PMID- 33898439
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210428
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 9
DP  - 2021
TI  - Fiber Derived Microbial Metabolites Prevent Acute Kidney Injury Through G-Protein 
      Coupled Receptors and HDAC Inhibition.
PG  - 648639
LID - 10.3389/fcell.2021.648639 [doi]
LID - 648639
AB  - Short-chain fatty acids (SCFA) derived from gut microbial fermentation of fiber 
      have been shown to exert anti-inflammatory and immune-modulatory properties in 
      acute kidney injury (AKI). However the direct mechanistic link between SCFAs, 
      diet and the gut microbiome is yet to be established. Using the murine model of 
      folic-acid nephropathy (FAN), we examined the effect of dietary fiber on 
      development of AKI (day 2) and subsequent chronic kidney disease (CKD) (day 28). 
      FAN was induced in wild-type and knockout mice lacking G protein-coupled 
      receptors GPR41, GPR43, or GPR109A. Mice were randomized to high-fiber or 
      normal-chow diets, or SCFAs in drinking water. We used 16S rRNA sequencing to 
      assess the gut microbiome and (1)H-NMR spectroscopy for metabolic profiles. Mice 
      fed high-fiber were partially protected against development of AKI and subsequent 
      CKD, exhibiting better kidney function throughout, less tubular injury at day 2 
      and less interstitial fibrosis and chronic inflammation at day 28 vs controls. 
      Fiber modified the gut microbiome and alleviated dysbiosis induced by AKI, 
      promoting expansion of SCFA-producing bacteria Bifidobacterium and Prevotella, 
      which increased fecal and serum SCFA concentrations. SCFA treatment achieved 
      similar protection, but not in the absence of GPR41 or GPR109A. Histone 
      deacetylase activity (HDAC) was inhibited in kidneys of high-fiber fed mice. We 
      conclude that dietary manipulation of the gut microbiome protects against AKI and 
      subsequent CKD, mediated by HDAC inhibition and activation of GPR41 and GPR109A 
      by SCFAs. This study highlights the potential of the gut microbiome as a 
      modifiable target in the prevention of AKI.
CI  - Copyright (c) 2021 Liu, Li, Loh, Singer, Zhu, Macia, Mackay, Wang, Chadban and Wu.
FAU - Liu, Yunzi
AU  - Liu Y
AD  - Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai, China.
AD  - Kidney Node Laboratory, The Charles Perkins Centre, University of Sydney, 
      Camperdown, NSW, Australia.
FAU - Li, Yan J
AU  - Li YJ
AD  - Kidney Node Laboratory, The Charles Perkins Centre, University of Sydney, 
      Camperdown, NSW, Australia.
AD  - Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
FAU - Loh, Yik W
AU  - Loh YW
AD  - Kidney Node Laboratory, The Charles Perkins Centre, University of Sydney, 
      Camperdown, NSW, Australia.
FAU - Singer, Julian
AU  - Singer J
AD  - Kidney Node Laboratory, The Charles Perkins Centre, University of Sydney, 
      Camperdown, NSW, Australia.
AD  - Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
FAU - Zhu, Weiping
AU  - Zhu W
AD  - Kidney Node Laboratory, The Charles Perkins Centre, University of Sydney, 
      Camperdown, NSW, Australia.
AD  - Department of Nephrology, The Fifth Affiliated Hospital of Sun Yat-sen 
      University, Zhuhai, China.
FAU - Macia, Laurence
AU  - Macia L
AD  - Nutritional Immuno-metabolism Laboratory, The Charles Perkins Centre, University 
      of Sydney, Camperdown, NSW, Australia.
AD  - School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, 
      Sydney, NSW, Australia.
FAU - Mackay, Charles R
AU  - Mackay CR
AD  - Infection and Immunity Program, Biomedicine Discovery Institute, Monash 
      University, Clayton, VIC, Australia.
FAU - Wang, Weiming
AU  - Wang W
AD  - Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai, China.
FAU - Chadban, Steven J
AU  - Chadban SJ
AD  - Kidney Node Laboratory, The Charles Perkins Centre, University of Sydney, 
      Camperdown, NSW, Australia.
AD  - Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
FAU - Wu, Huiling
AU  - Wu H
AD  - Kidney Node Laboratory, The Charles Perkins Centre, University of Sydney, 
      Camperdown, NSW, Australia.
AD  - Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
LA  - eng
PT  - Journal Article
DEP - 20210408
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC8060457
OTO - NOTNLM
OT  - SCFA
OT  - acute kidney injury
OT  - dietary fiber
OT  - gut microbiota
OT  - prebiotic
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/04/27 06:00
MHDA- 2021/04/27 06:01
PMCR- 2021/01/01
CRDT- 2021/04/26 05:57
PHST- 2021/01/01 00:00 [received]
PHST- 2021/03/16 00:00 [accepted]
PHST- 2021/04/26 05:57 [entrez]
PHST- 2021/04/27 06:00 [pubmed]
PHST- 2021/04/27 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2021.648639 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2021 Apr 8;9:648639. doi: 10.3389/fcell.2021.648639. 
      eCollection 2021.