ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
This article is part of the Research TopicMicrobiome and its Roles in Disease Diagnosis and Treatment: Pathogen Resistance Spectrum, Metabolism, Risk Model, and Vaccine DesignView all 9 articles
Integrative Metagenomic and Metabolomic Profiling Identifies Gut Microbiota and Metabolite Signatures Associated with Lymph Node Metastasis in Pancreatic Cancer
Provisionally accepted
Pengyu Li
Mingfei Wang
Hanyu Zhang
Xingyu GaoLixin Chen
Haomin Chen
Qiang Xu
Weijie ChenWenjing Liu
Menghua Dai*- Peking Union Medical College Hospital (CAMS), Beijing, China
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Background: Lymph node metastasis (LNM) is a prognostic factor for pancreatic cancer. The association between gut microbiota and LNM remains unexplored. This study aimed to characterize gut microbiota and metabolomic profiles associated with LNM and to investigate their potential as predictive biomarkers. Methods: Fecal samples from pancreatic cancer patients undergoing surgery were analyzed via metagenomic sequencing and untargeted metabolomics. Patients were categorized into LNM and non-LNM (NLNM) groups. Differential microbiome taxa were analyzed using the DESeq2 package. Random forest predictive models were developed based on metagenomic and metabolomic data, with performance assessed using leave-one-out cross-validation. Results: A total of 26 LNM and 29 NLNM patients were included. PCoA analysis revealed significant differences in microbiota composition between the two groups (Anosim, P = 0.047). The absolute counts of Ruminococcus gnavus and Blautia wexlera were significantly decreased in LNM. Tryptophan-derived metabolites indole-3-lactic acid (3-ILA) and Indole-3-acrylic acid (3-IA) were downregulated in LNM. Functional pathway analysis showed downregulation of tryptophan metabolism in LNM, while cancer-related pathways were upregulated. Correlation analysis revealed a significant positive association between Ruminococcus gnavus and 3-ILA/3-IA levels. Moreover, Ruminococcus gnavus was positively correlated with CD8⁺ T cells. Predictive models based on gut microbiota and metabolites distinguished LNM from NLNM, with AUCs of 0.854 and 0.940, respectively. Conclusion: Gut microbiota and metabolites exhibit significant alterations during lymph node metastasis in pancreatic cancer, especially Ruminococcus gnavus, Blautia wexlera, and tryptophan metabolites (3-ILA and 3-IA). Gut microbiota and metabolite signatures hold promise as potential non-invasive biomarkers for predicting LNM in pancreatic cancer. Further functional validation is required to determine whether and how gut microbiota and metabolites may mediate lymph node metastasis.
Keywords: Pancreatic Cancer, gut microbiome, gut metabolites, lymph node metastasis, predictivemodel
Received: 15 Sep 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Li, Wang, Zhang, Gao, Chen, Chen, Xu, Chen, Liu and Dai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Menghua Dai, daimh@pumch.cn
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