title: Galacto-oligosaccharides attenuate renal injury with microbiota modification.
abstract: Tubulointerstitial injury is central to the progression of end-stage renal disease. Recent studies have revealed that one of the most investigated uremic toxins, indoxyl sulfate (IS), caused tubulointerstitial injury through oxidative stress and endoplasmic reticulum (ER) stress. Because indole, the precursor of IS, is synthesized from dietary tryptophan by the gut microbiota, we hypothesized that the intervention targeting the gut microbiota in kidney disease with galacto-oligosaccharides (GOS) would attenuate renal injury. After 2 weeks of GOS administration for 5/6 nephrectomized (Nx) or sham-operated (Sham) rats, cecal indole and serum IS were measured, renal injury was evaluated, and the effects of GOS on the gut microbiota were examined using pyrosequencing methods. Cecal indole and serum IS were significantly decreased and renal injury was improved with decreased infiltrating macrophages in GOS-treated Nx rats. The expression levels of ER stress markers and apoptosis were significantly increased in the Nx rats and decreased with GOS. The microbiota analysis indicated that GOS significantly increased three bacterial families and decreased five families in the Nx rats. In addition, the analysis also revealed that the bacterial family Clostridiaceae was significantly increased in the Nx rats compared with the Sham rats and decreased with GOS. Taken altogether, our data show that GOS decreased cecal indole and serum IS, attenuated renal injury, and modified the gut microbiota in the Nx rats, and that the gut microbiota were altered in kidney disease. GOS could be a novel therapeutic agent to protect against renal injury.
authors.affiliation: Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan Division of Nephrology, Mitsui Memorial Hospital, Tokyo, Japan.
authors.forename: Satoshi U
authors.initials: SU
authors.lastname: Furuse
authors.affiliation: Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan.
authors.forename: Takamoto
authors.initials: T
authors.lastname: Ohse
authors.affiliation: Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan.
authors.forename: Airi
authors.initials: A
authors.lastname: Jo-Watanabe
authors.affiliation: Yakult Central Institute for Microbiological Research, Kunitachi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shigehisa
authors.affiliation: Yakult Central Institute for Microbiological Research, Kunitachi, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Yakult Central Institute for Microbiological Research, Kunitachi, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsuki
authors.affiliation: Yakult Central Institute for Microbiological Research, Kunitachi, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Chonan
authors.affiliation: Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
keywords: Endoplasmic reticulum stress; galacto‐oligosaccharides; gut microbiota; indoxyl sulfate; kidney disease