Impact of early life nutrition on gut health in children: a prospective clinical study

Delphine Ley, Laurent Beghin, Jules Morcel, Florence Flamein, Charles Garabedian, Bertrand Accart, Elodie Drumez, Julien Labreuche, Frederic Gottrand, Emmanuel Hermann, Delphine Ley, Laurent Beghin, Jules Morcel, Florence Flamein, Charles Garabedian, Bertrand Accart, Elodie Drumez, Julien Labreuche, Frederic Gottrand, Emmanuel Hermann

Abstract

Introduction: The first 1000 days of life could contribute to individual susceptibility to the later development of chronic non-communicable diseases. Nutrition in early life appears to be an important determinant factor for a sustainable child's health. In this study, we propose to investigate the impact of exclusive breast feeding on gut health in children.

Methods and analysis: A prospective cohort of newborns (n=350) will be recruited at birth and followed up to 4 years of age. The main objective is to evaluate the link between exclusive breast feeding for at least 3 months and the gut health of the child at 4 years. The primary endpoint of assessment of gut health will be based on the non-invasive measurement of faecal secretory IgA (sIgA) as a sensitive biomarker of the intestinal ecosystem. The presence of gastrointestinal disorders will be defined according to the clinical criteria of Rome IV. Information on parent's nutritional habits and life style, breastfeeding duration and child's complementary feeding will be collected along the follow-up. Cord blood cells and plasma at birth will be purified for further analysis. The meconium and stools collected at birth, 6 months, 2 years and 4 years of age will allow sIgA analysis.

Ethics and dissemination: This clinical study has obtained the approval from the national ethical committee. We plan to publish the results of the study in peer-review journals and by means of national and international conference.

Trial registration number: NCT04195425.

Keywords: immunology; microbiology; nutrition & dietetics; paediatric gastroenterology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Study schedules. PENSINE, Périnatalité, Environnement, Santé Intestinale et Nutrition de l'Enfant.

References

    1. Roseboom T, de Rooij S, Painter R. The Dutch famine and its long-term consequences for adult health. Early Hum Dev 2006;82:485–91. 10.1016/j.earlhumdev.2006.07.001
    1. Barker DJ, Winter PD, Osmond C, et al. . Weight in infancy and death from ischaemic heart disease. Lancet 1989;2:577–80. 10.1016/S0140-6736(89)90710-1
    1. Indrio F, Martini S, Francavilla R, et al. . Epigenetic matters: the link between early nutrition, microbiome, and long-term health development. Front Pediatr 2017;5:178. 10.3389/fped.2017.00178
    1. Ley D, Desseyn J-L, Mischke M, et al. . Early-Life origin of intestinal inflammatory disorders. Nutr Rev 2017;75:175–87. 10.1093/nutrit/nuw061
    1. Milani C, Duranti S, Bottacini F, et al. . The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev 2017;81. 10.1128/MMBR.00036-17. [Epub ahead of print: 08 11 2017].
    1. Ley D, Desseyn J-L, Gouyer V, et al. . Early life nutrition influences susceptibility to chronic inflammatory colitis in later life. Sci Rep 2019;9:18111. 10.1038/s41598-019-54308-6
    1. The World Health Organization . The optimal duration of exclusive breastfeeding. Report of an expert consultation. WHO/NHD/0109 2001.
    1. Victora CG, Bahl R, Barros AJD, et al. . Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet 2016;387:475–90. 10.1016/S0140-6736(15)01024-7
    1. Rozé J-C, Darmaun D, Boquien C-Y, et al. . The apparent breastfeeding paradox in very preterm infants: relationship between breast feeding, early weight gain and neurodevelopment based on results from two cohorts, EPIPAGE and lift. BMJ Open 2012;2:e000834. 10.1136/bmjopen-2012-000834
    1. Bridgman SL, Konya T, Azad MB, et al. . Infant gut immunity: a preliminary study of IgA associations with breastfeeding. J Dev Orig Health Dis 2016;7:68–72. 10.1017/S2040174415007862
    1. Martin RM, Patel R, Kramer MS, et al. . Effects of promoting longer-term and exclusive breastfeeding on adiposity and insulin-like growth factor-I at age 11.5 years: a randomized trial. JAMA 2013;309:1005–13. 10.1001/jama.2013.167
    1. Gale C, Logan KM, Santhakumaran S, et al. . Effect of breastfeeding compared with formula feeding on infant body composition: a systematic review and meta-analysis. Am J Clin Nutr 2012;95:656–69. 10.3945/ajcn.111.027284
    1. Differding MK, Doyon M, Bouchard L, et al. . Potential interaction between timing of infant complementary feeding and breastfeeding duration in determination of early childhood gut microbiota composition and BMI. Pediatr Obes 2020;15:e12642. 10.1111/ijpo.12642
    1. Heshmati J, Sepidarkish M, Shidfar F, et al. . Effect of breastfeeding in early life on cardiorespiratory and physical fitness: a systematic review and meta-analysis. Breastfeed Med 2018;13:248–58. 10.1089/bfm.2018.0001
    1. Boudry G, Charton E, Le Huerou-Luron L I, et al. . The relationship between breast milk components and the infant gut microbiota. Front Nutr 2021;8:629740. 10.3389/fnut.2021.629740
    1. Thai JD, Gregory KE. Bioactive factors in human breast milk attenuate intestinal inflammation during early life. Nutrients 2020;12. 10.3390/nu12020581. [Epub ahead of print: 23 Feb 2020].
    1. Parigi SM, Eldh M, Larssen P, et al. . Breast milk and solid food shaping intestinal immunity. Front Immunol 2015;6:415. 10.3389/fimmu.2015.00415
    1. Martin CR, Ling P-R, Blackburn GL. Review of infant feeding: key features of breast milk and infant formula. Nutrients 2016;8. 10.3390/nu8050279. [Epub ahead of print: 11 May 2016].
    1. Walker WA, Iyengar RS. Breast milk, microbiota, and intestinal immune homeostasis. Pediatr Res 2015;77:220–8. 10.1038/pr.2014.160
    1. Carr LE, Virmani MD, Rosa F, et al. . Role of human milk bioactives on infants' gut and immune health. Front Immunol 2021;12:604080. 10.3389/fimmu.2021.604080
    1. Macpherson AJ, Yilmaz B, Limenitakis JP, et al. . Iga function in relation to the intestinal microbiota. Annu Rev Immunol 2018;36:359–81. 10.1146/annurev-immunol-042617-053238
    1. Moon C, Baldridge MT, Wallace MA, et al. . Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation. Nature 2015;521:90–3. 10.1038/nature14139
    1. Rogier EW, Frantz AL, Bruno ME, et al. . Lessons from mother: long-term impact of antibodies in breast milk on the gut microbiota and intestinal immune system of breastfed offspring. Gut Microbes 2014;5:663–8. 10.4161/19490976.2014.969984
    1. Zeevenhooven J, Koppen IJN, Benninga MA. The new Rome IV criteria for functional gastrointestinal disorders in infants and toddlers. Pediatr Gastroenterol Hepatol Nutr 2017;20:1–13. 10.5223/pghn.2017.20.1.1
    1. Campeotto F, Barbaza M-O, Hospital V. Functional gastrointestinal disorders in outpatients aged up to 12 months: a French non-interventional study. Int J Environ Res Public Health 2020;17. 10.3390/ijerph17114031. [Epub ahead of print: 05 06 2020].
    1. Wagner S, Kersuzan C, Gojard S. Breastfeeding duration in France according to parents and birth characteristics. Results from the ELFE longitudinal French study, 2011. Bull Epidemiol Hebd 2015;29:522–32.
    1. Béghin L, Tims S, Roelofs M, et al. . Fermented infant formula (with Bifidobacterium breve C50 and Streptococcus thermophilus O65) with prebiotic oligosaccharides is safe and modulates the gut microbiota towards a microbiota closer to that of breastfed infants. Clin Nutr 2021;40:778–87. 10.1016/j.clnu.2020.07.024
    1. Brandtzaeg P. Secretory IgA: designed for anti-microbial defense. Front Immunol 2013;4:222. 10.3389/fimmu.2013.00222
    1. Bridgman SL, Konya T, Azad MB, et al. . High fecal IgA is associated with reduced Clostridium difficile colonization in infants. Microbes Infect 2016;18:543–9. 10.1016/j.micinf.2016.05.001
    1. Blondel B, Gonzalez L, Raynaud P. Enquête nationale périnatale 2016. les naissances et les établissements, situation et évolution depuis 2010 2016.
    1. World Health Organization . Breastfeeding: the World Health Organization, 2021. Available:
    1. Barnaba L, Intorre F, Azzini E, et al. . Evaluation of adherence to Mediterranean diet and association with clinical and biological markers in an Italian population. Nutrition 2020;77:110813. 10.1016/j.nut.2020.110813
    1. Benninga MA, Faure C, Hyman PE, et al. . Childhood functional gastrointestinal disorders: Neonate/Toddler. Gastroenterology 2016;150:1443–55. 10.1053/j.gastro.2016.02.016
    1. Buuren S, Groothuis-Oudshoorn K. Multivariate imputation by Chained equations in R. J Stat Softw 2011;45:1–67.
    1. Rubin DB. Multiple imputation for nonresponse in surveys. New York: John Wiley and Sons, 1987.
    1. Hayden D, Pauler DK, Schoenfeld D. An estimator for treatment comparisons among survivors in randomized trials. Biometrics 2005;61:305–10. 10.1111/j.0006-341X.2005.030227.x
    1. Maruyama K, Hida M, Kohgo T, et al. . Changes in salivary and fecal secretory IgA in infants under different feeding regimens. Pediatr Int 2009;51:342–5. 10.1111/j.1442-200X.2008.02748.x
    1. Kukkonen K, Kuitunen M, Haahtela T, et al. . High intestinal IgA associates with reduced risk of IgE-associated allergic diseases. Pediatr Allergy Immunol 2010;21:67–73. 10.1111/j.1399-3038.2009.00907.x
    1. Viljanen M, Kuitunen M, Haahtela T, et al. . Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants. Pediatr Allergy Immunol 2005;16:65–71. 10.1111/j.1399-3038.2005.00224.x
    1. Bäckhed F, Roswall J, Peng Y, et al. . Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 2015;17:690–703. 10.1016/j.chom.2015.04.004
    1. Yatsunenko T, Rey FE, Manary MJ, et al. . Human gut microbiome viewed across age and geography. Nature 2012;486:222–7. 10.1038/nature11053
    1. Roswall J, Olsson LM, Kovatcheva-Datchary P, et al. . Developmental trajectory of the healthy human gut microbiota during the first 5 years of life. Cell Host Microbe 2021;29:765–76. 10.1016/j.chom.2021.02.021

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit