Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use

K Korpela, M A C Zijlmans, M Kuitunen, K Kukkonen, E Savilahti, A Salonen, C de Weerth, W M de Vos, K Korpela, M A C Zijlmans, M Kuitunen, K Kukkonen, E Savilahti, A Salonen, C de Weerth, W M de Vos

Abstract

Background: Children with high body mass index (BMI) at preschool age are at risk of developing obesity. Early identification of factors that increase the risk of excessive weight gain could help direct preventive actions. The intestinal microbiota and antibiotic use have been identified as potential modulators of early metabolic programming and weight development. To test if the early microbiota composition is associated with later BMI, and if antibiotic use modifies this association, we analysed the faecal microbiota composition at 3 months and the BMI at 5-6 years in two cohorts of healthy children born vaginally at term in the Netherlands (N = 87) and Finland (N = 75). We obtained lifetime antibiotic use records and measured weight and height of all children.

Results: The relative abundance of streptococci was positively and the relative abundance of bifidobacteria negatively associated with the BMI outcome. The association was especially strong among children with a history of antibiotic use. Bacteroides relative abundance was associated with BMI only in the children with minimal lifetime antibiotic exposure.

Conclusions: The intestinal microbiota of infants are predictive of later BMI and may serve as an early indicator of obesity risk. Bifidobacteria and streptococci, which are indicators of microbiota maturation in infants, are likely candidates for metabolic programming of infants, and their influence on BMI appears to depend on later antibiotic use.

Keywords: Bifidobacteria; Childhood overweight; Early-life microbiota; Metabolic programming; Microarray.

Figures

Fig. 1
Fig. 1
Microbiota composition of 3-month-old infants in the Dutch (a) and Finnish (b) cohorts. The 16 most abundant genus-level taxa are shown. Colour codes are from top down on each column. Each column represents an individual child, and the squares below the columns show the BMI of the child at 5–6 years (white = 13, black = 21) and lifetime antibiotic use (white = 0 courses, black = 8 or more courses). Asterisks indicate infants who had received a course of antibiotics before sample collection
Fig. 2
Fig. 2
Association between selected bifidobacteria (a) and streptococci (b) at 3 months of age and deviance from expected BMI at 5–6 years in Finnish (red) and Dutch (blue) children. The deviance from expected is calculated based on birth weight and breastfeeding duration. See Table 2 for details. The trend lines (shading) show linear regression (95% confidence interval)
Fig. 3
Fig. 3
Association between genus-like bacterial groups with infant growth from birth to 6 months and BMI at 5–6 years in the total cohort, separately in the Dutch (NL) and Finnish (Fin) children and separately in children with minimal lifetime antibiotic use (minAB, 0–1 courses) and those with several antibiotic courses (maxAB, >1 courses)

References

    1. Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes. 2006;1(1):11–25. doi: 10.1080/17477160600586747.
    1. 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(5):474–488. doi: 10.1111/j.1467-789X.2008.00475.x.
    1. Cottrell E, Ozanne S. Early life programming of obesity and metabolic disease. Physiol Behav. 2008;94(1):17–28. doi: 10.1016/j.physbeh.2007.11.017.
    1. Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718–15723. doi: 10.1073/pnas.0407076101.
    1. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, Gordon JI. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214. doi: 10.1126/science.1241214.
    1. Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, Kim SG, Li H, Gao Z, Mahana D. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158(4):705–721. doi: 10.1016/j.cell.2014.05.052.
    1. Cox LM, Blaser MJ. Pathways in microbe-induced obesity. Cell Metab. 2013;17(6):883–894. doi: 10.1016/j.cmet.2013.05.004.
    1. Kalliomaki M, Collado MC, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008;87(3):534–538.
    1. Luoto R, Kalliomaki M, Laitinen K, Delzenne NM, Cani PD, Salminen S, Isolauri E. Initial dietary and microbiological environments deviate in normal-weight compared to overweight children at 10 years of age. J Pediatr Gastroenterol Nutr. 2011;52(1):90–95. doi: 10.1097/MPG.0b013e3181f3457f.
    1. 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 Pathogens. 2011;3:8. doi: 10.1186/1757-4749-3-8.
    1. Dogra S, Sakwinska O, Soh S, Ngom-Bru C, Brück WM, Berger B, Brüssow H, Lee YS, Yap F, Chong Y. Dynamics of infant gut microbiota are influenced by delivery mode and gestational duration and are associated with subsequent adiposity. MBio. 2015;6(1):e02419-14. doi: 10.1128/mBio.02419-14.
    1. Scheepers L, Penders J, Mbakwa C, Thijs C, Mommers M, Arts I. The intestinal microbiota composition and weight development in children: the KOALA Birth Cohort Study. Int J Obes. 2015;39(1):16–25. doi: 10.1038/ijo.2014.178.
    1. Ajslev TA, Andersen CS, Gamborg M, Sorensen 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(4):522–529. doi: 10.1038/ijo.2011.27.
    1. 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(1):16–23. doi: 10.1038/ijo.2012.132.
    1. 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(10):1290–1298. doi: 10.1038/ijo.2014.119.
    1. Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr. 2014;168(11):1063–1069. doi: 10.1001/jamapediatrics.2014.1539.
    1. 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(4):617–626. doi: 10.1542/peds.2014-3407.
    1. Cho I, Yamanishi S, Cox L, Methé BA, Zavadil J, Li K, Gao Z, Mahana D, Raju K, Teitler I. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012;488(7413):621–626. doi: 10.1038/nature11400.
    1. Nobel Y, Cox L, Blaser M, et al. Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment. Nat Commun. 2015;7483. doi:10.1038/ncomms8486.
    1. Thompson AL. Developmental origins of obesity: early feeding environments, infant growth, and the intestinal microbiome. Am J Hum Biol. 2012;24(3):350–360. doi: 10.1002/ajhb.22254.
    1. Li H, Zhou Y, Liu J. The impact of cesarean section on offspring overweight and obesity: a systematic review and meta-analysis. Int J Obes. 2013;37(7):893–899. doi: 10.1038/ijo.2012.195.
    1. Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484–489. doi: 10.1038/nature04330.
    1. Joyce SA, MacSharry J, Casey PG, Kinsella M, Murphy EF, Shanahan F, Hill C, Gahan CG. Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. Proc Natl Acad Sci U S A. 2014;111(20):7421–7426. doi: 10.1073/pnas.1323599111.
    1. Song MJ, Kim KH, Yoon JM, Kim JB. Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. Biochem Biophys Res Commun. 2006;346(3):739–745. doi: 10.1016/j.bbrc.2006.05.170.
    1. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmee E, Cousin B, Sulpice T, Chamontin B, Ferrieres J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761–1772. doi: 10.2337/db06-1491.
    1. Camp JG, Jazwa AL, Trent CM, Rawls JF. Intronic cis-regulatory modules mediate tissue-specific and microbial control of angptl4/fiaf transcription. PLoS Genet. 2012;8(3):e1002585. doi: 10.1371/journal.pgen.1002585.
    1. Lin HV, Frassetto A, Kowalik EJ, Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7(4):e35240. doi: 10.1371/journal.pone.0035240.
    1. Korpela K, Salonen A, Virta L, Kekkonen R, Forslund K, Bork P, de Vos W. Intestinal microbiome is associated with lifetime antibiotic use in Finnish pre-school children. Nat Commun. 2016;7:10410. doi: 10.1038/ncomms10410.
    1. Korpela K, Salonen A, Virta LJ, Kekkonen RA, de Vos WM. Association of early-life antibiotic use and protective effects of breastfeeding: role of the intestinal microbiota. JAMA Pediatr. 2016;170(8):750-757. doi:10.1001/jamapediatrics.2016.0585.
    1. Kuitunen M, Kukkonen K, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Haahtela T, Savilahti E. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol. 2009;123(2):335–341. doi: 10.1016/j.jaci.2008.11.019.
    1. Zijlmans MA, Korpela K, Riksen-Walraven JM, de Vos WM, de Weerth C. Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology. 2015;53:233–245. doi: 10.1016/j.psyneuen.2015.01.006.
    1. Adriaenssens N, Coenen S, Versporten A, Muller A, Minalu G, Faes C, Vankerckhoven V, Aerts M, Hens N, Molenberghs G. European Surveillance of Antimicrobial Consumption (ESAC): outpatient antibiotic use in Europe (1997–2009) J Antimicrob Chemother. 2011;66(suppl 6):vi3–vi12.
    1. Korpela K, Salonen A, Virta LJ, Kumpu M, Kekkonen RA, de Vos WM. Lactobacillus rhamnosus GG intake modifies preschool children’s intestinal microbiota, alleviates penicillin-associated changes, and reduces antibiotic use. PLoS One. 2016;11(4):e0154012. doi: 10.1371/journal.pone.0154012.
    1. Salonen A, Nikkila J, Jalanka-Tuovinen J, Immonen O, Rajilic-Stojanovic M, Kekkonen RA, Palva A, de Vos WM. Comparative analysis of fecal DNA extraction methods with phylogenetic microarray: effective recovery of bacterial and archaeal DNA using mechanical cell lysis. J Microbiol Methods. 2010;81(2):127–134. doi: 10.1016/j.mimet.2010.02.007.
    1. Rajilic-Stojanovic M, Heilig HGHJ, Molenaar D, Kajander K, Surakka A, Smidt H, de Vos WM. Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults. Environ Microbiol. 2009;11(7):1736–1751. doi: 10.1111/j.1462-2920.2009.01900.x.
    1. Lahti L, Torrente A, Elo LL, Brazma A, Rung J. A fully scalable online pre-processing algorithm for short oligonucleotide microarray atlases. Nucleic Acids Res. 2013;41(10):e110. doi: 10.1093/nar/gkt229.
    1. R Core Team: R . A language and environment for statistical computing. 2012.
    1. Oksanen J, Blanchet FG, Kindt R, Legendre P, Minchin PR, O'Hara RB, Simpson GL, Solymos P, Stevens MHH, Wagner H. vegan: Community Ecology Package. 2013.
    1. Pendyala S, Walker JM, Holt PR. A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology. 2012;142(5):1100–1101. doi: 10.1053/j.gastro.2012.01.034.
    1. Baird J, Fisher D, Lucas P, Kleijnen J, Roberts H, Law C. Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ. 2005;331(7522):929. doi: 10.1136/bmj.38586.411273.E0.
    1. Bergstrom A, Skov TH, Bahl MI, Roager HM, Christensen LB, Ejlerskov KT, Molgaard C, Michaelsen KF, Licht TR. Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants. Appl Environ Microbiol. 2014;80(9):2889–2900. doi: 10.1128/AEM.00342-14.
    1. Booijink CC, El‐Aidy S, Rajilić‐Stojanović M, Heilig HG, Troost FJ, Smidt H, Kleerebezem M, De Vos WM, Zoetendal EG. High temporal and inter-individual variation detected in the human ileal microbiota. Environ Microbiol. 2010;12(12):3213–3227. doi: 10.1111/j.1462-2920.2010.02294.x.
    1. Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson G, Delzenne NM. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50(11):2374–2383. doi: 10.1007/s00125-007-0791-0.
    1. Cani PD, Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des. 2009;15(13):1546–1558. doi: 10.2174/138161209788168164.
    1. Moya-Pérez A, Neef A, Sanz Y. Bifidobacterium pseudocatenulatum CECT 7765 reduces obesity-associated inflammation by restoring the lymphocyte-macrophage balance and gut microbiota structure in high-fat diet-fed mice. PLoS One. 2015;10(7):e0126976. doi: 10.1371/journal.pone.0126976.
    1. Safavi M, Farajian S, Kelishadi R, Mirlohi M, Hashemipour M. The effects of synbiotic supplementation on some cardio-metabolic risk factors in overweight and obese children: a randomized triple-masked controlled trial. Int J Food Sci Nutr. 2013;64(6):687–693. doi: 10.3109/09637486.2013.775224.
    1. Moratalla A, Gómez‐Hurtado I, Santacruz A, Moya Á, Peiró G, Zapater P, González‐Navajas JM, Giménez P, Such J, Sanz Y. Protective effect of Bifidobacterium pseudocatenulatum CECT7765 against induced bacterial antigen translocation in experimental cirrhosis. Liver Int. 2014;34(6):850–858. doi: 10.1111/liv.12380.
    1. Salazar N, Dewulf EM, Neyrinck AM, Bindels LB, Cani PD, Mahillon J, de Vos WM, Thissen J, Gueimonde M, Clara G. Inulin-type fructans modulate intestinal Bifidobacterium species populations and decrease fecal short-chain fatty acids in obese women. Clin Nutr. 2015;34(3):501–507. doi: 10.1016/j.clnu.2014.06.001.
    1. Chen JJ, Wang R, Li XF, Wang RL. Bifidobacterium longum supplementation improved high-fat-fed-induced metabolic syndrome and promoted intestinal Reg I gene expression. Exp Biol Med. 2011;236(7):823–831. doi: 10.1258/ebm.2011.010399.
    1. An HM, Park SY, Lee DK, Kim JR, Cha MK, Lee SW, Lim HT, Kim KJ, Ha NJ. Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats. Lipids Health Dis. 2011;10(1):116. doi: 10.1186/1476-511X-10-116.
    1. Cano PG, Santacruz A, Trejo FM, Sanz Y. Bifidobacterium CECT 7765 improves metabolic and immunological alterations associated with obesity in high-fat diet-fed mice. Obesity. 2013;21(11):2310–2321. doi: 10.1002/oby.20330.
    1. Mariam RS, Yap KW, Lim LC, Kharidah M, Shuhaimi M, Abdullah S, Ali AM, Atiqah AN, YAZID AM. Strain differences in deconjugation of bile acids in Bifidobacterium pseudocatenulatum isolates. Bioscience Microflora. 2004;23(2):93–98. doi: 10.12938/bifidus.23.93.
    1. Moya-Perez A, Romo-Vaquero M, Tomas-Barberan F, Sanz Y, García-Conesa M. Hepatic molecular responses to Bifidobacterium pseudocatenulatum CECT 7765 in a mouse model of diet-induced obesity. Nutr Metab Cardiovasc Dis. 2014;24(1):57–64. doi: 10.1016/j.numecd.2013.04.011.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する