Live Biotherapeutics Drug Discovery Services for Chronic Kidney Disease

The potential utilization of therapies modulating gut microbiota such as probiotics has emerged as an attractive strategy to treat chronic kidney disease (CKD). Equipped with world-leading technology platforms and professional scientific staff, Creative Biolabs is committed to providing overall solutions for next-generation probiotics (NGPs) discovery, focusing on innovative research and development of probiotics industrialization. Scientists at Creative Biolabs are pleased to share our experience in NGPs development for the treatment of CKD with our global clients and facilitate their meaningful researches.

Introduction of CKD

CKD, especially end-stage renal disease (ESRD), threatens global health and leads to various health problems. The progression of CKD might be influenced by several factors, such as dietary intake, mental stress, or medications. Recent studies revealed the importance of the gut microbiota in the development and progression of CKD. Dysbiosis of the intestinal microbiota increases urea toxins, which damage the epithelial tight junctions and increase the permeability of the intestinal wall via endotoxemia and systemic inflammation. As a consequence, intestinal endotoxins may go through the intestinal wall into the blood circulation, induce microinflammation in the kidney and cause renal endothelial dysfunction, fibrosis, and tubular damages. Unfortunately, most of the current treatments exhibit inherent disadvantages, such as side effects, high cost, and unavailability in patients with moderate CKD, and remain limited to experimental studies.

Production of uremic toxins during CKD. Fig.1 Production of uremic toxins during CKD. (Plata, 2019)

CKD and Probiotics

Due to their various health-promoting effects and inherent ability to fight specific diseases, probiotics are the focus of a thorough investigation as a natural biotreatment. Probiotics supplementation has emerged as adjuvant therapy for CKD in recent years because of the low cost of probiotics. Indeed, intestinal microbiota has recently emerged as an important player in the progression and complications of CKD. Many studies have shown that probiotics could slow down the progression of CKD by regulating the intestinal flora alteration and by reducing the urea toxin.

Lots of experimental and clinical studies using probiotics in CKD have been performed. However, high-quality interventional trials investigating probiotic treatment in CKD are lacking. Moreover, studies investigating the impact of probiotics on clinical endpoints have not been conducted so far. Besides, the quality, size, and design of trials are not sufficient enough to justify the widespread use of probiotics.

Table 1. Human studies reporting the use of probiotics in CKD. (Koppe, 2015)

Probiotics Study Results
Bifobacterium bifidum A218, Bifidobacterium catenulatum A302, Bifidobacterium longum A101, and Lactobacillus plantarum A87 Single-center, double-blind, placebo-controlled, randomized
n=39, peritoneal dialysis patients
6 months
↓ Serum TNF-α, IL-5, IL-6, and LPS Preservation of residual renal function.
Synbiotic: Lactobacillus, Bifidobacteria and Streptococcus genera + prebiotic (inulin, fructo-oligosaccarides, and galacto-oligosaccarides) Single-center, double-blind, placebo-controlled, randomized cross-over trial
n=37; CKD stage 4-5
6 weeks, with a 4-week washout before cross-over. Dietary advice (protein 0.8 g/kg BW/d) Single-center, double-blind, placebo-controlled n=18, HD
In process, primary outcomes: level of IS
Secondary outcomes: levels of PCS; LPS, TMAO, inflammation, and oxidative stress markers; renal function; quality of life.
Synbiotic: Lactobacillus plantarum, Lactobacillus casei subsp. rhamnosus, Lactobacillus gasseri, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus salivarius, Lactobacillus sporogenes, and Streptococcus thermophilus+, prebiotic (inulin and tapioca-resistant starch) Single-center, double-blind, placebo-controlled, randomized cross-over trial. n=30; CKD stage 3-4
4 weeks
↓Plasma p-cresol
Streptococcus thermophilus KB 19, Lactobacillus acidophilus KB 27, and Bifidobacterium longum KB 31 Single-center, double-blind, placebo-controlled, randomized cross-over trial n=22; HD
8 weeks
↑ Quality of life
Trend in a reduction of serum indoxyl glucuronide and C-reactive protein
Synbiotics: Lactobacillus casei strain Shirota and Bifidobacterium breve strain Yakult+prebiotic (galacto-oligosaccharides) Single-center, observational trial n=9; HD
4 weeks
↓ p-Cresol
Normalization of bowel habits
Lactobacillus acidophilus KB31, Streptococcus thermophilus KB27, and Bifidobacterium longum KB35 Single-center, prospective, randomized, double-blind, cross-over, placebo-controlled trial n=16; CKD stage 3-4
6 months
↓ BUN
↓ Uric acid concentration
↑ Quality of life
Bifidobacterium longum Single-center, observational trial n=27; CKD patients all stages
6 months
Slowing of the progression of kidney disease
Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis Single-center, observational trial n=25; HD
4 weeks
↓ Indican in feces and serum;
↓ p-Cresol in feces.

NGPs Discovery Service at Creative Biolabs

The interest in developing new probiotics in CKD has increased to fully explore their therapeutic potentials. Since lots of multifactorial physiological functions of probiotics are highly strain-specific, identification of probiotics based on their expression of functional biomarkers is critical. With years of research in live biotherapeutics drug discovery, Creative Biolabs has developed a cutting-edge platform for NGPs identification and functional characterization. Our scientists offer accurate and effective solutions for researchers who are committed to developing NGPs for the treatment of CKD.

The powerful platform, professional technical scientists, and abundant experience make Creative Biolabs a perfect partner to help our clients in the discovery of NGPs for CKD treatment. Just feel free to contact us and communicate with us about your specific puzzles. Our Ph.D. scientists will offer you professional solutions as soon as possible.

References

  1. Plata, C.; et al. The gut microbiota and its relationship with chronic kidney disease. International Urology and Nephrology. 2019, 51(12): 2209-26.
  2. Koppe, L.; et al. Probiotics and chronic kidney disease. Kidney international. 2015, 88(5): 958-66.

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