Microbiome最新文献

{"title":"Lactiplantibacillus plantarum attenuate gossypol-induced hepatic lipotoxicity by altering intestinal microbiota for enriching microbial tryptophan metabolites in Nile tilapia (Oreochromis niloticus).","authors":"Fei-Fei Ding, Nan-Nan Zhou, Yue-Jian Mao, Jing Yang, Samwel M Limbu, Jorge Galindo-Villegas, Zhen-Yu Du, Mei-Ling Zhang","doi":"10.1186/s40168-025-02172-0","DOIUrl":"10.1186/s40168-025-02172-0","url":null,"abstract":"<p><strong>Background: </strong>Free fatty acids (FFAs) are the main cause of fatty liver disease, which can be alleviated by modulation of intestinal microbiota. Lactiplantibacillus plantarum plays a key role in maintaining liver health, but the underlying mechanism remains unclear.</p><p><strong>Results: </strong>Here, a strain affiliated to Lactiplantibacillus plantarum was isolated from the intestine of Nile tilapia (Oreochromis niloticus). We used a gossypol-induced fatty liver disease model, which only increased the FFAs level in liver, to investigate the effectiveness of L. plantarum (YC17) in alleviating FFAs-induced lipotoxicity liver injury. We found that dietary gossypol (GOS) induced a significant increase of FFAs in liver, resulting in lipotoxicity in Nile tilapia compared to control. L. plantarum YC17 supplementation reduced FFAs content by restoring esterification process, and then relieved liver injury. Addition of L. plantarum YC17 effectively increased the abundances of Lactobacillus, Clostridium and Cetobacterium in fish intestine, as well as serum levels of the microbial tryptophan metabolites, notably indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). The addition of L. plantarum YC17 significantly inhibited P53 signaling pathway and up-regulated the expression of FFAs esterification genes. In vitro experiments demonstrated that IPA inhibited P53 through ubiquitination and enhanced FFAs esterification in an aryl hydrocarbon receptor (Ahr) dependent manner.</p><p><strong>Conclusion: </strong>The gut microbiota-derived tryptophan metabolites (IPA and IAA) alleviated FFAs induced lipotoxic liver injury by activating Ahr, which promoted P53 ubiquitination, leading to the enhanced FFAs esterification. Our findings demonstrated that gut microbial metabolites alleviated lipotoxicity by promoting the esterification of FFAs in the liver, offering new insights into the study of probiotics and microbial tryptophan metabolites in fatty liver disease. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"180"},"PeriodicalIF":12.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784643","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":"The influence of vaginal microbiota on ewe fertility: a metagenomic and functional genomic approach.","authors":"Edgar L Reinoso-Peláez, María Saura, Carmen González, Manuel Ramón, Jorge H Calvo, Magdalena Serrano","doi":"10.1186/s40168-025-02165-z","DOIUrl":"10.1186/s40168-025-02165-z","url":null,"abstract":"<p><strong>Background: </strong>Despite advancements in artificial insemination, sheep fertility rates remain suboptimal. Recent studies in other species highlight the critical role of reproductive microbiota in influencing fertility outcomes. This research explores the relationship between ovine vaginal microbiota, associated functional pathways, and fertility using advanced nanopore long-reading metagenomic sequencing on 297 ewes from three Spanish breeds across four herds. The study aimed to describe a core vaginal microbiota, analyse the complex interactions with herd, breed, age, and parity factors, and identify taxa and genes associated with reproductive success by artificial insemination.</p><p><strong>Results: </strong>The study identified Staphylococcus, Escherichia, and Histophilus as the most abundant genera. Microbial communities varied considerably between breeds and herds, with high predictive accuracy (> 90%) in classification models. Differential abundance analysis revealed that the genera Histophilus, Fusobacterium, Bacteroides, Campylobacter, Streptobacillus, Gemella, Peptoniphilus, Helococcus, Treponema, Tissierella, and Phocaeicola were more abundant in non-pregnant ewes. Some of these taxa were also associated with four COG entries and one KEGG orthologue significantly linked to non-pregnancy, primarily involving carbohydrate metabolism, defence mechanisms, and structural resilience. Age and parity were also associated with microbiota composition, particularly in ewes older than five years or with more than three parturitions, suggesting that cumulative physiological changes may contribute to microbial shifts over time.</p><p><strong>Conclusions: </strong>The ewe's vaginal microbiome appears to be mainly influenced by both herd and breed, though distinguishing genetic from environmental factors is challenging within our study design. While the overall microbiota showed a subtle effect on pregnancy, certain genera had a significant negative impact, likely due to pathogenic or inflammatory properties that disrupt reproductive health. The metagenomic approach used here enabled not only comprehensive taxonomic classification but also detailed functional analysis, providing deeper insights into the microbiome's role in reproductive outcomes. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"177"},"PeriodicalIF":12.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765067","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":"Granular activated carbon (GAC)-driven microbial electron shuttle boosts denitrification and mitigates N₂O in cold and carbon-limited biofilm system.","authors":"Xiangyu Yang, Mingchen Yao, Peng Li, Jan Peter van der Hoek, Lujing Zhang, Gang Liu","doi":"10.1186/s40168-025-02161-3","DOIUrl":"10.1186/s40168-025-02161-3","url":null,"abstract":"<p><strong>Background: </strong>Denitrification in wastewater treatment is severely limited under low-temperature and low-carbon (\"dual-low\") conditions, hindering sustainable nitrogen removal. Biofilm systems, though energy-efficient, suffer from reduced efficiency in such environments due to impaired interspecies electron transfer (IET). Granular activated carbon (GAC), a conductive mediator, offers potential to enhance IET between electroactive microorganisms (EAMs) and denitrifiers, yet its role in dual-low systems remains underexplored. This study investigates GAC's capacity to optimize biofilm functionality and mitigate greenhouse gas (GHG) emissions under these constraints.</p><p><strong>Results: </strong>Under dual-low conditions (4-6°C, C/N = 4), GAC increased denitrification efficiency by 19.4-21.9% and reduced N₂O emissions by 10.6-22.9%. Metatranscriptomes revealed upregulation of denitrifying genes (e.g., nosZ) and electron transport pathways (e.g., omcB in Geobacter). FISH/SEM confirmed GAC-driven coacervates of EAMs and denitrifiers, linked by nanowires, enhancing direct electron transfer. Microbial diversity decreased, but functional redundancy improved, with Pseudomonas fluorescens and Geobacter sulfurreducens dominating. TOC removal rose under low temperatures, indicating enhanced carbon utilization.</p><p><strong>Conclusions: </strong>GAC fosters synergistic EAM-denitrifier partnerships, enabling efficient denitrification and GHG mitigation in cold and carbon-limited (\"dual-low\") biofilm systems, advancing sustainable wastewater management. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"178"},"PeriodicalIF":12.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765066","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":"Soil microbial legacy mediated by buckwheat flavonoids enhances cabbage resistance to clubroot disease.","authors":"Jiabing Wu, Shilin Hu, Jing Chen, Lili Zhou, Shengdie Yang, Na Zhou, Lei Wu, Guoqing Niu, Yong Zhang, Xuesong Ren, Qinfei Li, Jun Yuan, Hongyuan Song, Jun Si","doi":"10.1186/s40168-025-02166-y","DOIUrl":"10.1186/s40168-025-02166-y","url":null,"abstract":"<p><strong>Background: </strong>The legacy of plant growth significantly impacts the health of subsequent plants, yet the mechanisms by which soil legacies in crop rotation systems influence disease resistance through rhizosphere plant-microbiome interactions remain unclear. Using a buckwheat-cabbage rotation model, we investigated how microbial soil legacies shape cabbage growth and clubroot disease resistance.</p><p><strong>Results: </strong>Three-year field trials revealed that buckwheat rotation sustainably reduced clubroot severity by 67%-97%, regardless of pathogen load. Soil sterilization eliminated this suppression, implicating a microbial basis. Using 16S rRNA sequencing, we identified buckwheat-enriched bacterial taxa (Microbacterium, Stenotrophomonas, Ralstonia) that colonized subsequent cabbage roots. Metabolomic profiling pinpointed buckwheat root-secreted flavonoids - 6,7,4'-trihydroxyisoflavone and 7,3',4'-trihydroxyflavone - as key drivers of microbial community restructuring. These flavonoids synergistically enhanced the efficacy of a synthetic microbial community (SynCom1, containing Microbacterium keratanolyticum, Stenotrophomonas maltophilia, and Ralstonia pickettii), boosting disease suppression by 34% in greenhouse trials. Co-application of flavonoids and SynCom1 improved bacterial colonization in root niches. Although SynCom1 partially activated jasmonic acid (JA)-associated defenses, its effectiveness depended primarily on flavonoid-driven microbial recruitment rather than direct immune induction.</p><p><strong>Conclusions: </strong>Buckwheat rotation induces flavonoid-mediated soil microbiomes that prime JA-dependent immunity in subsequent cabbage crops, thereby decoupling disease severity from pathogen load. This study elucidates how specialized metabolites orchestrate cross-crop microbial legacies for sustainable disease control, providing a blueprint for designing rotation systems through precision microbiome engineering. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"176"},"PeriodicalIF":12.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742600","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":"Metabolite-mediated interactions and direct contact between Fusobacterium varium and Faecalibacterium prausnitzii.","authors":"Koji Hosomi, Satoko Maruyama, Tsubasa Matsuoka, Mari Furuta, Yoko Tojima, Keita Uchiyama, Makiko Morita, Hitoshi Kawashima, Toshiki Kobayashi, Jun Kunisawa","doi":"10.1186/s40168-025-02168-w","DOIUrl":"10.1186/s40168-025-02168-w","url":null,"abstract":"<p><strong>Background: </strong>The human gut harbors a diverse microbiota that is crucial for maintaining health but also contributes to several diseases. Understanding how microbial communities are assembled and maintained is critical for advancing gut health.</p><p><strong>Results: </strong>We identified a unique interaction between the pathobiont Fusobacterium varium and the symbiont Faecalibacterium prausnitzii, both members of the gut microbial community; their interaction is driven by metabolites and direct cell-to-cell contact. Growth of F. varium was inhibited in the presence of F. prausnitzii because of a decrease in pH and an increase in β-hydroxybutyric acid. Conversely, the growth of F. prausnitzii was promoted in the presence of F. varium, likely via direct contact.</p><p><strong>Conclusions: </strong>These findings highlight the importance of metabolite-driven interactions and direct contact in shaping gut microbial communities and emphasize the potential of interactions between F. prausnitzii and F. varium in influencing gut health. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"175"},"PeriodicalIF":12.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732065","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":"Magnetite drives microbial community restructuring and stimulates aceticlastic methanogenesis of type II Methanosarcina in mangrove sediments.","authors":"Jinjie Zhou, Cui-Jing Zhang, Dayu Zou, Chengxiang Gu, Meng Li","doi":"10.1186/s40168-025-02157-z","DOIUrl":"10.1186/s40168-025-02157-z","url":null,"abstract":"<p><strong>Background: </strong>Mangrove wetlands are critical hotspots of methane emissions, yet the role of naturally occurring minerals in shaping their microbial communities and methanogenic processes is poorly understood. Magnetite, a common iron mineral in soils and sediments, has been reported to enhance aceticlastic methanogenesis and facilitate syntrophic methanogenesis. In this study, we integrated multi-omic profiling with cultivation-based approaches to investigate the impact of magnetite on methanogenesis of microbial consortia derived from mangrove sediments, using lactate as a substrate.</p><p><strong>Results: </strong>Across five serial transfers, mangrove microbial consortia converted lactate to propionate and acetate, which were subsequently degraded into methane. Magnetite addition significantly stimulated methane production, leading to notable changes in community structure, particularly for aceticlastic methanogens, with Methanosarcina predominating in the magnetite-amended cultures and Methanothrix in controls. Four Methanosarcina strains T3, T4, T13, and MeOH were subsequently isolated from magnetite-amended cultures. Combined analyses of metagenome-assembled genomes and the genomes of these isolates revealed that the enriched Methanosarcina in magnetite-amended cultures belonged to type II deficient in hydrogenotrophic methanogenesis pathway. Metatranscriptomic analyses suggested that magnetite addition stimulated aceticlastic methanogenesis of type II Methanosarcina and hydrogenotrophic methanogenesis of Methanomicrobiales in the consortia. Furthermore, pure culture experiments confirmed that magnetite stimulated aceticlastic methanogenesis by Methanosarcina sp. T3, although its gene expression patterns differed from those observed in the microbial consortia. Additionally, Methanofastidiosales, an uncultured archaeal lineage possessing H₂-dependent methylotrophic methanogenesis, was detected in all transfers.</p><p><strong>Conclusions: </strong>Our findings demonstrate that magnetite alters methanogenic consortia in mangrove sediments, selectively stimulating aceticlastic methanogenesis of type II Methanosarcina and modulating hydrogenotrophic activity in Methanomicrobiales. By integrating multi-omics analyses with pure culture validation, we demonstrate, for the first time, that magnetite directly enhances the aceticlastic methanogenesis of type II non-hydrogenotrophic Methanosarcina. This study provides new insights into the influence of magnetite on complex microbial consortia, offers a deeper understanding of the physiology of type II non-hydrogenotrophic Methanosarcina, and advances knowledge of mineral-mediated regulation of methanogenic networks in anoxic environments. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"174"},"PeriodicalIF":12.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718111","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":"Adaptive and metabolic convergence in rhizosphere and gut microbiomes.","authors":"Diana Ilyaskina, Safaa Altveş, Lemeng Dong, Harro Bouwmeester, Sahar El Aidy","doi":"10.1186/s40168-025-02179-7","DOIUrl":"10.1186/s40168-025-02179-7","url":null,"abstract":"<p><p>Microbial ecosystems such as the plant rhizosphere and the human gut microbiome are crucial for the health and functionality of their hosts. Despite their differences, these ecosystems share core evolutionary principles shaped by agriculture, lifestyle, and nutrient-driven selection, demonstrating resilience to environmental pressures. We introduce the concept of the human gut, particularly the colon, as an \"inside-out\" version of the rhizosphere, highlighting the functional and ecological parallels between the two. This review explores these analogies, focusing on metabolites and receptors involved in host-microbiome communication. By integrating insights from both ecosystems, we aim to bridge knowledge gaps and promote interdisciplinary approaches, with the potential to address global challenges in human health and agricultural sustainability. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"173"},"PeriodicalIF":12.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718110","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":"Magnoflorine alleviates colitis-induced anxiety-like behaviors by regulating gut microbiota and microglia-mediated neuroinflammation.","authors":"Lei Wang, Mengfan Li, Yue Dong, Jingyi Wang, Siqi Qin, Liying Li, Bingqing Li, Bangmao Wang, Hailong Cao","doi":"10.1186/s40168-025-02158-y","DOIUrl":"10.1186/s40168-025-02158-y","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) and anxiety are often comorbid and are interconnected through the microbiota-gut-brain axis. Therapeutic medications for anxiety are often constrained by adverse effects that limit their long-term use. Therefore, recent research has focused on identifying natural, safe drugs for anxiety, and elucidating the precise mechanisms underlying the interplay between drugs and the gut-brain axis in modulating mood.</p><p><strong>Results: </strong>We revealed a significant association between active ulcerative colitis (UC) and anxiety. The results of Mendelian randomization analysis suggested that UC has a causal relationship with anxiety, but not depression. We identified Ziziphus jujuba, a natural plant, as a dual therapeutic agent for both UC and anxiety using the Batman database. Magnoflorine, the predominant compound found in Ziziphus jujuba, exhibits promising therapeutic properties for the treatment of UC and anxiety disorders. We found that magnoflorine not only alleviated colitis but also reduced colitis-induced anxiety behaviors through the gut microbiota. Mechanistically, magnoflorine increased the abundance of Odoribacteraceae and Ruminococcus and regulated bile acid metabolism, especially hyodeoxycholic acid (HDCA) in mice with colitis. HDCA supplementation alleviated both colitis and colitis-induced anxiety. HDCA inhibited the binding of lipopolysaccharide to the TLR4/MD2 complex, thereby inhibiting microglial activation and alleviating neuroinflammation.</p><p><strong>Conclusion: </strong>Our study revealed that magnoflorine alleviated colitis-induced anxiety-like behaviors by regulating the gut microbiota and microglia-mediated neuroinflammation, which has the potential to treat patients with IBD and anxiety disorders. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"172"},"PeriodicalIF":12.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718112","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":"Bidirectional subsethood of shared marker profiles enables accurate virus classification.","authors":"Christopher Riccardi, Yuqiu Wang, Shibu Yooseph, Fengzhu Sun","doi":"10.1186/s40168-025-02159-x","DOIUrl":"10.1186/s40168-025-02159-x","url":null,"abstract":"<p><strong>Background: </strong>Due to the impact of viral metagenomic sequencing, the official virus taxonomy is updated several times a year, with labels being renamed even substantially across releases. While this helps reveal newer aspects on the classification of viruses, existing bioinformatic methods for classification struggle to stay in sync with this ever-improving resource.</p><p><strong>Results: </strong>We developed a new computer program, named VIRGO, that is able to correctly predict virus families from metagenomic data with an F1 score above 0.9 using a novel viral sequence similarity metric proposed in this work. Moreover, it ensures compatibility with any version of the official taxonomy of viruses.</p><p><strong>Conclusions: </strong>Virgo is designed to easily incorporate newer releases of the official taxonomy, thus representing a valuable resource in the virology community while raising awareness to develop computational methods that evolve alongside manually curated resources. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"170"},"PeriodicalIF":12.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708053","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":"Microbiome-derived reactivation of mycophenolate explains variations in enterohepatic recirculation in kidney transplant recipients.","authors":"Ole Martin Drevland, Eric J de Muinck, Pål Trosvik, Marta Hammerstad, Kine Eide Kvitne, Karsten Midtvedt, Anders Åsberg, Ida Robertsen","doi":"10.1186/s40168-025-02142-6","DOIUrl":"10.1186/s40168-025-02142-6","url":null,"abstract":"<p><strong>Background: </strong>The pivotal role of microbes in drug metabolism is increasingly recognized, as variation in the gut microbiome composition between individuals has been shown to impact systemic drug exposure, efficacy and toxicity. Mycophenolate mofetil (MMF) is a cornerstone in immunosuppressive therapy following solid organ transplantation. However, dosing and tolerance are challenged by significant pharmacokinetic variability among patients, largely due to variable degrees of enterohepatic recirculation of mycophenolic acid (MPA), the active moiety of MMF. It is hypothesized that the variability in MPA recirculation is driven by gut microbiome-derived β-glucuronidase (β-GUS) mediated cleavage of MPA-glucuronide (MPAG) excreted in the bile. Here, we investigated the bidirectional interaction between MPA and the gut microbiome in kidney transplant recipients, using a combination of in vivo and in vitro data.</p><p><strong>Results: </strong>We compared the fecal microbiomes of kidney transplant recipients (n = 21) both pre- and post-transplantation to healthy individuals (n = 15) using shotgun metagenomic sequencing. We also determined the individual microbiome-derived reactivation rate of MPAG to MPA and show a strong positive correlation between this reactivation rate and the degree of MPA enterohepatic recirculation in vivo. Through metagenomic analysis, the reactivation rate of MPA was linked to specific gut microbial species. In particular, specific β-GUS gene variants associated with Faecalibacterium prausnitzii showed a strong impact on the conversion of MPAG to MPA. Furthermore, our study confirmed a significant shift in microbial composition post-transplantation and revealed notable fluctuations in species such as F. prausnitzii and Akkermansia muciniphila across different time points after transplantation. Lastly, we provide evidence that the microbiome-derived reactivation rate of MPA is linked to specific beta-glucuronidase alleles.</p><p><strong>Conclusions: </strong>We highlight for the first time that the ex vivo determined reactivation rate of MPA explains the variation of enterohepatic recirculation, emphasizing the important role of F. prausnitzii in this process. More broadly, our findings suggest that the gut microbiome significantly influences the degree of enterohepatic recirculation of MPA, providing valuable insights that could be relevant for optimizing individualized immunosuppressive drug dosing in transplant patients. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"169"},"PeriodicalIF":12.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708055","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}