Abstract
OBJECTIVES: Growing evidence has linked gut microbiome abundance with adiposity regulation. A recent genome-wide association study (GWAS) identified 20 genetic variants related to gut microbiome abundance. We aimed to examine whether the genetically determined gut microbiome abundance was associated with 2-year changes in adiposity and body composition among overweight and obese individuals in weight-loss diet interventions. METHODS: The study included 692 overweight and obese participants from Preventing Overweight Using Novel Dietary Strategies trial (POUNDS Lost). We created a genetic risk score (GRS) for gut microbiome abundance using 20 single nucleotide polymorphisms identified from the most recent GWAS. A higher GRS indicates a higher gut microbiome abundance. Body composition was assessed using dual-energy X-ray absorptiometry (DXA). RESULTS: We found that the gut microbiome abundance GRS was significantly associated with waist circumference and body composition during a 2-year diet intervention. Participants with a higher genetically determined gut microbiome abundance had a greater reduction in waist circumference, whole body total fat %, and trunk fat %, and greater increase in lean mass % at 2 years, after adjustment for age, race, sex, body mass index, diet intervention, and baseline values of respective outcome traits (P < 0.05 for all). Least square means comparing the extreme tertiles (T3 vs. T1) were −6.6 vs. −4.4 cm for waist circumference, −3.0 vs. −1.4 for whole-body fat %, 3.0 vs. 1.4 for lean mass %, and −3.9 vs. −1.8 for trunk fat %, respectively. CONCLUSIONS: The higher genetically determined gut microbiome abundance is related to long-term improvement of whole-body and central fatness, as well as lean body mass in response to low-calorie diet interventions. FUNDING SOURCES: The study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383), the Fogarty International Center (TW010790), and Tulane Research Centers of Excellence Awards. Xiang Li was the recipient of the American Heart Association Predoctoral Fellowship Award (19PRE34380036).