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  • Synbiotics easing renal failure by improving gut microbiology (SYNERGY): A randomized trial

    Author(s)
    Rossi, Megan
    Johnson, David W
    Morrison, Mark
    Pascoe, Elaine M
    Coombes, Jeff S
    Forbes, Josephine M
    Szeto, Cheuk-Chun
    McWhinney, Brett C
    Ungerer, Jacobus PJ
    Campbell, Katrina L
    Griffith University Author(s)
    Campbell, Katrina
    Year published
    2016
    Metadata
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    Abstract
    Background and objectives: The generation of key uremic nephrovascular toxins, indoxyl sulfate (IS), and p-cresyl sulfate (PCS), is attributed to the dysbiotic gut microbiota in CKD. The aim of our study was to evaluate whether synbiotic (pre- and probiotic) therapy alters the gut microbiota and reduces serum concentrations of microbiome–generated uremic toxins, IS and PCS, in patients with CKD. Design, setting, participants, & measurements: Predialysis adult participants with CKD (eGFR=10–30 ml/min per 1.73 m2) were recruited between January 5, 2013 and November 12, 2013 to a randomized, double–blind, placebo–controlled, ...
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    Background and objectives: The generation of key uremic nephrovascular toxins, indoxyl sulfate (IS), and p-cresyl sulfate (PCS), is attributed to the dysbiotic gut microbiota in CKD. The aim of our study was to evaluate whether synbiotic (pre- and probiotic) therapy alters the gut microbiota and reduces serum concentrations of microbiome–generated uremic toxins, IS and PCS, in patients with CKD. Design, setting, participants, & measurements: Predialysis adult participants with CKD (eGFR=10–30 ml/min per 1.73 m2) were recruited between January 5, 2013 and November 12, 2013 to a randomized, double–blind, placebo–controlled, crossover trial of synbiotic therapy over 6 weeks (4-week washout). The primary outcome was serum IS. Secondary outcomes included serum PCS, stool microbiota profile, eGFR, proteinuria-albuminuria, urinary kidney injury molecule-1, serum inflammatory biomarkers (IL-1β, IL-6, IL-10, and TNF-α), serum oxidative stress biomarkers (F2-isoprostanes and glutathione peroxidase), serum LPS, patient-reported health, Gastrointestinal Symptom Score, and dietary intake. A prespecified subgroup analysis explored the effect of antibiotic use on treatment effect. Results: Of 37 individuals randomized (age =69±10 years old; 57% men; eGFR=24±8 ml/min per 1.73 m2), 31 completed the study. Synbiotic therapy did not significantly reduce serum IS (−2 μmol/L; 95% confidence interval [95% CI], −5 to 1 μmol/L) but did significantly reduce serum PCS (−14 μmol/L; 95% CI, −27 to −2 μmol/L). Decreases in both PCS and IS concentrations were more pronounced in patients who did not receive antibiotics during the study (n=21; serum PCS, −25 μmol/L; 95% CI, −38 to −12 μmol/L; serum IS, −5 μmol/L; 95% CI, −8 to −1 μmol/L). Synbiotics also altered the stool microbiome, particularly with enrichment of Bifidobacterium and depletion of Ruminococcaceae. Except for an increase in albuminuria of 38 mg/24 h (P=0.03) in the synbiotic arm, no changes were observed in the other secondary outcomes. Conclusion: In patients with CKD, synbiotics did not significantly reduce serum IS but did decrease serum PCS and favorably modified the stool microbiome. Large–scale clinical trials are justified.
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    Journal Title
    Clinical Journal of the American Society of Nephrology
    Volume
    11
    Issue
    2
    DOI
    https://doi.org/10.2215/CJN.05240515
    Subject
    Clinical sciences
    Science & Technology
    Life Sciences & Biomedicine
    Urology & Nephrology
    CHRONIC KIDNEY-DISEASE
    P-CRESYL SULFATE
    Publication URI
    http://hdl.handle.net/10072/407974
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    • Journal articles

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