1Background Obesity is a complex global health challenge. Although both low-carbohydrate 2 (low-carb) and low-fat diets can lead to weight loss, there is typically substantial variability 3 in weight and related outcomes for both diet approaches among obese but otherwise healthy 4 adults. Elucidating individual characteristics that might contribute to sustained weight loss is 5 critical to developing effective dietary intervention strategies. We hypothesized that structural 6 differences in the gut microbiota explained some portion of the weight loss variability among 7 people randomized to either a low-carb or low-fat diet, possibly related to its effects on dietary 8 compliance. 9 Results Our study included two staggered cohorts of obese adults enrolled in the Diet 10 Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study -11 a randomized clinical trial of either a low-fat or low-carb diet. In the discovery cohort (n=66), 12 161 pre-diet fecal samples were sequenced in addition to 157 samples collected after 10-weeks 13 of dietary intervention. In the validation cohort (n = 56), 106 pre-diet fecal samples were 14 sequenced. Pre-diet taxonomic features, such as the Prevotella/Bacteroides ratio, correlated to 15 weight loss in the discovery cohort were not confirmed in the validation cohort. The most robust 16 finding in the discovery cohort indicated that gut microbiota plasticity was linked to 12-month 17 weight loss in a diet-dependent manner; subjects with higher sustained weight loss on a low-fat 18 diet had higher pre-diet daily plasticity, whereas those most successful on the low-carb diet 19 had greater microbiota plasticity over 10 weeks of dietary intervention. Unfortunately, because 20 sample frequency and timing was quite different in the validation cohort, the relationship 21 between plasticity and weight loss could not be studied in this group. 22 Conclusions These findings suggest the potential importance of gut microbiota plasticity 23 in sustained weight loss. We highlight the importance of evaluating kinetic trends and in 24 assessing reproducibility in studies of the gut microbiota. 25 1 Background 27The global obesity pandemic has claimed one in three American adults and prevalences continue 28 to rise in many other countries as well [46]. Obesity comorbidities (e.g. cardiovascular diseases, 29 cancer, diabetes, and other chronic conditions) cost the US 8.65 billion/yr from loss of productivity 30 due to absenteeism alone [58,65,53,55,14]. The personal, social and economic costs provide an 31 urgent need for consistently effective, and possibly more personalized, weight-reduction therapies.
32Different dietary interventions, such as low-carbohydrate (low-carb) and low-fat diets, can lead 33 to weight loss, but not always; there remains substantial variability in diet success outcomes among 34 obese, but otherwise healthy, adults [37]. Additionally, adherence to dietary intervention strategies 35 has remained a major challenge, despite the clear dose-response rel...