{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T20:21:19Z","timestamp":1793996479795,"version":"4.8.0"},"reference-count":218,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    An intact intestinal barrier, representing the interface between inner and outer environments, is an integral regulator of health. Among several factors, bacteria and their products have been evidenced to contribute to gut barrier impairment and its increased permeability. Alterations of tight junction integrity - caused by both external factors and host metabolic state - are important for gut barrier, since they can lead to increased influx of bacteria or bacterial components (endotoxin, bacterial DNA, metabolites) into the host circulation. Increased systemic levels of bacterial endotoxins and DNA have been associated with an impaired metabolic host status, manifested in obesity, insulin resistance, and associated cardiovascular complications. Bacterial components and cells are distributed to peripheral tissues\n                    <jats:italic>via<\/jats:italic>\n                    the blood stream, possibly contributing to metabolic diseases by increasing chronic pro-inflammatory signals at both tissue and systemic levels. This response is, along with other yet unknown mechanisms, mediated by toll like receptor (TLR) transduction and increased expression of pro-inflammatory cytokines, which in turn can further increase intestinal permeability leading to a detrimental positive feedback loop. The modulation of gut barrier function through nutritional and other interventions, including manipulation of gut microbiota, may represent a potential prevention and treatment target for metabolic diseases.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2021.616506","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T01:59:35Z","timestamp":1615255175000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":124,"title":["Impaired Intestinal Barrier and Tissue Bacteria: Pathomechanisms for Metabolic Diseases"],"prefix":"10.3389","volume":"12","author":[{"given":"Lucas","family":"Massier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bl\u00fcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima M.","family":"Chakaroun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306825","article-title":"Epidemiology of Obesity and Diabetes and Their Cardiovascular Complications","volume":"118","author":"Bhupathiraju","year":"2016","journal-title":"Circ Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.02.005","article-title":"The treatment-naive microbiome in new-onset Crohn\u2019s disease","volume":"15","author":"Gevers","year":"2014","journal-title":"Cell Host Microbe"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12508","article-title":"The gut microbiota and metabolic disease: current understanding and future perspectives","volume":"280","author":"Arora","year":"2016","journal-title":"J Internal Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2895","article-title":"A complex microworld in the gut: gut microbiota and cardiovascular disease connectivity","volume":"18","author":"Howitt","year":"2012","journal-title":"Nat Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-306928","article-title":"Microbiota and diabetes: an evolving relationship","volume":"63","author":"Tilg","year":"2014","journal-title":"Gut"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e91","DOI":"10.1038\/ctg.2015.16","article-title":"The Influence of the Gut Microbiome on Obesity, Metabolic Syndrome and Gastrointestinal Disease","volume":"6","author":"Parekh","year":"2015","journal-title":"Clin Trans Gastroenterol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2016.01.024","article-title":"Gut microbiome and metabolic syndrome","volume":"10","author":"Mazidi","year":"2016","journal-title":"Diabetes Metab Syndrome"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00048.2015","article-title":"Homeostasis of the gut barrier and potential biomarkers","volume":"312","author":"Wells","year":"2017","journal-title":"Am J Physiol Gastrointestinal Liver Physiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1403","article-title":"Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice","volume":"57","author":"Cani","year":"2008","journal-title":"Diabetes"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar3318","article-title":"Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection","volume":"359","author":"Thaiss","year":"2018","journal-title":"Sci (N Y NY)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.112.5.783","article-title":"On the absorption of bacterial endotoxin from the gastro-intestinal tract of the normal and shocked animal","volume":"112","author":"Ravin","year":"1960","journal-title":"J Exp Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1042\/bst0021042","article-title":"Absorption of Intact Oligosaccharide in Health and Disease","volume":"2","author":"Menzies","year":"1974","journal-title":"Biochem Soc Trans"},{"key":"B13","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1084\/jem.110.3.389","article-title":"Effects of bacterial endotoxin on metabolism. 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