Session Time: 4:30pm-6:00pm
Presentation Time: 4:42pm-4:54pm
Location: Room 310
*Purpose: To investigate the impact of high fibre (HF) diet or dietary supplementation with the short chain fatty acid (SCFA) sodium acetate (SA) on kidney allograft rejection in a murine model of kidney transplantation
*Methods: Kidney transplants were performed from BALB/c to C57BL/6 mice as allografts. Allograft mice were fed a HF diet for 2 weeks prior and throughout experiments (WT+HF), or received SA 200mg/kg IP for 14 days post-transplantation then SA 150mM solution orally (WT+SA; GPR43-/-+SA). Allograft controls received normal chow only (WT+NC). Gut microbiota composition was assessed by 16S rRNA sequencing.
*Results: WT+HF allografts had prolonged survival compared to WT+NC allografts (Fig.1 p<0.01), and were protected from acute (day 14: lower creatinine (p<0.01), less tubulitis (p<0.001)) and chronic (day 100: lower creatinine (p<0.05) and less proteinuria (p<0.01) and glomerulosclerosis (p<0.001)) rejection. Transplantation led to dysbiosis in WT+NC mice, with a loss of normal gut microbial diversity at day 14, but not in WT+HF mice where microbial diversity was enhanced (Fig. 2, p<0.01). Clostridiales species (p<0.0001), known to produce SCFAs and to promote Treg development, and Bifidobacterium (p<0.05), known to produce SA, were both increased post-transplant in WT+HF mice yet diminished in WT+NC. In mechanistic experiments, WT+SA allografts exhibited superior survival to WT controls (p<0.05), were protected from rejection and exhibited donor specific tolerance, confirmed by acceptance of donor strain but rejection of 3rd party skin grafts (p<0.01). The survival benefit conferred by SA was broken by depletion of CD25+ Tregs by using anti-CD25mAb, and SA was ineffective in GPR43-/- allograft recipients (p<0.05).
*Conclusions: HF diet prevented transplant-associated dysbiosis and afforded protection against allograft rejection. Protection was mediated, at least in part, by SCFAs and was dependent on a CD4+CD25+Foxp3+ regulatory mechanism and signalling via GPR43. Dietary manipulation of the microbiome warrants evaluation in human transplantation.
To cite this abstract in AMA style:Singer JJ, Wu H, Kwan T, Loh Y, Wang C, Tan J, Macia L, Alexander S, Chadban S. High Fibre Diet Prevents Transplant-Associated Dysbiosis and Prevents Kidney Allograft Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/high-fibre-diet-prevents-transplant-associated-dysbiosis-and-prevents-kidney-allograft-rejection/. Accessed May 27, 2020.
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