Extended Data Fig. 4: Replication microbiome transplantation experiments.
From: Caloric restriction disrupts the microbiota and colonization resistance
a, Replication of experiment with transplantation of stool samples from five participants who lost most weight during conventional diet demonstrates significant differences in body weight between mice that received pre-diet and post-diet samples (Fig. 2b); there are no significant differences in body fat (b) or food consumption (c; npre-diet = 7, npost-diet = 8 mice, LMM). Each point in c represents the measurement for a single mouse on a single day. d, Transplantation of pooled faecal samples from five participants who lost most weight during VLCD reveals significantly more weight loss in post-diet sample recipient mice (LMM). e, f, Post-diet recipient mice also show a trend towards reduced body fat (e) and improved OGTT (f; P = 0.18 and P = 0.43 respectively, two-sided Mann–Whitney U test). In d–f, npre-diet = 5, npost-diet = 6 mice. g, Food intake was not significantly different between pre- and post-diet recipient mice over time or between groups (P = 0.70, LMM npost-diet = 6, npre-diet = 5 mice measured over 16 time points as in d). h, i, Transplantation of pooled faecal samples from the median four weight losers revealed a small but significant effect on weight gain in recipient mice (h; LMM, npre-diet = 13, npost-diet = 12 mice per time point) with an associated reduction in body fat as measured by epididymal fat pad weight (i; P = 0.036, one-tailed Welch’s t-test). j, This cohort showed no significant differences in OGTT results (AUC, P = 0.650, two-sided Mann–Whitney U test). Data shown as mean ± s.e.m. where relevant. TcdA/B ELISA demonstrates a lack of stable C. difficile colonization in k (CONVD) and l (VLCD) replication experiments (ELISA reactions shown for individual animals at days 4 and 20 after colonization, respectively). LMM with participant as random effect and Tukey two-sided all-pair comparison unless otherwise noted. In boxplots: centre line, median; box, first and third quartiles; whiskers, 1.5× interquartile range (IQR) with outliers individually plotted.
