Administration of the probiotic Lactiplantibacillus paraplantarum is effective in controlling hyperphosphatemia in 5/6 nephrectomy rat model.

AIMS: Several studies have linked gut microbes to human diseases. Most of the mechanisms by which lactic acid bacteria have beneficial effects on the human body are related to immune modulation. Controlled studies of the ability of lactic acid bacteria to absorb phosphorus directly from the intestine and thereby control serum phosphorus level in in vivo uremic animal models are limited. MATERIALS AND METHODS: We screened lactic acid bacteria living in Korean fermented foods to identify those that absorb the most phosphorus and noted Lactiplantibacillus paraplantarum KCCM 11826P. The mechanism through which better intracellular absorption of phosphorus occurs in this strain was studied using genomic DNA sequencing. After the strain was administered to 5/6 nephrectomized rats for 6 weeks, it was observed whether hyperphosphatemia had improved. KEY FINDINGS: The L. paraplantarum KCCM 11826P strain has a polyP gene cluster; thus, it absorbs phosphorus better than other bacteria and can suppress strains that produce indole. Supplementing the diets of 5/6 nephrectomized rats with this L. paraplantarum strain significantly decreased serum phosphate level (by 22 %) and reduced blood indoxyl sulphate concentration (by 40 %) compared with vehicle treatment. SIGNIFICANCE: These results suggest that Lactiplantibacillus preparations can be used for multiple purposes, such as the removal of phosphorus and uremic toxins from patients with chronic kidney disease (CKD). This study also demonstrates the novel concept of a probiotic phosphate binder.

CAR1 deletion by CRISPR/Cas9 reduces formation of ethyl carbamate from ethanol fermentation by Saccharomyces cerevisiae.

Enormous advances in genome editing technology have been achieved in recent decades. Among newly born genome editing technologies, CRISPR/Cas9 is considered revolutionary because it is easy to use and highly precise for editing genes in target organisms. CRISPR/Cas9 technology has also been applied for removing unfavorable target genes. In this study, we used CRISPR/Cas9 technology to reduce ethyl carbamate (EC), a potential carcinogen, which was formed during the ethanol fermentation process by yeast. Because the yeast CAR1 gene encoding arginase is the key gene to form ethyl carbamate, we inactivated the yeast CAR1 gene by the complete deletion of the gene or the introduction of a nonsense mutation in the CAR1 locus using CRISPR/Cas9 technology. The engineered yeast strain showed a 98 % decrease in specific activity of arginase while displaying a comparable ethanol fermentation performance. In addition, the CAR1-inactivated mutants showed reduced formation of EC and urea, as compared to the parental yeast strain. Importantly, CRISPR/Cas9 technology enabled generation of a CAR1-inactivated yeast strains without leaving remnants of heterologous genes from a vector, suggesting that the engineered yeast by CRISPR/Cas9 technology might sidestep GMO regulation.