Changes in the Gut Microbiota During a Weight Loss Intervention of Daily Caloric Restriction Versus Intermittent Fasting: The DRIFT2 Randomized Clinical Trial

Abstract

Abstract Objectives Intermittent fasting (IMF) is an alternative to the standard weight loss approach of daily caloric restriction (DCR). Although altered gut microbiota has been linked to obesity and may influence weight loss, it is unknown how the gut microbiota is impacted by these weight loss strategies or its association with responsiveness. In this study, we examine the gut microbial diversity and composition during an intervention of DCR versus IMF. Methods Fecal microbiota communities were profiled by 16S rRNA gene sequencing in 59 individuals with overweight and obesity (mean BMI: 33.1 (SD: 4.4) kg/m2, age: 40.7 (SD: 9.8) years; 76.3% female) undergoing a comprehensive, group-based behavioral weight loss intervention of DCR (n = 25) versus IMF (n = 34) at baseline and 3-months into the intervention. Mixed effects linear regressions, permutational ANOVA, and ANCOM were used to examine differences in gut microbiota over time and by intervention group, and regression-based methods were used to examine the association between baseline gut microbiota and percentage change in weight and waist circumference. Results Overall, participants lost 5.9 (SD: 3.7) kilograms at 3 months. Weight loss within groups is not reported, as the trial is ongoing. Alpha diversity increased in both intervention groups (P < 0.034), with no significant differences between groups (P > 0.847). Microbiota composition (beta diversity) changed significantly (R2 = 7.1%; P = 0.001) over the course of the intervention, with no significant differences between groups (P > 0.325). Numerous taxa showed changes over time with differences between groups (FDR < 0.05). Baseline gut microbiota composition significantly predicted change in waist circumference (P = 0.009) but not in weight (P = 0.172). Conclusions Our results support that a behavioral weight loss intervention of reduced energy intake impacts gut microbiota with some differences between DCR and IMF, which may provide insight into the physiological effects of these weight loss approaches. The baseline gut microbiota was significantly associated with decrease in waist circumference. These results may inform ways to target the gut microbiota before initiating weight loss in order to improve responsiveness. Funding Sources NIH NIDDK R01; AHA Innovative Project Award.