Dietary Protein and Fiber Affect Gut Microbiome and Treg/Th17 Commitment in Chronic Kidney Disease Mice

Abstract

Background: Patients with chronic kidney disease (CKD) have dysbiosis, dysmetabolism, and immune dysregulation. Gut microbiome plays an important role shaping the immune system which is an important modulator of CKD progression. Methods: We compared the effect of a diet low in protein and high in fiber (LP-HF; n = 7) to that of diet rich in protein, but low in fiber (HP-LF; n = 7) on gut microbiome and T-cell commitment in male CKD (Alb/TGF-β1) mice. The gut microbiomes of these mice were subjected to 16S rRNA taxonomic profiling at baseline, 6 weeks and 12 weeks of the study. Results: The LP-HF diet was associated with an increase in Butyricicoccus pullicaecorum BT, a taxon whose functions include those closely related to butyric acid synthesis (Kendall’s W statistic = 180 in analysis of microbiome composition). HP-LF diet was associated with increased abundance of two predominantly proteolytic bacterial strains related to Parabacteroides distasonis (W statistic = 173), Mucispirillum schaedleri, and Bacteroides dorei (W statistic = 192). Pathway analysis suggested that the LP-HF diet induced carbohydrate, lipid, and butyrate metabolism. As compared with HP-LF mice, LP-HF mice had 1.7-fold increase in CD4+Foxp3+Treg cells in spleen and 2.4-fold increase of these cells in peripheral blood. There was an 87% decrease in percentage of CD4+ Th17 + cells in spleen and an 85% decrease in peripheral blood, respectively, in LP-HF mice compared to the HP-LF mice. Conclusion: The LP-HF diet promotes the proliferation of saccharolytic bacteria and favors T-cell commitment toward Treg cells in a CKD mouse of model. Clinical significance of the finding needs to be further investigated.