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 CD25highCD127− 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.
Highlights
Patients with end-stage renal disease (ESRD) frequently suffer from chronic systemic inflammation
Recognizing the crucial role of dysregulated inflammation in the pathogenesis of numerous diseases, different approaches have been applied to revert to the imbalance between pro- and anti-inflammatory mechanisms, which underlie the process of chronic inflammation [5]
While the pre-treatment phase served as control to assess the baseline levels, the propionate treatment phase was designed to assess the immune changes during 30 days of treatment with 2 × 500 mg sodium propionate per day
Summary
Patients with end-stage renal disease (ESRD) frequently suffer from chronic systemic inflammation. This is associated with reoccurring infections, protein-energy-wasting, and cardiovascular events resulting in increased mortality and morbidity [1]. The reasons for the chronic inflammation are multifactorial and encompass oxidative stress, hyperazotemia, intestinal dysbiosis, acidosis, decreased cytokine elimination, and frequent infections [3, 4]. Recognizing the crucial role of dysregulated inflammation in the pathogenesis of numerous diseases, different approaches have been applied to revert to the imbalance between pro- and anti-inflammatory mechanisms, which underlie the process of chronic inflammation [5]. A very recent study reported on a reduction of pro-inflammatory parameters under the alimentary supplementation
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