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

Megan Rossi, David W Johnson, Mark Morrison, Elaine M Pascoe, Jeff S Coombes, Josephine M Forbes, Cheuk-Chun Szeto, Brett C McWhinney, Jacobus P J Ungerer, Katrina L Campbell

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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 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.

Original languageEnglish
Pages (from-to)223-231
Number of pages9
JournalClinical journal of the American Society of Nephrology : CJASN
Volume11
Issue number2
DOIs
Publication statusPublished - 5 Feb 2016
Externally publishedYes

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Synbiotics
Microbiology
Indican
Renal Insufficiency
Sulfates
Serum
Microbiota
Confidence Intervals
Albuminuria
Biomarkers
F2-Isoprostanes
Anti-Bacterial Agents
Prebiotics
Bifidobacterium
Probiotics
Therapeutics
Glutathione Peroxidase
Interleukin-1
Proteinuria
Interleukin-10

Cite this

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. / Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. In: Clinical journal of the American Society of Nephrology : CJASN. 2016 ; Vol. 11, No. 2. pp. 223-231.
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title = "Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial",
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.",
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Rossi, M, Johnson, DW, Morrison, M, Pascoe, EM, Coombes, JS, Forbes, JM, Szeto, C-C, McWhinney, BC, Ungerer, JPJ & Campbell, KL 2016, 'Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial' Clinical journal of the American Society of Nephrology : CJASN, vol. 11, no. 2, pp. 223-231. https://doi.org/10.2215/CJN.05240515

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; Campbell, Katrina L.

In: Clinical journal of the American Society of Nephrology : CJASN, Vol. 11, No. 2, 05.02.2016, p. 223-231.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Pascoe, Elaine M

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AU - Forbes, Josephine M

AU - Szeto, Cheuk-Chun

AU - McWhinney, Brett C

AU - Ungerer, Jacobus P J

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N2 - 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.

AB - 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.

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