The impact of synbiotic treatment on the levels of gut-derived uremic toxins, inflammation, and gut microbiome of chronic kidney disease patients- A randomized trial.

Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation

Aug 2022

DOI: 10.1053/j.jrn.2022.07.008

Citations:25

Influential Citations:1

Interventional (Human) Studies

Enhanced Details

Methods

Single-center, randomized, double-blind, placebo-controlled trial in nondialyzed CKD patients aged 18 years or older with eGFR 15-45 mL/min; 34 participants randomized (17 per group).

Intervention

Two capsules daily, before breakfast, for 12 weeks; each capsule contains Lactobacillus acidophilus CBTLA1 (16e9 CFU), Lactobacillus casei CBT LC5 (4e9 CFU), Bifidobacterium lactis CBT BL3 (8e9 CFU), and 1.6 g inulin.

Results

Synbiotic treatment enriched gut microbiota (Bifidobacteria, Lactobacillus, Subdoligranulum) and reduced serum indoxyl sulfate; eGFR improved (12% vs 8% in placebo); hsCRP decreased (−39.5% vs −8.5%). Intention-to-treat analyses showed IS dynamics −14.6% vs 5.3% (P=0.002) and TMAO dynamics −5.3% vs 1.6% (P=0.039). The treatment was generally safe; two intervention participants reported increased flatulence. Conclusion: Synbiotics could be a safe and effective strategy to lower gut-derived uremic toxins and microinflammation in CKD and may be used in daily practice.

Limitations

Small, single-center randomized trial (n=34); short duration (12 weeks); per-protocol analyses with some dropouts; limited generalizability and power; safety data limited to short term.

Abstract

OBJECTIVE Altering dysbiotic gut flora through synbiotic supplementation has recently been recognized as potential treatment strategy to reduce the levels of gut-derived uremic toxins and decrease inflammation. Assessing its efficacy and safety has been the main goal of our randomized, double-blind, placebo-controlled study. METHOD A total of 34 non-dialyzed chronic kidney disease patients, aged ≥18 years, with an estimated glomerular filtration rate between 15-45 ml/min, were randomized either to an intervention group (n=17) receiving synbiotic (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium lactis, 32 billion colony forming units per day plus 3.2 g of inulin), or control group (n=17), receiving placebo during twelve weeks. The impact of treatment on the dynamic of serum levels of gut-derived uremic toxins- total serum indoxyl sulfate, p-cresyl sulfate and trimethylamine N-oxide, was defined as the primary outcome of the study. Secondary outcomes included changes in the stool microbiome, serum interleukin-6 levels, high sensitivity C-reactive protein, estimated glomerular filtration rate, albuminuria, diet, gastrointestinal symptom dynamics, and safety. Serum levels of uremic toxins were determined using ultra-performance liquid chromatography. The stool microbiome analysis was performed using 16S ribosomal ribonucleic acid gene sequencing approach. RESULTS Synbiotic treatment significantly modified gut microbiome with Bifidobacteria, Lactobacillus and Subdoligranulum genera enrichment and consequently reduced serum level of indoxyl sulfate (ΔIS -21.5% vs 5.3%, p<0.001), improved estimated glomerular filtration rate (ΔeGFR 12% vs 8%, p=0.029) and decreased level of high sensitive C-reactive protein (hsCRP -39.5 vs -8.5%, p<0.001) in treated patients. Two patients of the intervention arm complained of increased flatulence. No other safety issues were noted. CONCLUSION Synbiotics could be available, safe, and an effective therapeutic strategy we could use in daily practice in order to decrease levels of uremic toxins and microinflammation in chronic kidney disease patients. show less