable bacterial strains from litchi exocarps and using correlation analysis, 16 candidate strains with potentially significant interactions with PP19 and P. litchii SC18 were identified. Plate antagonism, liquid co-culture, and leaf biocontrol efficacy analyses ultimately identified four representative strains (Sphingomonas sp. F14, Rhizobium sp. F26, Pseudomonas sp. F32, and Enterobacter cloacae F63) with significant interactions with either PP19 or P. litchii. Interaction, motility, and biofilm production analyses showed that PP19 interacted with the four litchi exocarp bacteria to prevent disease through various mechanisms, and enhanced their motility and biofilm production to varying degrees.</p><p><strong>Conclusions: </strong>PP19 regulates core microbial communities on litchi exocarps, maintaining community stability and enriching interacting strains which together inhibit the growth of P. litchii, thereby achieving biocontrol efficacy. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":"40"},"PeriodicalIF":12.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12829244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781062","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}
Background: The development of the small intestine is crucial during early life, with the gut microbiota and microbe-derived metabolites playing key roles in regulating intestinal epithelial barrier function and overall development. However, the underlying mechanism remains unclear. Here, chicks were used to investigate the influences of early-life crosstalk among bacteria, metabolites, and the host on small intestinal development.
Results: We investigated bacterial succession in the small intestine of broiler chicks at four time points during early development. After 3 days post-hatch, Bacillota became the dominant phylum. At the genus level, Lactobacillus and Ligilactobacillus emerged as the two dominant genera, and their abundance was significantly positively correlated with small intestine weight. Metabolome analysis revealed that indole-3-carboxaldehyde (IAld) is derived from both L. gallinarum C2-16-2 (LG) and L. salivarius D7-21 (LS). Moreover, we found that IAld can be converted into bioactive indole-3-carboxylic acid (ICA) in animals, which exhibited greater biological activity than IAld in vitro. Further chick feeding trials revealed that both bacteria (LG and LS) and metabolites (IAld and ICA) promoted epithelial barrier function and enhanced antioxidant capacity during early life in chicks. Moreover, both IAld and ICA promoted tight junction protein expression and enhanced antioxidant capacity by activating AHR-NRF2 signaling.
Conclusions: These findings suggest that specific bacterial strains (L. gallinarum C2-16-2 and L. salivarius D7-21) and metabolites (IAld and ICA) serve as effective promoters of intestinal epithelial barrier function and antioxidant capacity during early intestinal development in chicks Video Abstract.
{"title":"Gut microbiome-derived indole-3-carboxaldehyde promotes intestinal development via AHR-NRF2 signaling in the early-life of chicks.","authors":"Yu-Xuan Huang, Zhang-Chao Deng, Ke-Xin Cao, Jia-Cheng Yang, Meng Liu, Ling Zhao, Jin-Shui Zheng, Lv-Hui Sun","doi":"10.1186/s40168-025-02289-2","DOIUrl":"10.1186/s40168-025-02289-2","url":null,"abstract":"<p><strong>Background: </strong>The development of the small intestine is crucial during early life, with the gut microbiota and microbe-derived metabolites playing key roles in regulating intestinal epithelial barrier function and overall development. However, the underlying mechanism remains unclear. Here, chicks were used to investigate the influences of early-life crosstalk among bacteria, metabolites, and the host on small intestinal development.</p><p><strong>Results: </strong>We investigated bacterial succession in the small intestine of broiler chicks at four time points during early development. After 3 days post-hatch, Bacillota became the dominant phylum. At the genus level, Lactobacillus and Ligilactobacillus emerged as the two dominant genera, and their abundance was significantly positively correlated with small intestine weight. Metabolome analysis revealed that indole-3-carboxaldehyde (IAld) is derived from both L. gallinarum C2-16-2 (LG) and L. salivarius D7-21 (LS). Moreover, we found that IAld can be converted into bioactive indole-3-carboxylic acid (ICA) in animals, which exhibited greater biological activity than IAld in vitro. Further chick feeding trials revealed that both bacteria (LG and LS) and metabolites (IAld and ICA) promoted epithelial barrier function and enhanced antioxidant capacity during early life in chicks. Moreover, both IAld and ICA promoted tight junction protein expression and enhanced antioxidant capacity by activating AHR-NRF2 signaling.</p><p><strong>Conclusions: </strong>These findings suggest that specific bacterial strains (L. gallinarum C2-16-2 and L. salivarius D7-21) and metabolites (IAld and ICA) serve as effective promoters of intestinal epithelial barrier function and antioxidant capacity during early intestinal development in chicks Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":"34"},"PeriodicalIF":12.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768498","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}
Background: Habitat fragmentation and degradation have led to the critical endangerment of numerous wild plant species. Although significant achievements in the conservation of endangered wild plants in various regions worldwide, the interaction mechanisms between these plants and their associated rhizosphere microorganisms have yet to be fully elucidated.
Results: Here, we present a communication model between the endangered wild plant Qingdao lily (Lilium tsingtauense) and its associated rhizosphere microorganisms. We isolated a rhizosphere fungus, Trichoderma longibrachiatum QDAU 0920, which effectively colonizes the roots of Qingdao lily and significantly promotes root growth. This growth enhancement is mediated by multiple plant hormones, with auxin playing a particularly prominent role. Further investigation revealed that a non-canonical AUX/IAA protein of the LtIAA16 may augment the transcriptional activation activity of LtARF22 by competitively interacting with LtIAA6, LtIAA17, and LtIAA11, thereby facilitating root growth in Qingdao lily. The growth-promoting effects of this interaction were subsequently validated in several other plant species, including tomato, pepper, corn, pumpkin, and cucumber. Notably, T. longibrachiatum QDAU 0920 forms synthetic microbial consortia (SynComs) in conjunction with other Trichoderma and Penicillium species. These SynComs consistently enhance the growth of Qingdao lily as well as other lily species such as L. lancifolium, Lilium 'Avalon Sunset', and Lilium 'Deliana'.
Conclusion: Collectively, these findings underscore the considerable potential of native microorganisms in the development of plant growth-promoting agents and the conservation of endangered plant species. Video Abstract.
{"title":"Synthetic microbial community in pristine environment promotes the growth of the endangered plant Lilium tsingtauense.","authors":"Boda Liu, Xiang Li, Jinming Yang, Wanpei Lu, Guohao Tang, Yaru Shi, Jiaxing Li, Anning Ding, Hai Wang, Xuebin Song, Qingchao Liu, Xinqiang Jiang","doi":"10.1186/s40168-025-02281-w","DOIUrl":"10.1186/s40168-025-02281-w","url":null,"abstract":"<p><strong>Background: </strong>Habitat fragmentation and degradation have led to the critical endangerment of numerous wild plant species. Although significant achievements in the conservation of endangered wild plants in various regions worldwide, the interaction mechanisms between these plants and their associated rhizosphere microorganisms have yet to be fully elucidated.</p><p><strong>Results: </strong>Here, we present a communication model between the endangered wild plant Qingdao lily (Lilium tsingtauense) and its associated rhizosphere microorganisms. We isolated a rhizosphere fungus, Trichoderma longibrachiatum QDAU 0920, which effectively colonizes the roots of Qingdao lily and significantly promotes root growth. This growth enhancement is mediated by multiple plant hormones, with auxin playing a particularly prominent role. Further investigation revealed that a non-canonical AUX/IAA protein of the LtIAA16 may augment the transcriptional activation activity of LtARF22 by competitively interacting with LtIAA6, LtIAA17, and LtIAA11, thereby facilitating root growth in Qingdao lily. The growth-promoting effects of this interaction were subsequently validated in several other plant species, including tomato, pepper, corn, pumpkin, and cucumber. Notably, T. longibrachiatum QDAU 0920 forms synthetic microbial consortia (SynComs) in conjunction with other Trichoderma and Penicillium species. These SynComs consistently enhance the growth of Qingdao lily as well as other lily species such as L. lancifolium, Lilium 'Avalon Sunset', and Lilium 'Deliana'.</p><p><strong>Conclusion: </strong>Collectively, these findings underscore the considerable potential of native microorganisms in the development of plant growth-promoting agents and the conservation of endangered plant species. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":"36"},"PeriodicalIF":12.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768487","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}
Pub Date : 2025-12-16DOI: 10.1186/s40168-025-02294-5
Qiankun Chen, Leying Wang, Yuan Wei, Xizhan Xu, Zhenyu Wei, Yan Peng, Jinding Pang, Bo Peng, Qingquan Shi, Ahyan Ilman Qudsi, Qingfeng Liang
Background: The ocular surface microbiome (OSM) in patients with meibomian gland dysfunction (MGD) differs from that of healthy individuals. However, the precise role of OSM in MGD remains unknown. Therefore, we aimed to investigate the mechanism of OSM in the inflammation of MGD and the effects of topical sodium butyrate (SB) treatment in ApoE-/- mice.
Methods: ApoE-/- (n = 36) and wild-type C57BL/6J (n = 16) mice served as MGD models and healthy controls, respectively. MGD mice were treated with safety-confirmed concentrations of SB (1, 5, and 10 mM) and PBS for 3 weeks. OSM was analyzed by 16S rRNA gene sequencing (V3-V4). The slit-lamp biomicroscopy, tear cytokines, histopathology (oil red O/PAS/TUNEL staining), and TLR4/MyD88/NF-κB signaling (RT-qPCR, immunohistochemistry, and Western blotting) were evaluated.
Results: Five-month-old ApoE-/- mice exhibited typical clinical and histological features of MGD. These mice exhibited elevated tear levels of inflammatory cytokines and activation of the TLR4/NF-κB signaling pathway in the MGs and conjunctivae. Treatment with SB improved the corneal fluorescein staining score of MGD. The ApoE-/- mice demonstrated dysbiosis of OSM, characterized by an increase in Proteobacteria and a decrease in Bacteroidota. Additionally, the relative abundance of Muribacter and Muribacter muris increased in ApoE-/- mice, while that of Staphylococcus and Staphylococcus lentus decreased, and these alterations were restored by SB treatment. SB also reduced the expression of the TLR4/NF-κB p65 signaling pathway, inflammatory cytokines, and apoptosis in MGs and conjunctival tissues.
Conclusion: ApoE-/- mice exhibited characteristic features of MGD, accompanied by dysbiosis of OSM. Topical administration of SB modulated the OSM and reduced MGD-associated inflammation. Video Abstract.
{"title":"Sodium butyrate modulates ocular surface microbiome and attenuates inflammation of meibomian gland dysfunction in ApoE<sup>-/-</sup> mice.","authors":"Qiankun Chen, Leying Wang, Yuan Wei, Xizhan Xu, Zhenyu Wei, Yan Peng, Jinding Pang, Bo Peng, Qingquan Shi, Ahyan Ilman Qudsi, Qingfeng Liang","doi":"10.1186/s40168-025-02294-5","DOIUrl":"10.1186/s40168-025-02294-5","url":null,"abstract":"<p><strong>Background: </strong>The ocular surface microbiome (OSM) in patients with meibomian gland dysfunction (MGD) differs from that of healthy individuals. However, the precise role of OSM in MGD remains unknown. Therefore, we aimed to investigate the mechanism of OSM in the inflammation of MGD and the effects of topical sodium butyrate (SB) treatment in ApoE<sup>-/-</sup> mice.</p><p><strong>Methods: </strong>ApoE<sup>-/-</sup> (n = 36) and wild-type C57BL/6J (n = 16) mice served as MGD models and healthy controls, respectively. MGD mice were treated with safety-confirmed concentrations of SB (1, 5, and 10 mM) and PBS for 3 weeks. OSM was analyzed by 16S rRNA gene sequencing (V3-V4). The slit-lamp biomicroscopy, tear cytokines, histopathology (oil red O/PAS/TUNEL staining), and TLR4/MyD88/NF-κB signaling (RT-qPCR, immunohistochemistry, and Western blotting) were evaluated.</p><p><strong>Results: </strong>Five-month-old ApoE<sup>-/-</sup> mice exhibited typical clinical and histological features of MGD. These mice exhibited elevated tear levels of inflammatory cytokines and activation of the TLR4/NF-κB signaling pathway in the MGs and conjunctivae. Treatment with SB improved the corneal fluorescein staining score of MGD. The ApoE<sup>-/-</sup> mice demonstrated dysbiosis of OSM, characterized by an increase in Proteobacteria and a decrease in Bacteroidota. Additionally, the relative abundance of Muribacter and Muribacter muris increased in ApoE<sup>-/-</sup> mice, while that of Staphylococcus and Staphylococcus lentus decreased, and these alterations were restored by SB treatment. SB also reduced the expression of the TLR4/NF-κB p65 signaling pathway, inflammatory cytokines, and apoptosis in MGs and conjunctival tissues.</p><p><strong>Conclusion: </strong>ApoE<sup>-/-</sup> mice exhibited characteristic features of MGD, accompanied by dysbiosis of OSM. Topical administration of SB modulated the OSM and reduced MGD-associated inflammation. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":"33"},"PeriodicalIF":12.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12822004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768524","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}
Pub Date : 2025-12-15DOI: 10.1186/s40168-025-02224-5
Xi Chen, Fangxing Zhang, Lang Cheng, Decao Niu, Jianpei Hu, Shengzhu Huang, Fubo Wang, Guijian Pang, Caisheng Huang, Mingli Li, Chao Wang, Zengnan Mo
Background: The prevalence of calcium oxalate (CaOx) kidney stones is increasing, yet the underlying mechanisms remain incompletely understood. Emerging evidence suggests that gut microbiota-particularly short-chain fatty acid (SCFA)-producing bacteria-may modulate host metabolism and inflammation, thereby influencing stone formation. However, the mechanistic links between gut dysbiosis, metabolic disturbances, and CaOx stone pathophysiology remain to be fully elucidated. This study investigates gut microbiota composition, SCFA levels, and metabolomic alterations in CaOx stone formers (CSF), aiming to uncover potential pathophysiological mechanisms and therapeutic targets.
Results: Among 59 CSF and 60 healthy controls (HC), CSF exhibited significantly reduced microbial richness, with marked depletion of SCFA-producing bacteria such as Faecalibacterium prausnitzii and Eubacterium rectale. This dysbiosis was associated with decreased fecal and plasma SCFA levels, reduced 24-h urinary citrate, and widespread metabolic disturbances, particularly in tryptophan metabolism and the citrate cycle. Plasma SCFA levels were positively correlated with urinary citrate excretion, suggesting a regulatory link within the gut-kidney axis. Mendelian randomization analysis suggested that Bacteroides thetaiotaomicron may be a potential microbial risk factor for stone formation (OR = 1.26, 95% CI: 1.03-1.54, p = 0.028). In a hyperoxaluria rat model, interventions with F. prausnitzii, E. rectale, or sodium butyrate reduced renal CaOx crystal deposition and kidney injury.
Conclusions: Our findings highlight the central role of SCFA-producing bacteria and their metabolites in maintaining metabolic balance and protecting against CaOx stone formation. Gut dysbiosis and reduced SCFA levels appear to drive metabolic changes that contribute to stone development. B. thetaiotaomicron may increase stone risk, while F. prausnitzii, E. rectale, and sodium butyrate show therapeutic potential. These insights support further exploration of microbiome-based strategies for the prevention and personalized management of kidney stones. Video Abstract.
背景:草酸钙(CaOx)肾结石的患病率正在上升,但其潜在的机制仍不完全清楚。新出现的证据表明,肠道微生物群——尤其是产生短链脂肪酸(SCFA)的细菌——可能调节宿主的代谢和炎症,从而影响结石的形成。然而,肠道生态失调、代谢紊乱和CaOx结石病理生理之间的机制联系仍有待充分阐明。本研究探讨了CaOx结石患者(CSF)的肠道微生物群组成、SCFA水平和代谢组学改变,旨在揭示潜在的病理生理机制和治疗靶点。结果:在59例脑脊液和60例健康对照(HC)中,脑脊液的微生物丰富度显著降低,产生scfa的细菌如prausnitzii粪杆菌和直肠真杆菌明显减少。这种生态失调与粪便和血浆SCFA水平降低、24小时尿柠檬酸降低以及广泛的代谢紊乱(尤其是色氨酸代谢和柠檬酸循环紊乱)有关。血浆SCFA水平与尿柠檬酸排泄呈正相关,提示肠-肾轴内存在调节联系。孟德尔随机化分析提示拟杆菌可能是结石形成的潜在微生物危险因素(OR = 1.26, 95% CI: 1.03-1.54, p = 0.028)。在高草酸尿大鼠模型中,prausnitzii、rectale或丁酸钠干预可减少肾CaOx晶体沉积和肾损伤。结论:我们的研究结果强调了产生scfa的细菌及其代谢物在维持代谢平衡和防止CaOx结石形成方面的核心作用。肠道生态失调和SCFA水平降低似乎会推动代谢变化,从而导致结石的发生。B. taiotaomicron可能增加结石风险,而F. prausnitzii, E. rectale和丁酸钠具有治疗潜力。这些见解支持进一步探索基于微生物组的肾结石预防和个性化管理策略。视频摘要。
{"title":"Dysbiosis of the gut microbiota in calcium oxalate nephrolithiasis is associated with impaired short-chain fatty acid production and systemic metabolomic disruptions.","authors":"Xi Chen, Fangxing Zhang, Lang Cheng, Decao Niu, Jianpei Hu, Shengzhu Huang, Fubo Wang, Guijian Pang, Caisheng Huang, Mingli Li, Chao Wang, Zengnan Mo","doi":"10.1186/s40168-025-02224-5","DOIUrl":"10.1186/s40168-025-02224-5","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of calcium oxalate (CaOx) kidney stones is increasing, yet the underlying mechanisms remain incompletely understood. Emerging evidence suggests that gut microbiota-particularly short-chain fatty acid (SCFA)-producing bacteria-may modulate host metabolism and inflammation, thereby influencing stone formation. However, the mechanistic links between gut dysbiosis, metabolic disturbances, and CaOx stone pathophysiology remain to be fully elucidated. This study investigates gut microbiota composition, SCFA levels, and metabolomic alterations in CaOx stone formers (CSF), aiming to uncover potential pathophysiological mechanisms and therapeutic targets.</p><p><strong>Results: </strong>Among 59 CSF and 60 healthy controls (HC), CSF exhibited significantly reduced microbial richness, with marked depletion of SCFA-producing bacteria such as Faecalibacterium prausnitzii and Eubacterium rectale. This dysbiosis was associated with decreased fecal and plasma SCFA levels, reduced 24-h urinary citrate, and widespread metabolic disturbances, particularly in tryptophan metabolism and the citrate cycle. Plasma SCFA levels were positively correlated with urinary citrate excretion, suggesting a regulatory link within the gut-kidney axis. Mendelian randomization analysis suggested that Bacteroides thetaiotaomicron may be a potential microbial risk factor for stone formation (OR = 1.26, 95% CI: 1.03-1.54, p = 0.028). In a hyperoxaluria rat model, interventions with F. prausnitzii, E. rectale, or sodium butyrate reduced renal CaOx crystal deposition and kidney injury.</p><p><strong>Conclusions: </strong>Our findings highlight the central role of SCFA-producing bacteria and their metabolites in maintaining metabolic balance and protecting against CaOx stone formation. Gut dysbiosis and reduced SCFA levels appear to drive metabolic changes that contribute to stone development. B. thetaiotaomicron may increase stone risk, while F. prausnitzii, E. rectale, and sodium butyrate show therapeutic potential. These insights support further exploration of microbiome-based strategies for the prevention and personalized management of kidney stones. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":"35"},"PeriodicalIF":12.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12822354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763027","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}
Background: Although the roles of rumen microbiome in milk yield and milk protein synthesis have been widely recognized, knowledge on how ruminal microbiome dynamic changes affect these two traits during the whole lactation is lacking. Phages have been shown to affect the microbiota, but little is known about the shift patterns of ruminal phages and if they may modulate rumen microbiome during lactation. Herein, a longitudinal study was performed to identify the potential roles of ruminal phageome and bacteriome interactions, and metabolic function shift in affecting milk yield and protein content using metagenomic and metabolomic profiling of rumen microbiome from the peak, early, and later mid-lactation stages.
Results: A total of 780 ruminal bacterial phages were identified, which exhibited two primary shifting patterns: (1) decreasing then increasing; (2) decreasing then stabilizing through the lactation. Bacteriome also showed first increasing then stabilizing or continuously declining besides exhibiting two similar shifting patterns to those of phages. By associating the differentially abundant phages with their host bacteria, we observed that significantly increased Lactococcus phage BM13, Corynebacterium phage P1201, and Campylobacter phage CJIE4-5 in peak lactation, along with Lactobacillus phage Lv-1 in early and later mid-lactation, were positively correlated with the relative abundance of their hosts. However, significantly increased Bacillus phage BCU4 and the Enterococcus phage phiNASRA1 in early mid-lactation were negatively related to their host abundance. In terms of bacteria, Ruminococcus flavefaciens and Faecalibacterium sp. CAG 74 had the highest abundance in peak lactation, whereas most Prevotella species were more abundant in early and later mid-lactation. Notably, ruminal carbohydrate and amino acid metabolism functions were enhanced in early mid-lactation. Further structural equation model and network analysis revealed that abundant Bacillus phage BCU4 and Enterococcus phage phiNASRA1 in early mid-lactation were associated with increased relative abundance of Prevotella species, possibly due to a reduction in Bacillus cereus and Enterococcus faecalis. Additionally, these Prevotella species exhibited positive relationships with rumen metabolites, such as L-phenylalanine, phenylacetylglycine, N-acetyl-D-phenylalanine, and propionate content, which contributed to the improved milk protein yield.
Conclusions: This study revealed the bacteriome and phageome interactions at different lactation stages, and the key phages and bacteria regulating the rumen function and metabolism thus contributing to the milk traits of cows. The potential regulatory roles of phages in affecting the rumen bacteriome suggest that they can be powerful targets for future interventions to improve rumen functions. Video Abstract.
背景:虽然瘤胃微生物组在产奶量和乳蛋白合成中的作用已被广泛认识,但在整个哺乳过程中,瘤胃微生物组动态变化如何影响这两项性状的知识尚缺乏。噬菌体已被证明会影响微生物群,但对瘤胃噬菌体的转移模式以及它们是否可能在哺乳期调节瘤胃微生物群知之甚少。本研究通过对泌乳高峰期、泌乳早期和泌乳中期后期的瘤胃微生物组进行宏基因组和代谢组学分析,以确定瘤胃噬菌体和细菌组相互作用以及代谢功能转移在影响产奶量和蛋白质含量方面的潜在作用。结果:共鉴定出780个瘤胃细菌噬菌体,呈先减少后增加的两种主要变化规律;(2)在哺乳期先下降后稳定。细菌组除了表现出与噬菌体相似的两种变化模式外,还表现出先增加后稳定或持续下降的趋势。通过将噬菌体的丰度差异与其宿主菌相关联,我们发现乳酸菌噬菌体乳球菌BM13、杆状杆菌噬菌体P1201和弯曲杆菌噬菌体CJIE4-5在泌乳高峰期显著增加,乳酸菌噬菌体Lv-1在泌乳早期和后期中期显著增加,与宿主相对丰度呈正相关。而芽孢杆菌噬菌体BCU4和肠球菌噬菌体phiNASRA1在泌乳早期中期显著升高与其宿主丰度呈负相关。细菌方面,黄瘤球菌(Ruminococcus flavefaciens)和粪杆菌(Faecalibacterium sp. CAG 74)在泌乳高峰期丰度最高,而普雷沃氏菌(Prevotella)多数在泌乳早期和后期丰度较高。值得注意的是,泌乳早期中期瘤胃碳水化合物和氨基酸代谢功能增强。进一步的结构方程模型和网络分析显示,哺乳期早期中期丰富的噬菌体芽孢杆菌BCU4和噬菌体肠球菌phiNASRA1与普雷沃氏菌的相对丰度增加有关,可能是蜡样芽孢杆菌和粪肠球菌减少所致。此外,这些普雷沃菌种类与瘤胃代谢产物l-苯丙氨酸、苯乙酰甘氨酸、n -乙酰- d -苯丙氨酸和丙酸含量呈正相关,有助于提高乳蛋白产量。结论:本研究揭示了不同泌乳期细菌组与噬菌体的相互作用,以及调节瘤胃功能和代谢的关键噬菌体和细菌对奶牛产奶性状的影响。噬菌体在影响瘤胃细菌群方面的潜在调节作用表明,它们可以成为未来干预改善瘤胃功能的有力靶点。视频摘要。
{"title":"Unraveling the interaction between the phageome and bacteriome in the rumen and its role in influencing metabolome dynamics in dairy cows at different lactation stages.","authors":"Mengya Wang, Chenguang Zhang, Lichao Zhao, Qingyan Yin, Zhijie Cui, Xiaodong Chen, Jianrong Ren, Yue Wang, Ming Xu, Yangchun Cao, Shengru Wu, Junhu Yao","doi":"10.1186/s40168-025-02260-1","DOIUrl":"10.1186/s40168-025-02260-1","url":null,"abstract":"<p><strong>Background: </strong>Although the roles of rumen microbiome in milk yield and milk protein synthesis have been widely recognized, knowledge on how ruminal microbiome dynamic changes affect these two traits during the whole lactation is lacking. Phages have been shown to affect the microbiota, but little is known about the shift patterns of ruminal phages and if they may modulate rumen microbiome during lactation. Herein, a longitudinal study was performed to identify the potential roles of ruminal phageome and bacteriome interactions, and metabolic function shift in affecting milk yield and protein content using metagenomic and metabolomic profiling of rumen microbiome from the peak, early, and later mid-lactation stages.</p><p><strong>Results: </strong>A total of 780 ruminal bacterial phages were identified, which exhibited two primary shifting patterns: (1) decreasing then increasing; (2) decreasing then stabilizing through the lactation. Bacteriome also showed first increasing then stabilizing or continuously declining besides exhibiting two similar shifting patterns to those of phages. By associating the differentially abundant phages with their host bacteria, we observed that significantly increased Lactococcus phage BM13, Corynebacterium phage P1201, and Campylobacter phage CJIE4-5 in peak lactation, along with Lactobacillus phage Lv-1 in early and later mid-lactation, were positively correlated with the relative abundance of their hosts. However, significantly increased Bacillus phage BCU4 and the Enterococcus phage phiNASRA1 in early mid-lactation were negatively related to their host abundance. In terms of bacteria, Ruminococcus flavefaciens and Faecalibacterium sp. CAG 74 had the highest abundance in peak lactation, whereas most Prevotella species were more abundant in early and later mid-lactation. Notably, ruminal carbohydrate and amino acid metabolism functions were enhanced in early mid-lactation. Further structural equation model and network analysis revealed that abundant Bacillus phage BCU4 and Enterococcus phage phiNASRA1 in early mid-lactation were associated with increased relative abundance of Prevotella species, possibly due to a reduction in Bacillus cereus and Enterococcus faecalis. Additionally, these Prevotella species exhibited positive relationships with rumen metabolites, such as L-phenylalanine, phenylacetylglycine, N-acetyl-D-phenylalanine, and propionate content, which contributed to the improved milk protein yield.</p><p><strong>Conclusions: </strong>This study revealed the bacteriome and phageome interactions at different lactation stages, and the key phages and bacteria regulating the rumen function and metabolism thus contributing to the milk traits of cows. The potential regulatory roles of phages in affecting the rumen bacteriome suggest that they can be powerful targets for future interventions to improve rumen functions. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":"257"},"PeriodicalIF":12.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12739858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763123","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}
Background: Bovine endometritis is a prevalent uterine disease that directly curtails reproductive performance and indirectly reduces milk production by increasing calving intervals. Postpartum uterine bacterial infection is the primary cause of bovine endometritis, which is typically treated with prostaglandin F2α and antimicrobials. However, abuse of antimicrobials has led to the emergence of multidrug-resistant bacteria, threatening both human and animal health. To explore alternatives to antimicrobial therapy for bovine endometritis, we integrated uterine metagenomic and metabolomic analyses and identified a novel bioactive metabolite with therapeutic potential. The potential antibacterial and anti-inflammatory effects of this metabolite against bovine endometritis were evaluated by assessing its inhibitory effect on the growth of F. necrophorum in vitro, and by quantifying histopathological scores and inflammatory cytokine expression levels in an in vivo mouse model of endometritis, respectively.
Results: A total of 40 Holstein dairy cows at 21 days to 30 days postpartum were assigned into heathy cows (n = 15), subclinical endometritis cows (n = 12) and clinical endometritis cows (n = 13) according to clinical signs and laboratory tests for bovine endometritis. The uterine fluid was collected aseptically for metagenomics and metabolomics sequencing to identify bacterial species associated with bovine endometritis and metabolites that could potentially be used for treatment of bovine endometritis. A total of 17 bacterial species were significantly associated with bovine endometritis, with Fusobacterium necrophorum as the most significantly enriched in cows with clinical endometritis compared to healthy counterparts. In total, 391 metabolites were significantly differentially abundant between healthy and clinical endometritis cows. Among these, a plant-derived compound, tenacissoside G was significantly enriched in healthy cows. Notably, the abundance of F. necrophorum was significantly negatively associated with the concentration of tenacissoside G in clinical endometritis cows. Moreover, tenacissoside G significantly inhibited the growth of F. necrophorum in vitro and ameliorated inflammation in endometritis caused by F. necrophorum in a mice model.
Conclusion: This study provides new insights into the relationship between uterine microbiome and metabolites in bovine endometritis, potentially leading to novel strategies for treating bovine endometritis. Furthermore, tenacissoside G exhibits therapeutic effects against endometritis induced by F. necrophorum, and could serve as a potential alternative to antimicrobials for treating endometritis. Video Abstract.
{"title":"Integrated metagenomic and metabolomic analyses reveal tenacissoside G as a potential non-antimicrobial treatment for bovine endometritis.","authors":"Qiqi Cao, Zhaoju Deng, Moli Li, Shiquan Zhu, Yihui Huo, Hailong Dong, Ben Aernouts, Androniki Psifidi, Chuang Xu","doi":"10.1186/s40168-025-02264-x","DOIUrl":"10.1186/s40168-025-02264-x","url":null,"abstract":"<p><strong>Background: </strong>Bovine endometritis is a prevalent uterine disease that directly curtails reproductive performance and indirectly reduces milk production by increasing calving intervals. Postpartum uterine bacterial infection is the primary cause of bovine endometritis, which is typically treated with prostaglandin F2α and antimicrobials. However, abuse of antimicrobials has led to the emergence of multidrug-resistant bacteria, threatening both human and animal health. To explore alternatives to antimicrobial therapy for bovine endometritis, we integrated uterine metagenomic and metabolomic analyses and identified a novel bioactive metabolite with therapeutic potential. The potential antibacterial and anti-inflammatory effects of this metabolite against bovine endometritis were evaluated by assessing its inhibitory effect on the growth of F. necrophorum in vitro, and by quantifying histopathological scores and inflammatory cytokine expression levels in an in vivo mouse model of endometritis, respectively.</p><p><strong>Results: </strong>A total of 40 Holstein dairy cows at 21 days to 30 days postpartum were assigned into heathy cows (n = 15), subclinical endometritis cows (n = 12) and clinical endometritis cows (n = 13) according to clinical signs and laboratory tests for bovine endometritis. The uterine fluid was collected aseptically for metagenomics and metabolomics sequencing to identify bacterial species associated with bovine endometritis and metabolites that could potentially be used for treatment of bovine endometritis. A total of 17 bacterial species were significantly associated with bovine endometritis, with Fusobacterium necrophorum as the most significantly enriched in cows with clinical endometritis compared to healthy counterparts. In total, 391 metabolites were significantly differentially abundant between healthy and clinical endometritis cows. Among these, a plant-derived compound, tenacissoside G was significantly enriched in healthy cows. Notably, the abundance of F. necrophorum was significantly negatively associated with the concentration of tenacissoside G in clinical endometritis cows. Moreover, tenacissoside G significantly inhibited the growth of F. necrophorum in vitro and ameliorated inflammation in endometritis caused by F. necrophorum in a mice model.</p><p><strong>Conclusion: </strong>This study provides new insights into the relationship between uterine microbiome and metabolites in bovine endometritis, potentially leading to novel strategies for treating bovine endometritis. Furthermore, tenacissoside G exhibits therapeutic effects against endometritis induced by F. necrophorum, and could serve as a potential alternative to antimicrobials for treating endometritis. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":"32"},"PeriodicalIF":12.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12822356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752002","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}