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However, it is associated with significant adverse effects, namely liver injury, risk of infections, and metabolic derangements. In this review, the underlying causes of TPN\u2010associated adverse effects, specifically gut atrophy, dysbiosis of the intestinal microbiome, leakage of the epithelial barrier with bacterial invasion, and inflammation are first described. The role of the bile acid receptors farnesoid X receptor and Takeda G protein\u2010coupled receptor, of pleiotropic hormones, and growth factors is highlighted, and the mechanisms of insulin resistance, namely the lack of insulinotropic and insulinomimetic signaling of gut\u2010originating incretins as well as the potentially toxicity of phytosterols and pro\u2010inflammatory fatty acids mainly released from soybean oil\u2010based lipid emulsions, are discussed. Finally, novel approaches in the design of next generation lipid delivery systems are proposed. Propositions include modifying the physicochemical properties of lipid emulsions, the use of lipid emulsions generated from sustainable oils with favorable ratios of anti\u2010inflammatory n\u20103 to pro\u2010inflammatory n\u20106 fatty acids, beneficial adjuncts to TPN, and concomitant pharmacotherapies to mitigate TPN\u2010associated adverse effects.<\/jats:p>","DOI":"10.1002\/mnfr.201901270","type":"journal-article","created":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T16:25:02Z","timestamp":1588436702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Novel Strategies to Prevent Total Parenteral Nutrition\u2010Induced Gut and Liver Inflammation, and Adverse Metabolic Outcomes"],"prefix":"10.1002","volume":"65","author":[{"given":"Eliana","family":"Lucchinetti","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine and Cardiovascular Research Centre University of Alberta  Edmonton T6G 2R3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phing\u2010How","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Alberta  Edmonton T6G 2R3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Wawrzyniak","sequence":"additional","affiliation":[{"name":"Division of Clinical Chemistry and Biochemistry Children's Hospital Zurich  Zurich 8032 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Wawrzyniak","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Zurich  Zurich 8091 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Scharl","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Zurich  Zurich 8091 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Holtzhauer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences Department of Chemistry and Applied Biosciences ETH Zurich  Zurich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie D.","family":"Kr\u00e4mer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences Department of Chemistry and Applied Biosciences ETH Zurich  Zurich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-329X","authenticated-orcid":false,"given":"Martin","family":"Hersberger","sequence":"additional","affiliation":[{"name":"Division of Clinical Chemistry and Biochemistry Children's Hospital Zurich  Zurich 8032 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Rogler","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Zurich  Zurich 8091 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2016-8973","authenticated-orcid":false,"given":"Michael","family":"Zaugg","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine and Cardiovascular Research Centre University of Alberta  Edmonton T6G 2R3 Canada"},{"name":"Department of Pharmacology University of Alberta  Edmonton T6G 2R3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,25]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1177\/0884533617718472"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.08.047"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607113508783"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ehmc.2012.02.001"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2005.03.006"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-014-0031-y"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2018.08.037"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00155.2002"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2015.11.003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2015.08.009"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0590317"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-006-9678-z"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.6.1467"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0261-5614(94)90064-7"},{"key":"e_1_2_8_15_1","first-page":"603","volume":"130","author":"Heitman D. 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