Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency
Jørgensen, Silje Fjellgård; Macpherson, Magnhild Eide; Bjørnetrø, Tonje; Holm, Kristian; Kummen, Martin; Rashidi, Azita; Michelsen, Annika; Lekva, Tove; Halvorsen, Bente; Trøseid, Marius; Mollnes, Tom Eirik; Berge, Rolf Kristian; Yndestad, Arne; Ueland, Thor; Karlsen, Tom Hemming; Aukrust, Pål; Hov, Johannes Espolin Roksund; Fevang, Børre
Peer reviewed, Journal article
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Common variable immunodefciency (CVID) patients have reduced gut microbial diversity compared to healthy controls. The reduced diversity is associated with gut leakage, increased systemic infammation and ten “key” bacteria that capture the gut dysbiosis (dysbiosis index) in CVID. Rifaximin is a broadspectrum non-absorbable antibiotic known to reduce gut leakage (lipopolysaccharides, LPS) in liver disease. In this study, we explored as a ‘proof of concept’ that altering gut microbial composition could reduce systemic infammation, using CVID as a disease model. Forty adult CVID patients were randomized, (1:1) to twice-daily oral rifaximin 550mg versus no treatment for 2 weeks in an openlabel, single-centre study. Primary endpoints were reduction in plasma/serum levels of soluble (s) CD14, sCD25, sCD163, neopterin, CRP, TNF, LPS and selected cytokines measured at 0, 2 and 8 weeks. Secondary endpoint was changes in intra-individual bacterial diversity in stool samples. Rifaximinuse did not signifcantly change any of the infammation or gut leakage markers, but decreased gut microbial diversity compared with no treatment (p=0.002). Importantly, the gut bacteria in the CVID dysbiosis index were not changed by rifaximin. The results suggest that modulating gut microbiota by rifaximin is not the chosen intervention to afect systemic infammation, at least not in CVID.