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

Abstract

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 one of four 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.

Figure 1

Two-year changes in body composition and body fat distribution according to the LCT rs4988235 genotype and low- or high- protein diet White bars, AA genotype; gray bars, AG genotype; black bars, GG genotype. Data are means ± SE values (error bars) after adjustment for age, sex, body mass index and value for the respective outcome traits at the baseline examination. Abbreviation: DSAT, deep subcutaneous adipose tissue mass; SAT, superficial adipose tissue mass; VAT, visceral adipose tissue mass; TAT, total adipose tissue mass.

Figure 2

Trajectories of changes in body fat distribution according to LCT rs4988235 genotype in response to low- or high-protein diet over 2 years Dotted line, AA genotype; gray line, AG genotype; black line, GG genotype. Data are means ± SE values (error bars) after adjustment for age, sex, body mass index at the baseline examination and value for the respective outcome traits at the baseline examination. Abbreviation: DSAT, deep subcutaneous adipose tissue mass; SAT, superficial adipose tissue mass; VAT, visceral adipose tissue mass; TAT, total adipose tissue mass. P_{time×genotype-interaction}=0.08 (panel A); P_{time×genotype-interaction}=0.39 (panel B); P_{time×genotype-interaction}= 0.008 (panel C); P_{time×genotype-interaction}= 0.03 (panel D); P_{time×genotype-interaction}= 0.32 (panel E); P_{time×genotype-interaction}= 0.01 (panel F); P_{time×genotype-interaction}= 0.01 (panel G); P_{time×genotype-interaction}= 0.02 (panel H).