Gut Microbes最新文献

{"title":"Intra-species competition combats vancomycin-resistant enterococci.","authors":"Nadav Ben-Assa, Rawi Naddaf, Shaqed Carasso, Omri Dagan, Aviv Sason, Tal Gefen, Naama Geva-Zatorsky","doi":"10.1080/19490976.2026.2647529","DOIUrl":"10.1080/19490976.2026.2647529","url":null,"abstract":"<p><p>Vancomycin-resistant <i>Enterococcus</i> (VRE) is a leading cause of multidrug-resistant infections in hospitalized patients, yet no reproducible microbiota therapies exist to selectively displace it. Here we harness intra-species competition within <i>Enterococcus</i> to suppress VRE colonization. Through <i>in vitro</i> screening and mouse colonization models, we identified a single antibiotic-susceptible strain, <i>E. faecalis</i> X98, that significantly reduced VRE burden both <i>in vitro</i> and in mouse experiments, whereas multi-strain consortia failed due to competitive interference among consortium members. In parallel, we subjected the vancomycin-sensitive strain <i>E. faecalis</i> OG1RF to phage selection, which produced a prophage-integrated derivative with convergent glycosyltransferase mutations that secreted a VRE-killing factor, conferring enhanced antagonism even without exogenous phage. These findings reveal ecological and evolutionary principles for selecting strains as targeted microbial therapeutics. Exploiting intra-species antagonism and phage-driven evolution provides a practical framework for developing microbiota-based interventions that minimize collateral damage to the microbiome while addressing antibiotic-resistant pathogens.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2647529"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13011632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimally invasive capsule-string device enables spatially resolved microbiome profiling across the upper gastrointestinal tract.","authors":"Kathryn Garvey, J Kirk Harris, Glenn T Furuta, Kendra A Occhipinti, Brandie D Wagner, Joseph Fernandez, Mitchell VeDepo, Jennifer Fouquier, Emily B Hill, Charles E Robertson, Steven Ackerman, Robin Shandas","doi":"10.1080/19490976.2026.2675764","DOIUrl":"10.1080/19490976.2026.2675764","url":null,"abstract":"<p><p>Regional variation in the human gastrointestinal microbiome remains difficult to characterize because existing sampling methods either rely on invasive endoscopy or stool, which poorly reflects the upper gut. We evaluated a minimally invasive capsule-string device capable of collecting luminal and mucosal material from the esophagus, stomach, duodenum, and jejunum during natural transit. In healthy adults, compartment-level samples were anatomically localized using pH, bile staining, and string length, and microbial communities were profiled by 16S rRNA gene sequencing. The device was well tolerated and consistently recovered sufficient biomass from all upper GI regions. Distinct microbial signatures were evident across compartments, with the strongest differences observed between proximal (esophageal and gastric) and small-intestinal communities. Although the individual host exerted the dominant influence on the overall community structure, a reproducible regional signal persisted after accounting for between-person variation. These findings demonstrate that capsule-string sampling provides reliable access to spatially resolved upper GI microbiota without endoscopy. This approach enables more precise mapping of gut microbial organization in vivo and creates new opportunities for longitudinal, mechanistic, and disease-focused studies of host‒microbiome interactions in regions that have historically been inaccessible.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2675764"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muribaculum as a microbial contributor of rifaximin-induced mucosal protection during chemotherapy.","authors":"Carmen Correale, Martina Morandi, Antonio Gil-Gomez, Alessandra Silvestri, Andrea Gatti, Daniele Braga, Annalisa Maroli, Caterina Foppa, Stefano De Zanet, Francesca Algieri, Michela Lizier, Riccardo Rossetti, Sara Carloni, Giuseppe Penna, Antonino Spinelli, Paola Brescia, Maria Rescigno","doi":"10.1080/19490976.2026.2685994","DOIUrl":"10.1080/19490976.2026.2685994","url":null,"abstract":"<p><p>Chemotherapy-induced intestinal mucositis is a frequent and dose-limiting toxicity that compromises cancer treatment outcomes and lacks effective targeted interventions. Here, we investigate the mechanisms by which the nonabsorbable antibiotic rifaximin mitigates chemotherapy-induced intestinal injury, focusing on microbiota-mediated preservation of epithelial barrier integrity. In a murine model of 5-fluorouracil (5-FU)-induced intestinal injury, rifaximin pretreatment reduced mucosal inflammation and tissue damage, preserved epithelial and mucus barrier integrity, and limited systemic endotoxemia. Importantly, rifaximin did not impair the antitumor efficacy of 5-FU in Apc^Min/+C3arKO mice. To assess translational relevance, we employed a human intestinal <i>ex vivo</i> organ culture system (EVOC) and found that rifaximin preserved mucosal architecture, mucus balance, and tight junction integrity following inflammatory challenge. Microbiome profiling revealed that rifaximin reshaped the intestinal microbial community, preventing the depletion of health-associated taxa, including <i>Muribaculum</i> and <i>Parasutterella</i>. Functional experiments demonstrated that <i>Muribaculum intestinale</i> supplementation alone attenuated 5-FU-induced injury, reproducing key protective features of rifaximin treatment. Together, these findings identify <i>Muribaculum</i> as a microbial contributor to rifaximin's protective effects, supporting its potential role as a safe adjunctive strategy to improve gastrointestinal tolerability of cancer treatment.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2685994"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial constipation: Mucin-degrading intestinal commensal bacteria cause constipation.","authors":"Tomonari Hamaguchi, Noriaki Gibo, Misuzu Ohara, Mikako Ito, Tomoyuki Ogura, Jun-Ichi Takeda, Hiroshi Nishiwaki, Fei Zhao, Ryo Kinoshita-Daitoku, Masashi Hattori, Koji Nonogaki, Tetsuya Maeda, Kenichi Kashihara, Yoshio Tsuboi, Masaaki Hirayama, Mitsuhiro Fujishiro, Hiroki Kawashima, Kinji Ohno","doi":"10.1080/19490976.2025.2596809","DOIUrl":"10.1080/19490976.2025.2596809","url":null,"abstract":"<p><p>The contribution of gut microbes to constipation remains mechanistically underexplored, despite constipation being one of the most prevalent gastrointestinal disorders. Here, we identify cooperative induction of constipation by two mucin-degrading gut commensals: <i>Akkermansia muciniphila</i> and <i>Bacteroides thetaiotaomicron</i>. In constipated patients with Parkinson's disease (PD) and chronic idiopathic constipation (CIC), we observed that <i>A. muciniphila</i> and <i>B. thetaiotaomicron</i> were increased. Gnotobiotic mice colonized with either bacterium exhibited no constipation, whereas mice co-colonized with both bacteria developed constipation. Fecal mucins but not gastric mucins carry terminal sulfates. As fecal transcriptome of gnotobiotic mice suggested a sulfatase-dependent mechanism, we generated an anaerobic sulfatase-maturating enzyme (anSME)-deficient <i>B. thetaiotaomicron</i> strain that cannot catabolize the terminal sulfates of mucins. In the absence of anSME, constipation was ameliorated in co-colonized gnotobiotic mice. The synergic effect of the two bacteria is in accordance with our observation that <i>A. muciniphila</i> alone and constipation are not correlated in humans. As a bunch of intestinal bacteria other than <i>B. thetaiotaomicron</i> also catabolize mucin sulfates, they may substitute for <i>B. thetaiotaomicron</i> in patients with constipation. We propose bacterial constipation, in which cooperative degradation of colonic mucins by sulfatases and glycosylases by two commensal bacteria reduces lubrication and induces fecal dehydration, leading to the development of constipation. Targeting microbial sulfatase activity may be a promising therapeutic approach for patients with bacterial constipation.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2596809"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<b>Gut bacterial</b> <i><b>O</b></i><b>-demethylation modulates systemic exposure to oral etoposide</b>.","authors":"Ashutosh Tripathi, Toe Ein Kyawt, Jongoh Shin, Kyoung-Jae Won, Abigail T Armstrong, Giokdjen Ilktach, Peter Sullivan, Holly A Weilbaker, Yeonju Ko, Seongsoo Lee, Wooin Lee, Bruce R Cooper, Byung-Kwan Cho, Jimmy Orjala, Hyunwoo Lee, Hyunyoung Jeong","doi":"10.1080/19490976.2026.2628358","DOIUrl":"10.1080/19490976.2026.2628358","url":null,"abstract":"<p><p>Gut microbial <i>O</i>-demethylation has been reported for plant-derived dietary compounds containing <i>O</i>-methylated aromatic(s). However, the significance of gut microbial <i>O</i>-demethylation in drug metabolism and disposition remains unexplored. This study examined 64 clinically used oral drugs containing one or more methoxylated aromatics for gut microbial <i>O</i>-demethylation using high-resolution mass spectrometry (HRMS). For 35 of the tested drugs, including the anticancer agent etoposide, we detected metabolites corresponding to <i>O</i>-demethylation (i.e., a mass difference of -14 and its multiples) when individual drugs were incubated with mouse cecal contents. We confirmed that the <i>O</i>-demethylated metabolite (M1) of the model drug etoposide is etoposide catechol using HRMS and proton nuclear magnetic resonance spectroscopy. By testing an in-house collection of 56 gut bacteria individually, we identified seven previously unknown gut bacterial species that exhibit etoposide <i>O</i>-demethylating activity. Etoposide anticancer therapy has been associated with an increased risk of acute myeloid leukemia. We demonstrated that M1 is more genotoxic to myeloid cells when it is orally administered to mice, whereas M1 is less cytotoxic against MCF-7 and HeLa cancer cells than the parent etoposide, suggesting that the gut microbiota may contribute to the secondary genotoxicity of etoposide via <i>O</i>-demethylation. Comparative pharmacokinetic analysis of orally administered etoposide in control and antibiotic-treated mice showed that systemic exposure to etoposide increased 1.9-fold, while M1 exposure decreased 3.7-fold in antibiotic-treated mice, suggesting that gut microbial <i>O</i>-demethylation is a significant determinant of etoposide metabolism and disposition. Collectively, our study reveals the prevalence of gut bacteria with <i>O</i>-demethylation activity, illustrates the contribution of gut microbial <i>O</i>-demethylation to altering drug efficacy and toxicity with the model drug etoposide, and provides a knowledge basis for in-depth characterization of other drugs identified as being susceptible to gut microbial <i>O</i>-demethylation.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2628358"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Invasion of gut-derived escherichia coli extracellular vesicles exacerbates myocardial ischemia/reperfusion injury.","authors":"Junzhuo Wang, Ke Hu, He Lu, Ke Chen, Jian Zhang, Shaojun Wu, Lina Kang, Jun Xie, Biao Xu","doi":"10.1080/19490976.2026.2635818","DOIUrl":"10.1080/19490976.2026.2635818","url":null,"abstract":"<p><p>Recent studies have highlighted the close relationship between gut microbiota and the cardiovascular system; however, the precise mechanisms and modes of their interaction remain incompletely understood. Among the various factors involved, bacterial extracellular vesicles (EVs) are often overlooked, despite their potential roles in multiple pathological processes. To investigate the role of bacterial EVs in shaping the inflammatory microenvironment following myocardial ischemia-reperfusion injury, we colonized the intestines of Rosa26.tdTomato reporter mice with <i>Escherichia coli</i> (<i>E. coli</i>) expressing Cre recombinase. Using FACS-beads and immunofluorescence techniques, we found that myocardial ischemia-reperfusion injury in mice significantly enhanced the invasion of gut-derived bacterial EVs. Meanwhile, in patients with ST-segment elevation myocardial infarction, we also confirmed the invasion of bacterial EVs via the FACS-bead method, and there was a significant correlation between extracellular vesicles in peripheral blood and LPS, suggesting that these EVs can be key carriers for LPS translocation. In this pathological process, invading <i>E. coli</i> EVs exacerbate the mobilization and infiltration of systemic and local inflammatory cells, thereby aggravating myocardial damage and impairing cardiac function. Notably, glucagon-like peptide-2 can effectively alleviate inflammatory responses and myocardial injury by inhibiting the translocation of E. coli-derived EVs. In conclusion, our study is the first to confirm the impact of gut-derived EVs on myocardial ischemia-reperfusion injury, revealing that <i>E. coli</i> EVs can amplify inflammatory responses. These findings provide new insights into the gut-heart axis and offer a theoretical basis for the therapeutic potential of glucagon-like peptide-2 in cardiovascular diseases.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2635818"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal epithelial TLR4 knock out induces sex-specific effects on gut barrier and microbiome in an activity-based anorexia model.","authors":"Colin Salaün, Marion Huré, Charlène Guérin, Christine Bôle-Feysot, Audrey Valentin, Fatima Léon, Sarah Lenoir, Jean-Luc do-Rego, Jean-Claude do-Rego, Ludovic Langlois, David Ribet, Najate Achamrah, Moïse Coëffier","doi":"10.1080/19490976.2026.2637316","DOIUrl":"10.1080/19490976.2026.2637316","url":null,"abstract":"<p><p>The role of the microbiota‒gut‒brain axis in the pathophysiology of anorexia nervosa has emerged in recent decades. Increased expression of Toll-like receptor 4 (TLR4) has been reported in the intestinal epithelial cells (IEC) of activity-based anorexia (ABA) mice. The inducible TLR4 knockout in IEC (TLR4^IEC^-/-) was subsequently associated with behavioral and energy balance changes in ABA mice. Our study aimed to assess the intestinal response to TLR4^IEC^-/- in both male and female ABA mice by focusing on three components: inflammation, the gut barrier, and the gut microbiota composition. After 12 d of undernutrition with free wheel access, the colonic expression of 43 markers was measured by RT-qPCR. The gut microbiota composition was analyzed by Illumina sequencing of the 16S rRNA gene. First, TLR4^IEC^-/- was associated with more marked alterations in male control mice compared to females. Indeed, a reduction in the mRNA expression of eight inflammatory factors, seven tight junction proteins and fecal calprotectin levels was observed in males. Control TLR4^IEC^-/- females showed increased expression of four inflammatory markers and one target involved in the gut barrier. The levels of the <i>Bacillota</i> phylum and the <i>Deltaproteobacteria</i> class and their subdivisions, up to the <i>Desulfovibrio</i> genus, increased in the control TLR4^IEC^-/- males compared to wt. In females, only an increase in the <i>Alcaligenaceae</i> genus, which ranks from the <i>Betaproteobacteria</i> phylum, was observed. Interestingly, in both males and females, these alterations were not observed in response to ABA model in TLR4^IEC^-/- mice. Similarly, ABA increased <i>Tjp1</i> expression and <i>Lactobacillus</i> abundance, both of which were decreased by TLR4^IEC^-/-. Our study shows for the first time the impact of inducible TLR4^IEC^-/- on the intestinal response. TLR4^IEC^-/- induced sex-specific colonic alterations and changes in the gut microbiota, which disappeared after the ABA model. Further studies are warranted to decipher the underlying mechanisms.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2637316"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural microbiota confer life-long protection against obesity via an early-life, immune-mediated effect on brown adipocytes.","authors":"Shahar Azar, Oksana Gavrilova, Greta Baker, Ji Hoon Oh, Keisuke Fukutomi, Jun Seishima, Jianping Ma, Moonhwa Kwak, Jonathan H Badger, Giorgio Trinchieri, Benedikt Hild, Behdad Afzali, Margo P Emont, Barbara Rehermann","doi":"10.1080/19490976.2026.2718613","DOIUrl":"10.1080/19490976.2026.2718613","url":null,"abstract":"<p><p>Obesity, a major risk factor for metabolic disease, has increased in industrialized nations alongside a reduction in gut microbiota diversity. Reconstituting laboratory mice with complex, natural microbiota and commensals from wild mice resulted in protection against diet-induced obesity. These natural microbiota reduced weight gain in both male and female mice of different genetic backgrounds throughout their life and increased energy expenditure. Single-nuclei RNA sequencing identified a dominant adipocyte population in brown adipose tissue (BAT) with a transcriptional signature of increased thermogenic activity, while white adipose tissue mass and beiging were reduced. Protection against diet-induced obesity was transferable to adult germ-free mice via exposure to natural microbiota, indicating an association with the timing of immune response induction rather than BAT developmental programming. However, protection against diet-induced obesity did not require type 2 immune signaling, as shown in STAT6 knockout mice. Rather, it was associated with increased levels of chemokines and monocytes in BAT in early life, pointing to a role of infiltrating myeloid cells. Indeed, CCR2-deficient mice with natural microbiota lacked the BAT transcriptional signature of increased thermogenic activity, increased energy expenditure, and protection against diet-induced obesity that wild-type mice with natural microbiota exhibited. The latter was restored upon injection with wild-type bone marrow. Taken together, these findings identify a novel microbiota‒immune‒adipose tissue axis that results in increased BAT thermogenesis and improved energy balance throughout life.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2718613"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and diet in colorectal cancer: Converging determinants of carcinogenesis.","authors":"Bhupesh Kumar Thakur, Saurav Roy Choudhury, Williams Turpin, Alberto Martin","doi":"10.1080/19490976.2026.2664684","DOIUrl":"10.1080/19490976.2026.2664684","url":null,"abstract":"<p><p>Diet and the gut microbiome are major, interdependent determinants of colorectal cancer (CRC) risk. This review discusses current evidence on how dietary patterns reshape microbial ecology, modulate microbial virulence, and alter host metabolic, inflammatory, and oncogenic pathways to influence colorectal carcinogenesis. We highlight key CRC-associated microbes, including <i>pks⁺ Escherichia coli</i>, <i>Fusobacterium nucleatum</i>, enterotoxigenic <i>Bacteroides fragilis</i>, and <i>Streptococcus gallolyticus</i>, and discuss how diet governs their abundance, toxin production, and oncogenic potential. Mechanistic investigations into diet-microbe interactions reveal how pro-inflammatory, low-fiber Western-style diets foster mucosal inflammation, generation of reactive oxygen and nitrogen species, and genotoxic microbial niches, whereas fiber- and polyphenol-rich diets support protective commensals and production of anti-inflammatory metabolites. We also outline major challenges, including interindividual microbiome variability and limited translational models, and propose future directions for integrating dietary, microbial, and host-targeted strategies for CRC prevention and therapy.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2664684"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diet and microbiome shape small-molecule cytokinin pools in mammals.","authors":"Eman M Othman, Elena Bencurova, Pamela Ferretti, Peer Bork, Alvaro Rodriguez Del Rio, Jaime Huerta-Cepas, Ignazio Caruana, Rania Abdel-Latif, Aman Akash, Alfonso Albacete, Feras Lafi, Thomas Dandekar, Muhammad Naseem","doi":"10.1080/19490976.2026.2679497","DOIUrl":"10.1080/19490976.2026.2679497","url":null,"abstract":"<p><p>Cytokinins (CKs) are adenine-derived metabolites traditionally characterized as plant hormones, yet their origin, distribution, and functions in mammalian systems remain largely undefined. Using integrated metabolomics, microbiome, and metagenomics approaches, we provide a systematic characterization of CK occurrence and potential sources in mammals. Serum profiling across five animal species revealed consistent detection of multiple CK derivatives, with concentrations markedly lower than in plant tissue. The CK storage form, zeatin-O-glucoside, predominated in mammalian sera, followed by trans-zeatin and kinetin, indicating a CK composition distinct from that in plants. Species-specific differences, such as reduced trans-zeatin in mice and lower kinetin in humans, further suggest divergent regulatory patterns. In mice, CKs were present in vascular tissues of the kidney, heart, and liver, demonstrating systemic distribution. Dietary manipulation showed that starvation significantly reduced CK abundance in serum, colon, feces, and urine, confirming that diet is a major contributor to the mammalian CK pool. Meta-omics analysis of gut microbiomes identified CK-related genes across multiple microbial taxa, with the highest representation in human microbiomes, followed by those of mouse and pig. Germ-free mouse experiments showed substantially lower CK levels than conventionally raised counterparts, establishing a microbiome-dependent contribution. Collectively, our findings identify CKs as diet and microbiome modulated metabolites in mammals, warranting future investigation to elucidate their physiological significance in mammalian biology.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2679497"},"PeriodicalIF":15.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}