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Synbiotics easing renal failure by improving gut microbiology (SYNERGY): A randomized trial
Clinical Journal of the American Society of Nephrology
  • Megan Rossi, Princess Alexandra Hospital
  • David W Johnson, Princess Alexandra Hospital
  • Mark Morrison, Translational Research Institute, Brisbane, Queensland
  • Elaine Pascoe, University of Queensland
  • Jeff Coombes, University of Queensland
  • Josephine M Forbes, The University of Queensland, Australia
  • Cheuk-Chun Szeto, The Chinese University of Hong Kong
  • Brett McWhinney, Department of Chemical Pathology, Pathology Queensland
  • Jacobus P J Ungerer, Department of Chemical Pathology, Pathology Queensland, Brisbane
  • Katrina Campbell, Bond University
Date of this Version
2-5-2016
Document Type
Journal Article
Publication Details

Citation only

Rossi, M., Johnson, D. W., Morrison, M., Pascoe, E. M., Coombes, J. S., Forbes, J. M., Szeto, C. C., McWhinney, B., Ungerer, J., & Campbell, K. (2016). Synbiotics easing renal failure by improving gut microbiology (SYNERGY): A randomized trial. Clinical Journal of the American Society of Nephrology, 11(2), 223-231.

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Copyright © 2016 by the American Society of Nephrology.

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 m(2)) 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 m(2)), 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.

Citation Information
Megan Rossi, David W Johnson, Mark Morrison, Elaine Pascoe, et al.. "Synbiotics easing renal failure by improving gut microbiology (SYNERGY): A randomized trial" Clinical Journal of the American Society of Nephrology Vol. 11 Iss. 2 (2016) p. 223 - 231 ISSN: 1555-905X
Available at: http://works.bepress.com/katrina-campbell/3/