d2c9b61114b9a99607306f6d316e596f 252551.pdf a5acf9565cafb087a787f92af19e52c2b763657f 252551.pdf 17e9864abc9ec5265366e74d642d8ee1bde4f558b7e09466f77c96f30b0fe9cb 252551.pdf Title: A Commercial Probiotic Induces Tolerogenic and Reduces Pathogenic Responses in Experimental Autoimmune Encephalomyelitis Subject: Previous studies in experimental autoimmune encephalomyelitis (EAE) models have shown that some probiotic bacteria beneficially impact the development of this experimental disease. Here, we tested the therapeutic effect of two commercial multispecies probiotics—Lactibiane iki and Vivomixx—on the clinical outcome of established EAE. Lactibiane iki improves EAE clinical outcome in a dose-dependent manner and decreases central nervous system (CNS) demyelination and inflammation. This clinical improvement is related to the inhibition of pro-inflammatory and the stimulation of immunoregulatory mechanisms in the periphery. Moreover, both probiotics modulate the number and phenotype of dendritic cells (DCs). Specifically, Lactibiane iki promotes an immature, tolerogenic phenotype of DCs that can directly induce immune tolerance in the periphery, while Vivomixx decreases the percentage of DCs expressing co-stimulatory molecules. Finally, gut microbiome analysis reveals an altered microbiome composition related to clinical condition and disease progression. This is the first preclinical assay that demonstrates that a commercial probiotic performs a beneficial and dose-dependent effect in EAE mice and one of the few that demonstrates a therapeutic effect once the experimental disease is established. Because this probiotic is already available for clinical trials, further studies are being planned to explore its therapeutic potential in multiple sclerosis patients. Keywords: gut microbiota; probiotics; immune regulation; experimental autoimmune encephalomyelitis; multiple sclerosis; adaptive immunity; antigen presenting cells; gut microbiome; gut permeability Author: Laura Calvo-Barreiro, Herena Eixarch, Manuel Ponce-Alonso, Mireia Castillo, Rafael Lebrón-Galán, Leyre Mestre, Carmen Guaza, Diego Clemente, Rosa del Campo, Xavier Montalban and Carmen Espejo Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Tue Apr 7 16:14:47 2020 CEST ModDate: Tue Apr 7 16:14:47 2020 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4326804 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- RVNCFE+URWPalladioL-Ital Type 1 Custom yes yes no 133 0 LCMHXT+URWPalladioL-Bold Type 1 Custom yes yes no 134 0 ENXZUH+VnURWPalladioL-Bold Type 1 Custom yes yes no 135 0 FTIIXW+URWPalladioL-Roma Type 1 Custom yes yes no 136 0 AWHDWW+VnURWPalladioL Type 1 Custom yes yes no 137 0 IELMKZ+Rpxr Type 1 Builtin yes yes no 138 0 PFKOHU+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 143 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 160 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 161 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 162 0 JPUAMM+EURM10 Type 1 Builtin yes yes no 210 0 HHMDGK+Pxsy Type 1 Builtin yes yes no 211 0 YWGLGW+Rpxi Type 1 Builtin yes yes no 212 0 YSVTXE+Rpxmi Type 1 Builtin yes yes no 224 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 225 0 HIATQF+Pxsya Type 1 Builtin yes yes no 293 0 VSHNAE+Rpcxr Type 1 Builtin yes yes no 575 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-06-28 02:36:37 CEST RepresentationInformation: 252551.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-06-27 13:39:58 CEST Size: 4326804 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: きちぴづひどちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぉのつふっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぁびびづびびねづのぴぜ〴ぜ〰はてぜ〴ぜ〰ぅぁぅぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰きはぴはひぜ〴ぜ〰うふのっぴどはのぜ〴ぜ〰ぁびびづびびねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰あちっぴづひどちぬぜ〴ぜ〰こぴひちどのびぜ〴ぜ〰ちのつぜ〴ぜ〰ごひづちぴねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぅへぜ〴ぜ〰ざどぶはぜ〴ぜ〰こばぬづのはっべぴづぜ〴ぜ〰ぐひはぬどてづひちぴどぶづぜ〴ぜ〰ぃちばちっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰ぃべぴはにどのづぜ〴ぜ〰いづぴづっぴどはのぜ〴ぜ〰ぢべぜ〴ぜ〰がふねどのづへぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰げぎぁぜ〴ぜ〰ぉびはぬちぴどはの〬ぜ〴ぜ〰っいぎぁぜ〴ぜ〰こべのぴとづびどび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぱげご〭ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㠩‾㸊⡜㌷㙜㌷㝜〰うぬはぷぜ〴ぜ〰ぃべぴはねづぴひべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㤩‾㸊⡜㌷㙜㌷㝜〰えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㄰ Children: Item: Title: きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぉのつふっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぁびびづびびねづのぴぜ〴ぜ〰はてぜ〴ぜ〰ぅぁぅぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰きはぴはひぜ〴ぜ〰うふのっぴどはのぜ〴ぜ〰ぁびびづびびねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰あちっぴづひどちぬぜ〴ぜ〰こぴひちどのびぜ〴ぜ〰ちのつぜ〴ぜ〰ごひづちぴねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぅへぜ〴ぜ〰ざどぶはぜ〴ぜ〰こばぬづのはっべぴづぜ〴ぜ〰ぐひはぬどてづひちぴどぶづぜ〴ぜ〰ぃちばちっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰ぃべぴはにどのづぜ〴ぜ〰いづぴづっぴどはのぜ〴ぜ〰ぢべぜ〴ぜ〰がふねどのづへぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰げぎぁぜ〴ぜ〰ぉびはぬちぴどはの〬ぜ〴ぜ〰っいぎぁぜ〴ぜ〰こべのぴとづびどび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぱげご〭ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㠩‾㸊⡜㌷㙜㌷㝜〰うぬはぷぜ〴ぜ〰ぃべぴはねづぴひべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㤩‾㸊⡜㌷㙜㌷㝜〰えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㄰ Item: Title: ぉのつふっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぁびびづびびねづのぴぜ〴ぜ〰はてぜ〴ぜ〰ぅぁぅぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰きはぴはひぜ〴ぜ〰うふのっぴどはのぜ〴ぜ〰ぁびびづびびねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰あちっぴづひどちぬぜ〴ぜ〰こぴひちどのびぜ〴ぜ〰ちのつぜ〴ぜ〰ごひづちぴねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぅへぜ〴ぜ〰ざどぶはぜ〴ぜ〰こばぬづのはっべぴづぜ〴ぜ〰ぐひはぬどてづひちぴどぶづぜ〴ぜ〰ぃちばちっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰ぃべぴはにどのづぜ〴ぜ〰いづぴづっぴどはのぜ〴ぜ〰ぢべぜ〴ぜ〰がふねどのづへぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰げぎぁぜ〴ぜ〰ぉびはぬちぴどはの〬ぜ〴ぜ〰っいぎぁぜ〴ぜ〰こべのぴとづびどび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぱげご〭ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㠩‾㸊⡜㌷㙜㌷㝜〰うぬはぷぜ〴ぜ〰ぃべぴはねづぴひべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㤩‾㸊⡜㌷㙜㌷㝜〰えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㄰ Item: Title: きはぴはひぜ〴ぜ〰うふのっぴどはのぜ〴ぜ〰ぁびびづびびねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰あちっぴづひどちぬぜ〴ぜ〰こぴひちどのびぜ〴ぜ〰ちのつぜ〴ぜ〰ごひづちぴねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぅへぜ〴ぜ〰ざどぶはぜ〴ぜ〰こばぬづのはっべぴづぜ〴ぜ〰ぐひはぬどてづひちぴどぶづぜ〴ぜ〰ぃちばちっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰ぃべぴはにどのづぜ〴ぜ〰いづぴづっぴどはのぜ〴ぜ〰ぢべぜ〴ぜ〰がふねどのづへぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰げぎぁぜ〴ぜ〰ぉびはぬちぴどはの〬ぜ〴ぜ〰っいぎぁぜ〴ぜ〰こべのぴとづびどび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぱげご〭ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㠩‾㸊⡜㌷㙜㌷㝜〰うぬはぷぜ〴ぜ〰ぃべぴはねづぴひべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㤩‾㸊⡜㌷㙜㌷㝜〰えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㄰ Item: Title: あちっぴづひどちぬぜ〴ぜ〰こぴひちどのびぜ〴ぜ〰ちのつぜ〴ぜ〰ごひづちぴねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰ぅへぜ〴ぜ〰ざどぶはぜ〴ぜ〰こばぬづのはっべぴづぜ〴ぜ〰ぐひはぬどてづひちぴどぶづぜ〴ぜ〰ぃちばちっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰ぃべぴはにどのづぜ〴ぜ〰いづぴづっぴどはのぜ〴ぜ〰ぢべぜ〴ぜ〰がふねどのづへぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰げぎぁぜ〴ぜ〰ぉびはぬちぴどはの〬ぜ〴ぜ〰っいぎぁぜ〴ぜ〰こべのぴとづびどび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぱげご〭ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㠩‾㸊⡜㌷㙜㌷㝜〰うぬはぷぜ〴ぜ〰ぃべぴはねづぴひべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㤩‾㸊⡜㌷㙜㌷㝜〰えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㄰ Item: Title: ぅへぜ〴ぜ〰ざどぶはぜ〴ぜ〰こばぬづのはっべぴづぜ〴ぜ〰ぐひはぬどてづひちぴどぶづぜ〴ぜ〰ぃちばちっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰ぃべぴはにどのづぜ〴ぜ〰いづぴづっぴどはのぜ〴ぜ〰ぢべぜ〴ぜ〰がふねどのづへぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰げぎぁぜ〴ぜ〰ぉびはぬちぴどはの〬ぜ〴ぜ〰っいぎぁぜ〴ぜ〰こべのぴとづびどび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぱげご〭ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㠩‾㸊⡜㌷㙜㌷㝜〰うぬはぷぜ〴ぜ〰ぃべぴはねづぴひべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㤩‾㸊⡜㌷㙜㌷㝜〰えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㄰ Item: Title: ぃべぴはにどのづぜ〴ぜ〰いづぴづっぴどはのぜ〴ぜ〰ぢべぜ〴ぜ〰がふねどのづへぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰げぎぁぜ〴ぜ〰ぉびはぬちぴどはの〬ぜ〴ぜ〰っいぎぁぜ〴ぜ〰こべのぴとづびどび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぱげご〭ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㠩‾㸊⡜㌷㙜㌷㝜〰うぬはぷぜ〴ぜ〰ぃべぴはねづぴひべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㤩‾㸊⡜㌷㙜㌷㝜〰えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㄰ Item: Title: げぎぁぜ〴ぜ〰ぉびはぬちぴどはの〬ぜ〴ぜ〰っいぎぁぜ〴ぜ〰こべのぴとづびどび〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぱげご〭ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㠩‾㸊⡜㌷㙜㌷㝜〰うぬはぷぜ〴ぜ〰ぃべぴはねづぴひべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㤩‾㸊⡜㌷㙜㌷㝜〰えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㄰ Item: Title: うぬはぷぜ〴ぜ〰ぃべぴはねづぴひべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㤩‾㸊⡜㌷㙜㌷㝜〰えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㄰ Item: Title: えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㄰ Item: Title: ぉのぜ〴ぜ〰ざどぶはぜ〴ぜ〰ぉのぴづびぴどのちぬぜ〴ぜ〰ぐづひねづちぢどぬどぴべぜ〴ぜ〰こぴふつどづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄱ Item: Title: こぴははぬぜ〴ぜ〰こちねばぬづぜ〴ぜ〰ぃはぬぬづっぴどはの〬ぜ〴ぜ〰いぎぁぜ〴ぜ〰ぅへぴひちっぴどはの〬ぜ〴ぜ〰がどぢひちひべぜ〴ぜ〰ぐひづばちひちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰〱〶こぜ〴ぜ〰ひいぎぁぜ〴ぜ〰こづぱふづのっどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄲ Item: Title: きどっひはぢどはねづぜ〴ぜ〰あどはどのてはひねちぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄳ Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰ぉねばひはぶづびぜ〴ぜ〰ぴとづぜ〴ぜ〰ぅぁぅぜ〴ぜ〰ぃぬどのどっちぬぜ〴ぜ〰くふぴっはねづぜ〴ぜ〰どのぜ〴ぜ〰ちぜ〴ぜ〰いはびづ〭いづばづのつづのぴぜ〴ぜ〰きちののづひぜ〴ぜ〰ちびぜ〴ぜ〰ちぜ〴ぜ〰ごとづひちばづふぴどっぜ〴ぜ〰ぁばばひはちっとぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぐちぴとはでづのどっぜ〴ぜ〰げづびばはのびづびぜ〴ぜ〰ちひづぜ〴ぜ〰げづつふっづつぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰こばどのちぬぜ〴ぜ〰ぃはひつびぜ〴ぜ〰はてぜ〴ぜ〰ぐひはぢどはぴどっ〭ごひづちぴづつぜ〴ぜ〰ぅぁぅぜ〴ぜ〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰げづつふっづびぜ〴ぜ〰ぁのぴどでづの〭こばづっどてどっぜ〴ぜ〰ぐひはぬどてづひちぴどはのぜ〴ぜ〰ぢふぴぜ〴ぜ〰いはづびぜ〴ぜ〰ぎはぴぜ〴ぜ〰きはつどてべぜ〴ぜ〰いどびづちびづ〭げづぬちぴづつぜ〴ぜ〰ぃべぴはにどのづぜ〴ぜ〰ぐひはてどぬづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰ぉのっひづちびづびぜ〴ぜ〰ごひづでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰いどねどのどびとづびぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぐづひどばとづひべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰きはつふぬちぴづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎふねぢづひぜ〴ぜ〰ちのつぜ〴ぜ〰ぐとづのはぴべばづぜ〴ぜ〰はてぜ〴ぜ〰ぁのぴどでづのぜ〴ぜ〰ぐひづびづのぴどのでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぜ〵ぜ〰ぁぐぃびぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰つはぜ〴ぜ〰のはぴぜ〴ぜ〰ぁぬぴづひぜ〴ぜ〰ぉのぴづびぴどのちぬぜ〴ぜ〰ぐづひねづちぢどぬどぴべぜ〴ぜ〰ぢふぴぜ〴ぜ〰つはぜ〴ぜ〰きはつどてべぜ〴ぜ〰ぇふぴぜ〴ぜ〰きどっひはぢどはねづぜ〴ぜ〰ぃはねばはびどぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰こばづっどてどっぜ〴ぜ〰あちっぴづひどちぬぜ〴ぜ〰ごちへちぜ〴ぜ〰ちひづぜ〴ぜ〰ぁびびはっどちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰いどびづちびづぜ〴ぜ〰ぐひはでひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰ぉねばひはぶづびぜ〴ぜ〰ぴとづぜ〴ぜ〰ぅぁぅぜ〴ぜ〰ぃぬどのどっちぬぜ〴ぜ〰くふぴっはねづぜ〴ぜ〰どのぜ〴ぜ〰ちぜ〴ぜ〰いはびづ〭いづばづのつづのぴぜ〴ぜ〰きちののづひぜ〴ぜ〰ちびぜ〴ぜ〰ちぜ〴ぜ〰ごとづひちばづふぴどっぜ〴ぜ〰ぁばばひはちっとぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぐちぴとはでづのどっぜ〴ぜ〰げづびばはのびづびぜ〴ぜ〰ちひづぜ〴ぜ〰げづつふっづつぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰こばどのちぬぜ〴ぜ〰ぃはひつびぜ〴ぜ〰はてぜ〴ぜ〰ぐひはぢどはぴどっ〭ごひづちぴづつぜ〴ぜ〰ぅぁぅぜ〴ぜ〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰げづつふっづびぜ〴ぜ〰ぁのぴどでづの〭こばづっどてどっぜ〴ぜ〰ぐひはぬどてづひちぴどはのぜ〴ぜ〰ぢふぴぜ〴ぜ〰いはづびぜ〴ぜ〰ぎはぴぜ〴ぜ〰きはつどてべぜ〴ぜ〰いどびづちびづ〭げづぬちぴづつぜ〴ぜ〰ぃべぴはにどのづぜ〴ぜ〰ぐひはてどぬづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰ぉのっひづちびづびぜ〴ぜ〰ごひづでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰いどねどのどびとづびぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぐづひどばとづひべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰きはつふぬちぴづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎふねぢづひぜ〴ぜ〰ちのつぜ〴ぜ〰ぐとづのはぴべばづぜ〴ぜ〰はてぜ〴ぜ〰ぁのぴどでづのぜ〴ぜ〰ぐひづびづのぴどのでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぜ〵ぜ〰ぁぐぃびぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰つはぜ〴ぜ〰のはぴぜ〴ぜ〰ぁぬぴづひぜ〴ぜ〰ぉのぴづびぴどのちぬぜ〴ぜ〰ぐづひねづちぢどぬどぴべぜ〴ぜ〰ぢふぴぜ〴ぜ〰つはぜ〴ぜ〰きはつどてべぜ〴ぜ〰ぇふぴぜ〴ぜ〰きどっひはぢどはねづぜ〴ぜ〰ぃはねばはびどぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰こばづっどてどっぜ〴ぜ〰あちっぴづひどちぬぜ〴ぜ〰ごちへちぜ〴ぜ〰ちひづぜ〴ぜ〰ぁびびはっどちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰いどびづちびづぜ〴ぜ〰ぐひはでひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぐちぴとはでづのどっぜ〴ぜ〰げづびばはのびづびぜ〴ぜ〰ちひづぜ〴ぜ〰げづつふっづつぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰こばどのちぬぜ〴ぜ〰ぃはひつびぜ〴ぜ〰はてぜ〴ぜ〰ぐひはぢどはぴどっ〭ごひづちぴづつぜ〴ぜ〰ぅぁぅぜ〴ぜ〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰げづつふっづびぜ〴ぜ〰ぁのぴどでづの〭こばづっどてどっぜ〴ぜ〰ぐひはぬどてづひちぴどはのぜ〴ぜ〰ぢふぴぜ〴ぜ〰いはづびぜ〴ぜ〰ぎはぴぜ〴ぜ〰きはつどてべぜ〴ぜ〰いどびづちびづ〭げづぬちぴづつぜ〴ぜ〰ぃべぴはにどのづぜ〴ぜ〰ぐひはてどぬづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰ぉのっひづちびづびぜ〴ぜ〰ごひづでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰いどねどのどびとづびぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぐづひどばとづひべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰きはつふぬちぴづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎふねぢづひぜ〴ぜ〰ちのつぜ〴ぜ〰ぐとづのはぴべばづぜ〴ぜ〰はてぜ〴ぜ〰ぁのぴどでづのぜ〴ぜ〰ぐひづびづのぴどのでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぜ〵ぜ〰ぁぐぃびぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰つはぜ〴ぜ〰のはぴぜ〴ぜ〰ぁぬぴづひぜ〴ぜ〰ぉのぴづびぴどのちぬぜ〴ぜ〰ぐづひねづちぢどぬどぴべぜ〴ぜ〰ぢふぴぜ〴ぜ〰つはぜ〴ぜ〰きはつどてべぜ〴ぜ〰ぇふぴぜ〴ぜ〰きどっひはぢどはねづぜ〴ぜ〰ぃはねばはびどぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰こばづっどてどっぜ〴ぜ〰あちっぴづひどちぬぜ〴ぜ〰ごちへちぜ〴ぜ〰ちひづぜ〴ぜ〰ぁびびはっどちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰いどびづちびづぜ〴ぜ〰ぐひはでひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰げづつふっづびぜ〴ぜ〰ぁのぴどでづの〭こばづっどてどっぜ〴ぜ〰ぐひはぬどてづひちぴどはのぜ〴ぜ〰ぢふぴぜ〴ぜ〰いはづびぜ〴ぜ〰ぎはぴぜ〴ぜ〰きはつどてべぜ〴ぜ〰いどびづちびづ〭げづぬちぴづつぜ〴ぜ〰ぃべぴはにどのづぜ〴ぜ〰ぐひはてどぬづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰ぉのっひづちびづびぜ〴ぜ〰ごひづでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰いどねどのどびとづびぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぐづひどばとづひべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰きはつふぬちぴづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎふねぢづひぜ〴ぜ〰ちのつぜ〴ぜ〰ぐとづのはぴべばづぜ〴ぜ〰はてぜ〴ぜ〰ぁのぴどでづのぜ〴ぜ〰ぐひづびづのぴどのでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぜ〵ぜ〰ぁぐぃびぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰つはぜ〴ぜ〰のはぴぜ〴ぜ〰ぁぬぴづひぜ〴ぜ〰ぉのぴづびぴどのちぬぜ〴ぜ〰ぐづひねづちぢどぬどぴべぜ〴ぜ〰ぢふぴぜ〴ぜ〰つはぜ〴ぜ〰きはつどてべぜ〴ぜ〰ぇふぴぜ〴ぜ〰きどっひはぢどはねづぜ〴ぜ〰ぃはねばはびどぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰こばづっどてどっぜ〴ぜ〰あちっぴづひどちぬぜ〴ぜ〰ごちへちぜ〴ぜ〰ちひづぜ〴ぜ〰ぁびびはっどちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰いどびづちびづぜ〴ぜ〰ぐひはでひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: がちっぴどぢどちのづぜ〴ぜ〰どにどぜ〴ぜ〰ぉのっひづちびづびぜ〴ぜ〰ごひづでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰いどねどのどびとづびぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぐづひどばとづひべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰きはつふぬちぴづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎふねぢづひぜ〴ぜ〰ちのつぜ〴ぜ〰ぐとづのはぴべばづぜ〴ぜ〰はてぜ〴ぜ〰ぁのぴどでづのぜ〴ぜ〰ぐひづびづのぴどのでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぜ〵ぜ〰ぁぐぃびぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰つはぜ〴ぜ〰のはぴぜ〴ぜ〰ぁぬぴづひぜ〴ぜ〰ぉのぴづびぴどのちぬぜ〴ぜ〰ぐづひねづちぢどぬどぴべぜ〴ぜ〰ぢふぴぜ〴ぜ〰つはぜ〴ぜ〰きはつどてべぜ〴ぜ〰ぇふぴぜ〴ぜ〰きどっひはぢどはねづぜ〴ぜ〰ぃはねばはびどぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰こばづっどてどっぜ〴ぜ〰あちっぴづひどちぬぜ〴ぜ〰ごちへちぜ〴ぜ〰ちひづぜ〴ぜ〰ぁびびはっどちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰いどびづちびづぜ〴ぜ〰ぐひはでひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰きはつふぬちぴづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎふねぢづひぜ〴ぜ〰ちのつぜ〴ぜ〰ぐとづのはぴべばづぜ〴ぜ〰はてぜ〴ぜ〰ぁのぴどでづのぜ〴ぜ〰ぐひづびづのぴどのでぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぜ〵ぜ〰ぁぐぃびぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰つはぜ〴ぜ〰のはぴぜ〴ぜ〰ぁぬぴづひぜ〴ぜ〰ぉのぴづびぴどのちぬぜ〴ぜ〰ぐづひねづちぢどぬどぴべぜ〴ぜ〰ぢふぴぜ〴ぜ〰つはぜ〴ぜ〰きはつどてべぜ〴ぜ〰ぇふぴぜ〴ぜ〰きどっひはぢどはねづぜ〴ぜ〰ぃはねばはびどぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰こばづっどてどっぜ〴ぜ〰あちっぴづひどちぬぜ〴ぜ〰ごちへちぜ〴ぜ〰ちひづぜ〴ぜ〰ぁびびはっどちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰いどびづちびづぜ〴ぜ〰ぐひはでひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぃはねねづひっどちぬぜ〴ぜ〰ぐひはぢどはぴどっびぜ〴ぜ〰つはぜ〴ぜ〰のはぴぜ〴ぜ〰ぁぬぴづひぜ〴ぜ〰ぉのぴづびぴどのちぬぜ〴ぜ〰ぐづひねづちぢどぬどぴべぜ〴ぜ〰ぢふぴぜ〴ぜ〰つはぜ〴ぜ〰きはつどてべぜ〴ぜ〰ぇふぴぜ〴ぜ〰きどっひはぢどはねづぜ〴ぜ〰ぃはねばはびどぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰こばづっどてどっぜ〴ぜ〰あちっぴづひどちぬぜ〴ぜ〰ごちへちぜ〴ぜ〰ちひづぜ〴ぜ〰ぁびびはっどちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰いどびづちびづぜ〴ぜ〰ぐひはでひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: こばづっどてどっぜ〴ぜ〰あちっぴづひどちぬぜ〴ぜ〰ごちへちぜ〴ぜ〰ちひづぜ〴ぜ〰ぁびびはっどちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰いどびづちびづぜ〴ぜ〰ぐひはでひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: YSVTXE+Rpxmi FontSubset: true FirstChar: 13 LastChar: 13 FontDescriptor: FontName: YSVTXE+Rpxmi Flags: Symbolic FontBBox: -70, -289, 949, 802 FontFile: true Font: BaseFont: MPUDFL+PazoMath FontSubset: true FirstChar: 68 LastChar: 68 FontDescriptor: FontName: MPUDFL+PazoMath Flags: Symbolic FontBBox: -40, -283, 878, 946 FontFile: true Font: BaseFont: RVNCFE+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: 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