{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:34:19Z","timestamp":1792647259623,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Hyperammonemia 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\u2010lowering strategy,<jats:italic>Escherichia coli<\/jats:italic>Nissle 1917 bacterium was genetically modified to consume and convert ammonia to arginine (S\u2010ARG). S\u2010ARG was further modified to additionally synthesize butyrate (S\u2010ARG\u00a0+\u00a0BUT). Both strains were evaluated in bile\u2010duct ligated (BDL) rats; experimental model of CLD and HE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>One\u2010week post\u2010surgery, BDLs received non\u2010modified EcN (EcN), S\u2010ARG, S\u2010ARG\u00a0+\u00a0BUT (3x10<jats:sup>11<\/jats:sup>CFU\/day) or vehicle until sacrifice at 3 or 5\u00a0weeks. Plasma (ammonia\/pro\u2010inflammatory\/liver function), liver fibrosis (hydroxyproline), liver mRNA (pro\u2010inflammatory\/fibrogenic\/anti\u2010apoptotic) and colon mRNA (pro\u2010inflammatory) biomarkers were measured post\u2010sacrifice. Memory, motor\u2010coordination, muscle\u2010strength and locomotion were assessed at 5\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In BDL\u2010Veh rats, hyperammonemia developed at 3 and further increased at 5\u00a0weeks. This rise was prevented by S\u2010ARG and S\u2010ARG\u00a0+\u00a0BUT, whereas EcN was ineffective. Memory impairment was prevented only in S\u2010ARG\u00a0+\u00a0BUT vs BDL\u2010Veh. Systemic inflammation (IL\u201010\/MCP\u20101\/endotoxin) increased at 3 and 5\u00a0weeks in BDL\u2010Veh. S\u2010ARG\u00a0+\u00a0BUT attenuated inflammation at both timepoints (except 5\u2010week endotoxin) vs BDL\u2010Veh, whereas S\u2010ARG only attenuated IP\u201010 and MCP\u20101 at 3\u00a0weeks. Circulating ALT\/AST\/ALP\/GGT\/albumin\/bilirubin and gene expression of liver function markers (IL\u201010\/IL\u20106\/IL\u20101\u03b2\/TGF\u2010\u03b2\/\u03b1\u2010SMA\/collagen\u20101\u03b11\/Bcl\u20102) were not normalized by either strain. Colonic mRNA (TNF\u2010\u03b1\/IL\u20101\u03b2\/occludin) markers were attenuated by synthetic strains at both timepoints vs BDL\u2010Veh.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>S\u2010ARG and S\u2010ARG\u00a0+\u00a0BUT attenuated hyperammonemia, with S\u2010ARG\u00a0+\u00a0BUT additional memory protection likely due to greater anti\u2010inflammatory effect. These innovative strategies, particularly S\u2010ARG\u00a0+\u00a0BUT, have potential to prevent HE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14815","type":"journal-article","created":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T16:51:30Z","timestamp":1612630290000},"page":"1020-1032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Genetically engineered<i>E. coli<\/i>Nissle attenuates hyperammonemia and prevents memory impairment in bile\u2010duct ligated rats"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8211-4444","authenticated-orcid":false,"given":"Rafael","family":"Ochoa\u2010Sanchez","sequence":"first","affiliation":[{"name":"Hepato\u2010Neuro Laboratory CRCHUM Universit\u00e9 de Montr\u00e9al Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana M.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Hepato\u2010Neuro Laboratory CRCHUM Universit\u00e9 de Montr\u00e9al Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5395-5853","authenticated-orcid":false,"given":"M\u00e9lanie","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Hepato\u2010Neuro Laboratory CRCHUM Universit\u00e9 de Montr\u00e9al Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9gory","family":"Petrazzo","sequence":"additional","affiliation":[{"name":"Hepato\u2010Neuro Laboratory CRCHUM Universit\u00e9 de Montr\u00e9al Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha","family":"Pant","sequence":"additional","affiliation":[{"name":"Synlogic Inc Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2235-6019","authenticated-orcid":false,"given":"Cristina R.","family":"Bosoi","sequence":"additional","affiliation":[{"name":"Hepato\u2010Neuro Laboratory CRCHUM Universit\u00e9 de Montr\u00e9al Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mylene","family":"Perreault","sequence":"additional","affiliation":[{"name":"Synlogic Inc Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Querbes","sequence":"additional","affiliation":[{"name":"Synlogic Inc Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline B.","family":"Kurtz","sequence":"additional","affiliation":[{"name":"Synlogic Inc Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-6834","authenticated-orcid":false,"given":"Christopher F.","family":"Rose","sequence":"additional","affiliation":[{"name":"Hepato\u2010Neuro Laboratory CRCHUM Universit\u00e9 de Montr\u00e9al Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23128"},{"issue":"12","key":"e_1_2_10_3_1","first-page":"1","article-title":"A step\u2010by\u2010step approach to the diagnosis and management of hepatic encephalopathy in the United States","volume":"12","author":"Reau NSBR","year":"2016","journal-title":"J Gastroenterol Hepatol"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2014.06.004"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.112"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu10020140"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13300"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000001311"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.30.pt2.22S"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau7975"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i12.1519"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24273"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.225516"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-018-2119-7"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"8762345","DOI":"10.1155\/2016\/8762345","article-title":"Berberine Inhibition of fibrogenesis in a rat model of liver fibrosis and in hepatic stellate cells","volume":"2016","author":"Wang N","year":"2016","journal-title":"Evid Based Complement Alternat Med"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-13-0503"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23188"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu10101499"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37246-7"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12918-018-0667-6"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-012-9347-1"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21180"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-015-9715-8"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2009.11.006"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2017.05.006"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2016.00106"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2018.08.001"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.12.013"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2003.10.016"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.219"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01832"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/395895"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-110080"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11092259"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12695"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7FO01528C"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.7.4641"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.04.012"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(90)90132-B"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12021"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2012.07.002"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14815","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.14815","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14815","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T19:01:55Z","timestamp":1724439715000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.14815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1111\/liv.14815"],"URL":"https:\/\/doi.org\/10.1111\/liv.14815","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"2020-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}