KEY RESOURCES TABLE
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
|---|---|---|
| Antibodies | ||
| Goat anti-rabbit IgG-HRP | Cell Signaling Technology | Cat# 7074S; RRID: AB_2099233 |
| Goat anti-mouse IgG-HRP | Cell Signaling Technology | Cat# 7076S; RRID: AB_330924 |
| Goat anti-rabbit IgG Alexa Fluro 488 conjugate | Cell Signaling Technology | Cat# 4412; RRID: AB_1904025 |
| Goat anti-rabbit IgG Alexa Fluor 488 conjugate | Abcam | Cat# ab150077; RRID: AB_2890897 |
| Goat anti-rabbit IgG horseradish peroxidase conjugate | Servicebio | Cat# G1215 |
| Goat anti-mouse IgG BioMag | Qiagen | Cat# 310007 |
| Hamster anti-mouse CD11c APC conjugate | BD Biosciences | Cat# 550261; RRID: AB_398460 |
| Hamster anti-mouse CD28 | BD Biosciences | Cat# 553295; RRID: AB_394764 |
| Hamster anti-mouse CD3e | BD Biosciences | Cat# 553057; RRID: AB_394590 |
| Hamster anti-mouse CD3 PerCP-Cy5.5 conjugate | BD Biosciences | Cat# 551163; RRID: AB_ AB_394082 |
| HRP-conjugated monoclonal mouse anti-GAPDH | KangChen | Cat# KC-5G5 |
| Mouse monoclonal anti-Muc2 | Santa Cruz Biotechnology | Cat# sc-59859; RRID: AB_784653 |
| Mouse monoclonal anti-FXR/NR1H4 | Santa Cruz Biotechnology | Cat# sc-25309; RRID: AB_628039 |
| Rabbit monoclonal anti-Lysozyme | Abcam | Cat# ab108508; RRID: AB_10861277 |
| Rabbit monoclonal anti-Olfm4 | Cell Signaling Technology | Cat# 39141; RRID: AB_2650511 |
| Rabbit polyclonal anti-GFP | Abcam | Cat# ab290; RRID: AB_303395 |
| Rabbit polyclonal anti-CYP8B1 | Abcam | Cat# ab191910; RRID: AB_2828000 |
| Rabbit polyclonal anti-CYP7A1 | Abcam | Cat# ab65596; RRID: AB_1566114 |
| Rat Anti-Mouse CD16/CD32 | BD Biosciences | Cat# 553142 |
| Rat anti-mouse Ly-6G PE conjugate | BD Biosciences | Cat# 551461; RRID: AB_394208 |
| Rat anti-mouse CD45 BV510 conjugate | BD Biosciences | Cat# 563891; RRID: AB_2734134 |
| Rat anti-mouse CD11b BUV395 conjugate | BD Biosciences | Cat# 563553; RRID: AB_2738276 |
| Rat anti-mouse F4/80 FITC conjugate | Thermo Fisher Scientific | Cat# 11-4801-85; RRID: AB_2637192 |
| Rat anti-mouse CD326 (Ep-CAM) PE conjugate | Biolegend | Cat# 118205; RRID: AB_1134176 |
| 7-AAD | BD Biosciences | Cat# 559925; RRID: AB_2869266 |
| Bacterial and virus strains | ||
| AAV2/8-TBG-mCherry | Hanbio | N/A |
| AAV2/8-TBG-m-Cyp8b1-3xflag-null | Hanbio | N/A |
| AAV2/9-CMV-eGFP | Genomeditech | N/A |
| AAV2/9-CMV-m-Cyp8b1-shRNA | Genomeditech | N/A |
| Biological samples | ||
| Human: UC patient serum | Shanghai Tenth People’s Hospital | N/A |
| Human: Healthy adult serum | Shanghai Tenth People’s Hospital | N/A |
| Chemicals, peptides, and recombinant proteins | ||
| Alcian blue | Sigma-Aldrich | Cat#: 109-09; CAS: 33864-99-2 |
| Acetonitrile | Thermo Fisher Scientific | Cat#: A955-4; CAS: 75-05-8 |
| Bacitracin | meilunbio | Cat#: MB1374; CAS: 1405-87-4 |
| Bovine Serum Albumin (BSA) | Sigma-Aldrich | Cat#: V900933; CAS: 9048-46-8 |
| B27 | Gibco | Cat#: 17504044 |
| CHIR99021 | MedChemExpress | Cat#: HY-10182; CAS: 252917-06-9 |
| Chloroform | Sinopharm | Cat#: 10006818; CAS: 67-66-3 |
| Cholic acid (CA) | Sigma-Aldrich | Cat#: C1129; CAS: 81-25-4 |
| DAPI | Sigma-Aldrich | Cat#: D1306; CAS: 28718-90-3 |
| DAPI | Abcam | Cat#: ab104139; CAS: 28718-90-3 |
| Dextran sodium sulfate (DSS) | MP Biomedicals | SKU: 02160110-CF; CAS: 9011-18-1 |
| Dispase II | Sigma-Aldrich | Cat#: D4693; CAS: 42613-33-2 |
| DMEM/F12 | Gibco | Cat#: C11330500BT |
| DNase I | Sigma-Aldrich | Cat#: 10104159001 |
| Dimethyl sulfoxide (DMSO) | Sigma-Aldrich | Cat#: D4540; CAS: 67-68-5 |
| d5-TCA | Toronto research chemicals | Cat#: T008852; CAS: 81-24-3 |
| Epidermal growth factor (EGF) | Peprotech | Cat#: 315-09 |
| Fetal bovine serum (FBS) | Gibco | Cat#: AHW87326 |
| FITC-dextran 4KD | Sigma-Aldrich | Cat#: 68059 |
| Fixative for TEM | Servicebio | Cat#: G1102 |
| Formic acid | Tokyo Chemical Industry | Cat#: F0654; CAS: 64-18-6 |
| Gentle Cell Dissociation Reagent | STEMCELL Technologies | Cat#: 100-0485 |
| Glutamax | Gibco | Cat#: 35050061 |
| GW501516 | MedChemExpress | Cat#: HY-10838; CAS: 317318-70-0 |
| GW6471 | MedChemExpress | Cat#: HY-15372; CAS: 880635-03-0 |
| Hematoxylin and eosin (H&E) | Servicebio | Cat#: G1003 |
| HEPES | Gibco | Cat#: 15630080 |
| IntestiCult Organoid Growth Medium (Mouse) with Supplement 1 and 2 | STEMCELL Technologies | Cat#: 06005 |
| Isopropanol | Thermo Fisher Scientific | Cat#: A461-4; CAS: 67-63-0 |
| L-Carnitine Inner Salt | Sigma-Aldrich | Cat#: C0158; CAS: 541-15-1 |
| Lipopolysaccharide (LPS) | Sigma-Aldrich | Cat#: 2880; CAS: 297-473-0 |
| Matrigel Matrix for Organoid Culture, Phenol Red-free, LDEV-free | Corning | Cat#: 356255 |
| Metronidazole | Meilunbio | Cat#: MB2200; CAS: 443-48-1 |
| Mouse colony-stimulating factor | Peprotech | Cat#: AF-315-02 |
| Methanol | Sigma-Aldrich | Cat#: 34860; CAS: 67-56-1 |
| 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) | Sigma-Aldrich | Cat#: 2128; CAS: 298-93-1 |
| Na-Palmitate | Sigma-Aldrich | Cat#: P9767; CAS: 408-35-5 |
| N-acetylcysteine | Sigma-Aldrich | Cat#: A0737; CAS: 38520-57-9 |
| N2 | Gibco | Cat#: 17502001 |
| Neomycin | Meilunbio | Cat#: MB1716; CAS: 1405-10-3 |
| Nicotinamide | MedChemExpress | Cat#: HY-B0150; CAS: 98-92-0 |
| Noggin | Peprotech | Cat#: 250-38 |
| Obeticholic acid (OCA) | MedChemExpress | Cat#: HY-12222; CAS: 459789-99-2 |
| OsO4 | Ted Pella Inc. | Cat#: 18456; CAS: 20816-12-0 |
| Paraformaldehyde | Servicebio | Cat#: G1101 |
| Penicillin-Streptomycin | Gibco | Cat#: 15140122 |
| Periodic acid Schiff (PAS) | Servicebio | Cat#: G1008 |
| Pioglitazone | MedChemExpress | Cat#: HY-13956; CAS: 111025-46-8 |
| Protease inhibitor cocktail | Roche Life Science | Cat#: 11836170001 |
| RPMI 1640 | Gibco | Cat#: 72400047 |
| R-spondin-1 | Peprotech | Cat#: 315-32 |
| Scintillation cocktail | China Isotope & Radiation Corp. | Cat#: 1200-4 |
| Sodium dodecyl sulfate (SDS) | Sigma-Aldrich | Cat#: V900859; CAS: 151-21-3 |
| Streptomycin | Meilunbio | Cat#: MB1275; CAS: 3810-74-0 |
| Taurocholic acid (TCA) | Sigma-Aldrich | Cat#: T4009; CAS: 345909-26-4 |
| Trinitron-benzene-sulfonic acid (TNBS) | Sigma-Aldrich | Cat#: P2297; CAS: 2508-19-12 |
| Triton X-100 | Beyotime | Cat#: ST795 |
| TrypLE | Gibco | Cat#: 12604013 |
| Type IV collagenase | Sigma-Aldrich | Cat#: C4-28 |
| UltraPure 0.5 M EDTA | Invitrogen | Cat#: 1557520 |
| WY14643 | MedChemExpress | Cat#: HY-16995; CAS: 50892-23-4 |
| Y-27632 | MedChemExpress | Cat#: HY-10071; CAS: 146986-50-7 |
| 4% paraformaldehyde | Servicebio | Cat#: G1101 |
| 5-Ethynyl-2’-deoxyuridine (Edu) | MedChemExpress | Cat#: HY-118411; CAS: 61135-33-9 |
| [9,10-3H]- palmitic acid | PerkinElmer | Cat#: NET043001MC |
| Critical commercial assays | ||
| BCA protein assay kit | Thermo Fisher Scientific | Cat#: 23255 |
| EDU staining kit | RiboBio | Cat#: C10310 |
| FIREFLYGLO Luciferase Assay Kit | Meilunbio | Cat#: MA0519 |
| Hieff qPCR SYBR Green Master Mix (High Rox) | Yeasen | Cat#: 11203ES08 |
| Hifair II 1st Strand cDNA Synthesis SuperMix (gDNA digester plus) | Yeasen | Cat#: 11123ES60 |
| In-situ cell death detection kit | Roche | Cat#: 11684795910 |
| LANCE® Ultra cAMP Kit | PerkinElmer | Cat#: TRF0262 |
| Mouse TNF-α ELISA kit | BD Biosciences | Cat#: 560478 |
| Mouse IL-6 ELISA kit | BD Biosciences | Cat#: 555240 |
| Mouse IFN-γ ELISA kit | BD Biosciences | Cat#: 555138 |
| Mouse IL-17 ELISA kit | Thermo Fisher Scientific | Cat#: BMS6001 |
| Mouse IL-1β ELISA kit | Thermo Fisher Scientific | Cat#: 88-7013-88 |
| QIAquick PCR purification kit | Qiagen | Cat#: 28104 |
| RNeasy mini kit | Qiagen | Cat#: 74106 |
| RNA simple total RNA kit | Tiangen Biotech | Cat#: DP419 |
| SuperSignal West Pico PLUS Chemiluminescent Substrate | Thermo Fisher Scientific | Cat#: 34578 |
| Tissue protein extraction reagent | Thermo Fisher Scientific | Cat#: 78510 |
| Urine fecal occult blood test kit | Nanjing Jiancheng Bioengineering Institute | Cat#: C027-1-1 |
| Deposited data | ||
| The raw data of RNA-seq generated | This paper | GEO: GSE210290 |
| The raw data of 16S rRNA gene sequencing | This paper | SRA: PRJNA864099 |
| Experimental models: Cell lines | ||
| Experimental models: Organisms/strains | ||
| Mouse: C57BL/6J | Beijing Huafukang Bioscience Co. Inc. | N/A |
| Mouse: Il10-null | Gempharmatech | N/A |
| Mouse: Cyp8b1-null | Gempharmatech | N/A |
| Mouse: SCID | Gempharmatech | N/A |
| Mouse: Cas9LSL+/+ | The Jackson Laboratory | N/A |
| Mouse: Pparafl/fl | Luo et al., 2019 | N/A |
| Mouse: PparaΔIE | Luo et al., 2019 | N/A |
| Mouse: Fxr-null | Sinal et al., 2000 | N/A |
| Mouse: FxrΔIE | Kim et al., 2007 | N/A |
| Mouse: FxrΔHep | Kim et al., 2007 | N/A |
| Mouse: Lgr5-EGFP-IRES-creERT2 | Shanghai Model Organisms Center | NM-KI-200154 |
| Mouse: Tgr5-null | Provided by Prof. Xin Xie at Shanghai Institute of Materia Medica | N/A |
| Oligonucleotides | ||
| See Table S3 for qRT-PCR | This paper | N/A |
| Recombinant DNA | ||
| Software and algorithms | ||
| Adobe Photoshop | Adobe | https://www.adobe.com/products/photoshop.html |
| Endnote | Endnote | http://endnote.com; |
| Excel | Microsoft | https://www.microsoft.com/en-us/microsoft-365/excel |
| FlowJo_V10 | BD Biosciences | https://www.flowjo.com/solutions/flowjo; |
| Leica Application Suite X | Leica Microsystems | https://www.leica-microsystems.com/products/microscope-software/details/product/leica-las-x-ls/ |
| NDP.view 2 | Hamamatsu | https://www.hamamatsu.com/jp/en/product/type/U12388-01/index.html |
| Pannoramic Viewer | 3DHISTECH | http://www.3dhistech.com/pannoramic_viewer |
| Prism 8 | GraphPad software | https://www.graphpad.com/ |
| Progenesis QI | Waters Corp. | http://www.nonlinear.com/progenesis/qi-for-proteomics/ |
| SIMCA 16 | Umetrics | http://umetrics.com/products/simca |
| Xcalibur | Thermo Fisher Scientific | http://chemistry.unt.edu/~verbeck/LIMS/Manuals/XCAL_Quant.pdf |
| Other | ||
| Acquity UPLC/Synapt XS HDMS system | Waters Corp. | N/A |
| Acquity BEH C18 column | Waters Corp. | SKU: 186002352 |
| Applied Biosystems 7900HT B Fast Real-Time PCR System | Applied Biosystems | N/A |
| BD LSRFortessa Fortessa Flow Cytometer | BD Biosciences | N/A |
| BD FACSAriaII Flow Cytometer | BD Biosciences | N/A |
| ChemiDoc MP Imaging System | Bio-Rad | N/A |
| Hitachi HT-7800 TEM | Hitachi | N/A |
| Illumina NovaSeq 6000 | Illumina | N/A |
| InfinityLab Poroshell 120 Hilic-Z column | Agilent technologies | 675775-924 |
| Leica TCS SPS microscope | Leica Microsystems | N/A |
| Leica DM6B laser microdissection systems | Leica Microsystems | N/A |
| LTQ Orbitrap mass spectrometer | Thermo Fisher Scientific | N/A |
| Olympus CKX53 microscope | Olympus | N/A |
| Spectramax M5 microplate reader | Molecular Devices | N/A |
| UPLC CSH column | Waters Corp. | SKU: 186005297 |
| Vanquish™ UHPLC | Thermo Fisher Scientific | N/A |
| 2450 Microplate Counter | PerkinElmer | N/A |