Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid-Mediated Activation of G Protein-Coupled Receptors GPR43 and GPR109A.
Albuminuria
/ prevention & control
Animals
Diabetes Mellitus, Experimental
/ complications
Diabetic Nephropathies
/ prevention & control
Dietary Fiber
/ administration & dosage
Dysbiosis
Fatty Acids, Volatile
/ physiology
Gastrointestinal Microbiome
Male
Mice
Mice, Inbred C57BL
Receptors, G-Protein-Coupled
/ physiology
Streptozocin
chronic inflammation
diabetic nephropathy
metabolism
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
08
10
2019
accepted:
09
03
2020
pubmed:
3
5
2020
medline:
5
1
2021
entrez:
3
5
2020
Statut:
ppublish
Résumé
Studies have reported "dysbiotic" changes to gut microbiota, such as depletion of gut bacteria that produce short-chain fatty acids (SCFAs) through gut fermentation of fiber, in CKD and diabetes. Dietary fiber is associated with decreased inflammation and mortality in CKD, and SCFAs have been proposed to mediate this effect. To explore dietary fiber's effect on development of experimental diabetic nephropathy, we used streptozotocin to induce diabetes in wild-type C57BL/6 and knockout mice lacking the genes encoding G protein-coupled receptors GPR43 or GPR109A. Diabetic mice were randomized to high-fiber, normal chow, or zero-fiber diets, or SCFAs in drinking water. We used proton nuclear magnetic resonance spectroscopy for metabolic profiling and 16S ribosomal RNA sequencing to assess the gut microbiome. Diabetic mice fed a high-fiber diet were significantly less likely to develop diabetic nephropathy, exhibiting less albuminuria, glomerular hypertrophy, podocyte injury, and interstitial fibrosis compared with diabetic controls fed normal chow or a zero-fiber diet. Fiber beneficially reshaped gut microbial ecology and improved dysbiosis, promoting expansion of SCFA-producing bacteria of the genera Dietary fiber protects against diabetic nephropathy through modulation of the gut microbiota, enrichment of SCFA-producing bacteria, and increased SCFA production. GPR43 and GPR109A are critical to SCFA-mediated protection against this condition. Interventions targeting the gut microbiota warrant further investigation as a novel renoprotective therapy in diabetic nephropathy.
Sections du résumé
BACKGROUND
Studies have reported "dysbiotic" changes to gut microbiota, such as depletion of gut bacteria that produce short-chain fatty acids (SCFAs) through gut fermentation of fiber, in CKD and diabetes. Dietary fiber is associated with decreased inflammation and mortality in CKD, and SCFAs have been proposed to mediate this effect.
METHODS
To explore dietary fiber's effect on development of experimental diabetic nephropathy, we used streptozotocin to induce diabetes in wild-type C57BL/6 and knockout mice lacking the genes encoding G protein-coupled receptors GPR43 or GPR109A. Diabetic mice were randomized to high-fiber, normal chow, or zero-fiber diets, or SCFAs in drinking water. We used proton nuclear magnetic resonance spectroscopy for metabolic profiling and 16S ribosomal RNA sequencing to assess the gut microbiome.
RESULTS
Diabetic mice fed a high-fiber diet were significantly less likely to develop diabetic nephropathy, exhibiting less albuminuria, glomerular hypertrophy, podocyte injury, and interstitial fibrosis compared with diabetic controls fed normal chow or a zero-fiber diet. Fiber beneficially reshaped gut microbial ecology and improved dysbiosis, promoting expansion of SCFA-producing bacteria of the genera
CONCLUSIONS
Dietary fiber protects against diabetic nephropathy through modulation of the gut microbiota, enrichment of SCFA-producing bacteria, and increased SCFA production. GPR43 and GPR109A are critical to SCFA-mediated protection against this condition. Interventions targeting the gut microbiota warrant further investigation as a novel renoprotective therapy in diabetic nephropathy.
Identifiants
pubmed: 32358041
pii: ASN.2019101029
doi: 10.1681/ASN.2019101029
pmc: PMC7269358
doi:
Substances chimiques
Dietary Fiber
0
Fatty Acids, Volatile
0
Ffar2 protein, mouse
0
Hcar2 protein, mouse
0
Receptors, G-Protein-Coupled
0
Streptozocin
5W494URQ81
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1267-1281Informations de copyright
Copyright © 2020 by the American Society of Nephrology.
Références
PLoS One. 2014 Oct 23;9(10):e111053
pubmed: 25340336
Am J Kidney Dis. 2018 Aug;72(2):267-277
pubmed: 29866460
Gastroenterology. 2012 Oct;143(4):913-6.e7
pubmed: 22728514
Diabetes. 2012 Feb;61(2):364-71
pubmed: 22190648
Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1160-6
pubmed: 18796545
J Biol Chem. 2003 Mar 28;278(13):11312-9
pubmed: 12496283
J Am Soc Nephrol. 2015 Aug;26(8):1877-88
pubmed: 25589612
Kidney Int. 2013 Feb;83(2):308-15
pubmed: 22992469
Nat Rev Nephrol. 2018 Jul;14(7):442-456
pubmed: 29760448
Nature. 2009 Oct 29;461(7268):1282-6
pubmed: 19865172
Science. 2018 Jan 5;359(6371):97-103
pubmed: 29097493
Science. 2018 Jan 5;359(6371):91-97
pubmed: 29097494
Cell. 2016 Jun 2;165(6):1332-1345
pubmed: 27259147
Kidney Int. 2006 Jan;69(2):257-65
pubmed: 16408114
Biochem Biophys Res Commun. 2006 Jun 2;344(2):597-604
pubmed: 16630552
Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4410-5
pubmed: 23401498
J Biol Chem. 2005 Jul 22;280(29):26649-52
pubmed: 15929991
Adv Immunol. 2014;121:91-119
pubmed: 24388214
PLoS One. 2014 May 19;9(5):e97985
pubmed: 24842252
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2247-52
pubmed: 24390544
Nat Med. 2019 Jul;25(7):1096-1103
pubmed: 31263284
PLoS One. 2014 Dec 09;9(12):e114881
pubmed: 25490712
Kidney Int. 2012 Feb;81(3):300-6
pubmed: 22012132
Kidney Int. 2004 Aug;66(2):663-7
pubmed: 15253720
Science. 2017 Nov 3;358(6363):573
pubmed: 29097525
Clin J Am Soc Nephrol. 2017 Dec 7;12(12):2032-2045
pubmed: 28522654
FASEB J. 2019 Nov;33(11):11894-11908
pubmed: 31366236
Exp Clin Endocrinol Diabetes. 2017 Feb;125(2):98-105
pubmed: 28049222
J Chromatogr B Biomed Appl. 1995 Feb 17;664(2):415-20
pubmed: 7780595
Am J Nephrol. 2014;39(3):230-237
pubmed: 24643131
Gut Pathog. 2017 Oct 26;9:59
pubmed: 29090023
J Diabetes Res. 2015;2015:948417
pubmed: 25785280
Cell Rep. 2016 Jun 21;15(12):2809-24
pubmed: 27332875
Nat Commun. 2015 Apr 01;6:6734
pubmed: 25828455
Nat Immunol. 2017 May;18(5):552-562
pubmed: 28346408
J Clin Microbiol. 2005 Nov;43(11):5588-92
pubmed: 16272491
Gut. 1987 Oct;28(10):1221-7
pubmed: 3678950
PLoS One. 2012;7(4):e35240
pubmed: 22506074
Antibiot Annu. 1959-1960;7:230-5
pubmed: 13841501
J Appl Physiol. 1962 Mar;17:343-8
pubmed: 14005589
J Am Soc Nephrol. 2014 Apr;25(4):657-70
pubmed: 24231662
Br J Nutr. 2015 Jan;113 Suppl:S1-5
pubmed: 25498959
Nat Med. 2018 Apr 10;24(4):392-400
pubmed: 29634682
Kidney Int. 2015 Oct;88(4):722-33
pubmed: 26061548
Int J Clin Exp Pathol. 2014 Jan 15;7(2):481-95
pubmed: 24551269
Proc Natl Acad Sci U S A. 2013 May 28;110(22):9066-71
pubmed: 23671105
Sci Rep. 2018 May 29;8(1):8319
pubmed: 29844451
Kidney Int. 2015 Nov;88(5):958-66
pubmed: 26376131
Nature. 2016 Jun 08;534(7606):213-7
pubmed: 27279214
Transplantation. 1986 Oct;42(4):352-8
pubmed: 3094207