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

Abstract

<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> We compared the effect of a diet low in protein and high in fiber (LP-HF; <i>n</i> = 7) to that of diet rich in protein, but low in fiber (HP-LF; <i>n</i> = 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. <b><i>Results:</i></b> The LP-HF diet was associated with an increase in <i>Butyricicoccus pullicaecorum</i> 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 <i>Parabacteroides distasonis</i> (W statistic = 173), <i>Mucispirillum schaedleri</i>, and <i>Bacteroides dorei</i> (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. <b><i>Conclusion:</i></b> 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.