# Comprehensive identification of microbial and metabolomic factors impacting ICC recurrence **Authors:** Yuan Dang, Shaohua Xu, Jingyun Huang, Xing Peng, Yong Yang, Yingchao Wang, Yanan Yan, Fengle Jiang, Jianmin Wang, Jingfeng Liu PMC · DOI: 10.3389/fonc.2025.1703182 · Frontiers in Oncology · 2026-02-12 ## TL;DR This study identifies gut bacteria and metabolites linked to the recurrence of intrahepatic cholangiocarcinoma, offering potential biomarkers for tracking the disease. ## Contribution The study introduces a multiomics approach to identify microbial and metabolomic factors associated with ICC recurrence. ## Key findings - Bacteroides, Veillonella, and Enterococcus were significantly increased in ICC patients across all stages. - Microbial changes influence ICC through metabolites like kynurenic acid and bile acids. - Multiomics analysis improves ICC staging and highlights bile acids' role in prognosis. ## Abstract Intrahepatic cholangiocarcinoma (ICC) originates from intrahepatic bile duct epithelial cells and its global incidence is rising. Surgery remains the primary treatment, but postoperative recurrence rates remain high. We analyzed ICC patients' gut microbiota at four stages (preoperative, 7 days postoperative, 1 month postoperative, and during recurrence) using 16S rRNA sequencing and their serum metabolome via LC-MS/MS. Correlations among gut microbiota, metabolome, and clinical indicators were investigated, and candidate microorganisms and metabolites were integrated for multiomics clustering and staging. This revealed significant increases in Bacteroides, Veillonella, and Enterococcus in ICC patients compared to healthy controls across all stages, suggesting these bacteria as potential markers of ICC progression. Microbial and metabolite changes were observed, with gut microbes influencing ICC development through kynurenic acid, linoleic acid, creatine, cholic acid, L-arginine, and the tumor microenvironment. Multiomics analysis showed that cholangiocarcinoma staging improves patient prognosis, particularly highlighting bile acids' role in type II hepatic phenotypes related to cholesterol metabolism. Our study provides insights into ICC microbiome and metabolome associations with clinical features and survival. ## Linked entities - **Chemicals:** kynurenic acid (PubChem CID 3845), linoleic acid (PubChem CID 5280450), creatine (PubChem CID 586), cholic acid (PubChem CID 221493), L-arginine (PubChem CID 232) - **Diseases:** intrahepatic cholangiocarcinoma (MONDO:0003210), ICC (MONDO:0003210) ## Full-text entities - **Genes:** AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, GGTLC5P (gamma-glutamyltransferase light chain 5 pseudogene) [NCBI Gene 653590] {aka GGT}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, LOC102724197 (inactive glutathione hydrolase 2) [NCBI Gene 102724197] {aka GGT2} - **Diseases:** infection (MESH:D007239), bacteremia (MESH:D016470), urinary tract infections (MESH:D014552), metastasis (MESH:D009362), HCC (MESH:D006528), infectious (MESH:D003141), CSD (MESH:D012892), infective endocarditis (MESH:D004696), liver injury (MESH:D017093), intra-abdominal infections (MESH:D059413), cancer (MESH:D009369), anxiety (MESH:D001007), HBV infection (MESH:D006509), meningitis (MESH:D008580), chronic inflammation (MESH:D007249), intrahepatic bile duct stones (MESH:D002780), ICC (MESH:D018281), carcinogenesis (MESH:D063646) - **Chemicals:** amino acid (MESH:D000596), CTAB (MESH:D000077286), carbohydrates (MESH:D002241), L-arginine (MESH:D001120), creatine (MESH:D003401), L-kynurenic acid (-), bile acid (MESH:D001647), lysine (MESH:D008239), tryptophan (MESH:D014364), flavonoid (MESH:D005419), creatinine (MESH:D003404), D-glutamine (MESH:D005973), lipid (MESH:D008055), ammonium acetate (MESH:C018824), kynurenic acid (MESH:D007736), acetonitrile (MESH:C032159), Cholic acid (MESH:D019826), methanol (MESH:D000432), linoleic acid (MESH:D019787), PCD (MESH:C536778), hypoxanthine (MESH:D019271), geraniol (MESH:C007836), pyroglutamic acid (MESH:D011761), L-glutamic acid (MESH:D018698), L-kynurenine (MESH:D007737), SDS (MESH:D012967), cholesterol (MESH:D002784), polycyclic aromatic hydrocarbon (MESH:D011084), water (MESH:D014867) - **Species:** Lactococcus (lactic streptococci, genus) [taxon 1357], Bacteroides (genus) [taxon 816], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Homo sapiens (human, species) [taxon 9606], Lachnospira (genus) [taxon 28050], Subdoligranulum (genus) [taxon 292632], Rickettsia (genus) [taxon 780], gut metagenome (species) [taxon 749906], Alternaria embellisia (species) [taxon 230009], Peptostreptococcus (genus) [taxon 1257], Eubacterium (genus) [taxon 1730], Peptococcus (genus) [taxon 2740], Acinetobacter (genus) [taxon 469], Halomonas (genus) [taxon 2745], Faecalibacterium (genus) [taxon 216851], Wolfiporia cocos (species) [taxon 81056], Anaerobutyricum hallii (species) [taxon 39488], Enterococcus (genus) [taxon 1350], Veillonella (genus) [taxon 29465], Abiotrophia (genus) [taxon 46123], Brevibacterium (genus) [taxon 1696] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12935644/full.md ## Figures 9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12935644/full.md ## References 36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12935644/full.md --- Source: https://tomesphere.com/paper/PMC12935644