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.

Keywords: Chronic kidney disease; High-fiber diet; Immunity; Low-protein diet; Microbiome.

Conflict of interest statement

Conflict of Interest statement

We certify that the submission is original work and is not published previously, in whole or part, or is under review at any other publication. The authors have no conflicts of interest to declare.

© 2022 S. Karger AG, Basel.

Figures

Fig 1.

a db-RDA analysis shows the composition of the microbiomes and the relative abundance of taxa impacted by two factors, i.e., the diet and time of sample collection. Microbiomes with the HP-LF and LP-HF diets are color-coded by red and green, respectively. Each blue dot represents a taxon. The position of a taxon at bottom left on the db-RDA plot indicates that this taxon is enriched in the mice with the time after treatment and with the LP-HF diet. ANCOM analysis, to identify the relative abundance difference associated with diet with the results adjusted by the impact of the time. The significance and degree of the relative abundance changes were e quantified by the W statistic value and CLR mean difference, respectively. The names of taxa with a W statistic value higher than 0.7 are shown. Structural zeros represent taxa that are not detected in microbiomes with a certain diet. Pathway distribution differences in HP-LFr and LP-HF diets. The PRCRUSt algorithm [20] provided a provisional list of pathways and functions associated with each of the microbiome profiles. A Linear discriminant analysis Effect Size (LEfSe) analysis generated the differential expression of the samples taken from mice at 12 weeks. b Flow cytometry analysis of Th17 and Treg cell frequency in spleen and peripheral blood of mice after 12 weeks of LPHF or HPLF diet. Compared to mice on a HF-LP diet, mice on a LF-HP diet had a significantly higher percentage of Th17 cells in blood and spleen and a lower percentage of Treg cells in blood and spleen. (p<0.01)