Extended Data Fig. 7: Effects of peptide treatment on bacterial composition and richness over time.

a, Comparative effects of cyclic D,L-α-peptide-mediated remodeling of gut microbiota in LDLr^−/− mice over the course of a 10-wk study. The time course analysis shows the number of genera in feces samples that were significantly changed in abundance relative to vehicle treatment at the timepoint indicated (n = 7 animals for all groups). The two peptides initially targeted different bacterial genera (out of 50 total genera that were significantly changed in abundance by treatment with the two peptides [adjusted p-value < 0.1, as determined by a hypergeometric test], only four genera were affected in common by both peptides after 2-wk peptide treatments). Over the course of the study, the remodeled gut microbiome community induced by peptide treatments became more similar (after 10-wk treatment, 15 bacterial genera were inhibited in common out of 39 total genera affected by the peptides). b, Effect of peptide treatment on richness (Chao1 index) of gut microbiota from WD-fed LDLr^−/− mice (n = 7 animals for all groups). Samples were taken from feces after a 2-wk treatment period. The scatter plot is shown with mean ± SD. p values were determined by ANOVA. c, Peptide treatment shifted the ratio of Bacteroidetes to Firmicutes in feces of WD-fed mice toward that of the CHD-fed controls over the time periods shown. Scatter plots are shown with mean. p values were determined by two-tailed Student’s t-test. n = 5 per group. d, Principal-component analysis of genera abundance for CHD-fed mice and for WD-fed mice treated with peptides or vehicle (n = 6 animals each for CHD and WD groups; n = 8 animals each for c[wLwReQeR] and c[wLwKhShK] groups, data shown for 10-wk timepoint). e, Principal-component analysis of genera abundance for WD/vehicle and CHD/vehicle mice after 2-wk and 10-wk (n = 6 per group).