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.

  • Pediatric Original Article
  • Published:

The intestinal microbiota composition and weight development in children: the KOALA Birth Cohort Study

International Journal of Obesity volume 39, pages 16–25 (2015)Cite this article

Subjects

Abstract

Objective:

To investigate whether the intestinal microbiota composition in early infancy is associated with subsequent weight development in children.

Methods:

Analyses were conducted within the KOALA Birth Cohort Study (n=2834). This cohort originates from two recruitments groups: pregnant women with a conventional lifestyle (no selection based on lifestyle) and pregnant women recruited through alternative channels (organic shops, anthroposophic clinicians/midwives, Steiner schools and relevant magazines). From 909 one-month-old infants, fecal samples were collected and analyzed by quantitative PCR targeting bifidobacteria, Bacteroides fragilis group, Clostridium difficile, Escherichia coli, Lactobacilli and total bacteria counts. Between the ages of 1 and 10 years, parent-reported weight and height was collected at 7 time points. Age- and gender-standardized body mass index (BMI) z-scores were calculated. Data were analyzed using generalized estimating equation.

Results:

Colonization with B. fragilis group was borderline significantly associated with a higher BMI z-score of 0.15 (95% confidence interval (CI): −0.02 to 0.31), in the conventional subcohort. After stratification for fiber intake (Pforinteraction=0.003), colonization with B. fragilis group was associated with a 0.34 higher BMI z-score among children with a low-fiber intake in this subcohort (95% CI: 0.17–0.53). Higher counts among colonized children were positively associated with BMI z-score only in children within the conventional subcohort and a high-fiber diet (BMI z-score 0.08; 95% CI: 0.01–0.14), but inversely associated in children with a low-fiber diet (BMI z-score −0.05; 95% CI: −0.10 to 0.00), and in children recruited through alternative channels (BMI z-score −0.10; 95% CI: −0.17 to −0.03). The other bacteria were not associated with BMI z-scores, regardless of subcohort.

Conclusion:

Using a targeted approach, we conclude that the intestinal microbiota, particularly the B. fragilis group, is associated with childhood weight development. To identify the potential impact of additional bacterial taxa, further prospective studies applying an unconstrained in-depth characterization of the microbiota are needed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Bastien M, Poirier P, Lemieux I, Despres JP . Overview of epidemiology and contribution of obesity to cardiovascular disease. Prog Cardiovasc Dis 2014; 56: 369–381.

    Article  Google Scholar 

  2. Lakshman R, Elks CE, Ong KK . Childhood obesity. Circulation 2012; 126: 1770–1779.

    Article  Google Scholar 

  3. Schonbeck Y, Talma H, van Dommelen P, Bakker B, Buitendijk SE, Hirasing RA et al. Increase in prevalence of overweight in Dutch children and adolescents: a comparison of nationwide growth studies in 1980, 1997 and 2009. PLoS One 2011; 6 e27608.

    Article  Google Scholar 

  4. Raoult D . Obesity pandemics and the modification of digestive bacterial flora. Eur J Clin Microbiol Infect Dis 2008; 27: 631–634.

    Article  CAS  Google Scholar 

  5. Farooqi S, O’Rahilly S . Genetics of obesity in humans. Endocr Rev 2006; 27: 710–718.

    Article  CAS  Google Scholar 

  6. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 2006; 118: 511–521.

    Article  Google Scholar 

  7. Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI . Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 2005; 102: 11070–11075.

    Article  CAS  Google Scholar 

  8. 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: 1027–1031.

    Article  Google Scholar 

  9. Ley RE, Turnbaugh PJ, Klein S, Gordon JI . Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444: 1022–1023.

    Article  CAS  Google Scholar 

  10. Armougom F, Henry M, Vialettes B, Raccah D, Raoult D . Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS One 2009; 4: e7125.

    Article  Google Scholar 

  11. 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: 480–484.

    Article  CAS  Google Scholar 

  12. Zuo HJ, Xie ZM, Zhang WW, Li YR, Wang W, Ding XB et al. Gut bacteria alteration in obese people and its relationship with gene polymorphism. World J Gastroenterol 2011; 17: 1076–1081.

    Article  CAS  Google Scholar 

  13. Nadal I, Santacruz A, Marcos A, Warnberg J, Garagorri M, Moreno LA et al. Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents. Int J Obes 2009; 33: 758–767.

    Article  CAS  Google Scholar 

  14. Xu P, Li M, Zhang J, Zhang T . Correlation of intestinal microbiota with overweight and obesity in Kazakh school children. BMC Microbiol 2012; 12: 283.

    Article  Google Scholar 

  15. Schwiertz A, Taras D, Schafer K, Beijer S, Bos NA, Donus C et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 2010; 18: 190–195.

    Article  Google Scholar 

  16. Abdallah Ismail N, Ragab SH, Abd Elbaky A, Shoeib AR, Alhosary Y, Fekry D . Frequency of Firmicutes and Bacteroidetes in gut microbiota in obese and normal weight Egyptian children and adults. Arch Med Sci 2011; 7: 501–507.

    Article  Google Scholar 

  17. Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA 2009; 106: 2365–2370.

    Article  CAS  Google Scholar 

  18. Balamurugan R, George G, Kabeerdoss J, Hepsiba J, Chandragunasekaran AM, Ramakrishna BS . Quantitative differences in intestinal Faecalibacterium prausnitzii in obese Indian children. Br J Nutri 2010; 103: 335–338.

    Article  CAS  Google Scholar 

  19. 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 2008; 32: 1720–1724.

    Article  CAS  Google Scholar 

  20. Mai V, McCrary QM, Sinha R, Glei M . Associations between dietary habits and body mass index with gut microbiota composition and fecal water genotoxicity: an observational study in African American and Caucasian American volunteers. Nutr J 2009; 8.

  21. Karlsson CL, Onnerfalt J, Xu J, Molin G, Ahrne S, Thorngren-Jerneck K . The microbiota of the gut in preschool children with normal and excessive body weight. Obesity 2012; 20: 2257–2261.

    Article  Google Scholar 

  22. Bervoets L, Van Hoorenbeeck K, Kortleven I, Van Noten C, Hens N, Vael C et al. Differences in gut microbiota composition between obese and lean children: a cross-sectional study. Gut Pathog 2013; 5: 10.

    Article  Google Scholar 

  23. Million M, Maraninchi M, Henry M, Armougom F, Richet H, Carrieri P et al. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes 2012; 36: 817–825.

    Article  CAS  Google Scholar 

  24. Collado MC, Isolauri E, Laitinen K, Salminen S . Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr 2008; 88: 894–899.

    Article  CAS  Google Scholar 

  25. Santacruz A, Marcos A, Warnberg J, Marti A, Martin-Matillas M, Campoy C et al. Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity (Silver Spring) 2009; 17: 1906–1915.

    Article  Google Scholar 

  26. Kalliomäki M, Collado MC, Salminen S, Isolauri E . Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr 2008; 87: 534–538.

    Article  Google Scholar 

  27. Luoto R, Kalliomaki M, Laitinen K, Delzenne NM, Cani PD, Salminen S et al. Initial dietary and microbiological environments deviate in normal-weight compared to overweight children at 10 years of age. J Pediatr Gastroenterol Nutr 2011; 52: 90–95.

    Article  Google Scholar 

  28. Vael C, Verhulst SL, Nelen V, Goossens H, Desager KN . Intestinal microflora and body mass index during the first three years of life: an observational study. Gut Pathog 2011; 3: 8.

    Article  Google Scholar 

  29. White RA, Bjornholt JV, Baird DD, Midtvedt T, Harris JR, Pagano M et al. Novel developmental analyses identify longitudinal patterns of early gut microbiota that affect infant growth. PLoS Comput Biol 2013; 9: e1003042.

    Article  CAS  Google Scholar 

  30. Diamant M, Blaak EE, de Vos WM . Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes? Obes Rev 2011; 12: 272–281.

    Article  CAS  Google Scholar 

  31. Tremaroli V, Bäckhed F . Functional interactions between the gut microbiota and host metabolism. Nature 2012; 489: 242–249.

    Article  CAS  Google Scholar 

  32. Samuel BS, Shaito A, Motoike T, Rey FE, Bäckhed F, Manchester JK et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA 2008; 105: 16767–16772.

    Article  CAS  Google Scholar 

  33. Xiong Y, Miyamoto N, Shibata K, Valasek MA, Motoike T, Kedzierski RM et al. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci USA 2004; 101: 1045–1050.

    Article  CAS  Google Scholar 

  34. Kummeling I, Thijs C, Penders J, Snijders BEP, Stelma F, Reimerink J et al. Etiology of atopy in infancy: the KOALA Birth Cohort Study. Pediatr Allergy Immunol 2005; 16: 679–684.

    Article  Google Scholar 

  35. Bastiaanssen JM, de Bie RA, Bastiaenen CH, Heuts A, Kroese ME, Essed GG et al. Etiology and prognosis of pregnancy-related pelvic girdle pain; design of a longitudinal study. BMC Public Health 2005; 5: 1.

    Article  Google Scholar 

  36. Ott SJ, Musfeldt M, Ullmann U, Hampe J, Schreiber S . Quantification of intestinal bacterial populations by real-time PCR with a universal primer set and minor groove binder probes: a global approach to the enteric flora. J Clin Microbiol 2004; 42: 2566–2572.

    Article  CAS  Google Scholar 

  37. Rinttila T, Kassinen A, Malinen E, Krogius L, Palva A . Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR. J Appl Microbiol 2004; 97: 1166–1177.

    Article  CAS  Google Scholar 

  38. Nadkarni MA, Martin FE, Jacques NA, Hunter N . Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set. Microbiology 2002; 148: 257–266.

    Article  CAS  Google Scholar 

  39. Kwaliteitsinstituut voor Gezondheidszorg CBO. Diagnostiek en behandeling van obesitas bij volwassenen en kinderen, 2008.

  40. Dutman AE, Stafleu A, Kruizinga A, Brants HA, Westerterp KR, Kistemaker C et al. Validation of an FFQ and options for data processing using the doubly labelled water method in children. Public Health Nutr 2011; 14: 410–417.

    Article  Google Scholar 

  41. Stichting Nederlands Voedingsstoffenbestand. Nederlands voedingsstoffenbestad 2001 (Netherlands Food Composition Table 2001) 2001.

  42. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 2004; 101: 15718–15723.

    Article  Google Scholar 

  43. Singer MR, Moore LL, Garrahie EJ, Ellison RC . The tracking of nutrient intake in young children: the Framingham Children’s Study. Am J Public Health 1995; 85: 1673–1677.

    Article  CAS  Google Scholar 

  44. Bjelland M, Brantsaeter AL, Haugen M, Meltzer HM, Nystad W, Andersen LF . Changes and tracking of fruit, vegetables and sugar-sweetened beverages intake from 18 months to 7 years in the Norwegian Mother and Child Cohort Study. BMC Public Health 2013; 13: 793.

    Article  Google Scholar 

  45. Kallus SJ, Brandt LJ . The intestinal microbiota and obesity. J Clin Gastroenterol 2012; 46: 16–24.

    Article  Google Scholar 

  46. Azad MB, Konya T, Maughan H, Guttman DS, Field CJ, Chari RS et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ 2013; 185: 385–394.

    Article  Google Scholar 

  47. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO . Development of the human infant intestinal microbiota. PLoS Biol 2007; 5: 1556–1573.

    Article  CAS  Google Scholar 

  48. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M et al. Diversity of the human intestinal microbial flora. Science 2005 308 1635–1638.

    Article  Google Scholar 

  49. Rousseau C, Levenez F, Fouqueray C, Dore J, Collignon A, Lepage P . Clostridium difficile colonization in early infancy is accompanied by changes in intestinal microbiota composition. J Clin Microbiol 2011; 49: 858–865.

    Article  CAS  Google Scholar 

  50. Cardona S, Eck A, Cassellas M, Gallart M, Alastrue C, Dore J et al. Storage conditions of intestinal microbiota matter in metagenomic analysis. BMC Microbiol 2012; 12: 158.

    Article  CAS  Google Scholar 

  51. Spencer EA, Appleby PN, Davey GK, Key TJ . Validity of self-reported height and weight in 4808 EPIC-Oxford participants. Public Health Nutr 2002; 5: 561–565.

    Article  Google Scholar 

  52. Nyholm M, Gullberg B, Merlo J, Lundqvist-Persson C, Rastam L, Lindblad U . The validity of obesity based on self-reported weight and height: implications for population studies. Obesity (Silver Spring) 2007; 15: 197–208.

    Article  Google Scholar 

  53. Scholtens S, Brunekreef B, Visscher TL, Smit HA, Kerkhof M, de Jongste JC et al. Reported versus measured body weight and height of 4-year-old children and the prevalence of overweight. Eur J Public Health 2007; 17: 369–374.

    Article  Google Scholar 

  54. Shields M, Connor Gorber S, Janssen I, Tremblay MS . Obesity estimates for children based on parent-reported versus direct measures. Health Rep 2011; 22: 47–58.

    PubMed  Google Scholar 

  55. Timmermans SH, Mommers M, Gubbels JS, Kremers SP, Stafleu A, Stehouwer CD et al. Maternal smoking during pregnancy and childhood overweight and fat distribution: the KOALA Birth Cohort Study. Pediatr Obes 2013.

  56. Singh AS, Mulder C, Twisk JW, van Mechelen W, Chinapaw MJ . Tracking of childhood overweight into adulthood: a systematic review of the literature. Obes Rev 2008; 9: 474–488.

    Article  CAS  Google Scholar 

  57. Baker JL, Olsen LW, Sorensen TI . Childhood body-mass index and the risk of coronary heart disease in adulthood. N Engl J Med 2007; 357: 2329–2337.

    Article  CAS  Google Scholar 

  58. Ford AL, Hunt LP, Cooper A, Shield JP . What reduction in BMI SDS is required in obese adolescents to improve body composition and cardiometabolic health? Arch Dis Child 2010; 95: 256–261.

    Article  Google Scholar 

  59. Reinehr T, de Sousa G, Toschke AM, Andler W . Long-term follow-up of cardiovascular disease risk factors in children after an obesity intervention. Am J Clin Nutr 2006; 84: 490–496.

    Article  CAS  Google Scholar 

  60. Santacruz A, Collado MC, García-Valdés L, Segura MT, Martín-Lagos JA, Anjos T et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr 2010; 104: 83–92.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to the children and parents who participated in the KOALA Birth Cohort Study. The following sponsors contributed to data collection for the present study: Netherlands Organisation for Health Research and Development (ZonMw Grant No. 2100.0090), Netherlands Asthma Foundation (Grants No. 3.2.03.48 and No. 3.2.07.022), Netherlands Heart Foundation (Grant No. 2008B112), Triodos Foundation, Phoenix Foundation, Raphaël Foundation, Iona Foundation, Foundation for the Advancement of Heilpedagogiek, Royal Friesland Foods (currently FrieslandCampina); Netherlands Sugar Foundation and the Ministry of Economic affairs, all in The Netherlands. The sponsors had no influence on the analysis and reporting of the present study.

Author Contributions

LEJM Scheepers performed the literature search, carried out the statistical analyses, wrote the manuscript with the help of J Penders and ICW Arts and approved the final manuscript as submitted; J Penders contributed to the design of the study and collection of the data, performed the literature search, interpreted the data, contributed to the writing of the manuscript, critically reviewed and revised the manuscript and approved the final manuscript as submitted; C Mbakwa Akwi contributed to the analyses and interpretation of the data, reviewed and revised the manuscript and approved the final manuscript as submitted; C Thijs was the principal investigator and was responsible for the design and conduct of the study, contributed to the collection of the data, critically reviewed the manuscript and approved the final manuscript as submitted; M Mommers contributed to the design of the study and collection of the data, critically reviewed and revised the manuscript and approved the final manuscript as submitted; ICW Arts performed the literature search, interpreted the data, contributed to the writing of the manuscript, critically reviewed and revised the manuscript and approved the final manuscript as submitted.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Maastricht University, CAPHRI School for Public Health and Primary Care, Maastricht, The Netherlands

    L E J M Scheepers, J Penders, C A Mbakwa, C Thijs, M Mommers & I C W Arts

  2. Department of Medical Microbiology, Maastricht University Medical Centre, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht, The Netherlands

    J Penders

  3. Department of Epidemiology, Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht, The Netherlands

    I C W Arts

Authors
  1. L E J M Scheepers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Penders
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C A Mbakwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Thijs
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Mommers
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I C W Arts
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L E J M Scheepers.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scheepers, L., Penders, J., Mbakwa, C. et al. The intestinal microbiota composition and weight development in children: the KOALA Birth Cohort Study. Int J Obes 39, 16–25 (2015). https://doi.org/10.1038/ijo.2014.178

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2014.178

This article is cited by

Search

Advanced search

Quick links