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

Key Points Increasing plant diversity (≥30 plant foods/wk) reduced symptom burden and shifted the gut microbiome toward beneficial metabolite production. Increasing plant diversity was more effective for individuals with more advanced kidney disease and higher levels of uremic toxins at baseline. Increasing plant diversity, in addition to usual diet care, resulted in a substantial reduction in potential renal acid load of 47%. Background Research suggests that eating a plant-dominant dietary pattern is beneficial to people with CKD. The aim was to investigate how increasing the diversity of plant food intake would affect metabolomic, microbiome, and clinical parameters in people with CKD. Methods 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 time points (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, BP, biochemical, and anthropometric measures. Results 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% confidence interval, −16.28 to −3.64), and compared with the LDPD, decreased total symptom burden, including constipation (95% confidence interval, −4.11 to −0.54 and −0.91 to −0.22, respectively). It also shifted the gut microbiome toward increased production of beneficial metabolites such as butyrate/isobutyrate. By contrast, the LDPD reduced microbial diversity and decreased the abundance of 27 species and 33 functional genes. Conclusions 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. Clinical Trial registry name and registration number: ACTRN12619000442101.