Abstract
Common variable immunodeficiency (CVID) patients have reduced gut microbial diversity compared to healthy controls. The reduced diversity is associated with gut leakage, increased systemic inflammation and ten “key” bacteria that capture the gut dysbiosis (dysbiosis index) in CVID. Rifaximin is a broad-spectrum 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 inflammation, using CVID as a disease model. Forty adult CVID patients were randomized, (1:1) to twice-daily oral rifaximin 550 mg versus no treatment for 2 weeks in an open-label, 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. Rifaximin-use did not significantly change any of the inflammation 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 affect systemic inflammation, at least not in CVID.
Highlights
Over the last decade, numerous discoveries have highlighted the role of gut microbiota in critical processes to human health including digestion, absorption of nutrients, metabolism, growth, and immune responses[1]
We have previously reported increased plasma levels of LPS in common variable immunodeficiency (CVID) patients compared to healthy controls, negatively correlated with gut microbial diversity[7], suggesting that a less diverse gut microbiota is associated with increased bacterial translocation
(n = 1), nausea (n = 1), dyspepsia (n = 1), bad taste in the mouth (n = 2), abdominal pain (n = 1), loose stools (n = 1) and urticaria (n = 1)] were reported at the end of study visit. In this ‘proof of concept’ study, rifaximin had no significant effect on markers of systemic inflammation or LPS as a marker of gut leakage in CVID
Summary
Numerous discoveries have highlighted the role of gut microbiota in critical processes to human health including digestion, absorption of nutrients, metabolism, growth, and immune responses[1]. CVID patients have an underlying B-cell defect, but many patients display T-cell dysfunction and evidence of systemic immune activation with elevated levels of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-6, and soluble markers of monocyte/macrophage- (e.g., soluble [s]CD14) and T cell activation (i.e., sCD25)[11]. The reason for this persistent immune activation is not fully elucidated, but could at least partly reflect gut leakage mechanisms with a subsequent stimulation of innate immunity through interaction with Toll like receptors (TLRs) and related molecules[12]. There is negligible absorption of rifaximin from the gastrointestinal tract and thereby no direct antibacterial systemic effect which may bias the interpretation of a link between the gut and systemic inflammation[14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
