肠道菌群行业发展现状与未来趋势白皮书

◼ ◼ 20222023FDA20254 ◼ 1.1---------------------------07 1.2---------------------------081.2.1---------------------------081.2.2---------------------------091.2.3---------------------------091.3---------------------------101.4---------------------------12 2.1---------------------------142.1.1---------------------------142.1.2---------------------------162.1.3---------------------------172.2---------------------------192.3---------------------------202.4---------------------------222.5---------------------------232.6---------------------------252.7---------------------------272.8---------------------------28 ◼ 3.1---------------------------313.1.1——REBYOTA®---------------------------313.1.2——VOWST---------------------------333.2---------------------------343.3---------------------------383.4---------------------------40 4.1---------------------------464.1.1---------------------------464.1.2---------------------------48 5.1---------------------------515.1.1---------------------------515.1.2---------------------------525.1.3---------------------------535.2---------------------------545.2.1---------------------------545.2.2---------------------------555.3---------------------------565.4---------------------------57 ◼ •---------------------------59•---------------------------61•---------------------------63•---------------------------65•---------------------------67•---------------------------72•---------------------------73 CHAPTER1 1.1 1.1.1 (Superorganism)SelectionPressureHolobiontHologenome2001 EubacteriaArchaebacteriaEukaryotes ——·Carl R.Woese 5~7- pH BileAcid,BAAntimicrobialPeptides,AMPs pH FirmicutesProteobacteria 1.2 1.2.1 34200~30050100~1,000150 •0.1%AscomycotaBasidiomycotaZygomycetesInflammatoryBowelDisease,IBD •EuryarchaeotaCrenarchaeota •BlastocystisBlastocystis •99%150~170BacillotaBacteroidotaPseudomonadotaActinomycetotaVerrucomicrobiaFusobacteriaCyanobacteria98% 2011S.DuskoEhrlichEnterotypes123 /F/B,/IrritableBowelSyndrome,IBSF/B 1.2 1.2.2 ••99% •• •• 1.2.3 pH 100~1,000 ••Bile SaltspH 5.7~6.4•103~104CFU/ml• ••pH 7.3~7.7•107~109CFU/ml• ••pH 5.5~6.8•1010~1012CFU/ml• 1.3 1.3.1 1885Escherich1996WilsonBlitchington16S rRNA 2005Jeffrey Gordon2018Routy 17001958BenEisemanFaecalMicrobiota Transplant,FMTFDA20222023livebiotherapeutic products,LBPrecurrentClostridioides difficileinfection,rCDI FMT AlfredNissleNissle1917NissleMutaflor® BenEiseman 1.3 1.3.1 ForestRohwer(Siphophages) JeffreyGordon RobKnightQIIME -- FMTFMTCDIFMT TGABiomeBankBIOMICTRA REBYOTA®REBYOTA®FDAFDA VOWSTSeresTherapeuticsVOWSTFDAFDA 1.4 1.4.1 IlluminaPacBio OxfordNanopore FerringPharmaceutical SeresTherapeuticsII/III CHAPTER2 2.1 2.1.1 ◼ ·JuliaK Goodrich——TwinsUK1,126MicrobialGenome-wideAssociationStudies,mbGWAS9458.8%0.2050%ChristensenellaceaeLactase,LCT 2.1 2.1.1 ◼ 1000 Weaning Reaction —— ProtonPumpInhibitor,PPISelectiveSerotoninReuptakeInhibitor,SSRIPPI ◼ 2.1 2.1.2 Healthy First-Degree Relatives,HFDRsCrohn′s disease, CDCD FMT FMT 2.1 2.1.3 —— GasPak MALDI-TOF-MS116S rRNA98.65% 2.1 2.1.3 —— 16S rRNA •16S rRNA1500 bp•16S rRNA •DNAIlluminaPacBio Nanopore•• •RNA• —— /DNARNA 2.2 2.2.1    - 2.3 2.3.1 Smallintestinalbacterialovergrowth,SIBOFunctionalgastrointestinaldisorders,FGIDs / //CDICDI •24• / SIBO/SIBO ≥10⁵ CFU/mlSIBO 2.3 2.3.1 10%~20%FGIDsFGIDsPost-infectiousIrritableBowelSyndrome,PI-IBS IBSIBSVeillonellaLactobacillusIBSTollTLRIBS IBSPI-IBS Non-alcoholicfattyliverDisease,NAFLDNAFLD NAFLDSCFAs/ 2.4 2.4.1 ◼ 20 2006 ——BacteroidesthetaiotaomicronB.thetaiotaomicron 2 2Type2diabetes,T2D90%5%~15% 2 N-TrimethylamineN-oxide,TMAOTrimethylamine,TMATMATMAOTMAO 2.5 2.5.1 IgASecretoryIgA,sIgAToll5Toll-likereceptor5,TLR5 sIgAsIgA Toll(PatternRecognitionReceptors,PRRs)(Pathogen-associatedmolecularpatterns,PAMPs)TLRs BTBBBAFFAPRILBIgACD4+T-γ-17A IgATLRsNOD 2.5 2.5.1 BIgA ATPTTreg ✓InflammatoryBowelDisease,IBDUlcerativeColitis,UCCrohn‘sDisease,CD ✓ DNA Autoimmunekidneydiseases /MPO-ANCAGoodpasturesyndrome,GPS SCFASCFAs 2.6 - 2.6.1 2080BrainImaging-Gut–BrainAxis,GBAGBA- CentralNervousSystem,CNS GBAAutonomicNervousSystem,ANSEntericNervousSystem,ENS--Hypothalamic-Pituitary-Adrenal,HPA •ANSANSANSCNSANSANSENSANSENS/γ-Gamma-aminobutyricacid,GABA •ENSFilipeDe Vadder-ENS5-hydroxytryptamine,5-HT5-HTENSDeVadder5-HT5-HT •HPA——HPAHPA 2.6 - 2.6.1 Alzheimer′sdisease，AD20244,00020307,000 ADβ-amyloidβ-protein AβTauneurofibrillarytangles NFTAβ ◼ 2015KatlynNemani---- •blood-brain-barrier,BBB •, 20192.8 psychobioticsγ-5- 2.7 2.7.1 20201000100 1994  •/ •LPSLPS • • •DNA •StreptococcusanginosusDNA •DNATMyeloid-derivedsuppressorcells,MDSCs • 2.8 2.8.1   MEROPS •••••• •A•A•DK•D•BB•Cα 2.8 2.8.1 DietaryPattern CHAPTER3 3.1 2022FDAREBYOTA® 3.1.1——REBYOTA® 202211FDAFerringPharmaceuticalsREBYOTA®fecalmicrobiota,live-jslmRBX266018rCDIFDALiveBiotherapeutic ProductREBYOTA®FDA •R