Effect of potential probiotics on reducing uremic toxin indoxyl sulfate using the cisplatin-induced acute kidney injury rat model
Date Issued
2014
Date
2014
Author(s)
Pai, Yi-Hsin
Abstract
Numerous molecules that are either excreted or metabolized by the kidney accumulated in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) is a protein bound uremic toxin, which is unable to effectively eliminate by haemodialysis (HD). The accumulation of protein-bound uremic toxins has been suggested to be related to complications and mortality in HD patients. Indole, the precursor of IS, are produced by intestinal bacteria, such as Escherichia coli, from tryptophan. Since uremic toxins might be reduced by modulating microbiota in the colon, probiotics seem to be potential to reduce the concentration of intestinal nitrogenous metabolites. Thus, the aim of this study was to find potential probiotics which may improve renal function by reducing IS production.
Three strains, Lactobacillus plantarum, L. paracasei and Streptococcus thermophilus, were selected to have the ability to reduce indoxyl sulphate in vitro. Combination of strains (Pm-1) demonstrated a better IS removing ability than individual strains. We further investigated the uremic toxin-reducing probiotics by the cisplatin-induced acute kidney injury (AKI) rat model. Results indicated that oral administration of Pm-1 in cisplatin-induced acute kidney injury model significantly suppressed the accumulation of IS in the serum. Oral administration of Pm-1 also decreased in the number of E. coli and coliforms in feces.
We further optimized growth medium by response surface methodology (RSM) with sequential quadratic programming (SQP). Results indicated that the media with sugar yeast, maltodextrin and dipotassium as major component could yield the highest cell numbers to 9.01、8.71 and 8.94 log/mL, respectively. The cost of medium was reduced to less than 20% when compared with commercial MRS medium.
Our findings suggest that long term treatment with the strain combination Pm-1 might be a useful approach to decreasing IS accumulation in the serum and kidney. The possible mechanisms involved might include the binding/metabolizing IS in intestine and/or the modulation of bacterial growth in colon by Pm-1, both of which could decrease IS accumulation. The stimulation of anti-inflammatory cytokines and release of oxidative stress by Pm-1 might also be involved in the amelioration of AKI symptoms.
Subjects
慢性腎臟疾病
硫酸吲哚酚
益生菌
反應曲面法
Type
thesis
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