{"title":"Engineered T cells stimulate dendritic cell recruitment and antigen spreading for potent anti-tumor immunity.","authors":"Zhen Xiao, Jiajia Wang, Shidian He, Lin Wang, Jingxing Yang, Wenhui Li, Kaili Ma, Yabo Zhou, Xiaowei Liu, Shiyou Wang, Yu Yang, Minmin Ge, An Gao, Kun Tang, Jing Huang, Chen Wang, Liyuan Zhang, Hai-Xi Sun, Lianjun Zhang","doi":"10.1016/j.xcrm.2025.102307","DOIUrl":"10.1016/j.xcrm.2025.102307","url":null,"abstract":"<p><p>Current T cell-based immunotherapeutic strategies show limited success in treating solid tumors due to insufficient dendritic cell (DC) activity, particularly cross-presenting conventional type 1 dendritic cells (cDC1s). DC scarcity and dysfunction hinder T cell expansion and differentiation, greatly limiting anti-tumor responses. In this study, we propose a T cell engineering strategy to enhance interaction with XCR1<sup>+</sup> cDC1s. Adoptively transferred T cells engineered to secrete Flt3L and XCL1 (FX) promote DC trafficking and maturation and improve DC-T cell interaction, while maintaining a pool of TCF1<sup>+</sup>SlamF6<sup>+</sup> stem-like T cells. Importantly, FX-engineered T cells trigger robust antigen spreading and potent endogenous polyclonal T cell response, enabling the recognition and elimination of tumors with heterogeneous antigens and preventing immune escape. The therapeutic efficacy of FX-armed chimeric antigen receptor (CAR)-T cells is further validated in the Flt3KO&hFLT3LG humanized mouse model. This strategy offers a promising avenue for enhancing DC-T cell interactions, paving the way for more effective immunotherapy against solid tumors.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102307"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944736","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}
Cell Reports MedicinePub Date : 2025-09-16Epub Date: 2025-08-20DOI: 10.1016/j.xcrm.2025.102304
Ben Haladik, Margarita Maurer-Granofszky, Peter Zoescher, Raul Jimenez-Heredia, Alexandra Frohne, Anna Segarra-Roca, Chloe Casey, Felix Kartnig, Sarah Giuliani, Christina Rashkova, Peter Repiscak, Michael N Dworzak, Giulio Superti-Furga, Kaan Boztug
{"title":"Image-based drug screening combined with molecular profiling identifies signatures and drivers of therapy resistance in pediatric AML.","authors":"Ben Haladik, Margarita Maurer-Granofszky, Peter Zoescher, Raul Jimenez-Heredia, Alexandra Frohne, Anna Segarra-Roca, Chloe Casey, Felix Kartnig, Sarah Giuliani, Christina Rashkova, Peter Repiscak, Michael N Dworzak, Giulio Superti-Furga, Kaan Boztug","doi":"10.1016/j.xcrm.2025.102304","DOIUrl":"10.1016/j.xcrm.2025.102304","url":null,"abstract":"<p><p>Despite recent advances in the understanding of the genomic landscape of pediatric acute myeloid leukemia (pedAML), targeted treatments are only available for selected genomic alterations, and the functional link between genotype and outcome remains partially elusive. Functional precision medicine approaches to investigate treatment resistance and patient risk have not been applied systematically for pedAML. Here, we describe an advanced functional screening platform combining high-content imaging and deep learning-based phenotyping. In 45 patients with pedAML, we identify BCL2 and FLT3 inhibitors and standard chemotherapy as major drivers of the chemosensitivity landscape, reveal substantial differential sensitivities between risk groups, and may effectively predict individual measurable residual disease and patient risk. Integration with genomic and epigenomic data uncovers a chemotherapy-resistant primitive state vulnerable to combined BCL2 and MDM2 inhibition and HDAC inhibition. Overall, we identify early signatures of therapy resistance across genetic subgroups and prioritize targeted treatments for these functionally and epigenetically defined patient subsets.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102304"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944741","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}
Cell Reports MedicinePub Date : 2025-09-16Epub Date: 2025-08-26DOI: 10.1016/j.xcrm.2025.102306
Junhong Chen, Yongchao Gao, Yao Chen, Quanlin Wang, Yulong Zhang, Yujing Huang, Xiaoying Xian, Dingding Zhou, Honghao Zhou, Rong Liu, You Zou, Wei Zhang
{"title":"Identification and validation of intratumoral microbiome associated with sensitization to immune checkpoint inhibitors.","authors":"Junhong Chen, Yongchao Gao, Yao Chen, Quanlin Wang, Yulong Zhang, Yujing Huang, Xiaoying Xian, Dingding Zhou, Honghao Zhou, Rong Liu, You Zou, Wei Zhang","doi":"10.1016/j.xcrm.2025.102306","DOIUrl":"10.1016/j.xcrm.2025.102306","url":null,"abstract":"<p><p>As a part of the commensal microbiome, the regulatory role of the intratumoral microbiome in tumor immunity is gradually revealed. However, the relationship between the intratumoral microbiome and the efficacy of immune checkpoint inhibitors (ICIs) clinical treatment remains unclear. Here, we collect RNA sequencing (RNA-seq) data and clinical information from publicly available ICIs therapy cohorts. By developing an improved bioinformatics pipeline to identify the intratumoral microbiome and performing a comprehensive association analysis, we find that the intratumoral microbiome is associated with response to ICIs and characteristics of the tumor microenvironment (TME). In vivo experiments demonstrate that intratumoral injection of Burkholderia cepacia, Priestia megaterium, or Corynebacterium kroppenstedtii, which were selected from our analysis results, would synergize with anti-PD-1 therapy to inhibit tumor growth and enhance antitumor immunity. Our findings highlight the essential role of the intratumoral microbiome in the clinical effectiveness differences of ICIs, suggesting its potential in future ICIs combination therapy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102306"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944775","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":"Dynamic multi-omics profiling of islet and gut hormonal secretion and peripheral crosstalk in response to various nutrient loads.","authors":"Jiachen Wang, Ling Liu, Hechun Liu, Yu Qian, Sijie Zhang, Shuai Zheng, Hemin Jiang, Yue Zhou, Xiaoliang Cheng, Qi Fu, Hao Dai, Tao Yang","doi":"10.1016/j.xcrm.2025.102327","DOIUrl":"10.1016/j.xcrm.2025.102327","url":null,"abstract":"<p><p>Postprandial metabolism is a complex and dynamic process involving diverse biomolecules, with islet and gut hormones playing crucial roles. However, how these hormones interact with biomolecules after nutrient intake and coordinate with peripheral insulin resistance (IR) remains elusive. This study characterizes postprandial multi-omics dynamics under mixed meals and four distinct macronutrient loads, investigating hormone secretion patterns, associated responsive molecules, and their relationships with IR. Postprandial multi-omics data significantly elucidate insulin and glucagon secretion, highlighting differences from the fasting state, while glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are exclusively explained postprandially. Hormone secretion and molecular responses exhibit substantial heterogeneity among macronutrients. Postprandial multi-omics better predict IR, particularly with hepatic enrichment. Protein load shows the strongest association with both hepatic and muscular IR, while butter mostly connects with systemic IR. Several identified molecules mediate interactions between IR and islet α and β cell function, providing a molecular basis for advancing precision nutrition therapies in metabolic diseases.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102327"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999784","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}
Cell Reports MedicinePub Date : 2025-09-16Epub Date: 2025-09-05DOI: 10.1016/j.xcrm.2025.102334
Zhichao Liu, Guoqiang Wang, Yang Yang, Yuchen Su, Hong Zhang, Jun Liu, Peng Cui, Xuning Fan, Jinyu Yang, Zhihong Zhang, Xing Gao, Yinkai Chao, Bianca Mostert, J Jan B van Lanschot, Bas P L Wijnhoven, Simon Law, Chunguang Li, Shangli Cai, Zhigang Li
{"title":"ctDNA detects residual disease after neoadjuvant chemoradiotherapy and guides adjuvant therapy in esophageal squamous cell carcinoma.","authors":"Zhichao Liu, Guoqiang Wang, Yang Yang, Yuchen Su, Hong Zhang, Jun Liu, Peng Cui, Xuning Fan, Jinyu Yang, Zhihong Zhang, Xing Gao, Yinkai Chao, Bianca Mostert, J Jan B van Lanschot, Bas P L Wijnhoven, Simon Law, Chunguang Li, Shangli Cai, Zhigang Li","doi":"10.1016/j.xcrm.2025.102334","DOIUrl":"10.1016/j.xcrm.2025.102334","url":null,"abstract":"<p><p>The diagnostic accuracy of circulating tumor DNA (ctDNA) for detecting molecular residual disease (MRD) after multimodal treatment remains unclear. In a prospective cohort of 132 patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT) followed by clinical response evaluation and surgery, tumor-informed personalized-panel and fixed-panel ctDNA assays are applied to serial blood samples. Personalized ctDNA assay demonstrates a superior baseline detection rate (99.2%) and outperforms fixed panels in diagnosing post-nCRT residual disease. Integrating personalized ctDNA with conventional clinical diagnostic methods increases sensitivity for predicting non-pathological complete response (non-pCR) from 78.4%-80.7% to 92.0%-93.2%. Patients with detectable MRD post-nCRT and/or post-surgery exhibit worse survival outcomes. In non-pCR patients, adjuvant immunotherapy improves disease-free survival in post-surgery MRD-positive cases, whereas MRD-negative patients derive no benefit. These findings support incorporating ctDNA into response assessment to guide organ-sparing strategies and adjuvant therapy decisions in ESCC. This study is registered at ClinicalTrials.gov (NCT03937362).</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102334"},"PeriodicalIF":10.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008151","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":"CAR-T cells in solid tumors: Challenges and breakthroughs.","authors":"Giulia Escobar, Trisha R Berger, Marcela V Maus","doi":"10.1016/j.xcrm.2025.102353","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102353","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematologic malignancies, but its efficacy in solid tumors is limited by several challenges. Key obstacles include insufficient CAR-T cell trafficking to tumors, limited expansion and persistence, tumor relapse due to antigen loss or heterogeneity, and an immunosuppressive tumor microenvironment (TME) that dampens CAR-T cell functions. In this review, we discuss insights from recent successful clinical trials in advanced solid tumors and highlight groundbreaking strategies integrating synthetic biology and gene engineering to enhance CAR-T cell fitness, potency, and persistence, activate host immunity, reprogram the TME, and enable multi-antigen targeting. We examine strengths and weaknesses of current preclinical models for assessing the efficacy and safety of CAR-T cell therapies, including human xenografts in immunodeficient mice and humanized or syngeneic models. The array of cutting-edge approaches employed in next-generation CAR-T cell therapies is expected to transform the treatment landscape of solid tumors.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102353"},"PeriodicalIF":10.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-08-19Epub Date: 2025-07-16DOI: 10.1016/j.xcrm.2025.102240
Leonard Knoedler, Konstantin Herfeld, Daniel A Schaefer, Fortunay Diatta, James Clune, Brogan Evans, Michelle Seu, Bong-Sung Kim, Michael Alfertshofer, Thomas Schaschinger, Jasper Iske, Samuel Knoedler, Alexandre G Lellouch, Maxime Jeljeli, Alberto Carturan, Marco Ruella, Max Heiland, Hendrik Poeck, Markus Perl, Bohdan Pomahac, Martin Kauke-Navarro
{"title":"CAR-T cell therapy and reconstructive oncologic surgery in peripheral solid tumors-A narrative review.","authors":"Leonard Knoedler, Konstantin Herfeld, Daniel A Schaefer, Fortunay Diatta, James Clune, Brogan Evans, Michelle Seu, Bong-Sung Kim, Michael Alfertshofer, Thomas Schaschinger, Jasper Iske, Samuel Knoedler, Alexandre G Lellouch, Maxime Jeljeli, Alberto Carturan, Marco Ruella, Max Heiland, Hendrik Poeck, Markus Perl, Bohdan Pomahac, Martin Kauke-Navarro","doi":"10.1016/j.xcrm.2025.102240","DOIUrl":"10.1016/j.xcrm.2025.102240","url":null,"abstract":"<p><p>This review addresses the integration of chimeric antigen receptor (CAR)-T cell therapy with reconstructive oncologic surgery in treating peripheral solid tumors, including melanoma, sarcomas, breast cancer, and head and neck cancers. While CAR-T cells have demonstrated effectiveness in blood cancers, their efficacy in solid tumors has been limited due to tumor heterogeneity, immune suppression, and poor cellular infiltration. Emerging approaches involving localized CAR-T cell delivery, improved CAR design, and targeted antigen selection (such as HER2, MUC1, GD2, and B7-H3) are discussed as promising strategies to enhance therapeutic outcomes. Clinical studies highlighted in this review indicate improved local tumor control and potential to optimize surgical resections. Additionally, combining CAR-T therapy with surgery may reduce tumor recurrence and positively influence reconstructive outcomes. Overall, this review underscores CAR-T cell therapy as a potential adjunctive treatment in oncologic surgery, emphasizing the importance of interdisciplinary approaches to improve patient outcomes in solid tumor management.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102240"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658559","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}
Cell Reports MedicinePub Date : 2025-08-19Epub Date: 2025-07-25DOI: 10.1016/j.xcrm.2025.102254
Takahiro Tsuno, Jinghe Li, Kuniyuki Nishiyama, Yuka Imamura Kawasawa, Ryota Inoue, Esther Ong Yajima, Akira Nishiyama, Shigeharu G Yabe, Tatsuya Kin, Hitoshi Okochi, Tomohiko Tamura, A M James Shapiro, Seiichi Oyadomari, Tadahiro Kitamura, Yasuo Terauchi, Jun Shirakawa
{"title":"Imeglimin suppresses glucagon secretion and induces a loss of α cell identity.","authors":"Takahiro Tsuno, Jinghe Li, Kuniyuki Nishiyama, Yuka Imamura Kawasawa, Ryota Inoue, Esther Ong Yajima, Akira Nishiyama, Shigeharu G Yabe, Tatsuya Kin, Hitoshi Okochi, Tomohiko Tamura, A M James Shapiro, Seiichi Oyadomari, Tadahiro Kitamura, Yasuo Terauchi, Jun Shirakawa","doi":"10.1016/j.xcrm.2025.102254","DOIUrl":"10.1016/j.xcrm.2025.102254","url":null,"abstract":"<p><p>Dysregulated α cell function contributes to the development of diabetes. In this study, we find that treatment with imeglimin, an antidiabetic drug, prevents glucagon release and induces a loss of α cell identity through direct action on α cells. Mechanistically, imeglimin reduces Gsα expression to inhibit the exchange protein directly activated by cyclic adenosine monophosphate 2 (EPAC2)-mediated secretion of glucagon induced by low glucose, gastric inhibitory polypeptide (GIP), or adrenaline in an insulin-independent manner. Imeglimin also attenuates α cell Ca<sup>2+</sup> oscillations. MafB expression is downregulated by imeglimin to induce α cell dedifferentiation. In addition, imeglimin upregulates C/EBP homologous protein (CHOP) expression, which partly contributes to the reduction in Gsα and MafB expression to reduce glucagon secretion and induce α cell reprogramming without altering protein translation. These pleiotropic effects of imeglimin on glucagon secretion and α cell identity can be recapitulated in mouse models of diabetes in vivo. These data suggest that the imeglimin-mediated regulation of α cell plasticity, particularly via glucagon suppression, may contribute to glucose homeostasis.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102254"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717568","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}
Cell Reports MedicinePub Date : 2025-08-19Epub Date: 2025-07-30DOI: 10.1016/j.xcrm.2025.102259
Anthony L Komaroff, Robert Dantzer
{"title":"Causes of symptoms and symptom persistence in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.","authors":"Anthony L Komaroff, Robert Dantzer","doi":"10.1016/j.xcrm.2025.102259","DOIUrl":"10.1016/j.xcrm.2025.102259","url":null,"abstract":"<p><p>Debilitating symptoms for many years can follow acute COVID-19 (\"long COVID\"), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and various post-acute infection syndromes (PAISs). Together, long COVID and ME/CFS affect 60-400 million individuals, globally. Many similar underlying biological abnormalities have been identified in both conditions including autoantibodies against neural targets, endothelial dysfunction, acquired mitochondrial dysfunction, and a pro-inflammatory gut microbiome. Each of these abnormalities may directly cause some of the symptoms. In addition, the symptoms also may be caused by ancient, evolutionarily conserved symptomatic and metabolic responses to vital threats-sickness behavior and torpor-responses mediated by specific, recently discovered neural circuits. These neural circuits constitute a symptom-generating pathway, activated by neuroinflammation, which may be targeted by therapeutics to quell neuroinflammation. Many factors cause the symptoms to become chronic, including persistent infectious agents (and/or their nucleic acids and antigens) and the fact that many of the underlying biological abnormalities reinforce each other, creating ongoing physiological vicious cycles.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102259"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759281","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}
Cell Reports MedicinePub Date : 2025-08-19Epub Date: 2025-07-29DOI: 10.1016/j.xcrm.2025.102256
Matthew M Carter, Diane Demis, Dalia Perelman, Michelle St Onge, Christina Petlura, Kristen Cunanan, Kavita Mathi, Holden T Maecker, Jo May Chow, Jennifer L Robinson, Anice Sabag-Daigle, Erica D Sonnenburg, Rachael H Buck, Christopher D Gardner, Justin L Sonnenburg
{"title":"A human milk oligosaccharide alters the microbiome, circulating hormones, and metabolites in a randomized controlled trial of older adults.","authors":"Matthew M Carter, Diane Demis, Dalia Perelman, Michelle St Onge, Christina Petlura, Kristen Cunanan, Kavita Mathi, Holden T Maecker, Jo May Chow, Jennifer L Robinson, Anice Sabag-Daigle, Erica D Sonnenburg, Rachael H Buck, Christopher D Gardner, Justin L Sonnenburg","doi":"10.1016/j.xcrm.2025.102256","DOIUrl":"10.1016/j.xcrm.2025.102256","url":null,"abstract":"<p><p>Aging-related immune dysfunction is linked to cancer, atherosclerosis, and neurodegenerative diseases. This 6-week randomized controlled trial evaluated whether 2'-fucosyllactose (2'-FL), a human breast milk oligosaccharide with established benefits in infants and animal models, could improve gut microbiota and immune function in 89 healthy older adults (mean age 67.3 years). While the primary endpoint of cytokine response change was not met, 2'-FL supplementation increased gut Bifidobacterium levels and elevated serum insulin, high-density lipoprotein (HDL) cholesterol, and FGF21 hormone. Bifidobacterium \"responders\" experienced additional metabolic and proteomic changes and also performed better on a cognitive test of visual memory. Nonresponders were more likely to lack Bifidobacterium in their gut microbiota at the start of the intervention. Multi-omics analysis indicated a systemic response to 2'-FL, which could be detected in blood and urine, showcasing the potential of this prebiotic to provide diverse benefits for healthy aging. This trial was registered at ClinicalTrials.gov (NCT03690999).</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102256"},"PeriodicalIF":10.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752535","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
