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Gut Lactobacillus protects against the progression of renal damage by modulating the gut environment in rats.

Authors :
Ayumi Yoshifuji
Shu Wakino
Junichiro Irie
Takaya Tajima
Kazuhiro Hasegawa
Takeshi Kanda
Hirobumi Tokuyama
Koichi Hayashi
Hiroshi Itoh
Source :
Nephrology Dialysis Transplantation; Mar2016, Vol. 31 Issue 3, p401-412, 12p, 1 Diagram, 2 Charts, 5 Graphs
Publication Year :
2016

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]

Details

Language :
English
ISSN :
09310509
Volume :
31
Issue :
3
Database :
Complementary Index
Journal :
Nephrology Dialysis Transplantation
Publication Type :
Academic Journal
Accession number :
113310264
Full Text :
https://doi.org/10.1093/ndt/gfv353