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dc.contributor.authorMacpherson, Magnhild Eide
dc.contributor.authorHov, Johannes Espolin Roksund
dc.contributor.authorUeland, Thor
dc.contributor.authorDahl, Tuva Børresdatter
dc.contributor.authorKummen, Martin
dc.contributor.authorOtterdal, Kari
dc.contributor.authorHolm, Kristian
dc.contributor.authorBerge, Rolf Kristian
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorTrøseid, Marius
dc.contributor.authorHalvorsen, Bente
dc.contributor.authorAukrust, Pål
dc.contributor.authorFevang, Børre
dc.contributor.authorJørgensen, Silje Fjellgård
dc.date.accessioned2020-10-27T16:13:54Z
dc.date.available2020-10-27T16:13:54Z
dc.date.issued2020-09-16
dc.description.abstractA substantial proportion of patients with common variable immunodeficiency (CVID) have inflammatory and autoimmune complications of unknown etiology. We have previously shown that systemic inflammation in CVID correlates with their gut microbial dysbiosis. The gut microbiota dependent metabolite trimethylamine N-oxide (TMAO) has been linked to several metabolic and inflammatory disorders, but has hitherto not been investigated in relation to CVID. We hypothesized that TMAO is involved in systemic inflammation in CVID. To explore this, we measured plasma concentrations of TMAO, inflammatory markers, and lipopolysaccharide (LPS) in 104 CVID patients and 30 controls. Gut microbiota profiles and the bacterial genes <i>CutC</i> and <i>CntA</i>, which encode enzymes that can convert dietary metabolites to trimethylamine in the colon, were examined in fecal samples from 40 CVID patients and 86 controls. Furthermore, a food frequency questionnaire and the effect of oral antibiotic rifaximin on plasma TMAO concentrations were explored in these 40 patients. We found CVID patients to have higher plasma concentrations of TMAO than controls (TMAO 5.0 [2.9–8.6] vs. 3.2 [2.2–6.3], <i>p</i> = 0.022, median with IQR). The TMAO concentration correlated positively with tumor necrosis factor (<i>p</i> = 0.008, rho = 0.26), interleukin-12 (<i>p</i> = 0.012, rho = 0.25) and LPS (<i>p</i> = 0.034, rho = 0.21). Dietary intake of meat (<i>p</i> = 0.678), fish (<i>p</i> = 0.715), egg (<i>p</i> = 0.138), dairy products (<i>p</i> = 0.284), and fiber (<i>p</i> = 0.767) did not significantly impact on the TMAO concentrations in plasma, nor did a 2-week course of the oral antibiotic rifaximin (<i>p</i> = 0.975). However, plasma TMAO concentrations correlated positively with gut microbial abundance of <i>Gammaproteobacteria</i> (<i>p</i> = 0.021, rho = 0.36). Bacterial gene <i>CntA</i> was present in significantly more CVID samples (75%) than controls (53%), <i>p</i> = 0.020, potentially related to the increased abundance of <i>Gammaproteobacteria</i> in these samples. The current study demonstrates that elevated TMAO concentrations are associated with systemic inflammation and increased gut microbial abundance of <i>Gammaproteobacteria</i> in CVID patients, suggesting that TMAO could be a link between gut microbial dysbiosis and systemic inflammation. Gut microbiota composition could thus be a potential therapeutic target to reduce systemic inflammation in CVID.en_US
dc.identifier.citationMacpherson, Hov, Ueland, Dahl, Kummen, Otterdal, Holm, Berge, Mollnes, Trøseid, Halvorsen, Aukrust, Fevang, Jørgensen. Gut microbiota-dependent trimethylamine N-oxide associates with inflammation in common variable immunodeficiency. Frontiers in Immunology. 2020;57:574500:1-12en_US
dc.identifier.cristinIDFRIDAID 1840727
dc.identifier.doi10.3389/fimmu.2020.574500
dc.identifier.issn1664-3224
dc.identifier.urihttps://hdl.handle.net/10037/19684
dc.language.isoengen_US
dc.publisherFrontiers Mediaen_US
dc.relation.journalFrontiers in Immunology
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleGut microbiota-dependent trimethylamine N-oxide associates with inflammation in common variable immunodeficiencyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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