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Dysbiosis of the gut microbiota and neutrophil extracellular traps (NETs) formation are implicated in the increasing prevalence of chemoimmunotherapy resistance, which will need to be regulated to enable effective chemotherapy against CRC. To improve CRC therapy, inulin\u2010based oral chemotherapy microspheres (ZIF\u20108@OXA@Inulin) are constructed. Oral inulin\u2010based microspheres specifically adapt to the digestive system, which accurately release drugs in response to pH variations in the gastrointestinal tract. Moreover, ZIF\u20108@OXA@Inulin significantly enhances the intratumoral concentration and retention time of chemotherapeutic agents in an orthotopic colon tumor model, thereby further promoting pyroptosis. Additionally, ZIF\u20108@OXA@Inulin microspheres reshape the gut microbiota by increasing the abundance of beneficial bacterial genera (\n                    <jats:italic>Alistipes<\/jats:italic>\n                    ,\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    ,\n                    <jats:italic>Enterorhabdus<\/jats:italic>\n                    , and\n                    <jats:italic>Turicibacter<\/jats:italic>\n                    ) and suppressing the formation of NETs induced by chemotherapy\u2010associated side effects, ultimately facilitating T cell infiltration within the tumor microenvironment. ZIF\u20108@OXA@Inulin microspheres not only demonstrate excellent anti\u2010tumor performance and antimetastatic effect but also exhibit adjuvant effects to immunotherapy agents. Collectively, the oral inulin\u2010based microspheres (ZIF\u20108@OXA@Inulin) are capable of exhibiting anti\u2010tumor activities while promoting chemotherapy and immunotherapy effects. Therefore, they show substantial application potential for CRC therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202514318","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T20:10:46Z","timestamp":1769717446000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inulin\u2010Based Oral Chemotherapy Modulates Gut Microbiota and Immune Microenvironment through Inhibition of Neutrophil Extracellular Trap Formation for Improving Cancer Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Zhenhao","family":"Li","sequence":"first","affiliation":[{"name":"Department of General Surgery Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumors Nanfang Hospital Southern Medical University  Guangzhou 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