{"title":"Atractylodes macrocephala polysaccharide orchestrates anti-tumor immunity via a dual-network mechanism targeting the gut microbiota and spleen.","authors":"Yajing Shuai, Jieyu Xing, Xiaoxian Liu, Zijing Song, Siqi Lin, Chengyu Lu, Weiwei Zeng, Guixiang Wang","doi":"10.1038/s41522-026-01013-8","DOIUrl":null,"url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a common global malignancy, and its advanced stage is closely linked to a gut microbiota-metabolism-immunity vicious cycle requiring early intervention. In this study, anti-CRC effects of PAMK in CT26 tumor-bearing mice were explored. Results showed that PAMK significantly inhibited tumor growth and improved the quality of life of tumor-bearing mice by enhancing antitumor immunity, including increased NK cell infiltration and NKG2D expression, elevated CD4⁺:CD8⁺ ratios, and higher serum IFN-γ levels. However, therapeutic effects of PAMK were not observed in antibiotic‑induced microbiota depletion (AIMD) mice. Notably, following fecal microbiota transplantation (FMT), therapeutic effects of PAMK were largely restored. PAMK alleviated tumor-induced gut microbiota dysbiosis characterized by enriched g_Alistipes, and remodeled fatty acid and steroid metabolism, which was closely associated with enhanced antitumor immunity and a potential microbiota-metabolism-immunity axis. Meanwhile, PAMK modulated multiple metabolic, circadian and immune pathways in the spleen as verified by transcriptomics and qPCR. Integrative multi-omics analysis indicated that the gut microbiota-metabolite-spleen gene axis may act synergistically to mediate anti-CRC effects of PAMK in tumor-bearing mice. This study highlights the potential of PAMK in CRC tumor immune adjuvants, providing experimental and theoretical support for its clinical translation and novel tumor immunotherapies.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"12 1","pages":""},"PeriodicalIF":11.4000,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309544/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Biofilms and Microbiomes","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41522-026-01013-8","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Colorectal cancer (CRC) is a common global malignancy, and its advanced stage is closely linked to a gut microbiota-metabolism-immunity vicious cycle requiring early intervention. In this study, anti-CRC effects of PAMK in CT26 tumor-bearing mice were explored. Results showed that PAMK significantly inhibited tumor growth and improved the quality of life of tumor-bearing mice by enhancing antitumor immunity, including increased NK cell infiltration and NKG2D expression, elevated CD4⁺:CD8⁺ ratios, and higher serum IFN-γ levels. However, therapeutic effects of PAMK were not observed in antibiotic‑induced microbiota depletion (AIMD) mice. Notably, following fecal microbiota transplantation (FMT), therapeutic effects of PAMK were largely restored. PAMK alleviated tumor-induced gut microbiota dysbiosis characterized by enriched g_Alistipes, and remodeled fatty acid and steroid metabolism, which was closely associated with enhanced antitumor immunity and a potential microbiota-metabolism-immunity axis. Meanwhile, PAMK modulated multiple metabolic, circadian and immune pathways in the spleen as verified by transcriptomics and qPCR. Integrative multi-omics analysis indicated that the gut microbiota-metabolite-spleen gene axis may act synergistically to mediate anti-CRC effects of PAMK in tumor-bearing mice. This study highlights the potential of PAMK in CRC tumor immune adjuvants, providing experimental and theoretical support for its clinical translation and novel tumor immunotherapies.
期刊介绍：
npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.
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