Lactobacillus acidophilus KBL409 strain and application thereof
A technology of Lactobacillus acidophilus and strains, applied in the field of pharmaceutical compositions for the prevention or treatment of kidney disease, and animal feed compositions, which can solve the problems of no antibiotic-resistant plasmids and antibiotic sensitivity
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Embodiment 1
[0098] Example 1. Selection of lactic acid bacteria with p-cresol degrading ability
[0099]The precursors of p-cresol sulfate (PCS), indole sulfate (IS) and trimethylamine N-oxide (TMAO), which are the main nephrouremic toxins, are respectively p-cresol, indole, trimethylamine (TMA), and trimethylamine, and are waste products of phenylalanine (or tyrosine), tryptophan, and choline produced by gut microbes. The present invention focuses on identifying microorganisms capable of metabolizing / degrading nephrouremic toxin precursors, and the present inventors attempt to select probiotics that exhibit a therapeutic effect on nephropathy through the degradation of uremic toxins by selecting p-cresol decomposition as the main selection object bacterial strains. To this end, a total of 67 strains of Lactobacillus and Lactococcus of human origin and a total of 33 strains of Bifidobacterium were evaluated for their ability to degrade p-cresol. All strains were resistant to low pH and ...
Embodiment 2
[0109] Example 2. Determination of anti-inflammatory effect of KBL409
[0110] Since pyroptosis, one of the important mechanisms of cell death in kidney disease, occurs together with the inflammatory response, it is necessary to verify the nephroprotective effect through the improvement of the inflammatory response. To determine the anti-inflammatory effect and p-cresol degrading ability of KBL409, peripheral blood mononuclear cells (PBMC) were used to determine the expression levels of inflammatory and anti-inflammatory markers.
[0111] 2-1. Preparation of PBMC and treatment of strains
[0112] Human-derived PBMCs (Zen-Bio, Inc., Research Triangle Park, NC, USA) were grown in RPMI-1640 medium (Gibco, Paisley) containing 1% penicillin / streptomycin, 1% gentamicin and 10% FBS. UK) cultured. The cultured PBMCs (2 × 10 5 cells) in 96-well plates and treated with 1 μg / mL T-cell-activated anti-CD3 antibody (OKT3; ThermoFisher Scientific, Inc., Waltham, MA, USA), and then added a...
Embodiment 3
[0116] Example 3. Determination of the role of KBL409 in a mouse model of chronic renal failure induction
[0117] The method used to induce renal failure by feeding a diet containing adenine (0.2% adenine) is widely used as a model for renal failure induction because it does not require surgery, does not cause death, is relatively easy to ingest feed, and can be observed for a long time segment, avoid the need for nephrectomy, observe all renal failure in both kidneys, and obtain adequate tissue (Jia T et al. A new model of adenine-induced tubulointerstitial nephropathy in mice. BMC Nephrol 2013;14:116 ). In the present invention, using an adenine-induced renal failure model, the effects of improving changes in renal function, renal fibrosis, etc., and inflammation after administration of KBL409 were determined. In addition, the effect of reducing uremic toxins in the blood due to decreased renal function was also determined.
[0118] 3-1. Model generation of chronic renal ...
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