Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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) (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.

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.

Your institute does not have access to this article

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1
Fig. 2

References

  1. Turnbaugh PJ, Gordon JI. The core gut microbiome, energy balance and obesity. J Physiol. 2009;587:4153–8.

    CAS  Article  Google Scholar 

  2. Jumpertz R, Le DS, Turnbaugh PJ, Trinidad C, Bogardus C, Gordon JI, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr. 2011;94:58–65.

    CAS  Article  Google Scholar 

  3. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–31.

    Article  Google Scholar 

  4. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–4.

    CAS  Article  Google Scholar 

  5. Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488:178–84.

    CAS  Article  Google Scholar 

  6. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541–6.

    Article  Google Scholar 

  7. Wang J, Thingholm LB, Skieceviciene J, Rausch P, Kummen M, Hov JR, et al. Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nat Genet. 2016;48:1396–406.

    CAS  Article  Google Scholar 

  8. Turpin W, Espin-Garcia O, Xu W, Silverberg MS, Kevans D, Smith MI, et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat Genet. 2016;48:1413–7.

    CAS  Article  Google Scholar 

  9. Bonder MJ, Kurilshikov A, Tigchelaar EF, Mujagic Z, Imhann F, Vila AV, et al. The effect of host genetics on the gut microbiome. Nat Genet. 2016;48:1407–12.

    CAS  Article  Google Scholar 

  10. Hur KY, Lee MS. Gut microbiota and metabolic disorders. Diabetes Metab J. 2015;39:198–203.

    Article  Google Scholar 

  11. Pokusaeva K, Fitzgerald GF, van Sinderen D. Carbohydrate metabolism in Bifidobacteria. Genes Nutr. 2011;6:285–306.

    CAS  Article  Google Scholar 

  12. Sanchez B, Delgado S, Blanco-Miguez A, Lourenco A, Gueimonde M, Margolles A. Probiotics, gut microbiota, and their influence on host health and disease. Mol Nutr Food Res. 2017;61:1600240.

    Article  Google Scholar 

  13. Bersaglieri T, Sabeti PC, Patterson N, Vanderploeg T, Schaffner SF, Drake JA, et al. Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet. 2004;74:1111–20.

    CAS  Article  Google Scholar 

  14. Enattah NS, Jensen TG, Nielsen M, Lewinski R, Kuokkanen M, Rasinpera H, et al. Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture. Am J Hum Genet. 2008;82:57–72.

    CAS  Article  Google Scholar 

  15. Mathieson I, Lazaridis I, Rohland N, Mallick S, Patterson N, Roodenberg SA, et al. Genome-wide patterns of selection in 230 ancient Eurasians. Nature. 2015;528:499–503.

    CAS  Article  Google Scholar 

  16. Field Y, Boyle EA, Telis N, Gao Z, Gaulton KJ, Golan D, et al. Detection of human adaptation during the past 2000 years. Science. 2016;354:760–4.

    CAS  Article  Google Scholar 

  17. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Jarvela I. Identification of a variant associated with adult-type hypolactasia. Nat Genet. 2002;30:233–7.

    CAS  Article  Google Scholar 

  18. Manco L, Dias H, Muc M, Padez C. The lactase -13910C>T polymorphism (rs4988235) is associated with overweight/obesity and obesity-related variables in a population sample of Portuguese young adults. Eur J Clin Nutr. 2017;71:21–24.

    CAS  Article  Google Scholar 

  19. Hartwig FP, Horta BL, Smith GD, de Mola CL, Victora CG. Association of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with a systematic review and meta-analysis. Int J Epidemiol. 2016;45:1573–87.

    Article  Google Scholar 

  20. Almon R, Alvarez-Leon EE, Serra-Majem L. Association of the European lactase persistence variant (LCT-13910 C > T polymorphism) with obesity in the Canary Islands. PLoS ONE. 2012;7:e43978.

    CAS  Article  Google Scholar 

  21. Corella D, Arregui M, Coltell O, Portoles O, Guillem-Saiz P, Carrasco P, et al. Association of the LCT-13910C>T polymorphism withobesity and its modulation by dairy products in a Mediterranean population. Obesity (Silver Spring). 2011;19:1707–14.

    CAS  Article  Google Scholar 

  22. Kettunen J, Silander K, Saarela O, Amin N, Muller M, Timpson N, et al. European lactase persistence genotype shows evidence of association with increase in body mass index. Hum Mol Genet. 2010;19:1129–36.

    CAS  Article  Google Scholar 

  23. Albuquerque D, Nobrega C, Manco L. The lactase persistence -13910C>T polymorphism shows indication of association with abdominal obesity among Portuguese children. Acta Paediatr. 2013;102:e153–157.

    CAS  Article  Google Scholar 

  24. Malek AJ, Klimentidis YC, Kell KP, Fernandez JR. Associations of the lactase persistence allele and lactose intake with body composition among multiethnic children. Genes Nutr. 2013;8:487–94.

    CAS  Article  Google Scholar 

  25. Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50:2374–83.

    CAS  Article  Google Scholar 

  26. Schroeder BO, Backhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nat Med. 2016;22:1079–89.

    CAS  Article  Google Scholar 

  27. Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009;360:859–73.

    CAS  Article  Google Scholar 

  28. de Souza RJ, Bray GA, Carey VJ, Hall KD, LeBoff MS, Loria CM, et al. Effects of 4 weight-loss diets differing in fat, protein, and carbohydrate on fat mass, lean mass, visceral adipose tissue, and hepatic fat: results from the POUNDS LOST trial. Am J Clin Nutr. 2012;95:614–25.

    Article  Google Scholar 

  29. de Clercq NC, Groen AK, Romijn JA, Nieuwdorp M. Gut microbiota in obesity and undernutrition. Adv Nutr. 2016;7:1080–9.

    Article  Google Scholar 

  30. Szilagyi A, Shrier I, Heilpern D, Je J, Park S, Chong G, et al. Differential impact of lactose/lactase phenotype on colonic microflora. Can J Gastroenterol. 2010;24:373–9.

    Article  Google Scholar 

  31. Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500:585–8.

    CAS  Article  Google Scholar 

  32. Russell WR, Gratz SW, Duncan SH, Holtrop G, Ince J, Scobbie L, et al. High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr. 2011;93:1062–72.

    CAS  Article  Google Scholar 

  33. Duncan SH, Lobley GE, Holtrop G, Ince J, Johnstone AM, Louis P, et al. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes (Lond). 2008;32:1720–4.

    CAS  Article  Google Scholar 

  34. Chen J, Wang R, Li XF, Wang RL. Bifidobacterium adolescentis supplementation ameliorates visceral fat accumulation and insulin sensitivity in an experimental model of the metabolic syndrome. Br J Nutr. 2012;107:1429–34.

    CAS  Article  Google Scholar 

  35. Takahashi S, Anzawa D, Takami K, Ishizuka A, Mawatari T, Kamikado K, et al. Effect of Bifidobacterium animalis ssp. lactis GCL2505 on visceral fat accumulation in healthy Japanese adults: a randomized controlled trial. Biosci Micro Food Health. 2016;35:163–71.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

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

Funding

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lu Qi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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). https://doi.org/10.1038/s41366-018-0046-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-018-0046-9

Further reading

Search

Quick links