251. Gut Lactobacillus protects against the progression of renal damage by modulating the gut environment in rats.
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Ayumi Yoshifuji, Shu Wakino, Junichiro Irie, Takaya Tajima, Kazuhiro Hasegawa, Takeshi Kanda, Hirobumi Tokuyama, Koichi Hayashi, and Hiroshi Itoh
- Subjects
LACTOBACILLUS ,KIDNEY failure ,RAT reproduction ,COLON (Anatomy) ,LARGE intestine - Abstract
Background. The role of gut microbiota in the progression of chronic kidney disease (CKD) has not been fully elucidated. Methods. Renal failure was induced in 6-week-old spontaneously hypertensive rats by 5/6 nephrectomy (Nx). We analyzed the gut microbiota population to identify the relevant species potentially involved in inducing renal damage. Human colon Caco-2 cells were used to delineate the mechanism involved in the molecular changes in the gut of Nx rats. Results. Nx rats showed an increase in Bacteroides (Bact) and a decrease in Lactobacillus (Lact) species compared with shamoperated rats. Lact, but not Bact, populations were significantly associated with urinary protein excretion. Treatment of Nx rats with 1 × 1010 CFU/kg/day Lact ameliorated increased urinary protein excretion and higher serum levels of the uremic toxins, indoxyl sulfate and p-cresyl sulfate, and serum urea nitrogen levels. Lact also attenuated systemic inflammation in Nx rats, as evaluated by serum lipopolysaccharide, interleukin-6 and Creactive protein levels. Histologically, renal sclerosis in Nx rats was restored by Lact treatment. A reduction in the expression of tight junction proteins and the Toll-like receptor 2 (TLR2), a putative Lact receptor, in the colons of Nx rats were mitigated by Lact. Treatment of Caco-2 cells with indole downregulated tight junction protein expression, which was abolished by exposure to Lact. The effects of Lact were reversed by treatment with OxPAPC, a TLR inhibitor. Similarly, the increase in the permeability of the Caco-2 cell monolayer was reversed by the administration of Lact. Lact upregulated TLR2 expression in Caco-2 cells. Lact also attenuated the increase in serum indoxyl sulfate and urea levels and urinary protein excretion in Nx rats even in the pseudogerm-free environment. Conclusions. Lact supplementation mitigated the systemic inflammation and proteinuria associated with renal failure, suggesting that in the gut microbiota, Lact plays a protective role against the progression of CKD. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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