#279 The impact of synbiotics on the uremic toxins, inflammation, and gut microbiome of CKD patients—randomized, double-blind, placebo-controlled trial
Authors: Mitrović Miloš , Dimkovic Nada , Popovic Verica Stankovic 
Published: May 2024

Abstract

Background and Aims
The microbiome represents a complex system of microorganisms coexisting within the human body. The intestinal tract is the most densely populated region and is essential in preserving health and developing diseases such as chronic kidney disease (CKD). The relationship between the gut microbiome and the kidney is complex. CKD can significantly affect the composition of the gut microbiome, which, through the fermentation process, participates in the production of over 90 different uremic toxins with the potential to aggravate systemic inflammation, oxidative stress, and decrease renal function. Indoxyl-sulfate (IS), p-cresyl-sulfate (PCS), and trimethylamine-N-oxide (TMAO) are the most closely studied. Supplementation with pre-, pro-, or synbiotics could reduce the production and improve the intestinal clearance of uremic toxins. Assessing the efficacy and safety of this potential strategy has been the aim of our randomized, double-blind, placebo-controlled study.

Method
A total of 84 patients, aged over 18 years, with an estimated glomerular filtration rate (eGFR) between 15 and 45 ml/min, were randomized into two groups, the one treated with synbiotic—64 billion colonies of Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium lactis with 6.4 g of inulin in the form of capsules, and a control group treated with an identical number and appearance of capsules but with a total of 6.8 g of bioinert maltodextrin, over a period of 12 weeks. Strict control of the diet and the use of antibiotics and other probiotics was carried out. The study examined the effect of therapy on the serum level of the uremic toxins IS, PCS, and TMAO, the composition of the stool microbiome, the serum level of interleukin 6 (IL6), high-sensitivity C-reactive protein (hs-CRP), eGFR, albuminuria, degree of liver steatosis according to ultrasound elastomeric measurement, occurrence of gastrointestinal symptoms and gut transition time. The level of uremic toxins was determined using ultra-performance liquid chromatography. To determine the composition of the intestinal microbiome, we used 16s rRNA amplicon sequencing targeting the V3-V4 hypervariable region.

Results
The synbiotic treatment significantly reduced the levels of IS (−11% vs. 1%, p = 0.033) and PCS (−6% vs. 0%, p = 0.011) in the intervention arm. We also observed that treatment with the synbiotic significantly reduced hsCRP levels (ΔhsCRP 0 vs −29%, p = 0.03). Synbiotic treatment greatly enriched the intestinal microbiome with the genera Lactobacillus, Bifidobacterium, and Faecalibacterium by 81%, 55%, and 40%, respectively, with a reduction in the genera Ruminococcus and Enterobacterium by 35% and 40%. The use of synbiotics led to a significant reduction of liver steatosis according to the dynamics of the attenuation coefficient—ATT (ΔATT% −0.6 vs −2.3%, p = 0.33), with a decrease in the serum alanine aminotransferase—ALT (ΔALT −19% vs −28%, p = 0.035). A statistically significant shortening of the gut transition time—GTT was observed in the intervention arm (ΔGTT −5 h vs −10 h, p = 0.031), paralleled by a reduction in the intensity and prevalence of constipation symptoms. No side effects were observed.

Conclusion
Synbiotics could be an effective, safe, and affordable therapy that could be used to modify the intestinal microbiome of CKD patients and contribute to the reduction of the level of uremic toxins, inflammation, degree of fatty liver, shorten gut transit time and reduce the symptoms of constipation.