EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001005948EGAEGA study EGAS00001005948Microbiome cross talk, Fusobacterium n. and formate metaboliteEGArestrictedsodium salt, Colorectal Neoplasm, ammonium formate, Virulence, 13C-labeled, Cocultures, cadmium salt, Bowel, formiate, magnesium formate, Gut Microflora, Tumor, CG17228, zinc salt, Story, 1135/09, 1135/07, cobalt(II) formate dihydrate, Method, Accepted, 0451/09, Cell Invasion, HCO2 anion, Flora, Cocultivations, Fusibacterium, Atf4, Colorectal Tumors, 929, DmelCG8669, 0244/09, Ah, Beyond, stimulation by symbiont of host programmed cell death, Molecular, Chip, ChIP, DROPROSA, F20O9.210, alimentary tract, CHIP, Colorectal Carcinomas, CRUCIFERIN C, procedures, Colorectal Tumor, metabolic, 671/2, chip, g, Role Concepts, Invasion, Type 17 Helper T Cells, adult alimentary canal, alimentary system, INCREASED, Ecologic Systems, colorectal (colon or rectal) cancer, nickel salt, single organism signaling, Tumors, Observational Trial, close to, OBSERVATIONAL, Apply, l(2)k04405, Micro-organism, Gut Microbiome, cobalt (+2) salt, potp, observational study, Microorganisms, Test, Derived Flag, Procedure, Niche, Shift, Intestinal Microbiota, DmIKKgamma, Ahre, sodium (4:1:1) salt, Role Concept, Benign, magnesium salt, dIKK, 1316/02, Pathogenicity, Role, Normal Cell, Intestinal Microbiotas, BcDNA:HL08040, Cellular, numerical data, Fusobacteria, Colorectal Cancers, l(2)crc, Carcinomas, Coculture, IKK-gamma, 1167/13, formate, Benign Neoplasms, cromium (+3), Methodological, Enteric Microbiota, cancer of large bowel, TH-17, Malignant Neoplasms, experimental procedures, Gastrointestinal Microflora, ATF-4, GI, Phenotypes, gastrointestinal system, BHLHE76, AhR, activation by symbiont of host programmed cell death, Cells, ammonium (4:1) salt, cancer of the large bowel, Enteric Microflora Floras, l(1)16Fg, Nepal Bhasa, ATF4/crc, 0989/01, Cross-Talk, other neoplasm, lead (+2) salt, pds, Induced, HSPABP2, glutamine metabolism, Ahh, Microflora Floras, Colorectal Cancer, Clr, nickel formate dihydrate, fusobacteria, In Vitro as Topic, lead formate, Neoplasms, regulation by symbiont of host system process, aluminum salt, Microfloras, {Cells}, formylate, enteric tract, SCAR16, 0763/13, dIKK-gamma, Inducible, In Vitro Testing, colorectal cancer, Gus, Gur, Cellularity, New Lesion, Gut, DmelCG17228, DmelCG5203, ahr, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, DmIKK-gamma, Pathogenicity Factor, Gut Microbiotas, anon-EST:Liang-2.17, causality., anon-EST:Liang-2.11, Prosp, Technique, ahr1b, In Vitro Tests, Application, GI Microfloras, F15E12_6, In, gut, NY-CO-7, thallium (+1) salt, cell, rubidium salt, Inducing, Bacteria, methanoic acid, TH-17 Cell, l(3)rH013, cancer of the large intestine, Neoplasias, Study, Prodos, Biomes, CELLULAR, trigger, UBOX1, microorganism, 0671/02, Cancer, In Vivo, l(3)j12C8, New, NEW, Cellularity Grade, use, Enteric, Coculture Technique, Malignant Neoplasm, hemolysin activity, formate secretion, CG5203, Trigger, ion(1-), aminate, Factor, potassium formate, eth, copper (+2) salt, l(2)04405, Cell, Concept, near to, IKKgamma, gut tube, l(3)rL433, In Vitro Test, MT, l(3)rI160, 0441/16, cupric formate, Gastrointestinal Microbiomes, Neoplasm, Ah receptor, CRC, Crc, Induce, Microflora Flora, Vitro Testing, aluminum formate, Gastric, metabolism, MET, ATCMPG1, ATCMPG2, New Lesion Identification, Intestinal Microflora, cross-talk, primary cancer, lithium formate, Ldb, LDB, Dmikkgamma, increased number, Colorectal Carcinoma, Increased, Carcinogeneses, Gus-u, Gus-t, Gus-s, Chromatin Immunoprecipitation, crc, Gus-r, Cancers, CRIB, Understanding, Ecological Systems, CG16910, Intestinal Microbiome, malignant tumor, Derived Value, l(3)rK204, crt, colon cancer, signalling process, In Vitro Technique, vicinity of, Intestinal, Cell Types, Microbiotas, bHLHe76, cellular metabolism, Co culture, Microorganism, Neoplasia, l(3)rK137, host organism, Derived, Metabolic Process, Gastrointestinal Microbiota, zinc formate, positive regulation by symbiont of host non-apoptotic programmed cell death, lead salt, F20O9_210, Gastrointestinal Microbial Communities, GI Microbiome, Techniques, Readability, ammonium tetraformate, Roles, Mathematical Derivation, Cell Type, Concepts, pathogenesis, Ecological, TH-17 Cells, Class E basic helix-loop-helix protein 76, Newari, 2310040B03Rik, IKKg, KEY, Key, increased, T Helper 17 Cells, Observed, MUB3_18, Type 17 Helper T Cell, Oncogeneses, MUB3.18, l(3)j6E2, copper, Physical Shift, large intestine cancer, Fusobacteria <Fusobacteriota>, Pathogenicity Factors, Novel, 0320/10, DMPROSPER, lithium salt, Local Tumor Invasion, Methodological Studies, Visual Inspection, malignant neoplasm, AW046544, DERIVED, digestive tube, asd, Malignancies, ammonium (2:1) salt, somatic mutation, Single-Celled Organism, Carcinoma, Intestinal Microbiomes, l(3)rO534, PRO, Pro, statistics and numerical data, Microbiota, Fusobacteraeota, Initiator, Microbial, CYS, GI Microflora, Floras, Virulence Factor, Observational, Induction, PROS-1, PROS-2, TH 17 Cells, Inspection, pro, Kenny, modulation by symbiont of host system process, Custodian, Observation, General, nickel (+2) salt, and GLY protein 2, anon-EST:fe3D7, Fusobacteriota corrig. Garrity and Holt 2021, SDCCAG7, ammonium salt, Ecologic, and GLY protein 1, cruciferin 3, Driven, AI747421, Ecosystems, Factors, In Vitro, dLdb, Derivation, Voila, Metabolized, Tests, System, susceptibility to, 0664/07, cobaltous formate, in vivo, TAF[[II]], Methodological Study, TH 17 Cell, DmelCG16910, Patient, Oncogenesis, copper salt, Displacement, CG8669, cancer of large intestine, mKIAA0147, Person Responsible, accessory, AI118201, Gastric Microbiome, digestive canal, Gastric Microbiomes, Habitats, Gut Microbiomes, Tumorigeneses, Procedures, Testings, experimental, Gastrointestinal, cesium salt, 2210017D18Rik, dCHIP, Benign Neoplasm, Gastrointestinal Flora, Established, Malignant, autosomal dominant, supernumerary, hydrogen carboxylate, l(3)10419, formic acid, dmTAF8, Colorectal, Cellularity Measurement, Degree, potassium salt, dATF-4, utilization, Metabolism, 14C-labeled, HL-VIII, Sphaerophorus, Studies, anon-WO0140519.15, F15E12.6, dmIKKgamma, clone 2.11, IKK[[gamma]], Level, Co-culture, PROS, 0585/13, methods, Malignancy, Co-cultures, clone 2.17, experimental section, Enteric Bacteria, Scrb1, CG9429, CG7128, Biome, Tumor Invasion, Ire1, causes, calcium formate, Habitat, Responsible, Heightened, Gut Flora, prod, Cellularity Index, Percent Cellularity, IKK, Newar Language, vartul, Clients, DmelCG3924, Ecological System, Gastrointestinal Microbial Community, cromium (+3) salt, TAF, 0563/18, 0610033N24Rik, sodium formate, intestines, PP1131, Enteric Microflora, activation by organism of non-apoptotic programmed cell death in other organism, nickel formate, Ecologic System, SCRIB1, OBSERVATION, strontium formate, Th17 Cell, Gastrointestinal Microbiotas, strontium salt, Tumorigenesis, Client, Th17, Intestinal Flora, l(3)rJ806, Testing, Pros, Enteric Microbiotas, DRVFL, Applied, Systems, In Vitro Testings, TFIID, Cocultivation, Tumor Cell Invasion, Gut Microbiota, techniques, alimentary canal, Microbiome, Observational Study, large bowel cancer, Microbiomes, Responsible Person, Microflora, Metabolic, Microbial Community, patient, CG3924, chromic formate, Enteric Microflora Flora, methanoate, Got a Ride, Floor, DmelCG9429, present in greater numbers in organism, DmelCG7128, dLDB/Chip, Increase, approaches, calcium salt, DER, Microbe, T Helper 17 Cell, TAF8, Ecological Niche, GI Microbiomes, methodologyAnn Arbor Clinical Stage II, Derived, Derivation, Stage II Testicular Cancer, Ann Arbor Pathologic Stage II, Stage II Lung Cancer, Cell Lines, RNA-seq, Stage II Uterine Corpus Cancer AJCC v8, Stage II Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8, patient, Derived Flag, Stage II, Client, Cell, Derived Value, Stage II Renal Cell Cancer, Stage II Renal Cell Carcinoma AJCC v8, FIGO Stage II, Stage II Cancer of Testis, SIOP/COG/NWTSG Stage II, FIGO grade 2, Patient, DRVFL, stage II testicular cancer, Clients, Stage II Renal Cell Cancer AJCC v8, Stage II Testicular Cancer AJCC v7, Stage 2, Stage II Testicular Cancer AJCC v6, Mathematical Derivation, DER, Line, DERIVED, Stage II Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8, Whole Transcriptome Shotgun Sequencing, Stage II Lung Cancer AJCC v8, Stage II Testicular Cancer AJCC v6 and v7, Cell., Stage II Head and Neck Squamous Cell Cancer, Stage II Cancer of the Testis, Stage II Uterine (including Endometrial) Cancer, LinesfalseRNA-seq on patient-derived, stage II, CRC cell linesThe gut microbiome is a key player in the immunomodulatory and pro-tumorigenic microenvironment in colorectal cancer (CRC). It is well established that Fusobacterium’s virulence factors are responsible for its pro-tumorigenic properties, however the role of its metabolic cross-talk with the tumor remains unexplored. Here we use in vitro, in vivo, and in silico methods to describe a novel microbe-host interaction keystone: formate. Omics data reveals molecular signatures, linking a metabolically driven CRC phenotype with Fusobacteria. We observed a metabolic shift towards increased F. nucleatum formate secretion in gut-on-chip model co-cultures with patient-derived CRC cells, along with an accelerated cancer glutamine metabolism. We show that high formate levels trigger AhR signaling, increase cancer stemness and cellular invasion. Finally, we observed an expansion of Th17 cells accompanying F. nucleatum-induced tumorigenesis. Moving beyond observational studies, we applied new experimental approaches for gaining ecosystem-level mechanistic understanding of F. nucleatum’s role in cancer pathogenesis.2022-03-09 19:42:09EGAS000010059489606EGAD00001008533EGAC00001002491