Effects of Propolis Supplementation on Gut Microbiota and Uremic Toxin Profiles of Patients Undergoing Hemodialysis

Toxins (Basel). 2024 Sep 25;16(10):416. doi: 10.3390/toxins16100416.

Abstract

Propolis possesses many bioactive compounds that could modulate the gut microbiota and reduce the production of uremic toxins in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This clinical trial aimed to evaluate the effects of propolis on the gut microbiota profile and uremic toxin plasma levels in HD patients. These are secondary analyses from a previous double-blind, randomized clinical study, with 42 patients divided into two groups: the placebo and propolis group received 400 mg of green propolis extract/day for eight weeks. Indole-3 acetic acid (IAA), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) plasma levels were evaluated by reversed-phase liquid chromatography, and cytokines were investigated using the multiplex assay (Bio-Plex Magpix®). The fecal microbiota composition was analyzed in a subgroup of patients (n = 6) using a commercial kit for fecal DNA extraction. The V4 region of the 16S rRNA gene was then amplified by the polymerase chain reaction (PCR) using short-read sequencing on the Illumina NovaSeq PE250 platform in a subgroup. Forty-one patients completed the study, 20 in the placebo group and 21 in the propolis group. There was a positive correlation between IAA and TNF-α (r = 0.53, p = 0.01), IL-2 (r = 0.66, p = 0.002), and between pCS and IL-7 (r = 0.46, p = 0.04) at the baseline. No significant changes were observed in the values of uremic toxins after the intervention. Despite not being significant, microbial evenness and observed richness increased following the propolis intervention. Counts of the Fusobacteria species showed a positive correlation with IS, while counts of Firmicutes, Lentisphaerae, and Proteobacteria phyla were negatively correlated with IS. Two months of propolis supplementation did not reduce the plasma levels of uremic toxins (IAA, IS, and p-CS) or change the fecal microbiota.

Keywords: CKD; chronic kidney disease; hemodialysis; microbiome; propolis; uremic toxins.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Bacteria / classification
  • Bacteria / drug effects
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Cresols
  • Cytokines / blood
  • Dietary Supplements*
  • Double-Blind Method
  • Feces* / chemistry
  • Feces* / microbiology
  • Female
  • Gastrointestinal Microbiome* / drug effects
  • Humans
  • Indican / blood
  • Indoleacetic Acids / blood
  • Male
  • Middle Aged
  • Propolis*
  • Renal Dialysis*
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / microbiology
  • Renal Insufficiency, Chronic / therapy
  • Sulfuric Acid Esters / blood
  • Uremia / blood
  • Uremia / microbiology
  • Uremia / therapy
  • Uremic Toxins* / blood

Substances

  • Propolis
  • Uremic Toxins
  • Indican
  • Indoleacetic Acids
  • 4-cresol sulfate
  • Sulfuric Acid Esters
  • indoleacetic acid
  • Cytokines
  • Cresols

Grants and funding

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Amparo e Pesquisa do Estado do Rio de Janeiro (FAPERJ). This work was financially supported by KAUST Grant BAS/1/1096-01-0 (to Prof. A. S. Rosado).