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

Rossi, Megan, Johnson, David W., Morrison, Mark, Pascoe, Elaine M., Coombes, Jeff S., Forbes, Josephine M., Szeto, Cheuk-Chun, McWhinney, Brett C., Ungerer, Jacobus P. J. and Campbell, Katrina L. (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. doi:10.2215/CJN.05240515

Author Rossi, Megan
Johnson, David W.
Morrison, Mark
Pascoe, Elaine M.
Coombes, Jeff S.
Forbes, Josephine M.
Szeto, Cheuk-Chun
McWhinney, Brett C.
Ungerer, Jacobus P. J.
Campbell, Katrina L.
Title Synbiotics easing renal failure by improving gut microbiology (SYNERGY): a randomized trial
Journal name Clinical Journal of the American Society of Nephrology   Check publisher's open access policy
ISSN 1555-905X
Publication date 2016-02-05
Year available 2016
Sub-type Article (original research)
DOI 10.2215/CJN.05240515
Open Access Status Not Open Access
Volume 11
Issue 2
Start page 223
End page 231
Total pages 9
Place of publication Washington, DC United States
Publisher American Society of Nephrology
Collection year 2017
Language eng
Formatted 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, 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.
Keyword Chronic kidney disease
Indoxyl sulphate
Uremic toxins
P-cresyl sulphate
Glomerular filtration rate
Renal insufficiency, chronic
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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