Propionate supplementation promotes the expansion of peripheral regulatory T-Cells in patients with end-stage renal disease

Abstract

Patients with end-stage renal disease (ESRD) suffer from a progressively increasing low-grade systemic inflammation, which is associated with higher morbidity and mortality. Regulatory T cells (Tregs) play an important role in regulation of the inflammatory process. Previously, it has been demonstrated that short-chain fatty acids reduce inflammation in the central nervous system in a murine model of multiple sclerosis through an increase in tissue infiltrating Tregs. Here, we evaluated the effect of the short-chain fatty acid propionate on the chronic inflammatory state and T-cell composition in ESRD patients. Analyzing ESRD patients and healthy blood donors before, during, and 60 days after the propionate supplementation by multiparametric flow cytometry we observed a gradual and significant expansion in the frequencies of CD25 high CD127 − Tregs in both groups. Phenotypic characterization suggests that polarization of naïve T cells towards Tregs is responsible for the observed expansion. In line with this, we observed a significant reduction of inflammatory marker CRP under propionate supplementation. Of interest, the observed anti-inflammatory surroundings did not affect the protective pathogen-specific immunity as demonstrated by the stable frequencies of effector/memory T cells specific for tetanus/diphtheria recall antigens. Collectively, our data suggest that dietary supplements with propionate 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 protective pathogen-reactive immunity.

The Panda-Derived Lactobacillus plantarum G201683 Alleviates the Inflammatory Response in DSS-Induced Panda Microbiota-Associated Mice

“…This matched the higher predicted abundance of fermentation-related genes in this group (but not the other two dose groups) compared to the BlankD group. The induction of propionic acid specifically in the medium dose group could account for the increased serum levels of IL-10 specifically in the medium dose group, as prior human studies have found that propionic acid treatment increased serum IL-10 levels and peripheral regulatory T cells (55,56). Thus, L. plantarum G83 supplementation may promote recovery in the DPMA mouse by promoting gut microbial changes that increase SCFA production.…”

Review: The Nutritional Management of Multiple Sclerosis With Propionate

“…T-cell maturation in the intestinal tract occurs in the gut associated lymphoid tissue (GALT) and from there cells migrate to the intraepithelial layer or lamina propria. These T-cells are (31,33,34,36), and in human studies (16,(37)(38)(39). Supplementation with propionate enhances the activity and numbers of the anti-inflammatory Treg FoxP3 + cells and reduces the activity and numbers of Th17 and to a lesser extent Th1 pro-inflammatory T-cells via histone deacetylase inhibition (25,34,(40)(41)(42).…”

Renal Sensing of Bacterial Metabolites in the Gut-kidney Axis

“…Four weeks after ceasing the treatment, all improved parameters deteriorated again, evidencing the renoprotective effect of the ongoing SCFA supplementation 85 . Finally, Meyer et al showed that propionate supplementation (participants ingested 2 × 500 mg propionic acid per day) reduces the systemic inflammation in dialysis patients with ESRD and this effect was associated with the expansion of circulating regulatory T cells 86 . Together, these data suggest that SCFAs-related treatments can become therapeutic strategies for human kidney diseases.…”