Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-23T08:14:24.117Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of infant formula composition on long-term metabolic health

Part of: French DOHaD DOHaD on International Women's Day 2020

Published online by Cambridge University Press:  05 February 2018

M. Lemaire ,
I. Le Huërou-Luron  and
S. Blat
M. Lemaire
Affiliation:
INRA, INSERM, Univ Rennes, Nutrition Metabolisms and Cancer (NuMeCan), Rennes, France Lactalis R&D, Retiers, France
I. Le Huërou-Luron
Affiliation:
INRA, INSERM, Univ Rennes, Nutrition Metabolisms and Cancer (NuMeCan), Rennes, France
S. Blat*
Affiliation:
INRA, INSERM, Univ Rennes, Nutrition Metabolisms and Cancer (NuMeCan), Rennes, France
*
*Address for correspondence: S. Blat, INRA, INSERM, Univ Rennes, Nutrition Metabolisms and Cancer (NuMeCan), 16 Le Clos, Saint-Gilles, 35590, France. (Email [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Early nutrition may have long-lasting metabolic impacts in adulthood. Even though breast milk is the gold standard, most infants are at least partly formula-fed. Despite obvious improvements, infant formulas remain perfectible to reduce the gap between breastfed and formula-fed infants. Improvements such as reducing the protein content, modulating the lipid matrix and adding prebiotics, probiotics and synbiotics, are discussed regarding metabolic health. Numerous questions remain to be answered on how impacting the infant formula composition may modulate the host metabolism and exert long-term benefits. Interactions between early nutrition (composition of human milk and infant formula) and the gut microbiota profile, as well as mechanisms connecting gut microbiota to metabolic health, are highlighted. Gut microbiota stands as a key actor in the nutritional programming but additional well-designed longitudinal human studies are needed.

Keywords

early nutritiongut microbiotametabolismneonatal feedingnutritional programming
Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 6 , December 2018 , pp. 573 - 589
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. World Health Organization (WHO). Media centre – obesity and overweight, 2016. Retrieved July 2017 from www.who.int/mediacentre/factsheets/fs311/en/.Google Scholar
2. Hales, CN, Barker, DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992; 35, 595–601.Google Scholar
3. Mcmillen, IC, Robinson, JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev. 2005; 85, 571–633.Google Scholar
4. Nauta, AJ, Ben Amor, K, Knol, J, Garssen, J, van der Beek, EM. Relevance of pre- and postnatal nutrition to development and interplay between the microbiota and metabolic and immune systems. Am J Clin Nutr. 2013; 98, 586S–593S.Google Scholar
5. Thompson, AL. Developmental origins of obesity: early feeding environments, infant growth, and the intestinal microbiome. Am J Hum Biol. 2012; 24, 350–360.Google Scholar
6. Centers for Disease Control and Prevention (CDC). Breastfeeding report card 2016, 2016. Retrieved July 2017 from www.cdc.gov/breastfeeding/data/reportcard.htm.Google Scholar
7. Victora, CG, Bahl, R, Barros, AJ, et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet. 2016; 387, 475–490.Google Scholar
8. Wang, M, Monaco, MH, Donovan, SM. Impact of early gut microbiota on immune and metabolic development and function. Semin Fetal Neonatal Med. 2016; 21, 380–387.Google Scholar
9. Johnson, CC, Ownby, DR. The infant gut bacterial microbiota and risk of pediatric asthma and allergic diseases. Transl Res. 2017; 179, 60–70.Google Scholar
10. Dominguez, PR. The study of postnatal and later development of the taste and olfactory systems using the human brain mapping approach: an update. Brain Res Bull. 2011; 84, 118–124.Google Scholar
11. Nicklaus, S, Remy, E. Early origins of overeating: tracking between early food habits and later eating patterns. Curr Obes Rep. 2013; 2, 179–184.Google Scholar
12. Mennella, JA. Ontogeny of taste preferences: basic biology and implications for health. Am J Clin Nutr. 2014; 99, 704S–711S.Google Scholar
13. Mennella, JA, Reiter, AR, Daniels, LM. Vegetable and fruit acceptance during infancy: impact of ontogeny, genetics, and early experiences. Adv Nutr. 2016; 7, 211S–219S.Google Scholar
14. Koletzko, B, Brands, B, Grote, V, et al. Long-term health impact of early nutrition: the power of programming. Ann Nutr Metab. 2017; 70, 161–169.Google Scholar
15. Gruszfeld, D, Socha, P. Early nutrition and health: short- and long-term outcomes. World Rev Nutr Diet. 2013; 108, 32–39.Google Scholar
16. Andersen, LG, Holst, C, Michaelsen, KF, Baker, JL, Sorensen, TI. Weight and weight gain during early infancy predict childhood obesity: a case-cohort study. Int J Obes. 2012; 36, 1306–1311.Google Scholar
17. Druet, C, Stettler, N, Sharp, S, et al. Prediction of childhood obesity by infancy weight gain: an individual-level meta-analysis. Paediatr Perinat Epidemiol. 2012; 26, 19–26.Google Scholar
18. Botton, J, Heude, B, Maccario, J, Ducimetiere, P, Charles, MA. Postnatal weight and height growth velocities at different ages between birth and 5 y and body composition in adolescent boys and girls. Am J Clin Nutr. 2008; 87, 1760–1768.Google Scholar
19. Chomtho, S, Wells, JC, Williams, JE, et al. Infant growth and later body composition: evidence from the 4-component model. Am J Clin Nutr. 2008; 87, 1776–1784.Google Scholar
20. Rolland-Cachera, MF, Deheeger, M, Maillot, M, Bellisle, F. Early adiposity rebound: causes and consequences for obesity in children and adults. Int J Obes (Lond). 2006; 30, S11–S17.Google Scholar
21. Ailhaud, G, Massiera, F, Weill, P, et al. Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity. Prog Lipid Res. 2006; 45, 203–236.Google Scholar
22. Dewey, KG, Heinig, MJ, Nommsen, LA, Peerson, JM, Lonnerdal, B. Growth of breast-fed and formula-fed infants from 0 to 18 months: the DARLING Study. Pediatrics. 1992; 89, 1035–1041.Google Scholar
23. Johnson, L, van Jaarsveld, CH, Llewellyn, CH, Cole, TJ, Wardle, J. Associations between infant feeding and the size, tempo and velocity of infant weight gain: SITAR analysis of the Gemini twin birth cohort. Int J Obes (Lond). 2014; 38, 980–987.Google Scholar
24. Hawley, NL, Johnson, W, Nu’usolia, O, McGarvey, ST. The contribution of feeding mode to obesogenic growth trajectories in American Samoan infants. Pediatr Obes. 2014; 9, e1–e13.Google Scholar
25. Imai, CM, Gunnarsdottir, I, Thorisdottir, B, Halldorsson, TI, Thorsdottir, I. Associations between infant feeding practice prior to six months and body mass index at six years of age. Nutrients. 2014; 6, 1608–1617.Google Scholar
26. Mihrshahi, S, Battistutta, D, Magarey, A, Daniels, LA. Determinants of rapid weight gain during infancy: baseline results from the NOURISH randomised controlled trial. BMC Pediatr. 2011; 11, 99.Google Scholar
27. Rzehak, P, Oddy, WH, Mearin, ML, et al. Infant feeding and growth trajectory patterns in childhood and body composition in young adulthood. Am J Clin Nutr. 2017; 106, 568–580.Google Scholar
28. Bell, KA, Wagner, CL, Feldman, HA, Shypailo, RJ, Belfort, MB. Associations of infant feeding with trajectories of body composition and growth. Am J Clin Nutr. 2017; 106, 491–498.Google Scholar
29. Arenz, S, Ruckerl, R, Koletzko, B, von Kries, R. Breast-feeding and childhood obesity – a systematic review. Int J Obes Relat Metab Disord. 2004; 28, 1247–1256.Google Scholar
30. Horta, BL, Loret de Mola, C, Victora, CG. Long-term consequences of breastfeeding on cholesterol, obesity, systolic blood pressure and type 2 diabetes: a systematic review and meta-analysis. Acta Paediatr. 2015; 104, 30–37.Google Scholar
31. Rossiter, MD, Colapinto, CK, Khan, MK, et al. Breast, formula and combination feeding in relation to childhood obesity in Nova Scotia, Canada. Matern Child Health J. 2015; 19, 2048–2056.Google Scholar
32. Kramer, MS, Matush, L, Vanilovich, I, et al. A randomized breast-feeding promotion intervention did not reduce child obesity in Belarus. J Nutr. 2009; 139, 417S–421S.Google Scholar
33. Coppi, S, Iacoponi, F, Fommei, C, Strambi, M. Growth trend during the first six months of life in male infants with different type of feeding. Minerva Pediatrica. 2013; 65, 51–59.Google Scholar
34. van der Willik, EM, Vrijkotte, TG, Altenburg, TM, Gademan, MG, Kist-van Holthe, J. Exclusively breastfed overweight infants are at the same risk of childhood overweight as formula fed overweight infants. Arch Dis Child. 2015; 100, 932–937.Google Scholar
35. Betoko, A, Charles, MA, Hankard, R, et al. Determinants of infant formula use and relation with growth in the first 4 months. Matern Child Nutr. 2014; 10, 267–279.Google Scholar
36. Uwaezuoke, SN, Eneh, CI, Ndu, IK. Relationship between exclusive breastfeeding and lower risk of childhood obesity: a narrative review of published evidence. Clin Med Insights Pediatr. 2017; 11, doi:10.1177/1179556517690196.Google Scholar
37. Beyerlein, A, von Kries, R. Breastfeeding and body composition in children: will there ever be conclusive empirical evidence for a protective effect against overweight? Am J Clin Nutr. 2011; 94, 1772S–1775S.Google Scholar
38. Ong, KK, Petry, CJ, Emmett, PM, et al. Insulin sensitivity and secretion in normal children related to size at birth, postnatal growth, and plasma insulin-like growth factor-I levels. Diabetologia. 2004; 47, 1064–1070.Google Scholar
39. Owen, CG, Martin, RM, Whincup, PH, Smith, GD, Cook, DG. Does breastfeeding influence risk of type 2 diabetes in later life? A quantitative analysis of published evidence. Am J Clin Nutr. 2006; 84, 1043–1054.Google Scholar
40. Hui, LL, Kwok, MK, Nelson, EAS, et al. The association of breastfeeding with insulin resistance at 17 years: prospective observations from Hong Kong’s “Children of 1997” birth cohort. Matern Child Nutr. 2018; 14, e12490.Google Scholar
41. Axelsson, IE, Ivarsson, SA, Raiha, NC. Protein intake in early infancy: effects on plasma amino acid concentrations, insulin metabolism, and growth. Pediatr Res. 1989; 26, 614–617.Google Scholar
42. Manco, M, Alterio, A, Bugianesi, E, et al. Insulin dynamics of breast- or formula-fed overweight and obese children. J Am Coll Nutr. 2011; 30, 29–38.Google Scholar
43. Lucas, A, Sarson, DL, Blackburn, AM, et al. Breast vs bottle: endocrine responses are different with formula feeding. Lancet. 1980; 1, 1267–1269.Google Scholar
44. Newgard, CB, An, J, Bain, JR, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009; 9, 311–326.Google Scholar
45. O’Sullivan, A, He, X, McNiven, EM, et al. Early diet impacts infant rhesus gut microbiome, immunity, and metabolism. J Proteome Res. 2013; 12, 2833–2845.Google Scholar
46. Socha, P, Grote, V, Gruszfeld, D, et al. Milk protein intake, the metabolic-endocrine response, and growth in infancy: data from a randomized clinical trial. Am J Clin Nutr. 2011; 94, 1776S–1784S.Google Scholar
47. Wallensteen, M, Lindblad, BS, Zetterstrom, R, Persson, B. Acute C-peptide, insulin and branched chain amino acid response to feeding in formula and breast fed infants. Acta Paediatr Scand. 1991; 80, 143–148.Google Scholar
48. Tikanoja, T, Simell, O, Viikari, M, Jarvenpaa, AL. Plasma amino acids in term neonates after a feed of human milk or formula. II. Characteristic changes in individual amino acids. Acta Paediatr Scand. 1982; 71, 391–397.Google Scholar
49. Janas, LM, Picciano, MF, Hatch, TF. Indices of protein metabolism in term infants fed human milk, whey-predominant formula, or cow’s milk formula. Pediatrics. 1985; 75, 775–784.Google Scholar
50. Wang, TJ, Larson, MG, Vasan, RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011; 17, 448–453.Google Scholar
51. Roszkowska, R, Taranta-Janusz, K, Tenderenda-Banasiuk, E, Wasilewska, A. Increased circulating inflammatory markers may indicate that formula-fed children are at risk of atherosclerosis. Acta Paediatr. 2014; 103, e354–e358.Google Scholar
52. Wilson, AC, Forsyth, JS, Greene, SA, et al. Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study. BMJ. 1998; 316, 21–25.Google Scholar
53. Taittonen, L, Nuutinen, M, Turtinen, J, Uhari, M. Prenatal and postnatal factors in predicting later blood pressure among children: cardiovascular risk in young Finns. Pediatr Res. 1996; 40, 627–632.Google Scholar
54. Ramirez-Silva, I, Rivera, JA, Trejo-Valdivia, B, et al. Breastfeeding status at age 3 months is associated with adiposity and cardiometabolic markers at age 4 years in mexican children. J Nutr. 2015; 145, 1295–1302.Google Scholar
55. Owen, CG, Whincup, PH, Odoki, K, Gilg, JA, Cook, DG. Infant feeding and blood cholesterol: a study in adolescents and a systematic review. Pediatrics. 2002; 110, 597–608.Google Scholar
56. Wu, TC, Huang, IFs, Chen, YC, Chen, PH, Yang, LY. Differences in serum biochemistry between breast-fed and formula-fed infants. J Chin Med Assoc. 2011; 74, 511–515.Google Scholar
57. Owen, CG, Whincup, PH, Cook, DG. Breast-feeding and cardiovascular risk factors and outcomes in later life: evidence from epidemiological studies. Proc Nutr Soc. 2011; 70, 478–484.Google Scholar
58. Ronis, MJ, Chen, Y, Shankar, K, et al. Formula feeding alters hepatic gene expression signature, iron and cholesterol homeostasis in the neonatal pig. Physiol Genomics. 2011; 43, 1281–1293.Google Scholar
59. Izadi, V, Kelishadi, R, Qorbani, M, et al. Duration of breast-feeding and cardiovascular risk factors among Iranian children and adolescents: the CASPIAN III study. Nutrition. 2013; 29, 744–751.Google Scholar
60. Martin, RM, Patel, R, Kramer, MS, et al. Effects of promoting longer term and exclusive breastfeeding on cardiometabolic risk factors at age 11.5 years: a cluster-randomized, controlled rrial. Circulation. 2014; 129, 321–329.Google Scholar
61. Martin, RM, Ben-Shlomo, Y, Gunnell, D, et al. Breast feeding and cardiovascular disease risk factors, incidence, and mortality: the Caerphilly study. J Epidemiol Community Health. 2005; 59, 121–129.Google Scholar
62. Hamosh, M. Bioactive factors in human milk. Pediatr Clin North Am. 2001; 48, 69–86.Google Scholar
63. Schack-Nielsen, L, Michaelsen, KF. Advances in our understanding of the biology of human milk and its effects on the offspring. J Nutr. 2007; 137, 503S–510S.Google Scholar
64. Gidrewicz, DA, Fenton, TR. A systematic review and meta-analysis of the nutrient content of preterm and term breast milk. BMC Pediatr. 2014; 14, 216.Google Scholar
65. Mace, K, Steenhout, P, Klassen, P, Donnet, A. Protein quality and quantity in cow’s milk-based formula for healthy term infants: past, present and future. Nestle Nutr Workshop Ser Pediatr Program. 2006; 58, 189–203.Google Scholar
66. Alexy, U, Kersting, M, Sichert-Hellert, W, Manz, F, Schoch, G. Macronutrient intake of 3- to 36-month-old German infants and children: results of the DONALD Study. Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Ann Nutr Metab. 1999; 43, 14–22.Google Scholar
67. Heinig, MJ, Nommsen, LA, Peerson, JM, Lonnerdal, B, Dewey, KG. Energy and protein intakes of breast-fed and formula-fed infants during the first year of life and their association with growth velocity: the DARLING Study. Am J Clin Nutr. 1993; 58, 152–161.Google Scholar
68. Escribano, J, Luque, V, Ferre, N, et al. Effect of protein intake and weight gain velocity on body fat mass at 6 months of age: the EU Childhood Obesity Programme. Int J Obes. 2012; 36, 548–553.Google Scholar
69. Rolland-Cachera, MF, Deheeger, M, Akrout, M, Bellisle, F. Influence of macronutrients on adiposity development: a follow up study of nutrition and growth from 10 months to 8 years of age. Int J Obes Relat Metab Disord. 1995; 19, 573–578.Google Scholar
70. Gruszfeld, D, Weber, M, Gradowska, K, et al. Association of early protein intake and pre-peritoneal fat at five years of age: follow-up of a randomized clinical trial. Nutr Metab Cardiovasc Dis. 2016; 26, 824–832.Google Scholar
71. Voortman, T, Braun, KV, Kiefte-de Jong, JC, et al. Protein intake in early childhood and body composition at the age of 6 years: The Generation R Study. Int J Obes (Lond). 2016; 40, 1018–1025.Google Scholar
72. Koletzko, B, Chourdakis, M, Grote, V, et al. Regulation of early human growth: impact on long-term health. Ann Nutr Metab. 2014; 65, 101–109.Google Scholar
73. Savino, F, Fissore, MF, Grassino, EC, et al. Ghrelin, leptin and IGF-I levels in breast-fed and formula-fed infants in the first years of life. Acta Paediatr. 2005; 94, 531–537.Google Scholar
74. Chellakooty, M, Juul, A, Boisen, KA, et al. A prospective study of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 in 942 healthy infants: associations with birth weight, gender, growth velocity, and breastfeeding. J Clin Endocrinol Metab. 2006; 91, 820–826.Google Scholar
75. Martin, RM, Holly, JM, Smith, GD, et al. Could associations between breastfeeding and insulin-like growth factors underlie associations of breastfeeding with adult chronic disease? The Avon Longitudinal Study of Parents and Children. Clin Endocrinol (Oxf). 2005; 62, 728–737.Google Scholar
76. Hornell, A, Lagstrom, H, Lande, B, Thorsdottir, I. Protein intake from 0 to 18 years of age and its relation to health: a systematic literature review for the 5th Nordic Nutrition Recommendations. Food Nutr Res. 2013; 57, doi: 10.3402/fnr.v57i0.21083.Google Scholar
77. Patro-Golab, B, Zalewski, BM, Kouwenhoven, SM, et al. Protein concentration in milk formula, growth, and later risk of obesity: a systematic review. J Nutr. 2016; 146, 551–564.Google Scholar
78. Davis, AM, Harris, BJ, Lien, EL, Pramuk, K, Trabulsi, J. Alpha-lactalbumin-rich infant formula fed to healthy term infants in a multicenter study: plasma essential amino acids and gastrointestinal tolerance. Eur J Clin Nutr. 2008; 62, 1294–1301.Google Scholar
79. Sandstrom, O, Lonnerdal, B, Graverholt, G, Hernell, O. Effects of alpha-lactalbumin-enriched formula containing different concentrations of glycomacropeptide on infant nutrition. Am J Clin Nutr. 2008; 87, 921–928.Google Scholar
80. Fazzolari-Nesci, A, Domianello, D, Sotera, V, Raiha, NC. Tryptophan fortification of adapted formula increases plasma tryptophan concentrations to levels not different from those found in breast-fed infants. J Pediatr Gastroenterol Nutr. 1992; 14, 456–459.Google Scholar
81. Menezes, JS, Mucida, DS, Cara, DC, et al. Stimulation by food proteins plays a critical role in the maturation of the immune system. Int Immunol. 2003; 15, 447–455.Google Scholar
82. Koletzko, B, von Kries, R, Closa, R, et al. Lower protein in infant formula is associated with lower weight up to age 2 y: a randomized clinical trial. Am J Clin Nutr. 2009; 89, 1836–1845.Google Scholar
83. Koletzko, B, Beyer, J, Brands, B, et al. Early influences of nutrition on postnatal growth. Nestle Nutr Inst Workshop Ser. 2013; 71, 11–27.Google Scholar
84. Weber, M, Grote, V, Closa-Monasterolo, R, et al. Lower protein content in infant formula reduces BMI and obesity risk at school age: follow-up of a randomized trial. Am J Clin Nutr. 2014; 99, 1041–1051.Google Scholar
85. Putet, G, Labaune, JM, Mace, K, et al. Effect of dietary protein on plasma insulin-like growth factor-1, growth, and body composition in healthy term infants: a randomised, double-blind, controlled trial (Early Protein and Obesity in Childhood (EPOCH) study). Br J Nutr. 2016; 115, 271–284.Google Scholar
86. Koletzko, B, von Kries, R, Closa, R, et al. Can infant feeding choices modulate later obesity risk? Am J Clin Nutr. 2009; 89, 1502S–1508S.Google Scholar
87. Greer, FR, Kleinman, RE. An infant formula with decreased weight gain and higher IQ: are we there yet? Am J Clin Nutr. 2014; 99, 757–758.Google Scholar
88. Satue-Gracia, MT, Frankel, EN, Rangavajhyala, N, German, JB. Lactoferrin in infant formulas: effect on oxidation. J Agric Food Chem. 2000; 48, 4984–4990.Google Scholar
89. Fields, DA, Schneider, CR, Pavela, G. A narrative review of the associations between six bioactive components in breast milk and infant adiposity. Obesity (Silver Spring). 2016; 24, 1213–1221.Google Scholar
90. Ballard, O, Morrow, AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am. 2013; 60, 49–74.Google Scholar
91. Catli, G, Olgac Dundar, N, Dundar, BN. Adipokines in breast milk: an update. J Clin Res Pediatr Endocrinol. 2014; 6, 192–201.Google Scholar
92. Badillo-Suarez, PA, Rodriguez-Cruz, M, Nieves-Morales, X. Impact of metabolic hormones secreted in human breast milk on nutritional programming in childhood obesity. J Mammary Gland Biol Neoplasia. 2017; 22, 171–191.Google Scholar
93. Donovan, SM. The role of lactoferrin in gastrointestinal and immune development and function: a preclinical perspective. J Pediatr. 2016; 173, S16–S28.Google Scholar
94. Flachs, P, Rossmeisl, M, Bryhn, M, Kopecky, J. Cellular and molecular effects of n-3 polyunsaturated fatty acids on adipose tissue biology and metabolism. Clin Sci (Lond). 2009; 116, 1–16.Google Scholar
95. Oosting, A, Kegler, D, Boehm, G, et al. N-3 long-chain polyunsaturated fatty acids prevent excessive fat deposition in adulthood in a mouse model of postnatal nutritional programming. Pediatr Res. 2010; 68, 494–499.Google Scholar
96. Oosting, A, Kegler, D, van de Heijning, BJ, Verkade, HJ, van der Beek, EM. Reduced linoleic acid intake in early postnatal life improves metabolic outcomes in adult rodents following a Western-style diet challenge. Nutr Res. 2015; 35, 800–811.Google Scholar
97. Schipper, L, Bouyer, K, Oosting, A, Simerly, RB, van der Beek, EM. Postnatal dietary fatty acid composition permanently affects the structure of hypothalamic pathways controlling energy balance in mice. Am J Clin Nutr. 2013; 98, 1395–1401.Google Scholar
98. Massiera, F, Saint-Marc, P, Seydoux, J, et al. Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? J Lipid Res. 2003; 44, 271–279.Google Scholar
99. Patro-Golab, B, Zalewski, BM, Kolodziej, M, et al. Nutritional interventions or exposures in infants and children aged up to 3 years and their effects on subsequent risk of overweight, obesity and body fat: a systematic review of systematic reviews. Obes Rev. 2016; 17, 1245–1257.Google Scholar
100. Forsyth, JS, Willatts, P, Agostoni, C, et al. Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial. BMJ. 2003; 326, 953.Google Scholar
101. Delplanque, B, Gibson, R, Koletzko, B, Lapillonne, A, Strandvik, B. Lipid quality in infant nutrition: current knowledge and future opportunities. J Pediatr Gastroenterol Nutr. 2015; 61, 8–17.Google Scholar
102. Colombo, J, Jill Shaddy, D, Kerling, EH, Gustafson, KM, Carlson, SE. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) balance in developmental outcomes. Prostaglandins Leukot Essent Fatty Acids. 2017; 121, 52–56.Google Scholar
103. European Commission. Commission Delegated Regulation (EU) 2016/127 of 25 September 2015 supplementing Regulation (EU) No 609/2013 of the European Parliament and of the Council as regards the specific compositional and information requirements for infant formula and follow-on formula and as regards requirements on information relating to infant and young child feeding. Official J Eur Union. 2016:L25/1.Google Scholar
104. Koletzko, B, Carlson, SE, van Goudoever, JB. Should infant formula provide both omega-3 DHA and omega-6 arachidonic acid? Ann Nutr Metab. 2015; 66, 137–138.Google Scholar
105. Jasani, B, Simmer, K, Patole, SK, Rao, SC. Long chain polyunsaturated fatty acid supplementation in infants born at term. Cochrane Database Syst Rev. 2017; 3, CD000376.Google Scholar
106. Koletzko, B. Human milk lipids. Ann Nutr Metab. 2016; 69, 28–40.Google Scholar
107. Hernell, O, Timby, N, Domellof, M, Lonnerdal, B. Clinical benefits of milk fat globule membranes for infants and children. J Pediatr. 2016; 173, S60–S65.Google Scholar
108. Lopez, C, Cauty, C, Guyomarc’h, F. Organization of lipids in milks, infant milk formulas and various dairy products: role of technological processes and potential impacts. Dairy Sci Technol. 2015; 95, 863–893.Google Scholar
109. Cilla, A, Diego Quintaes, K, Barbera, R, Alegria, A. Phospholipids in human milk and infant formulas: benefits and needs for correct infant nutrition. Crit Rev Food Sci Nutr. 2016; 56, 1880–1892.Google Scholar
110. Timby, N, Lonnerdal, B, Hernell, O, Domellof, M. Cardiovascular risk markers until 12 mo of age in infants fed a formula supplemented with bovine milk fat globule membranes. Pediatr Res. 2014; 76, 394–400.Google Scholar
111. Lukoyanova, O, Borovik, T, Bushueva, T, et al. The lipid metabolism in infants fed formula supplemented with bovine milk fat and bovine milk fat globule membranes [abstract]. In Abstracts of the 50th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition; 2017, May 10–13; ESPGHAN, Prague; 2017. Abstract nr 576.Google Scholar
112. Oosting, A, Kegler, D, Wopereis, HJ, et al. Size and phospholipid coating of lipid droplets in the diet of young mice modify body fat accumulation in adulthood. Pediatr Res. 2012; 72, 362–369.Google Scholar
113. Oosting, A, van Vlies, N, Kegler, D, et al. Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood. Br J Nutr. 2014; 111, 215–226.Google Scholar
114. Baars, A, Oosting, A, Engels, E, et al. Milk fat globule membrane coating of large lipid droplets in the diet of young mice prevents body fat accumulation in adulthood. Br J Nutr. 2016; 115, 1930–1937.Google Scholar
115. Shek, L, Winokan, A, Abrahamse-Berkeveld, M, et al. An innovative infant milk formula with large, phospholipid-coated lipid droplets supports an adequate growth and is well-tolerated in healthy, term Asian infants [abstract]. In Abstracts of the 4th International Conference on Nutrition & Growth; 2017, March 2–4; N&G: Amsterdam; 2017. Abstract nr 71.Google Scholar
116. Gianni, ML, Roggero, P, Baudry, C, Le Ruyet, P, Mosca, F. Dairy lipids in infant formula: impact on growth and gastrointestinal tolerance in healthy infants [abstract]. In Abstracts of the 49th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition; 2016, May 25–28. ESPGHAN: Athens; 2016. Abstract nr 406.Google Scholar
117. Bayley, TM, Alasmi, M, Thorkelson, T, et al. Longer term effects of early dietary cholesterol level on synthesis and circulating cholesterol concentrations in human infants. Metabolism. 2002; 51, 25–33.Google Scholar
118. Demmers, TA, Jones, PJ, Wang, Y, et al. Effects of early cholesterol intake on cholesterol biosynthesis and plasma lipids among infants until 18 months of age. Pediatrics. 2005; 115, 1594–1601.Google Scholar
119. Ostlund, RE Jr, Lin, X. Regulation of cholesterol absorption by phytosterols. Curr Atheroscler Rep. 2006; 8, 487–491.Google Scholar
120. Claumarchirant, L, Matencio, E, Sanchez-Siles, LM, Alegria, A, Lagarda, MJ. Sterol composition in infant formulas and estimated intake. J Agric Food Chem. 2015; 63, 7245–7251.Google Scholar
121. Nommsen, LA, Lovelady, CA, Heinig, MJ, Lonnerdal, B, Dewey, KG. Determinants of energy, protein, lipid, and lactose concentrations in human milk during the first 12 mo of lactation: the DARLING Study. Am J Clin Nutr. 1991; 53, 457–465.Google Scholar
122. Srinivasan, M, Laychock, SG, Hill, DJ, Patel, MS. Neonatal nutrition: metabolic programming of pancreatic islets and obesity. Exp Biol Med (Maywood). 2003; 228, 15–23.Google Scholar
123. Bode, L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012; 22, 1147–1162.Google Scholar
124. Bode, L. The functional biology of human milk oligosaccharides. Early Hum Dev. 2015; 91, 619–622.Google Scholar
125. Jost, T, Lacroix, C, Braegger, C, Chassard, C. Impact of human milk bacteria and oligosaccharides on neonatal gut microbiota establishment and gut health. Nutr Rev. 2015; 73, 426–437.Google Scholar
126. Chichlowski, M, German, JB, Lebrilla, CB, Mills, DA. The influence of milk oligosaccharides on microbiota of infants: opportunities for formulas. Annu Rev Food Sci Technol. 2011; 2, 331–351.Google Scholar
127. McGuire, MK, Meehan, CL, McGuire, MA, et al. What’s normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically. Am J Clin Nutr. 2017; 105, 1086–1100.Google Scholar
128. Sela, DA, Mills, DA. Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides. Trends Microbiol. 2010; 18, 298–307.Google Scholar
129. Yu, ZT, Chen, C, Newburg, DS. Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes. Glycobiology. 2013; 23, 1281–1292.Google Scholar
130. Aakko, J, Kumar, H, Rautava, S, et al. Human milk oligosaccharide categories define the microbiota composition in human colostrum. Benef Microbes. 2017; 8, 563–567.Google Scholar
131. Lewis, ZT, Totten, SM, Smilowitz, JT, et al. Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants. Microbiome. 2015; 3, 13.Google Scholar
132. Smith-Brown, P, Morrison, M, Krause, L, Davies, PS. Mothers secretor status affects development of childrens microbiota composition and function: a pilot study. PLoS One. 2016; 11, e0161211.Google Scholar
133. Wang, M, Li, M, Wu, S, et al. Fecal microbiota composition of breast-fed infants is correlated with human milk oligosaccharides consumed. J Pediatr Gastroenterol Nutr. 2015; 60, 825–833.Google Scholar
134. Holscher, HD, Davis, SR, Tappenden, KA. Human milk oligosaccharides influence maturation of human intestinal Caco-2Bbe and HT-29 cell lines. J Nutr. 2014; 144, 586–591.Google Scholar
135. Chichlowski, M, De Lartigue, G, German, JB, Raybould, HE, Mills, DA. Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function. J Pediatr Gastroenterol Nutr. 2012; 55, 321–327.Google Scholar
136. Kuntz, S, Rudloff, S, Kunz, C. Oligosaccharides from human milk influence growth-related characteristics of intestinally transformed and non-transformed intestinal cells. Br J Nutr. 2008; 99, 462–471.Google Scholar
137. Ruhaak, LR, Stroble, C, Underwood, MA, Lebrilla, CB. Detection of milk oligosaccharides in plasma of infants. Anal Bioanal Chem. 2014; 406, 5775–5784.Google Scholar
138. Goehring, KC, Kennedy, AD, Prieto, PA, Buck, RH. Direct evidence for the presence of human milk oligosaccharides in the circulation of breastfed infants. PLoS One. 2014; 9, e101692.Google Scholar
139. Alderete, TL, Autran, C, Brekke, BE, et al. Associations between human milk oligosaccharides and infant body composition in the first 6 mo of life. Am J Clin Nutr. 2015; 102, 1381–1388.Google Scholar
140. Gibson, GR, Hutkins, R, Sanders, ME, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017; 14, 491–502.Google Scholar
141. Braegger, C, Chmielewska, A, Decsi, T, et al. Supplementation of infant formula with probiotics and/or prebiotics: a systematic review and comment by the ESPGHAN committee on nutrition. J Pediatr Gastroenterol Nutr. 2011; 52, 238–250.Google Scholar
142. Rao, S, Srinivasjois, R, Patole, S. Prebiotic supplementation in full-term neonates: a systematic review of randomized controlled trials. Arch Pediatr Adolesc Med. 2009; 163, 755–764.Google Scholar
143. Canfora, EE, Jocken, JW, Blaak, EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015; 11, 577–591.Google Scholar
144. Priyadarshini, M, Thomas, A, Reisetter, AC, et al. Maternal short-chain fatty acids are associated with metabolic parameters in mothers and newborns. Transl Res. 2014; 164, 153–157.Google Scholar
145. Closa-Monasterolo, R, Gispert-Llaurado, M, Luque, V, et al. Safety and efficacy of inulin and oligofructose supplementation in infant formula: results from a randomized clinical trial. Clin Nutr. 2013; 32, 918–927.Google Scholar
146. Veereman-Wauters, G, Staelens, S, Van de Broek, H, et al. Physiological and bifidogenic effects of prebiotic supplements in infant formulae. J Pediatr Gastroenterol Nutr. 2011; 52, 763–771.Google Scholar
147. Ashley, C, Johnston, WH, Harris, CL, et al. Growth and tolerance of infants fed formula supplemented with polydextrose (PDX) and/or galactooligosaccharides (GOS): double-blind, randomized, controlled trial. Nutr J. 2012; 11, 38.Google Scholar
148. Salvini, F, Riva, E, Salvatici, E, et al. A specific prebiotic mixture added to starting infant formula has long-lasting bifidogenic effects. J Nutr. 2011; 141, 1335–1339.Google Scholar
149. Simeoni, U, Berger, B, Junick, J, et al. Gut microbiota analysis reveals a marked shift to bifidobacteria by a starter infant formula containing a synbiotic of bovine milk-derived oligosaccharides and Bifidobacterium animalis subsp. lactis CNCM I-3446. Environ Microbiol. 2016; 18, 2185–2195.Google Scholar
150. Newburg, DS, Ruiz-Palacios, GM, Altaye, M, et al. Innate protection conferred by fucosylated oligosaccharides of human milk against diarrhea in breastfed infants. Glycobiology. 2004; 14, 253–263.Google Scholar
151. Puccio, G, Alliet, P, Cajozzo, C, et al. Effects of infant formula with human milk oligosaccharides on growth and morbidity: a randomized multicenter trial. J Pediatr Gastroenterol Nutr. 2017; 64, 624–631.Google Scholar
152. Steenhout, P, Sperisen, P, Martin, F-P, et al. Term infant formula supplemented with human milk oligosaccharides (2′fucosyllactose and lacto-N-neotetraose) shifts stool microbiota and metabolic signatures closer to that of breastfed infants. FASEB J. 2016; 30, 275.7.Google Scholar
153. Marriage, BJ, Buck, RH, Goehring, KC, Oliver, JS, Williams, JA. Infants fed a lower calorie formula with 2ʹFL show growth and 2ʹFL uptake like breast-fed infants. J Pediatr Gastroenterol Nutr. 2015; 61, 649–658.Google Scholar
154. Bode, L, Jantscher-Krenn, E. Structure-function relationships of human milk oligosaccharides. Adv Nutr. 2012; 3, 383S–391S.Google Scholar
155. Hunt, KM, Foster, JA, Forney, LJ, et al. Characterization of the diversity and temporal stability of bacterial communities in human milk. PLoS One. 2011; 6, e21313.Google Scholar
156. Cabrera-Rubio, R, Collado, MC, Laitinen, K, et al. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 2012; 96, 544–551.Google Scholar
157. Murphy, K, Curley, D, O’Callaghan, TF, et al. The composition of human milk and infant faecal microbiota over the first three months of life: a pilot study. Sci Rep. 2017; 7, 40597.Google Scholar
158. Bergmann, H, Rodriguez, JM, Salminen, S, Szajewska, H. Probiotics in human milk and probiotic supplementation in infant nutrition: a workshop report. Br J Nutr. 2014; 112, 1119–1128.Google Scholar
159. Boix-Amoros, A, Collado, MC, Mira, A. Relationship between milk microbiota, bacterial load, macronutrients, and human cells during lactation. Front Microbiol. 2016; 7, 492.Google Scholar
160. Pannaraj, PS, Li, F, Cerini, C, et al. Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatr. 2017; 171, 647–654.Google Scholar
161. Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO). Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria, 2001. Retrieved May 2017 from http://isappscience.org/wp-content/uploads/2015/12/FAO-WHO-2001-Probiotics-Report.pdf.Google Scholar
162. Hill, C, Guarner, F, Reid, G, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014; 11, 506–514.Google Scholar
163. Davis, EC, Wang, M, Donovan, SM. The role of early life nutrition in the establishment of gastrointestinal microbial composition and function. Gut Microbes. 2017; 8, 143–171.Google Scholar
164. Szajewska, H. What are the indications for using probiotics in children? Arch Dis Child. 2016; 101, 398–403.Google Scholar
165. Hojsak, I, Szajewska, H, Canani, RB, et al. Probiotics for the prevention of nosocomial diarrhea in children. J Pediatr Gastroenterol Nutr. 2018; 66, 3–9.Google Scholar
166. Szajewska, H, Canani, RB, Guarino, A, et al. Probiotics for the prevention of antibiotic-associated diarrhea in children. J Pediatr Gastroenterol Nutr. 2016; 62, 495–506.Google Scholar
167. Rinne, M, Kalliomaki, M, Salminen, S, Isolauri, E. Probiotic intervention in the first months of life: short-term effects on gastrointestinal symptoms and long-term effects on gut microbiota. J Pediatr Gastroenterol Nutr. 2006; 43, 200–205.Google Scholar
168. Maldonado-Lobon, JA, Gil-Campos, M, Maldonado, J, et al. Long-term safety of early consumption of Lactobacillus fermentum CECT5716: A 3-year follow-up of a randomized controlled trial. Pharmacol Res. 2015; 95-96, 12–19.Google Scholar
169. Scalabrin, D, Harris, C, Johnston, WH, Berseth, CL. Long-term safety assessment in children who received hydrolyzed protein formulas with Lactobacillus rhamnosus GG: a 5-year follow-up. Eur J Pediatr. 2017; 176, 217–224.Google Scholar
170. Endo, A, Prtty, A, Kalliomki, M, Isolauri, E, Salminen, S. Long-term monitoring of the human intestinal microbiota from the 2nd week to 13 years of age. Anaerobe. 2014; 28, 149–156.Google Scholar
171. Luoto, R, Kalliomaki, M, Laitinen, K, Isolauri, E. The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years. Int J Obes (Lond). 2010; 34, 1531–1537.Google Scholar
172. Hashemi, A, Villa, CR, Comelli, EM. Probiotics in early life: a preventative and treatment approach. Food Funct. 2016; 7, 1752–1768.Google Scholar
173. Petschow, BW, Figueroa, R, Harris, CL, et al. Effects of feeding an infant formula containing Lactobacillus GG on the colonization of the intestine: a dose-response study in healthy infants. J Clin Gastroenterol. 2005; 39, 786–790.Google Scholar
174. Yan, F, Liu, L, Cao, H, et al. Neonatal colonization of mice with LGG promotes intestinal development and decreases susceptibility to colitis in adulthood. Mucosal Immunol. 2017; 10, 117–127.Google Scholar
175. Mugambi, MN, Musekiwa, A, Lombard, M, Young, T, Blaauw, R. Synbiotics, probiotics or prebiotics in infant formula for full term infants: a systematic review. Nutr J. 2012; 11, 81.Google Scholar
176. Lee le, Y, Bharani, R, Biswas, A, et al. Normal growth of infants receiving an infant formula containing Lactobacillus reuteri, galacto-oligosaccharides, and fructo-oligosaccharide: a randomized controlled trial. Matern Health Neonatol Perinatol. 2015; 1, 9.Google Scholar
177. Szajewska, H, Ruszczynski, M, Szymanski, H, et al. Effects of infant formula supplemented with prebiotics compared with synbiotics on growth up to the age of 12 mo: a randomized controlled trial. Pediatr Res. 2017; 81, 752–758.Google Scholar
178. Perez-Munoz, ME, Arrieta, MC, Ramer-Tait, AE, Walter, J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome. 2017; 5, 48.Google Scholar
179. Mueller, NT, Bakacs, E, Combellick, J, Grigoryan, Z, Dominguez-Bello, MG. The infant microbiome development: mom matters. Trends Mol Med. 2015; 21, 109–117.Google Scholar
180. Francino, MP. Early development of the gut microbiota and immune health. Pathogens. 2014; 3, 769–790.Google Scholar
181. Funkhouser, LJ, Bordenstein, SR. Mom knows best: the universality of maternal microbial transmission. PLoS Biol. 2013; 11, e1001631.Google Scholar
182. Vyas, U, Ranganathan, N. Probiotics, prebiotics, and synbiotics: gut and beyond. Gastroenterol Res Pract. 2012; 2012, 872716.Google Scholar
183. van den Nieuwboer, M, Claassen, E, Morelli, L, Guarner, F, Brummer, RJ. Probiotic and synbiotic safety in infants under two years of age. Beneficial Microbes. 2014; 5, 45–60.Google Scholar
184. White, RA, Bjornholt, JV, Baird, DD, et al. Novel developmental analyses identify longitudinal patterns of early gut microbiota that affect infant growth. PLoS Comput Biol. 2013; 9, e1003042.Google Scholar
185. O’Sullivan, A, Farver, M, Smilowitz, JT. The influence of early infant-feeding practices on the intestinal microbiome and body composition in infants. Nutr Metab Insights. 2015; 8, 1–9.Google Scholar
186. Scheepers, LE, Penders, J, Mbakwa, CA, et al. The intestinal microbiota composition and weight development in children: the KOALA Birth Cohort Study. Int J Obes (Lond). 2015; 39, 16–25.Google Scholar
187. Dogra, S, Sakwinska, O, Soh, SE, et al. Dynamics of infant gut microbiota are influenced by delivery mode and gestational duration and are associated with subsequent adiposity. MBio. 2015; 6, e02419–e02414.Google Scholar
188. Cox, LM, Yamanishi, S, Sohn, J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014; 158, 705–721.Google Scholar
189. Yatsunenko, T, Rey, FE, Manary, MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012; 486, 222–227.Google Scholar
190. Palmer, C, Bik, EM, DiGiulio, DB, Relman, DA, Brown, PO. Development of the human infant intestinal microbiota. PLoS Biol. 2007; 5, e177.Google Scholar
191. Rodriguez, JM, Murphy, K, Stanton, C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015; 26, 26050.Google Scholar
192. Marques, TM, Wall, R, Ross, RP, et al. Programming infant gut microbiota: influence of dietary and environmental factors. Curr Opin Biotechnol. 2010; 21, 149–156.Google Scholar
193. Azad, MB, Konya, T, Maughan, H, et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ. 2013; 185, 385–394.Google Scholar
194. Bezirtzoglou, E, Tsiotsias, A, Welling, GW. Microbiota profile in feces of breast- and formula-fed newborns by using fluorescence in situ hybridization (FISH). Anaerobe. 2011; 17, 478–482.Google Scholar
195. Fallani, M, Young, D, Scott, J, et al. Intestinal microbiota of 6-week-old infants across Europe: geographic influence beyond delivery mode, breast-feeding, and antibiotics. J Pediatr Gastroenterol Nutr. 2010; 51, 77–84.Google Scholar
196. Klaassens, ES, Boesten, RJ, Haarman, M, et al. Mixed-species genomic microarray analysis of fecal samples reveals differential transcriptional responses of bifidobacteria in breast- and formula-fed infants. Appl Environ Microbiol. 2009; 75, 2668–2676.Google Scholar
197. Thompson, AL, Monteagudo-Mera, A, Cadenas, MB, Lampl, ML, Azcarate-Peril, MA. Milk- and solid-feeding practices and daycare attendance are associated with differences in bacterial diversity, predominant communities, and metabolic and immune function of the infant gut microbiome. Front Cell Infect Microbiol. 2015; 5, 3.Google Scholar
198. Eggesbo, M, Moen, B, Peddada, S, et al. Development of gut microbiota in infants not exposed to medical interventions. APMIS. 2011; 119, 17–35.Google Scholar
199. Ding, T, Schloss, PD. Dynamics and associations of microbial community types across the human body. Nature. 2014; 509, 357–360.Google Scholar
200. Luoto, R, Kalliomaki, M, Laitinen, K, 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.Google Scholar
201. 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.Google Scholar
202. 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, 534–538.Google Scholar
203. Pham, VT, Lacroix, C, Braegger, CP, Chassard, C. Early colonization of functional groups of microbes in the infant gut. Environ Microbiol. 2016; 18, 2246–2258.Google Scholar
204. Backhed, 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.Google Scholar
205. Bokulich, NA, Chung, J, Battaglia, T, et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med. 2016; 8, 343–382.Google Scholar
206. Martin, FP, Moco, S, Montoliu, I, et al. Impact of breast-feeding and high- and low-protein formula on the metabolism and growth of infants from overweight and obese mothers. Pediatr Res. 2014; 75, 535–543.Google Scholar
207. Hascoet, JM, Hubert, C, Rochat, F, et al. Effect of formula composition on the development of infant gut microbiota. J Pediatr Gastroenterol Nutr. 2011; 52, 756–762.Google Scholar
208. Oda, H, Wakabayashi, H, Yamauchi, K, Abe, F. Lactoferrin and bifidobacteria. Biometals. 2014; 27, 915–922.Google Scholar
209. Mastromarino, P, Capobianco, D, Campagna, G, et al. Correlation between lactoferrin and beneficial microbiota in breast milk and infant’s feces. Biometals. 2014; 27, 1077–1086.Google Scholar
210. Yaron, S, Shachar, D, Abramas, L, et al. Effect of high beta-palmitate content in infant formula on the intestinal microbiota of term infants. J Pediatr Gastroenterol Nutr. 2013; 56, 376–381.Google Scholar
211. Nejrup, RG, Licht, TR, Hellgren, LI. Fatty acid composition and phospholipid types used in infant formulas modifies the establishment of human gut bacteria in germ-free mice. Sci Rep. 2017; 7, 3975.Google Scholar
212. Le Huerou-Luron, I, Bouzerzour, K, Ferret-Bernard, S, et al. A mixture of milk and vegetable lipids in infant formula changes gut digestion, mucosal immunity and microbiota composition in neonatal piglets. Eur J Nutr. 2016, doi: 10.1007/s00394-016-1329-3.Google Scholar
213. Donovan, SM, Wang, M, Li, M, et al. Host-microbe interactions in the neonatal intestine: role of human milk oligosaccharides. Adv Nutr. 2012; 3, 450S–455S.Google Scholar
214. Prentice, P, Vervoort, J, Dingess, K, et al. Human milk short chain fatty acid composition is associated with infancy adiposity outcomes [abstract]. In Abstracts of the 49th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition; 2016, May 25–28. ESPGHAN: Athens; 2016. Abstract nr 634.Google Scholar
215. Layden, BT, Angueira, AR, Brodsky, M, Durai, V, Lowe, WL Jr. Short chain fatty acids and their receptors: new metabolic targets. Transl Res. 2013; 161, 131–140.Google Scholar
216. Kaji, I, Karaki, S, Kuwahara, A. Short-chain fatty acid receptor and its contribution to glucagon-like peptide-1 release. Digestion. 2014; 89, 31–36.Google Scholar
217. Zadeh-Tahmasebi, M, Duca, FA, Rasmussen, BA, et al. Activation of short and long chain fatty acid sensing machinery in the ileum lowers glucose production in vivo. J Biol Chem. 2016; 291, 8816–8824.Google Scholar
218. Chambers, ES, Viardot, A, Psichas, A, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015; 64, 1744–1754.Google Scholar
219. Tolhurst, G, Heffron, H, Lam, YS, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012; 61, 364–371.Google Scholar
220. Psichas, A, Sleeth, ML, Murphy, KG, et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes (Lond). 2015; 39, 424–429.Google Scholar
221. Everard, A, Cani, PD. Gut microbiota and GLP-1. Rev Endocr Metab Disord. 2014; 15, 189–196.Google Scholar
222. Baggio, LL, Drucker, DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007; 132, 2131–2157.Google Scholar
223. Tian, L, Jin, T. The incretin hormone GLP-1 and mechanisms underlying its secretion. J Diab. 2016; 8, 753–765.Google Scholar
224. Wu, T, Rayner, CK, Horowitz, M. Incretins. Handb Exp Pharmacol. 2016; 233, 137–171.Google Scholar
225. Delzenne, NM, Neyrinck, AM, Backhed, F, Cani, PD. Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat Rev Endocrinol. 2011; 7, 639–646.Google Scholar
226. Alvaro, A, Sola, R, Rosales, R, et al. Gene expression analysis of a human enterocyte cell line reveals downregulation of cholesterol biosynthesis in response to short-chain fatty acids. IUBMB Life. 2008; 60, 757–764.Google Scholar
227. Gao, Z, Yin, J, Zhang, J, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009; 58, 1509–1517.Google Scholar
228. Zaibi, MS, Stocker, CJ, O’Dowd, J, et al. Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids. FEBS Lett. 2010; 584, 2381–2386.Google Scholar
229. Xiong, Y, Miyamoto, N, Shibata, K, et al. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci U S A. 2004; 101, 1045–1050.Google Scholar
230. Ye, J, Wu, W, Li, Y, Li, L. Influences of the gut microbiota on DNA methylation and histone modification. Dig Dis Sci. 2017; 62, 1155–1164.Google Scholar
231. Bhat, MI, Kapila, R. Dietary metabolites derived from gut microbiota: critical modulators of epigenetic changes in mammals. Nutr Rev. 2017; 75, 374–389.Google Scholar
232. Majnik, AV, Lane, RH. The relationship between early-life environment, the epigenome and the microbiota. Epigenomics. 2015; 7, 1173–1184.Google Scholar
233. Woo, V, Alenghat, T. Host-microbiota interactions: epigenomic regulation. Curr Opin Immunol. 2017; 44, 52–60.Google Scholar
234. Aoyama, M, Kotani, J, Usami, M. Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways. Nutrition. 2010; 26, 653–661.Google Scholar
235. Davie, JR. Inhibition of histone deacetylase activity by butyrate. J Nutr. 2003; 133, 2485S–2493S.Google Scholar
236. Sanderson, IR. Short chain fatty acid regulation of signaling genes expressed by the intestinal epithelium. J Nutr. 2004; 134, 2450S–2454S.Google Scholar
237. Remely, M, Aumueller, E, Merold, C, et al. Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity. Gene. 2014; 537, 85–92.Google Scholar
238. Krautkramer, KA, Kreznar, JH, Romano, KA, et al. Diet-microbiota interactions mediate global epigenetic programming in multiple host tissues. Molecular Cell. 2016; 64, 982–992.Google Scholar
239. Kumar, H, Lund, R, Laiho, A, et al. Gut microbiota as an epigenetic regulator: pilot study based on whole-genome methylation analysis. MBio. 2014; 5, e02113–e02114.Google Scholar
240. Mischke, M, Plosch, T. More than just a gut instinct-the potential interplay between a baby’s nutrition, its gut microbiome, and the epigenome. Am J Physiol Regul Integr Comp Physiol. 2013; 304, R1065–1069.Google Scholar
241. Brands, B, Demmelmair, H, Koletzko, B. How growth due to infant nutrition influences obesity and later disease risk. Acta Paediatr. 2014; 103, 578–585.Google Scholar
242. Perfilyev, A, Dahlman, I, Gillberg, L, et al. Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial. Am J Clin Nutr. 2017; 105, 991–1000.Google Scholar
243. Singh, N, Shirdel, EA, Waldron, L, et al. The murine caecal microRNA signature depends on the presence of the endogenous microbiota. Int J Biol Sci. 2012; 8, 171–186.Google Scholar
244. Dalmasso, G, Nguyen, HT, Yan, Y, et al. Microbiota modulate host gene expression via microRNAs. PLoS One. 2011; 6, e19293.Google Scholar
245. Weber, JA, Baxter, DH, Zhang, S, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010; 56, 1733–1741.Google Scholar
246. Alsaweed, M, Hartmann, PE, Geddes, DT, Kakulas, F. MicroRNAs in breastmilk and the lactating breast: potential immunoprotectors and developmental regulators for the infant and the mother. Int J Environ Res Public Health. 2015; 12, 13981–14020.Google Scholar
247. Golan-Gerstl, R, Elbaum Shiff, Y, Moshayoff, V, et al. Characterization and biological function of milk-derived miRNAs. Mol Nutr Food Res. 2017; 61, doi: 10.1002/mnfr.201700009.Google Scholar
248. Izumi, H, Kosaka, N, Shimizu, T, et al. Bovine milk contains microRNA and messenger RNA that are stable under degradative conditions. J Dairy Sci. 2012; 95, 4831–4841.Google Scholar
249. Roura, E, Koopmans, SJ, Lalles, JP, et al. Critical review evaluating the pig as a model for human nutritional physiology. Nutr Res Rev. 2016; 29, 60–90.Google Scholar