Gut microbiota plasticity is correlated with sustained weight loss on a low-carb or low-fat dietary intervention

Abstract

While low-carbohydrate and low-fat diets can both lead to weight-loss, a substantial variability in achieved long-term outcomes exists among obese but otherwise healthy adults. We examined the hypothesis that structural differences in the gut microbiota explain a portion of variability in weight-loss using two cohorts of obese adults enrolled in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study. A total of 161 pre-diet fecal samples were sequenced from a discovery cohort (n = 66) and 106 from a validation cohort (n = 56). An additional 157 fecal samples were sequenced from the discovery cohort after 10 weeks of dietary intervention. We found no specific bacterial signatures associated with weight loss that were consistent across both cohorts. However, the gut microbiota plasticity (i.e. variability), was correlated with long-term (12-month) weight loss in a diet-dependent manner; on the low-fat diet subjects with higher pre-diet daily plasticity had higher sustained weight loss, whereas on the low-carbohydrate diet those with higher plasticity over 10 weeks of dieting had higher 12-month weight loss. Our findings suggest the potential importance of gut microbiota plasticity for sustained weight-loss. We highlight the advantages of evaluating kinetic trends and assessing reproducibility in studies of the gut microbiota.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

Pre-diet microbial community composition not correlated with weight loss success. Pre-diet fecal microbiota collected from subjects in the (a) discovery and (b) validation cohorts prior to a low-carb (left) or low-fat (right) dietary intervention. Each point represents a single fecal sample and samples corresponding to the same subject are connected forming edges or triangles. Colors indicate 12-month weight loss success: very successful (VS), >10% weight loss; moderately successful (MS), 3–10% weight loss; and unsuccessful (US), <3% weight loss. The faded background polygons show convex hulls for corresponding success categories. Principal coordinates analysis was computed with Bray-Curtis distance on inverse-hyperbolic-sine transformed counts.

Figure 2

Gut microbiota plasticity over different periods. Pairwise β-diversity is shown between daily pre-diet samples (BL v. BL), between daily samples taken 10 weeks after initiation of the dietary intervention (10wk v. 10wk), and between BL and 10-week samples (BL v. 10wk). Bray-Curtis dissimilarities are shown for low-carb (left) and low-fat (right) diets. Grey points indicate computed pairwise dissimilarities between samples; colored points correspond to the average dissimilarity for each subject and are colored by weight loss category: US – Unsuccessful, <3% weight loss; MS – Moderately successful, 3–10% weight loss; VS – Very successful, >10% weight loss. Results with other β-diversity metrics are shown in Supplementary Figs. S2 and S3. The Wilcoxon rank sum test was performed to compare the mean difference in plasticity between US and VS groups.

Figure 3

Gut microbiota plasticity correlated with dietary change in a sex- and diet-dependent manner. Spearman’s rank correlations between (a) dietary change or (b) dietary adherence and plasticity (measured as Bray-Curtis dissimiliarity) between daily pre-diet samples (BL v. BL) and between pre-diet and 10-week samples (BL v. 10wk) are shown for low-carb (left) and low-fat (right) diets. Male (purple) and female (green) subjects show opposite correlations in many cases.

Figure 4

Differences in Prevotella/Bacteroides (P/B) ratio among weight loss success groups. Subjects on the low-carb diet are shown in the left panels; those on the low-fat diet are shown in the right panels. Grey points indicate P/B ratio for individual samples; colored points correspond to the average P/B ratio for each subject. Data from the (a) discovery and (b) validation cohort are displayed by subject’s weight loss success category at 12 months after the start of the dietary intervention: US – Unsuccessful; MS – Moderately successful; VS – Very successful. P-values shown for Wilcoxon rank-sum test comparing US and VS groups.

Figure 5

Taxa differentially abundant between weight loss success groups. ASV-clusters found differentially abundant when comparing subjects that were VS compared to US at 12-month weight loss on the low-carb diet. ASV-clusters were normalized and inverse-hyperbolic-sine-transformed for variance stabilization prior to analysis; the normalized, transformed values are shown on the y-axis. ASV-clusters have a median 96.8% sequence similarity (a taxonomic description can be found in Table 2). No taxa were found differentially abundant on the low-fat diet. Grey points represent individual samples and triangles represent the mean value for each subject. Triangle color represents the average log2-fold change (logFC) between subjects in the US vs VS groups; positive values indicate higher counts in VS subjects and negative values indicate higher counts in US subjects.