PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) comprised a multi-centre, 3-year lifestyle intervention in overweight adults with pre-diabetes conducted in 8 countries, that aimed to decrease the incidence of T2D. In the present study, we study the gut microbiota from a subset of participants who followed an 8-week total meal replacement low-energy diet (LED) in the PREVIEW trial, from Finland and New Zealand (N=211), by Illumina sequencing of the 16S rRNA gene. We aimed to track changes in the composition and function of the gut microbiota during LED-induced weight loss, and to determine whether baseline microbiota configuration is associated with host metabolic response to the LED.

BackgroundRecent small-scale studies suggest that low energy diets (LEDs) are associated with marked changes in the gut microbiota. The gut microbiota may also modify the effect of LED on host metabolism and weight loss. We investigated how the gut microbiota changed during 8 weeks of LED and whether these changes were associated with host response in a sub-study of 211 overweight adults with pre-diabetes participating in the large multicentre PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and aroundthe World) clinical trial. Results Based on 16S rRNA gene amplicon sequencing data, the composition of the gut microbiota changed markedly from pre- to post-LED (P=0.001), along with increased richness and diversity (both P<0.001). Following the intervention, the relative abundance of several genera previously associated with metabolic improvements (e.g. Akkermansia and Christensenellaceae R-7 group) was significantly increased (P<0.001), while flagellated Pseudobutyrivibrio, some other butyrate-producing genera but also the acetogenic Blautia were decreased (all P<0.001), as well as Bifidobacterium spp. (P<0.001). The changes in microbiota composition and predicted functions were significantly associated with body weight loss (P<0.05). The baseline gut microbiota features were able to explain ~25% of variation in total body fat change (post-pre LED).ConclusionsThe gut microbiota and individual taxa were significantly influenced by the LED intervention and correlated with changes in total body fat and body weight in individuals with overweight and pre-diabetes. Despite inter-individual variation, the baseline gut microbiota was a strong predictor of total body fat change during the energy restriction period.