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dc.contributor.authorOchoa‐Sanchez, Rafael
dc.contributor.authorOliveira, Mariana M.
dc.contributor.authorTremblay, Mélanie
dc.contributor.authorPetrazzo, Grégory
dc.contributor.authorPant, Asha
dc.contributor.authorBosoi, Cristina R.
dc.contributor.authorPerreault, Mylene
dc.contributor.authorQuerbes, William
dc.contributor.authorKurtz, Caroline B.
dc.contributor.authorRose, Christopher
dc.date.accessioned2021-02-11T15:03:57Z
dc.date.availableMONTHS_WITHHELD:12fr
dc.date.available2021-02-11T15:03:57Z
dc.date.issued2021-02-06
dc.identifier.urihttp://hdl.handle.net/1866/24783
dc.publisherWileyfr
dc.subjectAmmoniafr
dc.subjectArgininefr
dc.subjectBile‐duct ligaturefr
dc.subjectButyratefr
dc.subjectCirrhosisfr
dc.subjectE. coli Nisslefr
dc.subjectHepatic encephalopathyfr
dc.subjectInflammationfr
dc.subjectMemoryfr
dc.subjectProbioticsfr
dc.titleGenetically engineered E. coli Nissle attenuates hyperammonemia and prevents memory impairment in bile‐duct ligated ratsfr
dc.typeArticlefr
dc.contributor.affiliationUniversité de Montréal. Faculté de médecine. Département de médecinefr
dc.identifier.doi10.1111/liv.14815
dcterms.abstractHyperammonemia associated with chronic liver disease (CLD) is implicated in the pathogenesis of hepatic encephalopathy (HE). The gut is a major source of ammonia production that contributes to hyperammonemia in CLD and HE and remains the primary therapeutic target for lowering hyperammonemia. As an ammonia‐lowering strategy, Escherichia coli Nissle 1917 bacterium was genetically modified to consume and convert ammonia to arginine (S‐ARG). S‐ARG was further modified to additionally synthesize butyrate (S‐ARG+BUT). Both strains were evaluated in bile‐duct ligated (BDL) rats; experimental model of CLD and HE. Methods One‐week post‐surgery, BDLs received non‐modified EcN (EcN), S‐ARG, S‐ARG+BUT (3x1011 CFU/day) or vehicle until sacrifice at 3‐ or 5‐weeks. Plasma (ammonia/pro‐inflammatory/liver‐function), liver fibrosis (hydroxyproline), liver mRNA (pro‐inflammatory/fibrogenic/anti‐apoptotic) and colon mRNA (pro‐inflammatory) biomarkers were measured post‐sacrifice. Memory, motor‐coordination, muscle‐strength, and locomotion were assessed at 5‐weeks. Results In BDL‐Veh rats, hyperammonemia developed at 3‐ and further increased at 5‐weeks. This rise was prevented by S‐ARG and S‐ARG+BUT, whereas EcN was ineffective. Memory impairment was prevented only in S‐ARG+BUT vs BDL‐Veh. Systemic inflammation (IL‐10/MCP‐1/endotoxin) increased at 3‐ and 5‐weeks in BDL‐Veh. S‐ARG+BUT attenuated inflammation at both timepoints (except 5‐week endotoxin) vs BDL‐Veh, whereas S‐ARG only attenuated IP‐10 and MCP‐1 at 3‐weeks. Circulating (ALT/AST/ALP/GGT/albumin/bilirubin) and gene expression liver‐function markers (IL‐10/IL‐6/IL‐1β/TGF‐β/α‐SMA/collagen‐1α1/Bcl‐2) were not normalized by either strain. Colonic mRNA (TNF‐α/IL‐1β/occludin) markers were attenuated by synthetic strains at both timepoints vs BDL‐Veh. Conclusion S‐ARG and S‐ARG+BUT attenuated hyperammonemia, with S‐ARG+BUT additional memory protection likely due to greater anti‐inflammatory effect. These innovative strategies, particularly S‐ARG+BUT, have potential to prevent HE.fr
dcterms.isPartOfurn:ISSN:1478-3223fr
dcterms.isPartOfurn:ISSN:1478-3231fr
dcterms.languageengfr
UdeM.ReferenceFournieParDeposant10.1111/liv.14815fr
UdeM.VersionRioxxVersion acceptée / Accepted Manuscriptfr
oaire.citationTitleLiver internationalfr


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