Background: 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.

Gut dysbiosis, characterized by an imbalance in the gut microbiota, has emerged as a potential factor influencing CKD progression. This condition plays a crucial role in the gut-kidney axis, where changes in microbial composition can contribute to systemic inflammation and uremic toxin production and ultimately exacerbate kidney damage. Understanding the dynamics of the gut-kidney axis provides new insights into potential therapeutic strategies to mitigate CKD progression. Diet is the primary driver of gut microbiota composition. Therefore, an approach emphasizing healthy nutritional patterns is recommended for improving overall health, cardiovascular disease, and profoundly altered metabolic patterns in patients with CKD. Dietary modifications have been explored as therapeutic strategies targeting the microbiome to improve outcomes in CKD. An emerging therapeutic target is the production of dysmetabolites by the gut microbiota, which may help alleviate uremic and cardiovascular toxicity. In addition, future research should broaden the scope to include other microorganisms, such as fungi, archaea, and viruses. This expanded focus will enable a more comprehensive understanding of the gut-kidney axis and pave the way for more personalized and effective treatment strategies for patients with CKD. This review explores the role of lifestyle, particularly diet, in kidney health; highlights new gut microbiome therapies; and identifies research opportunities in CKD.