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Clin J Am Soc Nephrol. 2016 Feb 5;11(2):223-31. doi: 10.2215/CJN.05240515. Epub 2016 Jan 15.

Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial.

Author information

1
School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia; Nephrology Department, Princess Alexandra Hospital, Brisbane, Queensland, Australia; megan.rossi@uq.net.au.
2
School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia; Nephrology Department, Princess Alexandra Hospital, Brisbane, Queensland, Australia;
3
Translational Research Institute, Brisbane, Queensland, Australia; Diamantina Institute.
4
School of Medicine.
5
Human Movement and Nutrition Sciences, and.
6
School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia; Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia;
7
Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; and.
8
Department of Chemical Pathology, Pathology Queensland, Brisbane, Queensland, Australia.

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.

KEYWORDS:

chronic kidney disease; glomerular filtration rate; humans; indoxyl sulphate; microbiota; p-cresyl sulphate; probiotics; renal insufficiency, chronic; synbiotics; uremic toxins

PMID:
26772193
PMCID:
PMC4741035
DOI:
10.2215/CJN.05240515
[Indexed for MEDLINE]
Free PMC Article

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