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However, the structure and function of community\u2010level topologies related to colorectal neoplasia (CRN) remain unclear. We analyzed 3807 newly sequenced stool metagenomes from participants (2725 healthy controls, 759 non\u2010advanced adenomas, 297 advanced adenomas, and 26 colorectal cancers) in a multicenter TARGET\u2010C screening trial and validated our findings in multiple independent cohorts. We identified a CRN\u2010associated network (14 species, including\n                    <jats:italic>Clostridium symbiosum<\/jats:italic>\n                    ) and a negatively associated network (37 species, including\n                    <jats:italic>Roseburia<\/jats:italic>\n                    and\n                    <jats:italic>Lachnospira<\/jats:italic>\n                    ), forming a \u201cseesaw\u2010like\u201d microbial association pattern characterized by within\u2010group co\u2010occurrence and between\u2010group co\u2010exclusion. The structures were stable across the independent datasets. A composite score derived from the microbial topology stratified CRN risk, and diagnostic models based solely on the presence\/absence status of the topological species achieved moderate accuracy across the cohorts (area under the curve ranging from 0.66 to 0.87). Functionally, changes in CRN\u2010related microbial association patterns were associated with microbe\u2010derived metabolites. Our findings provide novel insights into the microbial topology associated with CRN and support its potential application in non\u2010invasive risk stratification. However, the utility of these topological features in colorectal cancer remains exploratory and requires further validation in larger colorectal cancer cohorts.\n                  <\/jats:p>","DOI":"10.1002\/advs.77991","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:20:20Z","timestamp":1790655620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbial Topology and Metabolic Signatures Associated With Colorectal Neoplasia"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4459-7059","authenticated-orcid":false,"given":"Kai","family":"Song","sequence":"first","affiliation":[{"name":"Center for Prevention and Early Intervention National Infrastructures for Translational Medicine Institute of Clinical Medicine Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing 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