{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:06:45Z","timestamp":1790006805884,"version":"4.0.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Laterally spreading tumors (LSTs) are pathologically classified into adenomas, including low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN), and sessile serrated lesions (SSL). HGIN has a higher risk of progressing to colorectal cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study compared the gut microbiome across these three pathological subtypes using fecal shotgun metagenomic sequencing and non-targeted metabolomics in 53 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall community structure was similar among groups by Bray-Curtis NMDS and ANOSIM, although HGIN exhibited higher alpha diversity than SSL and enrichment of inflammation-associated and opportunistic taxa (e.g., Desulfovibrio, Bilophila, Helicobacter, Acinetobacter) alongside depletion of selected commensal taxa associated with mucosal homeostasis, including Bifidobacterium-, Lachnospiraceae-, and Ruminococcus-related species. Functionally, the HGIN-associated microbiome showed an expanded resistome and increased mobile genetic element-related potential, particularly in the HGIN versus LGIN comparison, with enrichment of beta-lactamase genes, MCR-family genes, and mobileOG features related to DNA transfer, recombination, transposition, plasmid maintenance, secretion, pilus-associated functions, and phage-linked mobility. In exploratory analyses, untargeted metabolomics suggested a bile- and lipid-rich metabolic pattern in HGIN, with nominal increases (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05; none significant after FDR correction) in lithocholyltaurine, LysoPE(P-16:0\/0:0), tridecanoic acid and cortexolone. GSEA revealed nominal enrichment of unsaturated fatty acid biosynthesis, pyruvate metabolism, and propanoate metabolism. Exploratory species-metabolite correlations linked HGIN-enriched pathobionts with lipid\/steroid-, bile-acid-, amino-acid-, and fatty-acid-related metabolites, while HGIN-depleted commensals were associated with amino-acid and organic-acid metabolic features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Together, these findings identify microbial and metabolic features associated with high-grade histopathology within the LST spectrum, including FDR-supported microbial remodeling\u2014pathobiont enrichment and expanded resistome and mobile genetic potential\u2014accompanied by exploratory, nominally significant metabolomic alterations involving bile\/lipid- and SCFA-related metabolites.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1844759","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:53:30Z","timestamp":1790006010000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Metagenomic and metabolomic profiling of laterally spreading tumors identifies a microbiome with putative pro-tumorigenic features in high-grade intraepithelial neoplasia"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhenjiang","family":"Wang","sequence":"first","affiliation":[{"name":"Zhuhai People\u2019s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)","place":["Zhuhai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyi","family":"Guo","sequence":"additional","affiliation":[{"name":"Zhuhai People\u2019s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)","place":["Zhuhai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaiwei","family":"Huang","sequence":"additional","affiliation":[{"name":"Zhuhai People\u2019s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)","place":["Zhuhai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Zhuhai People\u2019s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)","place":["Zhuhai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhuhai People\u2019s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)","place":["Zhuhai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linmin","family":"Lai","sequence":"additional","affiliation":[{"name":"Zhuhai People\u2019s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)","place":["Zhuhai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Zhuhai People\u2019s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)","place":["Zhuhai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Zhuhai People\u2019s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)","place":["Zhuhai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfei","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhuhai People\u2019s Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)","place":["Zhuhai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1186\/1477-7819-12-164","article-title":"Secondary bile acids: An underrecognized cause of colon cancer.","volume":"12","author":"Ajouz","year":"2014","journal-title":"World J. 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