{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:56:54Z","timestamp":1787162214856,"version":"build-2736575974"},"reference-count":57,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,8]]},"abstract":"<jats:p>\n                    Microbial translocation is a poorly understood consequence of several disorders such as environmental enteropathy (EE) and hepatosplenic schistosomiasis (HSS). Herein, we compared biomarkers of microbial origin and immune activation in adults with these disorders and in healthy controls. A cross-sectional study was conducted in participants with EE recruited from Misisi compound, Lusaka, Zambia; HSS patients and healthy controls from the University Teaching Hospital, Lusaka. Plasma lipopolysaccharides (LPSs) was measured by limulus amoebocyte lysate assay, plasma 16S ribosomal RNA (16S rRNA) gene copy number was quantified by quantitative real-time polymerase chain reaction, Toll-like receptor ligand (TLRL) activity by QUANTI-Blue detection medium, and cytokines from cell culture supernatant by Cytometric Bead Array. In univariate analysis LPS, 16S rRNA gene copy number, and TLR activity were all high and correlated with each other and with cytokines tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-6 (IL-6), IL-10, and IL-4 secreted by the RAW-Blue cells. After controlling for baseline characteristic, biomarkers of microbial translocation in blood were predictors of TNF-\u03b1, IL-6, and IL-10 activation in cell culture supernatant from EE participants and HSS patients but not in healthy controls. TLR activity showed the strongest correlation with TNF-\u03b1. These data provide correlative evidence that microbial translocation contributes to systemic cytokine activation in two disorders common in the tropics, with total TLR ligand estimation showing the strongest correlation with TNF-\u03b1 (\n                    <jats:italic>r<\/jats:italic>\n                    = 0.66,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001).\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.17-0365","type":"journal-article","created":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T03:00:28Z","timestamp":1503975628000},"page":"1603-1610","source":"Crossref","is-referenced-by-count":12,"title":["Direct Biomarkers of Microbial Translocation Correlate with Immune Activation in Adult Zambians with Environmental Enteropathy and Hepatosplenic Schistosomiasis"],"prefix":"10.4269","volume":"97","author":[{"given":"Patrick","family":"Kaonga","sequence":"first","affiliation":[{"name":"Tropical Gastroenterology and Nutrition Group, The University of Zambia School of Medicine, Lusaka, Zambia;"},{"name":"Department of Internal Medicine, The University of Zambia School of Medicine, Lusaka, Zambia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evans","family":"Kaimoyo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Zambia, Lusaka, Zambia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Besa","sequence":"additional","affiliation":[{"name":"Tropical Gastroenterology and Nutrition Group, The University of Zambia School of Medicine, Lusaka, Zambia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanekwa","family":"Zyambo","sequence":"additional","affiliation":[{"name":"Tropical Gastroenterology and Nutrition Group, The University of Zambia School of Medicine, Lusaka, Zambia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edford","family":"Sinkala","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, The University Teaching Hospital, Lusaka, Zambia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Kelly","sequence":"additional","affiliation":[{"name":"Tropical Gastroenterology and Nutrition Group, The University of Zambia School of Medicine, Lusaka, Zambia;"},{"name":"Blizard Institute Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Trends Mol Med","first-page":"328","article-title":"Environmental enteropathy: critical implications of a poorly understood condition","volume":"18","author":"Korpe","year":"2012"},{"key":"b2","series-title":"PLoS Negl Trop Dis","first-page":"e0004600","article-title":"Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy","volume":"10","author":"Kelly","year":"2016"},{"key":"b3","series-title":"Pediatr Res","first-page":"306","article-title":"Chronic T cell-mediated enteropathy in rural west African children: relationship with nutritional status and small bowel function","volume":"54","author":"Campbell","year":"2003"},{"key":"b4","series-title":"Cell Mol Gastroenterol Hepatol","first-page":"158","article-title":"Environmental enteric dysfunction includes a broad spectrum of inflammatory responses and epithelial repair processes","volume":"2","author":"Yu","year":"2016"},{"key":"b5","series-title":"J Gastroenterol Hepatol","first-page":"450","article-title":"Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis","volume":"28","author":"Vlachogiannakos","year":"2013"},{"key":"b6","series-title":"Am J Trop Med Hyg","first-page":"965","article-title":"High Schistosoma mansoni disease burden in a rural district of western Zambia","volume":"91","author":"Mutengo","year":"2014"},{"key":"b7","series-title":"Liver Int","first-page":"145","article-title":"Hepatosplenic schistosomiasis is characterised by high blood markers of translocation, inflammation and fibrosis","volume":"36","author":"Sinkala","year":"2016"},{"key":"b8","series-title":"Gut","first-page":"A511","article-title":"PTH-231 pathways of epithelial leakage and zinc malabsorption in environmental enteropathy imaged by confocal endomicroscopy","volume":"64","author":"Kelly","year":"2015"},{"key":"b9","series-title":"PLoS Negl Trop Dis","first-page":"e0005039","article-title":"Biomarkers of environmental enteropathy are positively associated with immune responses to an oral cholera vaccine in Bangladeshi children","volume":"10","author":"Uddin","year":"2016"},{"key":"b10","series-title":"J Clin Microbiol","first-page":"3691","article-title":"Novel sensitive real-time PCR for quantification of bacterial 16S rRNA genes in plasma of HIV-infected patients as a marker for microbial translocation","volume":"49","author":"Kramski","year":"2011"},{"key":"b11","series-title":"J Acquir Immune Defic Syndr","first-page":"149","article-title":"Correlation between different methods to measure microbial translocation and its association with immune activation in long-term suppressed HIV-1-infected individuals","volume":"64","author":"Abad-Fernandez","year":"2013"},{"key":"b12","series-title":"Annu Rev Immunol","first-page":"437","article-title":"Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin","volume":"13","author":"Ulevitch","year":"1995"},{"key":"b13","series-title":"Am J Trop Med Hyg","first-page":"412","article-title":"Responses of small intestinal architecture and function over time to environmental factors in a tropical population","volume":"70","author":"Kelly","year":"2004"},{"key":"b14","series-title":"BMC Gastroenterol","first-page":"1","article-title":"High dose multiple micronutrient supplementation improves villous morphology in environmental enteropathy without HIV enteropathy: results from a double-blind randomised placebo controlled trial in Zambian adults","volume":"14","author":"Louis-Auguste","year":"2014"},{"key":"b15","series-title":"FEBS Lett","first-page":"96","article-title":"Structure of the 16 S ribosomal RNA of the thermophilic cyanobacterium Chlorogloeopsis HTF (\u2018Mastigocladus laminosus HTF\u2019) strain PCC7518, and phylogenetic analysis","volume":"317","author":"Wilmotte","year":"1993"},{"key":"b16","series-title":"Tissue Eng Part C Methods","first-page":"198","article-title":"Assessment of cell viability in three-dimensional scaffolds using cellular autofluorescence","volume":"18","author":"Dittmar","year":"2012"},{"key":"b17","series-title":"Nat Rev Immunol","first-page":"799","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009"},{"key":"b18","series-title":"Gut","first-page":"61","article-title":"Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn\u2019s disease","volume":"56","author":"Zeissig","year":"2007"},{"key":"b19","series-title":"AIDS","first-page":"1385","article-title":"Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4+ cell count","volume":"25","author":"Marchetti","year":"2011"},{"key":"b20","series-title":"J Ethnopharmacol","first-page":"286","article-title":"Anti-inflammatory effects of Scutellaria baicalensis water extract on LPS-activated RAW 264.7 macrophages","volume":"125","author":"Yoon","year":"2009"},{"key":"b21","series-title":"Int J Endocrinol","first-page":"12","article-title":"Inflammatory factors and exercise in chronic kidney disease","volume":"2013","author":"Dungey","year":"2013"},{"key":"b22","series-title":"Inflamm Bowel Dis","first-page":"269","article-title":"Serum lipopolysaccharide-binding protein in endotoxemic patients with inflammatory bowel disease","volume":"13","author":"Pastor Rojo","year":"2007"},{"key":"b23","series-title":"Nat Med","first-page":"1365","article-title":"Microbial translocation is a cause of systemic immune activation in chronic HIV infection","volume":"12","author":"Brenchley","year":"2006"},{"key":"b24","series-title":"J Infect Dis","first-page":"1177","article-title":"Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection","volume":"199","author":"Jiang","year":"2009"},{"key":"b25","series-title":"Am J Trop Med Hyg","first-page":"756","article-title":"Enteropathies in the developing world: neglected effects on global health","volume":"86","author":"Prendergast","year":"2012"},{"key":"b26","series-title":"Curr HIV Res","first-page":"148","article-title":"HIV persistence in the gut mucosa of HIV-infected subjects undergoing antiretroviral therapy correlates with immune activation and increased levels of LPS","volume":"9","author":"D\u2019Ettorre","year":"2011"},{"key":"b27","series-title":"J Infect Dis","first-page":"176","article-title":"Plasma levels of bacterial DNA in HIV infection: the limits of quantitative polymerase chain reaction","volume":"202","author":"Ferri","year":"2010"},{"key":"b28","series-title":"Microbiol Immunol","first-page":"375","article-title":"Polymerase chain reaction detection of bacterial 16S rRNA gene in human blood","volume":"52","author":"Moriyama","year":"2008"},{"key":"b29","series-title":"Inflamm Bowel Dis","first-page":"856","article-title":"Lipopolysaccharide exposure is linked to activation of the acute phase response and growth failure in pediatric Crohn\u2019s disease and murine colitis","volume":"16","author":"Pasternak","year":"2010"},{"key":"b30","series-title":"Nat Commun","first-page":"8020","article-title":"Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection","volume":"6","author":"Hao","year":"2015"},{"key":"b31","series-title":"Nat Commun","first-page":"7806","article-title":"Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model","volume":"6","author":"Brown","year":"2015"},{"key":"b32","series-title":"Gut","first-page":"1389","article-title":"Kupffer cells are activated in cirrhotic portal hypertension and not normalised by TIPS","volume":"60","author":"Holland-Fischer","year":"2011"},{"key":"b33","series-title":"Exp Neurol","first-page":"8","article-title":"Molecular mechanisms linking neuroinflammation and neurodegeneration in MS","volume":"262","author":"Ellwardt","year":"2014"},{"key":"b34","series-title":"J Endotoxin Res","first-page":"225","article-title":"Modulatory effects of sCD14 and LBP on LPS-host cell interactions","volume":"11","author":"Kitchens","year":"2005"},{"key":"b35","series-title":"J Infect Dis","first-page":"780","article-title":"Plasma levels of soluble CD14 independently predict mortality in HIV infection","volume":"203","author":"Sandler","year":"2011"},{"key":"b36","series-title":"Egypt Heart J","first-page":"89","article-title":"C-reactive protein, inflammation and coronary heart disease","volume":"67","author":"Shrivastava","year":"2015"},{"key":"b37","series-title":"J Adv Res","first-page":"445","article-title":"Hepatic and intestinal schistosomiasis Review","volume":"4","author":"Elbaz","year":"2013"},{"key":"b38","series-title":"Nephrol Dial Transplant","first-page":"S239","article-title":"Assessment of environmental enteropathy in the MAL-ED cohort study: theoretical and analytic framework","volume":"59","author":"Kosek","year":"2014"},{"key":"b39","series-title":"J Pharm Nutr Sci","first-page":"207","article-title":"Immunomodulatory effects of Lycii radicis cortex water extract on lipopolysaccharide-activated RAW 264.7 mouse macrophages","volume":"4","author":"Park","year":"2014"},{"key":"b40","series-title":"J Agric Food Chem","first-page":"3060","article-title":"Biflavonoids from Caper (Capparis spinosa L.) fruits and their effects in inhibiting NF-kappa B activation","volume":"59","author":"Zhou","year":"2011"},{"key":"b41","series-title":"Antimicrob Agents Chemother","first-page":"1738","article-title":"Macrophage reporter cell assay for screening immunopharmacological activity of cell wall-active antifungals","volume":"58","author":"Lewis","year":"2014"},{"key":"b42","series-title":"Lab Invest","first-page":"1139","article-title":"Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells","volume":"85","author":"Prasad","year":"2005"},{"key":"b43","series-title":"Sci STKE","first-page":"pe1","article-title":"The significance of interferon-\u03b3\u2013triggered internalization of tight-junction proteins in inflammatory bowel disease","volume":"2006","author":"Chiba","year":"2006"},{"key":"b44","series-title":"Adv Drug Deliv Rev","first-page":"303","article-title":"Modulation of tight junction structure and function by cytokines","volume":"41","author":"Walsh","year":"2000"},{"key":"b45","series-title":"Evid Based Complement Alternat Med","first-page":"735176","article-title":"Inhibition of inflammatory response by Artepillin C in activated RAW264. 7 macrophages","volume":"2013","author":"Szliszka","year":"2013"},{"key":"b46","series-title":"Cytokine","first-page":"24","article-title":"Analysis of enteropathy induced by tumour necrosis factor \u03b1","volume":"5","author":"Garside","year":"1993"},{"key":"b47","series-title":"Liver","first-page":"380","article-title":"Endotoxin and its binding proteins in chronic liver disease: the effect of transjugular intrahepatic portosystemic shunting","volume":"22","author":"Kaser","year":"2002"},{"key":"b48","series-title":"Gastroenterology","first-page":"1476","article-title":"Obesity and the microbiota","volume":"136","author":"Tilg","year":"2009"},{"key":"b49","series-title":"Cytokine","first-page":"189","article-title":"Neutralization of IL-6 and TNF-\u03b1 ameliorates intestinal permeability in DSS-induced colitis","volume":"83","author":"Xiao","year":"2016"},{"key":"b50","series-title":"J Biol Chem","first-page":"31263","article-title":"Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium","volume":"286","author":"Suzuki","year":"2011"},{"key":"b51","series-title":"Immunology","first-page":"87","article-title":"Circulating CD4+ and CD8+ T cells are activated in inflammatory bowel disease and are associated with plasma markers of inflammation","volume":"140","author":"Funderburg","year":"2013"},{"key":"b52","series-title":"Sci Rep","first-page":"42791","article-title":"Interleukin 10 inhibits pro-inflammatory cytokine responses and killing of Burkholderia pseudomallei","volume":"7","author":"Kessler","year":"2017"},{"key":"b53","series-title":"Mediators Inflamm","first-page":"561459","article-title":"The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis","volume":"2014","author":"Wojdasiewicz","year":"2014"},{"key":"b54","series-title":"Gastroenterology","first-page":"1461","article-title":"Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn\u2019s disease","volume":"119","author":"Schreiber","year":"2000"},{"key":"b55","series-title":"J Virol","first-page":"13015","article-title":"Lack of interleukin-10-mediated anti-inflammatory signals and upregulated interferon gamma production are linked to increased intestinal epithelial cell apoptosis in pathogenic Simian immunodeficiency virus infection","volume":"88","author":"Pan","year":"2014"},{"key":"b56","series-title":"Genome Biol","first-page":"1","article-title":"Identification of signaling components required for the prediction of cytokine release in RAW 264.7 macrophages","volume":"7","author":"Pradervand","year":"2006"},{"key":"b57","series-title":"Cytokine Growth Factor Rev","first-page":"61","article-title":"The multifaceted relationship between IL-10 and adaptive immunity: putting together the pieces of a puzzle","volume":"15","author":"Mocellin","year":"2004"}],"container-title":["The American Journal of Tropical Medicine and 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