High-Diversity Plant-Based Diet and Gut Microbiome, Plasma Metabolome, and Symptoms in Adults with CKD.

Abstract

<h4>Background</h4>Research suggests that eating a plant-dominant dietary pattern is beneficial to people with chronic kidney disease (CKD). The aim was to investigate how increasing the diversity of plant food intake would impact metabolomic, microbiome and clinical parameters in people with CKD.<h4>Methods</h4>This study was a cross-over, randomized controlled trial involving 25 Australian adults diagnosed with stage 3-4 CKD. Participants were randomly allocated to follow two diets for 6 weeks each, separated by a minimum 4-week washout period: a high-diversity plant-based diet (HDPD, ≥30 unique plant foods weekly) and a low-diversity plant-based diet (LDPD, ≤15 unique plant foods weekly), alongside a usual kidney diet prescription. Data collection was completed at four timepoints (beginning and end of each intervention period). Primary outcome included a change in uremic toxins (indoxyl sulfate and p-Cresyl sulfate) concentrations. Secondary and exploratory outcomes included diet quality and nutritional status, fecal microbiome composition and diversity, plasma metabolome, symptom burden, quality of life scores, blood pressure, biochemical and anthropometric measures.<h4>Results</h4>Plasma and urinary uremic toxin levels did not consistently decrease across the cohort; however, significant reductions were observed in responders to the HDPD, particularly those with poorer kidney function and higher baseline uremic toxin levels. Neither diet caused electrolyte imbalances. The HDPD significantly improved diet quality, reduced potential renal acid load by an average of 47% from baseline, with an estimated marginal mean reduction of 9.96 (95% CI: -16.28 to -3.64), and compared to the LDPD, decreased total symptom burden, including constipation (95% CI: -4.11 to -0.54 and -0.91 to -0.22, respectively). It also shifted the gut microbiome toward increased production of beneficial metabolites like butyrate/isobutyrate. In contrast, the LDPD reduced microbial diversity and decreased the abundance of 27 species and 33 functional genes.<h4>Conclusions</h4>This study demonstrated the safety and clinically relevant therapeutic benefits of aiming to incorporate 30 or more unique plant foods weekly in the diet of individuals with moderate CKD. It was observed that individuals with more advanced kidney disease and higher levels of uremic toxins may derive the greatest benefit from adopting a HDPD.<h4>Trial registration</h4>ACTRN12619000442101.