Preview

Current Pediatrics

Advanced search

Targeted Development of Infant Microbiota on Formula Feeding: Modern Options

https://doi.org/10.15690/vsp.v20i6.2354

Abstract

The review provides the analysis of recent publications covering the biological significance of infant microbiome and showing modern research technologies. Correlations of quantitative and qualitative characteristics of intestinal microbiota with delayed health issues were evaluated. Various concepts of newborn microbiome origin, timing, and stages of bacterial colonization of gastrointestinal tract were considered. Data on the role of delivery method on infant microbiota development is presented (including the significance of contamination with maternal vaginal flora where ontogenetic priority belongs to lactobacilli). It was revealed that Lactobacillus fermentum was the basis microflora providing the conditions for the subsequent successful colonization of the child’s intestines with obligate symbionts. The significance of breastfeeding in adequate microbiota development was confirmed. In case of mandatory formula feeding, it is necessary to enrich infant milk formulas with components that promote the selection of symbiotic microflora such as: long-chain polyunsaturated fatty acids, prebiotics, oligosaccharides, and probiotics of specific action. The innovative formula based on synbiotic/combiotic concept will be able to partially compensate impaired microbiota development in infant on mandatory formula feeding.

About the Authors

Irina A. Belyaeva
Research Institute of Pediatrics and Children’s Health in “Central Clinical Hospital of the Russian Academy of Sciences”;Pirogov Russian National Research Medical University;Morozovskaya Children’s City Hospital
Russian Federation

Moscow


Disclosure of interest:

lecturing for pharmaceutical com panies “Progress”, “Medela”, “Akrikhin”, Nestle, HiPP Russ LLC



Leyla S. Namazova-Baranova
Research Institute of Pediatrics and Children’s Health in “Central Clinical Hospital of the Russian Academy of Sciences”; Pirogov Russian National Research Medical University
Russian Federation

Moscow


Disclosure of interest:

Receiving research grants from pharmaceutical companies Pierre Fabre, Genzyme Europe B.V, AstraZeneca PLC, Gilead / PRA “Pharmaceutical Research Associates CIS”, Teva Branded Pharmaceutical products R&D, Inc / “PPD Development LLC (Smolensk)” LLC, “Stallerzhen S.A.” / “Quintiles GMBH” (Austria), Sanofi Aventis Group, Bionorica, Nutricia



Elena P. Bombardirova
Research Institute of Pediatrics and Children’s Health in “Central Clinical Hospital of the Russian Academy of Sciences”
Russian Federation

Moscow


Disclosure of interest:

The other contributors confirmed the absence of a reportable conflict of interests



Tatiana V. Turti
Research Institute of Pediatrics and Children’s Health in “Central Clinical Hospital of the Russian Academy of Sciences”; Pirogov Russian National Research Medical University; Research Institute for Healthcare Organization and Medical Management
Russian Federation

Moscow


Disclosure of interest:

lecturing for pharmaceutical companies “Progress”, “Akrikhin”



Pavel E. Sadchikov
Research Institute of Pediatrics and Children’s Health in “Central Clinical Hospital of the Russian Academy of Sciences”; Pirogov Russian National Research Medical University
Russian Federation

Moscow


Disclosure of interest:

The other contributors confirmed the absence of a reportable conflict of interests



References

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(4):e00036-17. doi: 10.1128/MMBR.00036-17

2. Sommer F, Backhed F. The gut microbiota — masters of host development and physiology. Nat Rev Microbiol. 2013;11(4): 227–238. doi: 10.1038/nrmicro2974

3. Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016;14(8):e1002533. doi: 10.1371/journal.pbio.1002533

4. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65. doi: 10.1038/nature08821

5. Manor O, Dai CL, Kornilov SA, et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Nat Commun. 2020;11(1):5206. doi: 10.1038/s41467-020-18871-1

6. DeGruttola AK, Low D, Mizoguchi A, et al. Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis. 2016;22(5):1137–1150. doi: 10.1097/MIB.0000000000000750

7. Yang T, Santisteban MM, Rodriguez V, et al. Gut dysbiosis is linked to hypertension. Hypertension. 2015;65(6):1331–1340. doi: 10.1161/HYPERTENSIONAHA.115.05315

8. Battson ML, Lee DM, Jarrell DK, et al. Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction. Am J Physiol Endocrinol Metab. 2018;314(5):E468–E477. doi: 10.1152/ajpendo.00187.2017

9. Heintz-Buschart A, Wilmes P. Human Gut Microbiome: Function Matters. Trends Microbiol. 2018;26(7):563–574. doi: 10.1016/j.tim.2017.11.002

10. Cenit MC, Sanz Y, Codoñer-Franch P. Influence of gut microbiota on neuropsychiatric disorders. World J Gastroenterol. 2017; 23(30):5486–5498. doi: 10.3748/wjg.v23.i30.5486

11. Indiani CMDSP, Rizzardi KF, Castelo PM, et al. Childhood Obesity and Firmicutes/Bacteroidetes Ratio in the Gut Microbiota: A Systematic Review. Child Obes. 2018;14(8):501–509. doi: 10.1089/chi.2018.0040

12. Ley RE, Backhed F, Turnbaugh P, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. 2005;102(31):11070–11075. doi: 10.1073/pnas.0504978102

13. Kalliomaki M, Collado MC, Salminen S, et al. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008;87(3):534–538. doi: 10.1093/ajcn/87.3.534

14. Kalliomaki M, Kirjavainen P, Eerola E, et al. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol. 2001;107(1):129–134. doi: 10.1067/mai.2001.111237

15. Fujimura KE, Sitarik AR, Havstad S, et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med. 2016;22(10):1187–1191. doi: 10.1038/nm.4176

16. Permall DL, Pasha AB, Chen X-Q, Lu H-Y. The lung microbiome in neonates. Turk J Pediatr. 2019;61(6):821–830. doi: 10.24953/turkjped.2019.06.001

17. Turroni F, Milani C, Duranti S, et al. The infant gut microbiome as a microbial organ influencing host well-being. Ital J Pediatr. 2020;46(1):16. doi: 10.1186/s13052-020-0781-0

18. Izaskun GM, Alcantara C, Selma-Royo M, et al. MAMI: a birth cohort focused on maternalinfant microbiota during early life. BMC Pediatr. 2019;19(1):140. doi: 10.1186/s12887-019-1502-y

19. Jimenez E, Marin ML, Martin R, et al. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008;159(3):187–193. doi: 10.1016/j.resmic.2007.12.007

20. Gosalbes MJ, Llop S, Valles Y, et al. Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants. Clin Exp Allergy. 2013;43(2):198–211. doi: 10.1111/cea.12063

21. Aagaard K, Ma J, Antony KM, et al. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra65. doi: 10.1126/scitranslmed.3008599

22. Collado MC, Rautava S, Aakko J, et al. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep. 2016;6:23129. doi: 10.1038/srep23129

23. Zheng J, Xiao X, Zhang Q, et al. The Placental Microbiome Varies in Association with Low Birth Weight in Full-Term Neonates. Nutrients. 2015;7(8):6924–6937. doi: 10.3390/nu7085315

24. Perez-Muñoz ME, Arrieta MC, Ramer-Tait AE, et al. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome. 2017;5(1):48. doi: 10.1186/s40168-017-0268-4

25. Lauder AP, Roche AM, Sherrill-Mix S, et al. Comparison of placenta samples with contamination controls does not provide evidence for a distinct placenta microbiota. Microbiome. 2016;4(1):29. doi: 10.1186/s40168-016-0172-3

26. Rautava S. Microbial Composition of the Initial Colonization of Newborns. Nestle Nutr Inst Workshop Ser. 2017;88:11–21. doi: 10.1159/000455209

27. Del CF, Vernocchi P, Petrucca A, et al. Phylogenetic and metabolic tracking of gut microbiota during perinatal development. PLoS One. 2015;10(9):e0137347. doi: 10.1371/journal.pone.0137347

28. Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA. 2010;107(26):11971–11975. doi: 10.1073/pnas.1002601107

29. Al-Balawi M, Morsy FM. Enterococcus faecalis Is a Better Competitor Than Other Lactic Acid Bacteria in the Initial Colonization of Colon of Healthy Newborn Babies at First Week of Their Life. Front Microbiol. 2020;11:2017. doi: 10.3389/fmicb.2020.02017

30. Friedman ES, Bittinger K, Esipova TV, et al. Microbes vs. chemistry in the origin of the anaerobic gut lumen. Proc Natl Acad Sci USA. 2018;115(16):4170–4175. doi: 10.1073/pnas.1718635115

31. Bischoff SC, Boirie Y, Cederholm T, et al. Towards a multi-disciplinary approach to understand and manage obesity and related diseases. Clin Nutr. 2017;36(4):917–938. doi: 10.1016/j.clnu.2016.11.007

32. Coscia A, Bardanzellu F, Caboni E, et al. When a Neonate Is Born, So Is a Microbiota. Life (Basel). 2021;11(2):148. doi: 10.3390/life11020148

33. de Goffau MC, Lager S, Sovio U, et al. Human placenta has no microbiome but can contain potential pathogens. Nature. 2019;572(7769):329–334. doi: 10.1038/s41586-019-1451-5

34. Grönlund MM, Grześkowiak Ł, Isolauri E, et al. Influence of mother’s intestinal microbiota on gut colonization in the infant. Gut Microbes. 2011;2(4):227–233. doi: 10.4161/gmic.2.4.16799

35. Kim H, Sitarik AR, Woodcroft K, et al. Breastfeeding, Pet Exposure, and Antibiotic Use: Associations With the Gut Microbiome and Sensitization in Children. Curr Allergy Asthma Rep. 2019;19(4):22. doi: 10.1007/s11882-019-0851-9

36. Shao Y, Forster SC, Tsaliki E, et al. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature. 2019;574(7776):117–121. doi: 10.1038/s41586-019-1560-1

37. Yang B, Chen Y, Stanton C, et al. Bifidobacterium and Lactobacillus Composition at Species Level and Gut Microbiota Diversity in Infants before 6 Weeks. Int J Mol Sci. 2019;20(13):3306. doi: 10.3390/ijms20133306

38. Nagpal R, Tsuji H, Takahashi T, et al. Ontogenesis of the Gut Microbiota Composition in Healthy, Full-Term, Vaginally Born and Breast-Fed Infants over the First 3 Years of Life: A Quantitative Bird’s-Eye View. Front Microbiol. 2017;8:1388. doi: 10.3389/fmicb.2017.01388

39. Kim G, Bae J, Kim MJ, et al. Delayed Establishment of Gut Microbiota in Infants Delivered by Cesarean Section. Front Microbiol. 2020;11:2099. doi: 10.3389/fmicb.2020.02099

40. Jakobsson HE, Abrahamsson TR, Jenmalm MC, et al. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut. 2014;63(4):559–566. doi: 10.1136/gutjnl-2012-303249

41. Sitarik AR, Havstad SL, Johnson CC, et al. Association between cesarean delivery types and obesity in preadolescence. Int J Obes (Lond). 2020;44(10):2023–2034. doi: 10.1038/s41366-020-00663-8

42. 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(6):690–703. doi: 10.1016/j.chom.2015.04.004

43. Tapiainen T, Paalanne N, Tejesvi MV, et al. Maternal influence on the fetal microbiome in a population-based study of the firstpass meconium. Pediatr Res. 2018;84(3):371–379. doi: 10.1038/pr.2018.29

44. Le Doare K, Holder B, Bassett A, et al. Mother’s Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity. Front Immunol. 2018;9:361. doi: 10.3389/fimmu.2018.00361

45. Lyons KE, Ryan CA, Dempsey EM, et al. Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health. Nutrients. 2020;12(4):1039. doi: 10.3390/nu12041039

46. Eshaghi M, Bibalan MH, Rohani M, et al. Bifidobacterium obtained from mother’s milk and their infant stool; A comparative genotyping and antibacterial analysis. Microb Pathog. 2017;111:94–98. doi: 10.1016/j.micpath.2017.08.014

47. Khodayar-Pardo P, Mira-Pascual L, Collado MC, et al. Impact of lactation stage, gestational age and mode of delivery on breast milk microbiota. J Perinatol. 2014;34(8):599–605. doi: 10.1038/jp.2014.47

48. Moossavi S, Azad MB. Origins of human milk microbiota: New evidence and arising questions. Gut Microbes. 2020;12(1):1667722. doi: 10.1080/19490976.2019.1667722

49. Łubiech K, Twaruzek M. Lactobacillus Bacteria in Breast Milk. Nutrients. 2020;12(12):3783. doi: 10.3390/nu12123783

50. Toscano M, De Grandi R, Grossi E, et al. Role of the Human Breast Milk-Associated Microbiota on the Newborns’ Immune System: A Mini Review. Front Microbiol. 2017;8:2100. doi: 10.3748/wjg.v21.i29.8787

51. Soto A, Martín V, Jiménez E, et al. Lactobacilli and bifidobacteria in human breast milk: Influence of antibiotherapy and other host and clinical factors. J Pediatric Gastroenterol Nutr. 2014;59(1):78–88. doi: 10.1097/MPG.0000000000000347

52. Mastromarino P, Capobianco D, Miccheli A, et al. Administration of a multistrain probiotic product (VSL#3) to women in the perinatal period di_erentially a_ects breast milk beneficial microbiota in relation to mode of delivery. Pharmacol Res. 2015;95–96:63–70. doi: 10.1016/j.phrs.2015.03.013

53. Abrahamsson TR, Sinkiewicz G, Jakobsson T, et al. Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life. J Pediatric Gastroenterol Nutr. 2009;49:349–354. doi: 10.1016/j.phrs.2015.03.013

54. Arroyo R, Martín V, Maldonado A, et al. Treatment of infectious mastitis during lactation: Antibiotics versus oral administration of lactobacilli isolated from breast milk. Clin Infect Dis. 2010;50: 1551–1558. doi: 10.1086/652763

55. Beasley SS, Saris PEJ. Nisin-producing Lactococcus lactis trains isolated from human milk. Appl Environ Microbiol. 2004;70(8): 5051–5053. doi: 10.1128/AEM.70.8.5051-5053.2004

56. Díaz-Ropero M, Martín R, Sierra S, et al. Two Lactobacillus strains, isolated from breast milk, differently modulate the immune response. J Appl Microbiol. 2007;102(2):337–343. doi: 10.1111/j.1365-2672.2006.03102.x

57. Jones KM, Power ML, Queenan JT, et al. Racial and Ethnic Disparities in Breastfeeding. Breastfeed Med. 2015;10(4): 186–196. doi: 10.1089/bfm.2014.0152

58. Azad MB, Nickel NC, Bode L, et al. Breastfeeding and the origins of health: Interdisciplinary perspectives and priorities. Matern Child Nutr. 2021;17(2):e13109. doi: 10.1111/mcn.13109

59. Reshetnik LA. Vskarmlivanie detei pervogo goda: Tutorial. Irkutsk: Irkutsk State Medical University; 2019. 51 p. (In Russ).

60. Lönnerdal B. Infant formula and infant nutrition: bioactive proteins of human milk and implications for composition of infant formulas. Am J Clin Nutr. 2014;99(3):712S–717S. doi: 10.3945/ajcn.113.071993

61. Almeida CC, Mendonça Pereira BF, Leandro KC, et al. Bioactive Compounds in Infant Formula and Their Effects on Infant Nutrition and Health: A Systematic Literature Review. Int J Food Sci. 2021;2021:8850080. doi: 10.1155/2021/8850080

62. Smilowitz JT, O’Sullivan A, Barile D, et al. The human milk metabolome reveals diverse oligosaccharide profiles. J Nutr. 2013; 143(11):1709–1718. doi: 10.3945/jn.113.178772

63. Browne PD, Aparicio M, Alba C, et al. Human milk microbiome and maternal postnatal psychosocial distress. Front Microbiol. 2019;10:2333. doi: 10.3389/fmicb.2019.02333

64. Anjum J, Nazir S, Tariq M, et al. Lactobacillus commensals autochthonous to human milk have the hallmarks of potent probio tics. Microbiology (Reading). 2020;166(10):966–980. doi: 10.1099/mic.0.000966

65. Azagra-Boronat I, Tres A, Massot-Cladera M, et al. Rodríguez-Lagunas. Lactobacillus fermentum CECT5716 Supplementation in Rats during Pregnancy and Lactation Impacts Maternal and O_spring Lipid Profile, Immune System and Microbiota. Cells. 2020;9(3):575. doi: 10.3390/cells9030575

66. Maldonado J, Cañabate F, Sempere L, et al. Human milk probiotic Lactobacillus fermentum CECT5716 reduces the incidence of gastrointestinal and upper respiratory tract infections in infants. J Pediatr Gastroenterol Nutr. 2012;54(1):55–61. doi: 10.1097/MPG.0b013e3182333f18

67. Gil-Campos M, López MÁ, Rodriguez-Benítez MV, et al. Lactobacillus fermentum CECT 5716 is safe and well tolerated in infants of 1–6 months of age: A randomized controlled trial. Pharmacol Res. 2012;65(2):231–238. doi: 10.1016/j.phrs.2011.11.016

68. Martín R, Langa S, Reviriego C, et al. Human milk is a source of lactic acid bacteria for the infant gut. J Pediatr. 2003;143:754–758. doi: 10.1016/j.jpeds.2003.09.028

69. Kocabay S, Çetinkaya S. Probiotic Properties of a Lactobacillus fermentum Isolated from Newborn Faeces. J Oleo Sci. 2020; 69(12):1579–1584. doi: 10.5650/jos.ess20224

70. Maldonado-Lobón 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. doi: 10.1016/j.phrs.2015.01.006

71. Pérez-Cano FJ, Dong H, Yaqoob P. In vitro immunomodulatory activity of Lactobacillus fermentum CECT5716 and Lactobacillus salivarius CECT5713: two probiotic strains isolated from human breast milk. Immunobiology. 2010;215(12):996–1004. doi: 10.1016/j.imbio.2010.01.004

72. Maldonado J, Gil-Campos M, Maldonado-Lobón JA, et al. Evaluation of the safety, tolerance and efficacy of 1-year consumption of infant formula supplemented with Lactobacillus fermentum CECT5716 Lc40 or Bifidobacterium breve CECT7263: a randomized controlled trial. BMC Pediatr. 2019;19(1):361. doi: 10.1186/s12887-019-1753-7

73. López-Huertas E. Safety and efficacy of human breast milk Lactobacillus fermentum CECT 5716. A mini-review of studies with infant formulae. Benef Microbes. 2015;6(2):219–224. doi: 10.3920/BM2014.0091

74. Ben XM, Li J, Feng ZT, et al. Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli. World J Gastroenterol. 2008;14(42):6564–6568. doi: 10.3748/wjg.14.6564

75. Fanaro S, Marten B, Bagna R, et al. Galacto-oligosaccharides are bifidogenic and safe at weaning: a double-blind randomized multicenter study. J Pediatr Gastroenterol Nutr. 2009;48(1):82–88. doi: 10.1097/MPG.0b013e31817b6dd2

76. Olivares M, Díaz-Ropero MP, Sierra S, et al. Oral intake of Lactobacillus fermentum CECT5716 enhances the effects of influenza vaccination. Nutrition. 2007;23(3):254–260. doi: 10.1016/j.nut.2007.01.004

77. Drover JR, Hoffman DR, Castañeda YS, et al. Cognitive function in 18-month-old term infants of the DIAMOND study: a randomized, controlled clinical trial with multiple dietary levels of docosahexaenoic acid. Early Hum Dev. 2011;87(3):223–230. doi: 10.1016/j.earlhumdev.2010.12.047

78. Mie A, Andersen HR, Gunnarsson S, et al. Human health implications of organic food and organic agriculture: a comprehensive review. Environ Health. 2017;16(1):111. doi: 10.1186/s12940-017-0315-4

79. Średnicka-Tober D, Barański M, Seal CJ, et al. Higher PUFA and n-3 PUFA, conjugated linoleic acid, α-tocopherol and iron, but lower iodine and selenium concentrations in organic milk: a systema tic literature review and meta-and redundancy analyses. Br J Nutr. 2016;115(6):1043–1060. doi: 10.1017/S0007114516000349

80. Woods VB, Fearon AM. Dietary sources of unsaturated fatty acids for animals and their transfer into meat, milk and eggs: a review. Livest Sci. 2009;126(1):1–20. doi: 10.1016/j.livsci.2009.07.002


Review

For citations:


Belyaeva I.A., Namazova-Baranova L.S., Bombardirova E.P., Turti T.V., Sadchikov P.E. Targeted Development of Infant Microbiota on Formula Feeding: Modern Options. Current Pediatrics. 2021;20(6):484-491. (In Russ.) https://doi.org/10.15690/vsp.v20i6.2354

Views: 786


ISSN 1682-5527 (Print)
ISSN 1682-5535 (Online)