The Mechanism of Decreased Serum Phosphorus Levels in Rats with Chronic Kidney Disease after Oral Administration of <i>Bifidobacterium longum</i>

Abstract

Chronic kidney disease (CKD) patients are prone to disturbances in the intestinal microbiota, which contributes to CKD progression and complications. We previously reported a reduction of serum phosphorus (P) levels in hemodialysis patients receiving oral encapsulated bifidobacteria. The present study was conducted to clarify the mechanisms of P-lowering effect of bifidobacteria on CKD rats. CKD was induced in rats by 5/6 nephrectomy. Five weeks later, the rats were fed for 4 weeks on a powder diet containing encapsulated bifidobacteria. At the end of the study, intestinal contents were sampled for analyses of pH, intestinal flora and short-chain fatty acids (SCFAs). Oral administration of bifidobacteria halted the onset and progression of hyperphosphatemia in CKD rats. The increased number of bifidobacteria was confirmed in the cecum. In addition, the increase in intestinal pH in CKD rats was decreased after bifidobacteria treatment, along with increases in some SCFAs. Furthermore, positive correlation between serum P levels and intestinal pH was observed. In conclusion, the mechanism for the P-lowering effect of bifidobacteria was supposed as follows: CKD conditions increase aerobic bacteria which hydrolyze urea into ammonia. Elevated pH decreases ionization of intestinal calcium (Ca) which leads to an increase in free phosphate ions through reduction of Ca phosphate crystal precipitation. Administered bifidobacteria fer-* Corresponding author. N. Nagano et al. 532mented carbohydrates to produce SCFAs, resulting in acidification of the intestinal lumen. The resulting low intestinal pH increases Ca ionization, which binds with free phosphate ions as an intrinsic P binder, resulting in the reduction of serum P levels.

Alleviation of low-fiber diet-induced constipation by probiotic <i>Bifidobacterium bifidum</i> G9-1 is based on correction of gut microbiota dysbiosis

“…The concentrations of organic acids in the cecal contents were measured according to the method of Nagano et al [15].…”

Ameliorating effect of probiotics in a rat model of chronic kidney disease

“…Bifidobacteria produce SCFA and makes the intestinal lumen more acidic and, therefore, enhances Ca ionisation. Ionised Ca binds free phosphate ions, resulting in reduced serum P levels [ 87 ].…”

In vitro–in vivo extrapolation of bexarotene metabolism in the presence of chronic kidney disease and acute kidney injury in rat using physiologically based pharmacokinetic modeling and extrapolation to human

“…The rat GI pH was set to 3.9, 5.8, 6.6, 6.7, 7.2, and 6.6 for the stomach, duodenum, jejunum, upper ileum, lower ileum, and cecum, respectively, for both healthy and AKI rats (Afonso‐Pereira et al., 2018). Rats with CKD showed an increase in the pH of jejunum to 6.6, ileum to 7.4, and cecum to 6.5 (Afonso‐Pereira et al., 2018; Nagano et al., 2015). The intestinal expression of CYP 3A in rats was set to 40%, 56%, and 12% of the hepatic expression in control (GmbH, 2017), AKI (Okabe et al., 2003a), and CKD (Leblond et al., 2001) rats, respectively.…”