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



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.


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.


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) (Pinteraction < 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.


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.

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The authors thank all of the participants in the study for their dedication and contribution to the research.


The study is supported by NIH grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK078616), the Boston Obesity Nutrition Research Center (DK46200), and United States–Israel Binational Science Foundation Grant 2011036. LQ was a recipient of the American Heart Association Scientist Development Award (0730094N). YH was a recipient of a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and the Overseas Research Fellowship from the JSPS. The sponsors had no role in the design or conduct of the study.

Author contributions

YH contributed to the study concept and design, analysis and interpretation of data, drafting and revising the manuscript, statistical analysis, and study supervision. WM, DS, and YZ contributed to the analysis and interpretation of data, and drafting and revising the manuscript. CMC, GAB, and FMS contributed to acquisition of data, interpretation of data, and drafting and revising the manuscript. LQ contributed to the study concept and design, acquisition of data, analysis and interpretation of data, drafting and revising the manuscript, statistical analysis, and funding and study supervision. All authors were involved in the writing and revising of the manuscript and approved the final version of this article. LQ had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Lu Qi.

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Heianza, Y., Sun, D., Ma, W. et al. Gut-microbiome-related LCT genotype and 2-year changes in body composition and fat distribution: the POUNDS Lost Trial. Int J Obes 42, 1565–1573 (2018).

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