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Epidemiology and population health

Does birth mode modify associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome?



Mother-to-newborn transmission of obesity-associated microbiota may be modified by birth mode (vaginal vs. Cesarean delivery). Prospective data to test this hypothesis are still sparse.


To examine prospective associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome by birth-mode strata.


In 335 mother–infant pairs in the New Hampshire Birth Cohort, we ascertained data from questionnaires and medical records, and generated microbiome data from 6-week-old infants’ stool using Illumina 16s rRNA gene sequencing (V4–V5 region). Analyses were stratified by birth mode and conducted before and after adjusting for potential confounders, which included maternal age, education, parity, and Mediterranean diet score.


Among 335 mothers, 56% had normal pre-pregnancy BMI ( < 25, referent), 27% were overweight (BMI 25–30), and 18% obese (BMI > 30). Among the 312 mothers with weight gain data, 10% had inadequate weight gain, 30% adequate (referent), and 60% excess. Birth mode modified associations of pre-pregnancy BMI with several genera, including the most abundant genus, Bacteroides (P for interaction = 0.05). In the vaginal-delivery group, maternal overweight or obesity was associated with higher infant gut microbiome diversity and higher relative abundance of 15 operational taxonomic units (OTUs), including overrepresentation of Bacteroides fragilis, Escherichia coli, Veillonella dispar, and OTUs in the genera Staphylococcus and Enterococcus. In the Cesarean-delivered group, there were no significant associations of pre-pregnancy BMI with infant microbiome (alpha) diversity or OTUs. Gestational weight gain was not associated with differential relative abundance of infant gut microbial OTUs or with measures of microbial diversity in infants delivered vaginally or by Cesarean section.


Among vaginally-delivered infants, maternal overweight and obesity was associated with altered infant gut microbiome composition and higher diversity. These associations were not observed in Cesarean-delivered infants, whose microbiome development differs from vaginally-delivered infants. Our study provides additional evidence of birth-mode dependent associations of maternal body weight status with the infant gut microbiota. The role of these associations in mediating the intergenerational cycle of obesity warrants further examination.

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  1. 1.

    Skinner AC, Ravanbakht SN, Skelton JA, Perrin EM, Armstrong SC. Prevalence of Obesity and Severe Obesity in US Children, 1999-2016. Pediatrics. 2018;141:e20173459.

  2. 2.

    Hales CM, Fryar CD, Carroll MD, Freedman DS, Ogden CL. Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007-2008 to 2015-2016. JAMA. 2018;319:1723–1725.

  3. 3.

    Hruby A, Hu FB. The epidemiology of obesity: A big picture. Pharmacoeconomics. 2015;33:673–89.

  4. 4.

    Joint child malnutrition estimates–levels and trends. United Nations Children’s Fund, World Health Organization, The World Bank Group; 2017.

  5. 5.

    Collaboration NCDRF. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet. 2017;390:2627–42.

  6. 6.

    Naess M, Holmen TL, Langaas M, Bjorngaard JH, Kvaloy K. Intergenerational transmission of overweight and obesity from parents to their adolescent offspring-The HUNT Study. PLoS ONE. 2016;11:e0166585.

  7. 7.

    Whitaker KL, Jarvis MJ, Beeken RJ, Boniface D, Wardle J. Comparing maternal and paternal intergenerational transmission of obesity risk in a large population-based sample. Am J Clin Nutr. 2010;91:1560–7.

  8. 8.

    Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH. Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med. 1997;337:869–73.

  9. 9.

    Llewellyn CH, Trzaskowski M, Plomin R, Wardle J. Finding the missing heritability in pediatric obesity: the contribution of genome-wide complex trait analysis. Int J Obes (Lond). 2013;37:1506–9.

  10. 10.

    Wexler HM. Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev. 2007;20:593–621.

  11. 11.

    Bjerke GA, Wilson R, Storro O, Oyen T, Johnsen R, Rudi K. Mother-to-child transmission of and multiple-strain colonization by Bacteroides fragilis in a cohort of mothers and their children. Appl Environ Microbiol. 2011;77:8318–24.

  12. 12.

    Korpela K, Costea P, Coelho LP, Kandels-Lewis S, Willemsen G, Boomsma DI, et al. Selective maternal seeding and environment shape the human gut microbiome. Genome Res. 2018;28:561–8.

  13. 13.

    Singh S, Karagas MR, Mueller NT. Charting the maternal and infant microbiome: What is the role of diabetes and obesity in pregnancy? Curr Diab Rep. 2017;17:11.

  14. 14.

    Tun HM, Bridgman SL, Chari R, Field CJ, Guttman DS, Becker AB, et al. Roles of birth mode and infant gut microbiota in intergenerational transmission of overweight and obesity from mother to offspring. JAMA Pediatr. 2018;72:368–77.

  15. 15.

    Mueller NT, Shin H, Pizoni A, Werlang IC, Matte U, Goldani MZ, et al. Birth mode-dependent association between pre-pregnancy maternal weight status and the neonatal intestinal microbiome. Sci Rep. 2016;6:23133.

  16. 16.

    Madan JC, Hoen AG, Lundgren SN, Farzan SF, Cottingham KL, Morrison HG, et al. Association of cesarean delivery and formula supplementation with the intestinal microbiome of 6-week-old infants. JAMA Pediatr. 2016;170:212–9.

  17. 17.

    Gilmore LA, Redman LM. Weight gain in pregnancy and application of the 2009 IOM guidelines: toward a uniform approach. Obesity (Silver Spring, Md) . 2015;23:507–11.

  18. 18.

    Institute of Medicine and National Research Council Committee to Reexamine IOM Pregnancy Weight Guidelines in Weight Gain During Pregnancy: Reexamining the Guidelines (eds Rasmussen, K. M. & Yaktine, A. L.) (National Academies Press, Washington DC, 2009).

  19. 19.

    Wu GD, Lewis JD, Hoffmann C, Chen YY, Knight R, Bittinger K, et al. Sampling and pyrosequencing methods for characterizing bacterial communities in the human gut using 16S sequence tags. BMC Microbiol. 2010;10:206.

  20. 20.

    Degnan PH, Ochman H. Illumina-based analysis of microbial community diversity. ISME J. 2012;6:183–94.

  21. 21.

    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.

  22. 22.

    Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13:581–3.

  23. 23.

    Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–6.

  24. 24.

    DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol. 2006;72:5069–72.

  25. 25.

    McDonald D, Clemente JC, Kuczynski J, Rideout JR, Stombaugh J, Wendel D, et al. The Biological Observation Matrix (BIOM) format or: how I learned to stop worrying and love the ome-ome. Gigascience. 2012;1:7.

  26. 26.

    McMurdie PJ, Holmes S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE. 2013;8:e61217.

  27. 27.

    McDonald D, Price MN, Goodrich J, Nawrocki EP, DeSantis TZ, Probst A, et al. An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. ISME J. 2012;6:610–8.

  28. 28.

    Lozupone C, Knight R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol. 2005;71:8228–35.

  29. 29.

    Lozupone CA, Hamady M, Kelley ST, Knight R. Quantitative and qualitative beta diversity measures lead to different insights into factors that structure microbial communities. Appl Environ Microbiol. 2007;73:1576–85.

  30. 30.

    Vazquez-Baeza Y, Pirrung M, Gonzalez A, Knight R. EMPeror: a tool for visualizing high-throughput microbial community data. Gigascience. 2013;2:16.

  31. 31.

    Jari Oksanen FGB, Friendly M, Kindt R, Legendre P, McGlinn D, Minchin PR, et al. Eduard Szoecs and Helene Wagner. vegan: Community ecology package. R Package Version. 2017;2:4–5.

  32. 32.

    Rigby RAS, Stasinopoulos DM. Generalized additive models for location, scale and shape,(with discussion). Appl Stat. 2005;54:507–54.

  33. 33.

    Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.

  34. 34.

    McMurdie PJ, Holmes S. Waste not, want not: why rarefying microbiome data is inadmissible. PLoS Comput Biol. 2014;10:e1003531.

  35. 35.

    Collado MC, Isolauri E, Laitinen K, Salminen S. Effect of mother’s weight on infant’s microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy. Am J Clin Nutr. 2010;92:1023–30.

  36. 36.

    Galley JD, Bailey M, Kamp Dush C, Schoppe-Sullivan S, Christian LM. Maternal obesity is associated with alterations in the gut microbiome in toddlers. PLoS ONE. 2014;9:e113026.

  37. 37.

    Stanislawski MA, Dabelea D, Wagner BD, Sontag MK, Lozupone CA, Eggesbo M. Pre-pregnancy weight, gestational weight gain, and the gut microbiota of mothers and their infants. Microbiome. 2017;5:113.

  38. 38.

    Bokulich NA, Chung J, Battaglia T, Henderson N, Jay M, Li H, et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med. 2016;8:343ra82.

  39. 39.

    Azad MB, Konya T, Persaud RR, Guttman DS, Chari RS, Field CJ, et al. Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. BJOG. 2016;123:983–93.

  40. 40.

    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.

  41. 41.

    Ignacio A, Fernandes MR, Rodrigues VA, Groppo FC, Cardoso AL, Avila-Campos MJ, et al. Correlation between body mass index and faecal microbiota from children. Clin Microbiol Infect. 2016;22:258 e1–8.

  42. 42.

    Scheepers LE, Penders J, Mbakwa CA, Thijs C, Mommers M, Arts IC. The intestinal microbiota composition and weight development in children: the KOALA Birth Cohort Study. Int J Obes (Lond). 2015;39:16–25.

  43. 43.

    Rogers MB, Firek B, Shi M, Yeh A, Brower-Sinning R, Aveson V, et al. Disruption of the microbiota across multiple body sites in critically ill children. Microbiome. 2016;4:66.

  44. 44.

    Collado MC, Calabuig M, Sanz Y. Differences between the fecal microbiota of coeliac infants and healthy controls. Curr Issues Intest Microbiol. 2007;8:9–14.

  45. 45.

    de Meij TG, de Groot EF, Eck A, Budding AE, Kneepkens CM, Benninga MA, et al. Characterization of microbiota in children with chronic functional constipation. PLoS ONE. 2016;11:e0164731.

  46. 46.

    Wopereis H, Sim K, Shaw A, Warner JO, Knol J, Kroll JS. Intestinal microbiota in infants at high risk for allergy: Effects of prebiotics and role in eczema development. J Allergy Clin Immunol. 2018;141:1334–42 e5.

  47. 47.

    Wang F, Yu T, Huang G, Cai D, Liang X, Su H, et al. Gut microbiota community and its assembly associated with age and diet in Chinese centenarians. J Microbiol Biotechnol. 2015;25:1195–204.

  48. 48.

    Yan Q, Gu Y, Li X, Yang W, Jia L, Chen C, et al. Alterations of the gut microbiome in hypertension. Front Cell Infect Microbiol. 2017;7:381.

  49. 49.

    Million M, Tidjani Alou M, Khelaifia S, Bachar D, Lagier JC, Dione N, et al. Increased gut redox and depletion of anaerobic and methanogenic prokaryotes in severe acute malnutrition. Sci Rep. 2016;6:26051.

  50. 50.

    Drell T, Lutsar I, Stsepetova J, Parm U, Metsvaht T, Ilmoja ML, et al. The development of gut microbiota in critically ill extremely low birth weight infants assessed with 16S rRNA gene based sequencing. Gut Microbes. 2014;5:304–12.

  51. 51.

    Stryjewski ME, Corey GR. Methicillin-resistant Staphylococcus aureus: an evolving pathogen. Clin Infect Dis. 2014;58:S10–9.

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We would like to extend our sincerest gratitude to the participants of the New Hampshire Birth Cohort. Furthermore, we would like to thank Michael S. Zens, and John Hudson for their unending patience and extensive technological help.


Research reported in this publication was supported by The Mid-Atlantic Nutrition Obesity Research Center (NORC) under NIH award number P30DK072488. Research reported in this publication was also supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number K01HL141589 (PI: Mueller), National Institutes of Health (grants NIGMS P20GM104416 (Karagas), NIEHS P01ES022832 (Karagas), NLM K01LM011985 (Hoen), NLM R01LM012723 (Hoen), the US Environmental Protection Agency (RD83544201) (Karagas).

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The authors declare that they have no conflict of interest.

Correspondence to Noel T. Mueller.

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