Gut Microbial Metabolites Induce Donor-Specific Tolerance of Kidney Allografts through Induction of T Regulatory Cells by Short-Chain Fatty Acids.
Acute Disease
Allografts
/ immunology
Animals
Butyric Acid
/ pharmacology
Chronic Disease
Dietary Fiber
/ administration & dosage
Dietary Supplements
Dysbiosis
/ etiology
Fatty Acids, Volatile
/ immunology
Gastrointestinal Microbiome
/ drug effects
Graft Rejection
/ pathology
Graft Survival
/ drug effects
Immune Tolerance
/ drug effects
Kidney Transplantation
/ adverse effects
Lymphocyte Activation
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Receptors, G-Protein-Coupled
/ genetics
Sodium Acetate
/ pharmacology
T-Lymphocytes, Regulatory
acute allograft rejection
chronic allograft rejection
immunology
tolerance
transplantation
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:
07 2020
07 2020
Historique:
received:
28
08
2019
accepted:
22
03
2020
pubmed:
3
6
2020
medline:
25
2
2021
entrez:
3
6
2020
Statut:
ppublish
Résumé
Short-chain fatty acids derived from gut microbial fermentation of dietary fiber have been shown to suppress autoimmunity through mechanisms that include enhanced regulation by T regulatory cells (Tregs). Using a murine kidney transplantation model, we examined the effects on alloimmunity of a high-fiber diet or supplementation with the short-chain fatty acid acetate. Kidney transplants were performed from BALB/c(H2 Wild-type mice fed normal chow exhibited dysbiosis after receiving a kidney allograft but not an isograft, despite the avoidance of antibiotics and immunosuppression for the latter. A high-fiber diet prevented dysbiosis in allograft recipients, who demonstrated prolonged survival and reduced evidence of rejection compared with mice fed normal chow. Allograft mice receiving supplemental sodium acetate exhibited similar protection from rejection, and subsequently demonstrated donor-specific tolerance. Depletion of CD25 Manipulation of the microbiome by a high-fiber diet or supplementation with sodium acetate modified alloimmunity in a kidney transplant model, generating tolerance dependent on Tregs and GPR43. Diet-based therapy to induce changes in the gut microbiome can alter systemic alloimmunity in mice, in part through the production of short-chain fatty acids leading to Treg cell development, and merits study as a potential clinical strategy to facilitate transplant acceptance.
Sections du résumé
BACKGROUND
Short-chain fatty acids derived from gut microbial fermentation of dietary fiber have been shown to suppress autoimmunity through mechanisms that include enhanced regulation by T regulatory cells (Tregs).
METHODS
Using a murine kidney transplantation model, we examined the effects on alloimmunity of a high-fiber diet or supplementation with the short-chain fatty acid acetate. Kidney transplants were performed from BALB/c(H2
RESULTS
Wild-type mice fed normal chow exhibited dysbiosis after receiving a kidney allograft but not an isograft, despite the avoidance of antibiotics and immunosuppression for the latter. A high-fiber diet prevented dysbiosis in allograft recipients, who demonstrated prolonged survival and reduced evidence of rejection compared with mice fed normal chow. Allograft mice receiving supplemental sodium acetate exhibited similar protection from rejection, and subsequently demonstrated donor-specific tolerance. Depletion of CD25
CONCLUSIONS
Manipulation of the microbiome by a high-fiber diet or supplementation with sodium acetate modified alloimmunity in a kidney transplant model, generating tolerance dependent on Tregs and GPR43. Diet-based therapy to induce changes in the gut microbiome can alter systemic alloimmunity in mice, in part through the production of short-chain fatty acids leading to Treg cell development, and merits study as a potential clinical strategy to facilitate transplant acceptance.
Identifiants
pubmed: 32482686
pii: ASN.2019080852
doi: 10.1681/ASN.2019080852
pmc: PMC7350991
doi:
Substances chimiques
Dietary Fiber
0
Fatty Acids, Volatile
0
Ffar2 protein, mouse
0
Receptors, G-Protein-Coupled
0
Butyric Acid
107-92-6
Sodium Acetate
4550K0SC9B
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1445-1461Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 by the American Society of Nephrology.
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