Author(s)

Nobuo Nagano^1,2*, Mayuko Futaya², Mamiko Kohno³, Osami Nakano³, Norihisa Nishida³, Yoichi Matsuura³, Mikiko Shimada¹, Kyoko Ito¹, Tetsuo Ando¹, Takaaki Tsutsui¹, Yoshitaka Ando¹, Kiyotsugu Omae⁴, Kosaku Nitta⁵, Hiroshi Sakura², Tetsuya Ogawa²

¹Kidney Disease and Dialysis Center, Hidaka-kai, Takasaki, Gunma, Japan.
²Department of Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan.
³Research and Development Division, Morishita Jintan Co., Ltd., Osaka, Japan.
⁴Department of Internal Medicine, Yoshikawa Clinic, Tokyo, Japan.
⁵Department of Medicine, Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan.

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 fermented 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.

Bifidobacteria, CKD-MBD, Dysbiosis, Hyperphosphatemia, Intestinal pH, Short-Chain Fatty Acids

Nagano, N. , Futaya, M. , Kohno, M. , Nakano, O. , Nishida, N. , Matsuura, Y. , Shimada, M. , Ito, K. , Ando, T. , Tsutsui, T. , Ando, Y. , Omae, K. , Nitta, K. , Sakura, H. and Ogawa, T. (2015) The Mechanism of Decreased Serum Phosphorus Levels in Rats with Chronic Kidney Disease after Oral Administration of Bifidobacterium longum. Advances in Microbiology, 5, 531-540. doi: 10.4236/aim.2015.57055.