{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:07:36Z","timestamp":1793333256996,"version":"4.5.0"},"reference-count":140,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Diet-induced metabolic endotoxemia is an important factor in the development of many chronic diseases in animals and man. The gut epithelium is an efficient barrier that prevents the absorption of liposaccharide (LPS). Structural changes to the intestinal epithelium in response to dietary alterations allow LPS to enter the bloodstream, resulting in an increase in the plasma levels of LPS (termed metabolic endotoxemia). LPS activates Toll-like receptor-4 (TLR4) leading to the production of numerous pro-inflammatory cytokines and, hence, low-grade systemic inflammation. Thus, metabolic endotoxemia can lead to several chronic inflammatory conditions. Obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) can also cause an increase in gut permeability and potential pharmacological and dietary interventions could be used to reduce the chronic low-grade inflammation associated with endotoxemia.<\/jats:p>","DOI":"10.3389\/fimmu.2020.594150","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T21:47:03Z","timestamp":1610488023000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":541,"title":["Role of Metabolic Endotoxemia in Systemic Inflammation and Potential Interventions"],"prefix":"10.3389","volume":"11","author":[{"given":"Shireen","family":"Mohammad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Thiemermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"B1","article-title":"Metabolic Endotoxemia Initiates Obesity and InsulinResistance","volume-title":"Diabetes","author":"Cani","year":"2007"},{"key":"B2","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1017\/S0007114515002093","article-title":"Low-grade inflammation, diet composition and health: current research evidence and its translation","volume":"114","author":"Minihane","year":"2015","journal-title":"Br J Nutr"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(02)01604-0","article-title":"Structure and function of lipopolysaccharides","volume":"4","author":"Erridge","year":"2002","journal-title":"Microbes Infect"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2013.97","article-title":"Recognition of lipopolysaccharide pattern by TLR4 complexes","volume":"45","author":"Park","year":"2013","journal-title":"Exp Mol Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15761\/GIMCI.1000152","article-title":"Lipopolysaccharide, structure and biological effects","volume":"3","author":"Schultz","year":"2018","journal-title":"Gen Intern Med Clin Innov"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2016.09.001","article-title":"Bilayer Properties of Lipid A from Various Gram-Negative Bacteria","volume":"111","author":"Kim","year":"2016","journal-title":"Biophys J"},{"key":"B7","doi-asserted-by":"publisher","first-page":"90","DOI":"10.5217\/ir.2014.12.2.90","article-title":"Lipopolysaccharide: Basic Biochemistry, Intracellular Signaling, and Physiological Impacts in the Gut","volume":"12","author":"Rhee","year":"2014","journal-title":"Intest Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/80.3.550","article-title":"Saturated fats: What dietary intake","volume":"80","author":"German","year":"2004","journal-title":"Am J Clin Nutr"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.ESP-0001-2018","article-title":"Function and biogenesis of lipopolysaccharides","volume":"8","author":"Bertani","year":"2018","journal-title":"EcoSal Plus"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/794143","article-title":"An Overview of Pathogen Recognition Receptors for Innate Immunity inDental Pulp","volume":"2015","author":"Jang","year":"2015","journal-title":"Mediators Inflamm"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-08","article-title":"Pathogen recognition and inflammatory signaling in innate immune defenses","volume":"22","author":"Mogensen","year":"2009","journal-title":"Clin Microbiol Rev"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000315914","article-title":"Endotoxin in the Pathogenesis of Sepsis","volume":"167","author":"JC","year":"2010","journal-title":"Contrib Nephrol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"31","DOI":"10.2174\/1875041901104010031","article-title":"Pathogen Associated Molecular Patterns, Pattern Recognition Receptors and Pediatric Sepsis","volume":"4","author":"Doughty","year":"2011","journal-title":"Open Inflamm J"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.09.002","article-title":"Signaling to NF-\u03baB by Toll-like receptors","volume":"13","author":"Kawai","year":"2007","journal-title":"Trends Mol Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-like receptor signaling pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1124\/pr.114.010090","article-title":"Toll-like receptors in the vascular system: Sensing the dangers within","volume":"68","author":"Goulopoulou","year":"2016","journal-title":"Pharmacol Rev"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/intimm\/dxh186","article-title":"Toll-like receptors in innate immunity","volume":"17","author":"Takeda","year":"2005","journal-title":"Int Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(85)90275-2","article-title":"Establishment of dorsal-ventral polarity in the drosophila embryo: The induction of polarity by the Toll gene product","volume":"423","author":"Anderson","year":"1985","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4110\/in.2019.19.e37","article-title":"Aging and the immune system: The impact of immunosenescence on viral infection, immunity and vaccine immunogenicity","volume":"19","author":"Oh","year":"2019","journal-title":"Immune Netw"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxp017","article-title":"The roles of TLRs, RLRs and NLRs in pathogen recognition","volume":"21","author":"Kawai","year":"2009","journal-title":"Int Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01523","article-title":"Toll-Like Receptors, Associated Biological Roles, and Signaling Networks in Non-Mammals","volume":"9","author":"Nie","year":"2018","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000788","article-title":"A dimer of the toll-like receptor 4 cytoplasmic domain provides a specific scaffold for the recruitment of signalling adaptor proteins","volume":"2","author":"Miguel","year":"2007","journal-title":"PloS One"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/240365","article-title":"Current views of toll-like receptor signalingpathways","volume":"2010","author":"Takeda","year":"2010","journal-title":"Gastroenterol Res Pract"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/cddis.2016.140","article-title":"The emerging role of toll-like receptor 4 in myocardial inflammation","volume":"7","author":"Yang","year":"2016","journal-title":"Cell Death Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2645465","article-title":"Tight junction in the intestinal epithelium: Its association with diseases and regulation by phytochemicals","volume":"2018","author":"Lee","year":"2018","journal-title":"J Immunol Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-010-0130-3","article-title":"Intestinal stem cells","volume":"12","author":"Umar","year":"2010","journal-title":"Curr Gastroenterol Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10229","article-title":"Gut instincts: Thoughts on intestinal epithelial stem cells","volume":"105","author":"Booth","year":"2000","journal-title":"J Clin Invest"},{"key":"B29","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/s12276-018-0126-x","article-title":"Mechanisms regulating intestinal barrier integrity and its pathological implications","volume":"50","author":"Chelakkot","year":"2018","journal-title":"Exp Mol Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.4291\/wjgp.v8.i4.150","article-title":"Paneth cells in intestinal physiology and pathophysiology","volume":"8","author":"Gassler","year":"2017","journal-title":"World J Gastrointest Pathophysiol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/proteomes6020017","article-title":"Molecular pathophysiology of epithelial barrier dysfunction in inflammatory bowel diseases","volume":"6","author":"Lee","year":"2018","journal-title":"Proteomes"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/s12199-018-0740-1","article-title":"Inflammation and cancer","volume":"23","author":"Murata","year":"2018","journal-title":"Environ Health Prev Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2015.04.015","article-title":"Inflammation and cancer: Till death tears them apart","volume":"205","author":"Raposo","year":"2015","journal-title":"Vet J"},{"key":"B34","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s11845-016-1464-0","article-title":"From inflammation to cancer","volume":"186","author":"Korniluk","year":"2017","journal-title":"Ir J Med Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3945\/jn.110.135657","article-title":"Regulation of Tight Junction Permeability by Intestinal Bacteria and Dietary Components","volume":"141","author":"Ulluwishewa","year":"2011","journal-title":"J Nutr"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029181","article-title":"Cell-cell junctions organize structural and signaling networks toregulate epithelial tissue homeostasis","volume":"10","author":"Garcia","year":"2018","journal-title":"Cold Spring Harb PerspectBiol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.yexcr.2017.03.061","article-title":"Interplay between tight junctions & adherens junctions","volume":"358","author":"Campbell","year":"2017","journal-title":"Exp Cell Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2007.07.012","article-title":"Adherens and tight junctions: Structure, function and connections to the actin cytoskeleton","volume":"1778","author":"Hartsock","year":"2008","journal-title":"Biochim Biophys Acta - Biomembr"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphys.2018.01942","article-title":"Tight junction proteins and signaling pathways in cancer and inflammation: A functional crosstalk","volume":"10","author":"Bhat","year":"2019","journal-title":"Front Physiol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/B978-0-12-394311-8.00005-4","article-title":"Structure, Function and Regulation of Desmosomes","volume":"116","author":"Kowalczyk","year":"2013","journal-title":"Prog Mol Biol Transl Sci"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2007.07.014","article-title":"Desmosome structure, composition and function","volume":"1778","author":"Garrod","year":"2008","journal-title":"Biochim Biophys Acta - Biomembr"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20110587","article-title":"Protein kinase C\u03b6 phosphorylates occludin and promotes assembly of epithelial tight junctions","volume":"437","author":"Jain","year":"2011","journal-title":"Biochem J"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00173.2003","article-title":"TNF- \u03b1 -induced increase in intestinal epithelial tight junction permeability requires NF-\u03baB activation","volume":"1","author":"Ma","year":"2011","journal-title":"Am J Physiol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2010.208","article-title":"Interferon-\u03b3-induced increases in intestinal epithelial macromolecular permeability requires the Src kinase Fyn","volume":"91","author":"Smyth","year":"2011","journal-title":"Lab Investig"},{"key":"B45","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1152\/ajpgi.00318.2005","article-title":"Molecular mechanism of tumor necrosis factor-\u03b1 modulation of intestinal epithelial tight junction barrier","volume":"290","author":"Ye","year":"2006","journal-title":"Am J Physiol - Gastrointest Liver Physiol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pbio.1002533","article-title":"Revised Estimates for the Number of Human and Bacteria Cells in the Body","volume":"14","author":"Sender","year":"2016","journal-title":"PloS Biol"},{"key":"B47","article-title":"Gut bacteria in health and disease","volume":"9","author":"Quigley","year":"2013","journal-title":"Gastroenterol Hepatol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s11695-017-2670-1","article-title":"Sleeve Gastrectomy Alters Intestinal Permeability in Diet-Induced Obese Mice","volume":"27","author":"Blanchard","year":"2017","journal-title":"Obes Surg"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047713","article-title":"High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway","volume":"7","author":"Kim","year":"2012","journal-title":"PloS One"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.10.014","article-title":"Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14","volume":"182","author":"Guo","year":"2013","journal-title":"Am J Pathol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.biochi.2015.06.020","article-title":"Metabolic endotoxemia with obesity: Is it real and is it relevant","volume":"124","author":"Boutagy","year":"2016","journal-title":"Biochimie"},{"key":"B52","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00592-014-0662-3","article-title":"Endotoxemia, nutrition, and cardiometabolic disorders","volume":"52","author":"Kallio","year":"2015","journal-title":"Acta Diabetol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2012.27","article-title":"Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations","volume":"6","author":"Zhang","year":"2012","journal-title":"ISME J"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005963107","article-title":"Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa","volume":"107","author":"Filippo","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1403","article-title":"Changes in Gut Microbiota Control Metabolic Endotoxemia-InducedInflammation in High-Fat Diet\u2013Induced Obesity and Diabetes in Mice","volume":"57","author":"Cani","year":"2008","journal-title":"Diabetes"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1677\/JOE-09-0260","article-title":"Current views on type 2 diabetes","volume":"204","author":"Lin","year":"2010","journal-title":"J Endocrinol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00302.2006","article-title":"Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes","volume":"292","author":"Creely","year":"2007","journal-title":"Am J Physiol - Endocrinol Metab"},{"key":"B58","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.atherosclerosis.2008.06.018","article-title":"Ethnic and sex differences in circulating endotoxin levels: A novel marker of atherosclerotic and cardiovascular risk in a British multi-ethnic population","volume":"203","author":"Miller","year":"2009","journal-title":"Atherosclerosis"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181c7bdf1","article-title":"Endotoxin and plasminogen activator inhibitor-1 serum levels associated with nonalcoholic steatohepatitis in children","volume":"50","author":"Alisi","year":"2010","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208344","article-title":"Linking long-term dietary patterns with gut microbial enterotypes","volume":"334","author":"Wu","year":"2011","journal-title":"Sci (80- )"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-09-0835","article-title":"Upregulation of monocyte tissue factor activity is significantly associated with low-grade chronic inflammation and insulin resistance in patients with metabolic syndrome","volume":"74","author":"Nakagomi","year":"2010","journal-title":"Circ J"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.20960\/nh.1792","article-title":"Alfenas, Dysbiosis and metabolic endotoxemia induced by high-fatdiet","volume":"35","author":"C\u00e2ndido","year":"2018","journal-title":"Nutr Hosp"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/87.5.1219","article-title":"Energy intake is associated with endotoxemia in apparently healthy men","volume":"87","author":"Amar","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0979","article-title":"Increase in plasma endotoxin concentrations and the expression oftoll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat,high-carbohydrate meal","volume":"32","author":"Ghanim","year":"2009","journal-title":"DiabetesCare"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.01.034","article-title":"A high-fat diet is associated with endotoxemia that originates fromthe gut","volume":"142","author":"Pendyala","year":"2012","journal-title":"Gastroenterology"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28898","article-title":"TLR4 links innate immunity and fatty acid-induced insulinresistance","volume":"116","author":"Shi","year":"2006","journal-title":"J Clin Invest"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-16504","article-title":"High-fat diet induces toll-like receptor 4-dependent macrophage\/Microglial cell activation and retinal impairment","volume":"56","author":"Lee","year":"2015","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"B68","doi-asserted-by":"publisher","first-page":"3878","DOI":"10.1038\/ncomms4878","article-title":"Hepatocyte toll-like receptor 4 regulates obesity-inducedinflammation and insulin resistance","volume":"5","author":"Jia","year":"2014","journal-title":"Nat Commun"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.249847","article-title":"Toll-like receptor 4 eficiency decreases atherosclerosis but doesnot rpotect against inflammation inobese LDL receptor-deficient mice","volume":"32","author":"Ding","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/nm1008","article-title":"Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways","volume":"10","author":"Bj\u00f6rkbacka","year":"2004","journal-title":"Nat Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-0340","article-title":"A marker of endotoxemia is associated with obesity and related metabolic disrders in apparently healthy Chinese","volume":"33","author":"Sun","year":"2010","journal-title":"Diabetes Care"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1743-7075-7-19","article-title":"Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats","volume":"7","author":"Suzuki","year":"2010","journal-title":"Nutr Metab"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00024.2006","article-title":"Increased intestinal permeability in obese mice: New evidence in the pathogenesis of nonalcoholic steatohepatitis","volume":"292","author":"Brun","year":"2007","journal-title":"Am J Physiol - Gastrointest Liver Physiol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-33928-4","article-title":"Diet induced obesity is independent of metabolic endotoxemia and TLR4 signalling, but markedly increases hypothalamic expression of the acute phase protein, SerpinA3N","volume":"8","author":"Dalby","year":"2018","journal-title":"Sci Rep"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.4161\/viru.25965","article-title":"Anti-endotoxin vaccines: Back to the future","volume":"5","author":"Cross","year":"2014","journal-title":"Virulence"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00064-16","article-title":"Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes","volume":"30","author":"Poirel","year":"2017","journal-title":"Clin Microbiol Rev"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pmed.1002184","article-title":"Will 10 Million People Die a Year due to Antimicrobial Resistance by 2050","volume":"13","author":"de Kraker","year":"2016","journal-title":"PloS Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.11.017","article-title":"Antimicrobial peptides","volume":"26","author":"Zhang","year":"2016","journal-title":"CURBIO"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fcimb.2016.00194","article-title":"Antimicrobial peptides: An emerging category of therapeutic agents","volume":"6","author":"Mahlapuu","year":"2016","journal-title":"Front Cell Infect Microbiol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3390\/biom8010004","article-title":"Antimicrobial peptides: Diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo","volume":"8","author":"Kumar","year":"2018","journal-title":"Biomolecules"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphar.2018.00281","article-title":"Antimicrobial peptides and their therapeutic potential for bacterial skin infections and wounds","volume":"9","author":"Pfalzgraff","year":"2018","journal-title":"Front Pharmacol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00404","article-title":"\u201cAntimicrobial peptides in human sepsis","volume":"6","author":"Martin","year":"2015","journal-title":"Front Immunol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3402\/ehtj.v2i0.7078","article-title":"Host defence peptides: antimicrobial and immunomodulatory activity and potential applications for tackling antibiotic-resistant infections","volume":"2","author":"Nijnik","year":"2009","journal-title":"Emerg Health Threats J"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16743","article-title":"Antimicrobial peptides with selective antitumor mechanisms: Prospect for anticancer applications","volume":"8","author":"Deslouches","year":"2017","journal-title":"Oncotarget"},{"key":"B85","doi-asserted-by":"publisher","first-page":"R3","DOI":"10.1186\/cc11920","article-title":"The anti-inflammatory effect of the synthetic antimicrobial peptide 19-2.5 in a murine sepsis model: A prospective randomized study","volume":"17","author":"Schuerholz","year":"2013","journal-title":"Crit Care"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2018.03072","article-title":"B-Defensins: Farming the microbiome for homeostasis and health","volume":"10","author":"Meade","year":"2019","journal-title":"Front Immunol"},{"key":"B87","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.cofs.2017.02.010","article-title":"Gut microbiota and antimicrobial peptides","volume":"13","author":"Sivieri","year":"2017","journal-title":"Curr Opin Food Sci"},{"key":"B88","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.3390\/molecules23082040","article-title":"A dynamic overview of antimicrobial peptides and their complexes","volume":"23","author":"De Paula","year":"2018","journal-title":"Molecules"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/nri1180","article-title":"Defensins: Antimicrobial peptides of innateimmunity","volume":"3","author":"Ganz","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/cc11220","article-title":"Antimicrobial peptides and their potential application ininflammation and sepsis","volume":"16","author":"Brandenburg","year":"2012","journal-title":"Crit Care"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2017.00647","article-title":"Guardians of the gut: Enteric defensins","volume":"8","author":"Sankaran-Walters","year":"2017","journal-title":"Front Microbiol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.108.5.1687","article-title":"Developmental regulation of cryptdin, a corticostatin\/defensin precursor mRNA in mouse small intestinal crypt epithelium","volume":"108","author":"Ouellette","year":"1989","journal-title":"J Cell Biol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1136\/gut.47.1.16","article-title":"Antimicrobial peptides in innate intestinal host defence","volume":"47","author":"Cunliffe","year":"2000","journal-title":"Gut"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5437.113","article-title":"Regulation of intestinal \u03b1-defensin activation by the metalloproteinase matrilysin in innate host defense","volume":"286","author":"Wilson","year":"1999","journal-title":"Sci (80- )"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.76","article-title":"Pro-inflammatory effects of matrix metalloproteinase 7 in acute inflammation","volume":"7","author":"Vandenbroucke","year":"2014","journal-title":"Mucosal Immunol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/ni.1825","article-title":"Enteric defensins are essential regulators of intestinal microbial ecology","volume":"11","author":"Salzman","year":"2010","journal-title":"Nat Immunol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00875-17","article-title":"Bacterial Periplasmic Oxidoreductases Control the Activity of Oxidized Human Antimicrobial \u03b2-Defensin 1","volume":"86","author":"Wendler","year":"2018","journal-title":"Infect Immun"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2017.03.040","article-title":"Orexin activation counteracts decreases in nonexercised activity thermogenesis (NEAT) caused by high fat diet","volume":"176","author":"Bunney","year":"2017","journal-title":"Physiol Behav"},{"key":"B99","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2013.00143","article-title":"The human cathelicidin antimicrobial peptide LL-37 as a potential treatment for polymicrobial infected wounds","volume":"4","author":"Duplantier","year":"2013","journal-title":"Front Immunol"},{"key":"B100","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12916-019-1268-y","article-title":"Cathelicidin-related antimicrobial peptide protects against myocardial ischemia\/reperfusion injury","volume":"17","author":"Bei","year":"2019","journal-title":"BMC Med"},{"key":"B101","doi-asserted-by":"publisher","first-page":"74","DOI":"10.4103\/2249-4987.172500","article-title":"Role of antimicrobial peptides in periodontal innate defense mechanism","volume":"7","author":"Mishra","year":"2015","journal-title":"J Oral Res Rev"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2012.05.014","article-title":"Antimicrobial peptides: Clinical relevance and therapeuticimplications","volume":"36","author":"Pinheiro Da Silva","year":"2012","journal-title":"Peptides"},{"key":"B103","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1042\/0264-6021:3410501","article-title":"Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity","volume":"341","author":"Oren","year":"1999","journal-title":"Biochem J"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302005","article-title":"Big Effects: The Role of LL-37 in Inflammation and Autoimmune Disease","volume":"191","author":"Kahlenberg","year":"2013","journal-title":"J Immunol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2011.04.041","article-title":"Biophysical mechanisms of endotoxin neutralization by cationic amphiphilic peptides","volume":"100","author":"Kaconis","year":"2011","journal-title":"Biophys J"},{"key":"B106","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep37277","article-title":"The synthetic antimicrobial peptide 19-2.5 attenuates septic cardiomyopathy and prevents down-regulation of SERCA2 in polymicrobial sepsis","volume":"6","author":"Martin","year":"2016","journal-title":"Sci Rep"},{"key":"B107","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2018.01704","article-title":"Inhibition of lipopolysaccharide- and lipoprotein-induced inflammation by antitoxin peptide Pep19-2.5","volume":"9","author":"Heinbockel","year":"2018","journal-title":"Front Immunol"},{"key":"B108","first-page":"163","article-title":"Alcohol and Gut-Derived Inflammation","volume":"38","author":"Bishehsari","year":"2017","journal-title":"Alcohol Res"},{"key":"B109","doi-asserted-by":"publisher","first-page":"4462","DOI":"10.1038\/s41598-017-04669-7","article-title":"Quantity of alcohol drinking positively correlates with serum levels of endotoxin and markers of monocyte activation","volume":"7","author":"Liangpunsakul","year":"2017","journal-title":"Sci Rep"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6239","article-title":"Genomic evidence for two functionally distinct gene classes","volume":"95","author":"Rivera","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B111","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1042\/CS20171055","article-title":"Intestinal dysbiosis and permeability: The yin and yang in alcohol dependence and alcoholic liver disease","volume":"132","author":"St\u00e4rkel","year":"2018","journal-title":"Clin Sci"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22470","article-title":"The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88","volume":"48","author":"Hritz","year":"2008","journal-title":"Hepatology"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal4069","article-title":"The effects of micronutrient deficiencies on bacterial species from the human gut microbiota","volume":"9","author":"Hibberd","year":"2017","journal-title":"Sci Transl Med"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/138.9.1664","article-title":"Zinc Deficiency Induces Membrane Barrier Damage and Increases Neutrophil Transmigration in Caco-2 Cells","volume":"138","author":"Finamore","year":"2008","journal-title":"J Nutr"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00398.2007","article-title":"Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier","volume":"294","author":"Kong","year":"2007","journal-title":"Am J Physiol - Gastrointest Liver Physiol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1093\/advances\/nmy013","article-title":"Microbiome-mediated effects of the Mediterranean diet on inflammation","volume":"9","author":"Bailey","year":"2018","journal-title":"Adv Nutr"},{"key":"B117","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1743-7075-10-6","article-title":"Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia","volume":"10","author":"Mani","year":"2013","journal-title":"Nutr Metab"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2011.01.030","article-title":"Synthetic surfactant food additives can cause intestinal barrier dysfunction","volume":"76","author":"Cs\u00e1ki","year":"2011","journal-title":"Med Hypotheses"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.034520","article-title":"Effect of dietary additives on intestinal permeability in bothDrosophila and a human cell co-culture","volume":"11","author":"Pereira","year":"2018","journal-title":"DMM Dis Model Mech"},{"key":"B120","doi-asserted-by":"publisher","first-page":"291","DOI":"10.4093\/dmj.2015.39.4.291","article-title":"Probiotics as complementary treatment for metabolic disorders","volume":"39","author":"Le Barz","year":"2015","journal-title":"Diabetes Metab J"},{"key":"B121","doi-asserted-by":"publisher","first-page":"20","DOI":"10.4103\/2230-8210.91178","article-title":"Management of metabolic syndrome through probiotic and prebiotic interventions","volume":"16","author":"Grover","year":"2012","journal-title":"Indian J Endocrinol Metab"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/602832","article-title":"Microencapsulated Bifidobacterium longum subsp. infantis ATCC 15697 Favorably Modulates Gut Microbiota and Reduces Circulating Endotoxins in F344 Rats","volume":"2014","author":"Rodes","year":"2014","journal-title":"Biomed Res Int"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.05.105","article-title":"Sterilized bifidobacteria suppressed fat accumulation and blood glucose level","volume":"501","author":"Kikuchi","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i43.16079","article-title":"Gut microbiota and metabolic syndrome","volume":"20","author":"Festi","year":"2014","journal-title":"World J Gastroenterol"},{"key":"B125","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13578-017-0183-1","article-title":"Gut microbiota as a potential target of metabolic syndrome: The role of probiotics and prebiotics","volume":"7","author":"He","year":"2017","journal-title":"Cell Biosci"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2014.06.001","article-title":"Inulin-type fructans modulate intestinal Bifidobacterium species populations and decrease fecal short-chain fatty acids in obese women","volume":"34","author":"Salazar","year":"2015","journal-title":"Clin Nutr"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2006.144618","article-title":"Evidence for endotoxin contamination in plastic Na+-heparin blood collection tube lots","volume":"56","author":"Newhall","year":"2010","journal-title":"Clin Chem"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-8-20","article-title":"Changes in endotoxin levels in T2DM subjects on anti-diabetictherapies","volume":"8","author":"Al-Attas","year":"2009","journal-title":"Cardiovasc Diabetol"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-198512000-00016","article-title":"Elimination of false-positive limulus amebocyte lysate tests in patients with hyperlipidemia","volume":"13","author":"Yoshiya","year":"1985","journal-title":"Crit Care Med"},{"key":"B130","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pbio.2006607","article-title":"Saving the horseshoe crab: A synthetic alternative to horseshoe crab blood for endotoxin detection","volume":"16","author":"Maloney","year":"2018","journal-title":"PloS Biol"},{"key":"B131","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0164978","article-title":"Is endotoxemia in stable hemodialysis patients an artefact? Limitations of the limulus amebocyte lysate assay and role of (1\u21923)-\u03b2-D Glucan","volume":"11","author":"Wong","year":"2016","journal-title":"PloS One"},{"key":"B132","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1179\/096805105X35215","article-title":"Apolipoproteins modulate the inflammatory response to lipopolysaccharide","volume":"11","author":"Berb\u00e9e","year":"2005","journal-title":"J Endotoxin Res"},{"key":"B133","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3109\/10408363.2015.1123215","article-title":"Chasing a ghost? \u2013 Issues with the determination of circulating levels of endotoxin in human blood","volume":"53","author":"Gnauck","year":"2016","journal-title":"Crit Rev Clin Lab Sci"},{"key":"B134","doi-asserted-by":"publisher","first-page":"428","DOI":"10.3390\/diagnostics10060428","article-title":"Metabolic endotoxemia, feeding studies and the use of the limulus amebocyte (LAL) assay; Is it fit for purpose","volume":"10","author":"Pearce","year":"2020","journal-title":"Diagnostics"},{"key":"B135","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/nu12103009","article-title":"Effects of the human gut microbiota on cognitive performance, brain structure and function: A narrative review","volume":"12","author":"Tooley","year":"2020","journal-title":"Nutrients"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.10.017","article-title":"The next generation of antimicrobial peptides (AMPs) as molecular therapeutic tools for the treatment of diseases with social and economic impacts","volume":"22","author":"da Cunha","year":"2017","journal-title":"Drug Discovery Today"},{"key":"B137","article-title":"Antimicrobial resistance. Global report on surveillance","volume":"61","year":"2014","journal-title":"World Heal Organ"},{"key":"B138","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep31577","article-title":"Synthetic antimicrobial and LPS-neutralising peptides suppress inflammatory and immune responses in skin cells and promote keratinocyte migration","volume":"6","author":"Pfalzgraff","year":"2016","journal-title":"Sci Rep"},{"key":"B139","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.drup.2016.04.002","article-title":"Mechanisms and consequences of bacterial resistance to antimicrobial peptides","volume":"26","author":"Andersson","year":"2016","journal-title":"Drug Resist Updat"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2015.0292","article-title":"Bacterial strategies of resistance to antimicrobial peptides","volume":"371","author":"Joo","year":"2016","journal-title":"Philos Trans R Soc B Biol Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.594150\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T23:47:40Z","timestamp":1610581660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.594150\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":140,"alternative-id":["10.3389\/fimmu.2020.594150"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.594150","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]},"article-number":"594150"}}