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Abstract: FR-PO775

Short-Chain Fatty Acids Increase CD25HighCD127Low-Regulatory T-Cells in Patients with ESRD

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Meyer, Fabian, University Hospital Marien Hospital Herne, Herne, Germany
  • Stervbo, Ulrik, University Hospital Marien Hospital Herne, Herne, Germany
  • Seibert, Felix S., University Hospital Marien Hospital Herne, Herne, Germany
  • Bauer, Frederic, University Hospital Marien Hospital Herne, Herne, Germany
  • Rohn, Benjamin, Marien Hospital Herne, Herne, Germany
  • Nienen, Mikalai, University Hospital Marien Hospital Herne, Herne, Germany
  • Westhoff, Timm H., University Hospital Marien Hospital Herne, Herne, Germany
  • Babel, Nina, University Hospital Marien Hospital Herne, Herne, Germany
Background

Patients with End Stage Renal Disease (ESRD) suffer from an elevated systemic inflammation, which can lead to an increased morbidity and mortality. Previous data obtained from the EAE mouse model of MS, revealed the potential of disease amelioration by short-chain fatty acids. This clinical improvement was accompanied by increased frequency of regulatory T-cells (Treg). We hypothesized that the elevated systemic inflammation of patients with ESRD could be reduced though a dietary supplement with a short-chain fatty acid.

Methods

ESRD patients and healthy volunteers supplemented their diet with a daily dose of 2 x 500 mg propionic acid (PA) for 30 days. PBMCs were isolated at day 0, 15, and 30 of the PA supplement and 60 days later for a follow-up after PA supplementation. The baseline status and possible physiological oscillations in cell numbers were assessed through sampling at days -60, -45, and -30. We established a 12 color flow cytometry panel to quantify Tregs, and characterized them with respect to their developmental and gut homing phenotype through expression of CCR7/CD45RA and CCR9/β7 integrin, respectively. We also analyzed changes in functional activity of antigen-specific memory/effector T cells by stimulation with recall antigens. Here, we used stimulation with Tetanus/Diphteria vaccine and subsequent evaluation by 13 parameter flow cytometry.

Results

We observed a gradual and significant expansion in the frequencies of CD25highCD127low Tregs in the ESRD patients and healthy volunteers already at day 15 of PA supplementation. At day 30, an increase of 20-35% as compared to Treg baseline counts was observed in both study groups. Treg numbers returned to baseline values after discontinuation of the PA supplement. Despite significant expansion of Tregs during PA diet, the responsiveness and functionality of effector T cells remained stable as demonstrated by the stable frequencies of antigen-specific T effector cells upon ex vivo stimulation.

Conclusion

Our data revealed that dietary supplements with short-chain fatty acids might have a beneficial effect on the elevated systemic inflammation of ESRD patients. The effect can be achieved through an expansion of circulating Tregs without affecting the antigen-specific memory response.

Funding

  • Government Support - Non-U.S.