Skip to main content

Thank you for visiting 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.


Implication of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation



In animal studies early life antibiotic exposure causes metabolic abnormalities including obesity through microbiota disruption, but evidence from human studies is scarce. We examined involvement of gut microbiota in the associations between infant antibiotic exposure and childhood adiposity.


Infant antibiotic exposure in the first year of life was ascertained using parental reports during interviewer-administered questionnaires. Primary outcomes were childhood obesity [body mass index (BMI) z-score > 95th percentile] and adiposity [abdominal circumference (AC) and skinfold (triceps + subscapular (SST)) measurements] determined from ages 15–60 months. At age 24 months, when the gut microbiota are more stable, stool samples (n = 392) were collected for the gut microbiota profiling using co-abundancy networks. Associations of antibiotic exposure with obesity and adiposity (n = 1016) were assessed using multiple logistic and linear mixed effects regressions. Key bacteria associated with antibiotics exposure were identified by partial redundancy analysis and multivariate association with linear models.


Antibiotic exposure was reported in 38% of study infants. In a fully adjusted model, a higher odds of obesity from 15–60 months of age was observed for any antibiotic exposure [OR(95% CI) = 1.45(1.001, 2.14)] and exposure to ≥3 courses of antibiotics [2.78(1.12, 6.87)]. For continuous adiposity indicators, any antibiotic exposure was associated with higher BMI z-score in boys [β = 0.15(0.01, 0.28)] but not girls [β = −0.04(−0.19, 0.11)] (P interaction = 0.026). Similarly, exposure to ≥3 courses of antibiotics was associated with higher AC in boys [1.15(0.05, 2.26) cm] but not girls [0.57(−1.32, 2.45) cm] (P interaction not significant). Repeated exposure to antibiotics was associated with a significant reduction (FDR-corrected P values < 0.05) in a microbial co-abundant group (CAG) represented by Eubacterium hallii, whose proportion was negatively correlated with childhood adiposity. Meanwhile, a CAG represented by Tyzzerella 4 was positively correlated with the repeated use of antibiotics and childhood adiposity.


Infant antibiotic exposure was associated with disruption of the gut microbiota and the higher risks of childhood obesity and increased adiposity.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Co-abundant network analysis of the child gut microbiota at 24 months and key co-abundant groups associated with the antibiotic exposure by partial redundancy analysis (partial RDA).
Fig. 2: Heatmap of key co-abundant groups (CAGs) associated with antibiotic exposure identified by the partial RDA and Spearman’s correlation between identified CAGs and the accumulation of adiposity at 24 months.


  1. 1.

    The Lancet. Managing the tide of childhood obesity. Lancet. 2015;385:2434.

    Google Scholar 

  2. 2.

    Saari A, Virta LJ, Sankilampi U, Dunkel L, Saxen H. Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life. Pediatrics. 2015;135:617–26.

    Article  Google Scholar 

  3. 3.

    Murphy R, Stewart AW, Braithwaite I, Beasley R, Hancox RJ, Mitchell EA. Antibiotic treatment during infancy and increased body mass index in boys: an international cross-sectional study. Int J Obes. 2014;38:1115–9.

    Article  Google Scholar 

  4. 4.

    Azad MB, Bridgman SL, Becker AB, Kozyrskyj AL. Infant antibiotic exposure and the development of childhood overweight and central adiposity. Int J Obes. 2014;38:1290–8.

    CAS  Article  Google Scholar 

  5. 5.

    Scott FI, Horton DB, Mamtani R, Haynes K, Goldberg DS, Lee DY, et al. Administration of antibiotics to children before age 2 years increases risk for childhood obesity. Gastroenterology. 2016;151:120–.e5.

    CAS  Article  Google Scholar 

  6. 6.

    Mbakwa CA, Scheres L, Penders J, Mommers M, Thijs C, Arts ICW. Early life antibiotic exposure and weight development in children. J Pediatr. 2016;176:105–.e2.

    CAS  Article  Google Scholar 

  7. 7.

    Ajslev TA, Andersen CS, Gamborg M, Sørensen TIA, Jess T. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics. Int J Obes. 2011;35:522–9.

    CAS  Article  Google Scholar 

  8. 8.

    Trasande L, Blustein J, Liu M, Corwin E, Cox LM, Blaser MJ. Infant antibiotic exposures and early-life body mass. Int J Obes. 2013;37:16–23.

    CAS  Article  Google Scholar 

  9. 9.

    Schwartz BS, Pollak J, Bailey-Davis L, Hirsch AG, Cosgrove SE, Nau C, et al. Antibiotic use and childhood body mass index trajectory. Int J Obes. 2016;40:615–21.

    CAS  Article  Google Scholar 

  10. 10.

    Gerber JS, Bryan M, Ross RK, Daymont C, Parks EP, Localio AR. et al. Antibiotic exposure during the first 6 months of life and weight gain during childhood. JAMA. 2016;315:1258–65.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Li D-K, Chen H, Ferber J, Odouli R, Ha C, Lam Y, et al. Infection and antibiotic use in infancy and risk of childhood obesity: a longitudinal birth cohort study. Lancet Diabetes Endocrinol. 2016;0:16498–517.

    CAS  Google Scholar 

  12. 12.

    Isolauri E, Salminen S, Rautava S. Early microbe contact and obesity risk: evidence of causality. J Pediatr Gastroenterol Nutr. 2016;63(Suppl 1):S3–5.

    PubMed  Google Scholar 

  13. 13.

    Cox LM, Blaser MJ. Pathways in microbe-induced obesity. Cell Metab. 2013;17:883–94.

    CAS  Article  Google Scholar 

  14. 14.

    Goulet O. Potential role of the intestinal microbiota in programming health and disease. Nutr Rev. 2015;73:32–40.

    Article  Google Scholar 

  15. 15.

    Cho I, Yamanishi S, Cox L, Methé BA, Zavadil J, Li K, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012;488:621–6.

    CAS  Article  Google Scholar 

  16. 16.

    Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158:705–21.

    CAS  Article  Google Scholar 

  17. 17.

    Soh SE, Tint MT, Gluckman PD, Godfrey KM, Rifkin-Graboi A, Chan YH, et al. Cohort profile: Growing up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort study. Int J Epidemiol. 2013.

    Article  PubMed  Google Scholar 

  18. 18.

    Chen L-W, Aris I, Bernard J, Tint M-T, Chia A, Colega M, et al. Associations of maternal dietary patterns during pregnancy with offspring adiposity from birth until 54 months of age. Nutrients. 2016;9:2.

    Article  Google Scholar 

  19. 19.

    National Healthcare Group Polyclinics. Age and gender-specific national BMI cut-offs. Singapore: National Healthcare Group Polyclinics; 2010.

  20. 20.

    Hamilton CM, Strader LC, Pratt JG, Maiese D, Hendershot T, Kwok RK, et al. The PhenX Toolkit: get the most from your measures. Am J Epidemiol. 2011;174:253–60.

    Article  Google Scholar 

  21. 21.

    Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15:539–53.

    CAS  Article  Google Scholar 

  22. 22.

    Chong Y-S, Cai S, Lin H, Soh SE, Lee Y-S, Leow MK-S, et al. Ethnic differences translate to inadequacy of high-risk screening for gestational diabetes mellitus in an Asian population: a cohort study. BMC Pregnancy Childbirth. 2014;14:345.

    Article  Google Scholar 

  23. 23.

    Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med. 2016;22:713–22.

    CAS  Article  Google Scholar 

  24. 24.

    Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012;6:1621–4.

    CAS  Article  Google Scholar 

  25. 25.

    Tong X, Xu J, Lian F, Yu X, Zhao Y, Xu L, et al. Structural alteration of gut microbiota during the amelioration of human type 2 diabetes with hyperlipidemia by metformin and a traditional chinese herbal formula: a multicenter, randomized, open label clinical trial. MBio. 2018;9.

  26. 26.

    WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr. 2006;450:76–85.

    Google Scholar 

  27. 27.

    Finucane MM, Samet JH, Horton NJ. Translational methods in biostatistics: linear mixed effect regression models of alcohol consumption and HIV disease progression over time. Epidemiol Perspect Innov. 2007;4:8.

    Article  Google Scholar 

  28. 28.

    Friedman J, Alm EJ. Inferring correlation networks from genomic survey data. PLoS Comput Biol. 2012;8:e1002687.

    CAS  Article  Google Scholar 

  29. 29.

    Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012;13:R79.

    CAS  Article  Google Scholar 

  30. 30.

    Miles RD, Butcher GD, Henry PR, Littell RC. Effect of antibiotic growth promoters on broiler performance, intestinal growth parameters, and quantitative morphology. Poult Sci. 2006;85:476–85.

    CAS  Article  Google Scholar 

  31. 31.

    Ong SF, Chan W-CS, Shorey S, Chong YS, Klainin-Yobas P, He H-G. Postnatal experiences and support needs of first-time mothers in Singapore: A descriptive qualitative study. Midwifery. 2014;30:772–8.

    Article  Google Scholar 

  32. 32.

    Zhang C, Yin A, Li H, Wang R, Wu G, Shen J, et al. Dietary modulation of gut microbiota contributes to alleviation of both genetic and simple obesity in children. EBioMedicine. 2015;2:968–84.

    Article  Google Scholar 

  33. 33.

    Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341:1241214.

    Article  Google Scholar 

  34. 34.

    Xu J, Lian F, Zhao L, Zhao Y, Chen X, Zhang X, et al. Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula. ISME J. 2015;9:552–62.

    Article  Google Scholar 

  35. 35.

    Duncan SH, Louis P, Flint HJ. Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. Appl Environ Microbiol. 2004;70:5810–7.

    CAS  Article  Google Scholar 

  36. 36.

    Shetty SA, Ritari J, Paulin L, Smidt H, De Vos WM. Complete Genome Sequence of Eubacterium hallii Strain L2-7. Genome Announc. 2017;5.

  37. 37.

    Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte RS, Bartelsman JFWM, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–.e7.

    CAS  Article  Google Scholar 

  38. 38.

    Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915–20.

    Article  Google Scholar 

  39. 39.

    Kang Y, Li Y, Du Y, Guo L, Chen M, Huang X, et al. Konjaku flour reduces obesity in mice by modulating the composition of the gut microbiota. Int J Obes. 2018.

    Article  Google Scholar 

  40. 40.

    Zhang M, Differding MK, Benjamin-Neelon SE, Østbye T, Hoyo C, Mueller NT. Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome. Ann Clin Microbiol Antimicrob. 2019;18:18.

    Article  Google Scholar 

  41. 41.

    VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the E-Value. Ann Intern Med. 2017;167:268–74.

    Article  Google Scholar 

Download references


The authors thank the GUSTO study group, which includes Allan Sheppard, Amutha Chinnadurai, Anne Eng Neo Goh, Anne Rifkin-Graboi, Anqi Qiu, Arijit Biswas, Bee Wah Lee, Birit F.P. Broekman, Boon Long Quah, Borys Shuter, Carolina Un Lam, Chai Kiat Chng, Cheryl Ngo, Choon Looi Bong, Christiani Jeyakumar Henry, Claudia Chi, Cornelia Yin Ing Chee, Yam Thiam Daniel Goh, Doris Fok, E Shyong Tai, Elaine Tham, Elaine Quah Phaik Ling, Evelyn Xiu Ling Loo, FY, Falk Mueller-Riemenschneider, George Seow Heong Yeo, Helen Chen, Heng Hao Tan, Hugo P. S. van Bever, Iliana Magiati, Inez Bik Yun Wong, Ivy Yee-Man Lau, IBMA, Jeevesh Kapur, Jenny L. Richmond, Jerry Kok Yen Chan, Joanna D. Holbrook, Joanne Yoong, Joao N. Ferreira., Jonathan Tze Liang Choo, Jonathan Y. Bernard, Joshua J. Gooley, KMG, Kenneth Kwek, KHT, Krishnamoorthy Niduvaje, Kuan Jin Lee, Leher Singh, Lieng Hsi Ling, Lin Lin Su, LWC, Lourdes Mary Daniel, LP-CS, Marielle V. Fortier, Mark Hanson, Mary Foong-Fong Chong, Mary Rauff, Mei Chien Chua, Melvin Khee-Shing Leow, Michael Meaney, MTT, NK, Ngee Lek, Oon Hoe Teoh, P. C. Wong, Paulin Tay Straughan, PDG, Pratibha Agarwal, Queenie Ling Jun Li, Rob M. van Dam, Salome A. Rebello, Seang-Mei Saw, See Ling Loy, S. Sendhil Velan, Seng Bin Ang, Shang Chee Chong, Sharon Ng, Shiao-Yng Chan, Shirong Cai, Shu-ES, Sok Bee Lim, Stella Tsotsi, Chin-Ying Stephen Hsu, Sue Anne Toh, Swee Chye Quek, Victor Samuel Rajadurai, Walter Stunkel, Wayne Cutfield, Wee Meng Han, Wei Wei Pang, Y-SC, Yin Bun Cheung, Yiong Huak Chan, YSL, and Zhongwei Huang.


This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore—NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore. Study sponsors were not involved in the design of the study, statistical analysis and results interpretation. KMG is supported by the UK Medical Research Council (MC_UU_12011/4), National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515–10042), NIHR Southampton 1000DaysPlus Global Nutrition Research Group and NIHR Southampton Biomedical Research Centre) and by the European Union (Erasmus+ Programme Early Nutrition eAcademy Southeast Asia-573651-EPP-1-2016-1-DE-EPPKA2-CBHE-JP).

Author information




L-WC conducted statistical analysis, interpreted the data, and wrote the first draft of the paper. JX conducted the microbiota analysis, interpreted the data, and co-wrote the first draft of the paper. SES acquired antibiotic exposure data. NK and JAG generated the microbiota data and contributed to the microbiota analysis. L-WC, JX, SES, IMA, and MT-T contributed to data collection, cleaning, and analysis. PDG, KHT, LP-CS, Y-SC, FY, KMG, and YSL designed the GUSTO study. All authors critically revised and approved the final manuscript. YSL had primary responsibility for the final content.

Corresponding author

Correspondence to Yung Seng Lee.

Ethics declarations

Conflict of interest

KMG, Y-SC, and YSL have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. NK, KMG, and Y-SC are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors have no financial or personal conflict of interest to declare.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chen, LW., Xu, J., Soh, S.E. et al. Implication of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation. Int J Obes 44, 1508–1520 (2020).

Download citation

Further reading


Quick links