Gut-microbiome related LCT genotype and 2-year changes in body composition and fat distribution: the POUNDS Lost Trial

BACKGROUND/OBJECTIVES: Gut microbiome regulates host energy metabolism and adiposity. A recent study identified a genome-wide significant variant in the lactase (LCT) gene that determines gut microbiome abundance. We investigated whether the LCT variant influenced long-term changes in adiposity among overweight and obese individuals. SUBJECTS/METHODS: We included 583 whites with LCT variant rs4988235 (G allele as Bifidobacterium-abundance-increasing allele) who were randomly assigned to 1 of 4 weight-loss diets varying in macronutrient contents. Two-year changes in adiposity measures were assessed according to the LCT genotype and weight-loss diets. RESULTS: We observed a significant interaction between the LCT genotype and dietary protein intake on changes in whole body total fat mass %, trunk fat %, superficial adipose tissue mass (SAT), visceral adipose tissue mass (VAT), and total adipose tissue mass (TAT) (P(interaction) <0.05 for all). In response to high-protein diet, carrying the G allele of LCT variant rs4988235 was associated with greater reduction of whole body total fat mass % (β [SE] –0.9 [0.43], p=0.04), trunk fat % (–1.06 [0.58], p=0.07), SAT (–0.89 [0.42], p=0.04), VAT (–0.63 [0.27], p=0.03), and TAT (–1.69 [0.76], p=0.03). Conversely, increasing numbers of the G allele tended to be related to less reduction of these outcomes in response to low-protein diet. CONCLUSIONS: Long-term improvement of body fat composition and distribution was significantly influenced by the Bifidobacterium-related LCT genotype and dietary protein intake. Overweight and obese individuals with the G allele of LCT variant rs4988235 may benefit improving adiposity by eating a low-calorie, high-protein diet.