Associations Between Human Milk Oligosaccharides and Infant Growth in a Bangladeshi Mother-infant Cohort

Overview

Journal Pediatr Res

Specialties Biology
Pediatrics

Date 2023 Dec 5

PMID 38052861

Authors

Miranda G Loutet

Arash Narimani

Huma Qamar

Chloe Yonemitsu

Lisa G Pell

Abdullah Al Mahmud

Tahmeed Ahmed

Lars Bode

Diego G Bassani

Daniel E Roth

Affiliations

Soon will be listed here.

Abstract

Background: We aimed to estimate associations between human milk oligosaccharides (HMOs) and infant growth (length-for-age (LAZ) and weight-for-length (WLZ) z-scores) at 12 months postnatal age.

Methods: In this secondary analysis of data from a maternal vitamin D trial in Dhaka, Bangladesh (N = 192), absolute concentrations of HMOs were measured in 13 ± 1 week(s) postpartum milk samples, infant anthropometric measurements were obtained soon after birth and at 12 months postpartum, and infant feeding was classified during 6 months postpartum. Associations between individual HMOs or HMO groups and LAZ or WLZ were estimated by multivariable linear regression adjusting for infant feeding pattern, maternal secretor status, and other potential confounders.

Results: The concentrations of 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated HMOs were inversely associated with LAZ at 12 months of age, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months. These associations were robust in analyses restricted to infants who were primarily exclusively/predominantly fed human milk during the first 3 (or 6) months.

Conclusions: Since HMOs are both positively and negatively associated with postnatal growth, there is a need for randomized trials to estimate the causal benefits and risks of exogenously administered HMOs on infant growth and other health outcomes.

Impact: 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated human milk oligosaccharides (HMOs) were inversely associated with length-for-age z-scores (LAZ) at 12 months, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months among Bangladeshi infants. Associations between individual and grouped HMOs with infant length growth at 12 months were as strong or stronger in analyses restricted to infants who were exclusively or predominantly fed human milk up to 3 (or 6) months. Randomized trials are needed to characterize the effects of specific HMOs on infant growth, particularly in countries where postnatal linear growth faltering is common.

Citing Articles

The Role of Milk Oligosaccharides in Enhancing Intestinal Microbiota, Intestinal Integrity, and Immune Function in Pigs: A Comparative Review.

Gormley A, Garavito-Duarte Y, Kim S Biology (Basel). 2024; 13(9).

PMID: 39336091 PMC: 11428639. DOI: 10.3390/biology13090663.

References

Christian P, Smith E, Lee S, Vargas A, Bremer A, Raiten D . The need to study human milk as a biological system. Am J Clin Nutr. 2021; 113(5):1063-1072. PMC: 8106761. DOI: 10.1093/ajcn/nqab075. View

Ma J, Palmer D, Geddes D, Lai C, Stinson L . Human Milk Microbiome and Microbiome-Related Products: Potential Modulators of Infant Growth. Nutrients. 2022; 14(23). PMC: 9737635. DOI: 10.3390/nu14235148. View

Bode L . Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012; 22(9):1147-62. PMC: 3406618. DOI: 10.1093/glycob/cws074. View

Zivkovic A, German J, Lebrilla C, Mills D . Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci U S A. 2010; 108 Suppl 1:4653-8. PMC: 3063602. DOI: 10.1073/pnas.1000083107. View

Gnoth M, Kunz C, Kinne-Saffran E, Rudloff S . Human milk oligosaccharides are minimally digested in vitro. J Nutr. 2000; 130(12):3014-20. DOI: 10.1093/jn/130.12.3014. View

Engfer M, Stahl B, Finke B, Sawatzki G, Daniel H . Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. Am J Clin Nutr. 2000; 71(6):1589-96. DOI: 10.1093/ajcn/71.6.1589. View

Bridgman S, Azad M, Field C, Haqq A, Becker A, Mandhane P . Fecal Short-Chain Fatty Acid Variations by Breastfeeding Status in Infants at 4 Months: Differences in Relative versus Absolute Concentrations. Front Nutr. 2017; 4:11. PMC: 5385454. DOI: 10.3389/fnut.2017.00011. View

Gustafsson A, Hultberg A, Sjostrom R, Kacskovics I, Breimer M, Boren T . Carbohydrate-dependent inhibition of Helicobacter pylori colonization using porcine milk. Glycobiology. 2005; 16(1):1-10. DOI: 10.1093/glycob/cwj031. View

Simon P, Goode P, Mobasseri A, Zopf D . Inhibition of Helicobacter pylori binding to gastrointestinal epithelial cells by sialic acid-containing oligosaccharides. Infect Immun. 1997; 65(2):750-7. PMC: 176121. DOI: 10.1128/iai.65.2.750-757.1997. View

10.

Bode L . The functional biology of human milk oligosaccharides. Early Hum Dev. 2015; 91(11):619-22. DOI: 10.1016/j.earlhumdev.2015.09.001. View

11.

Rudloff S, Obermeier S, Borsch C, Pohlentz G, Hartmann R, Brosicke H . Incorporation of orally applied (13)C-galactose into milk lactose and oligosaccharides. Glycobiology. 2006; 16(6):477-87. DOI: 10.1093/glycob/cwj092. View

12.

Rudloff S, Pohlentz G, Borsch C, Lentze M, Kunz C . Urinary excretion of in vivo ¹³C-labelled milk oligosaccharides in breastfed infants. Br J Nutr. 2011; 107(7):957-63. DOI: 10.1017/S0007114511004016. View

13.

Rudloff S, Pohlentz G, DIEKMANN L, EGGE H, Kunz C . Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula. Acta Paediatr. 1996; 85(5):598-603. DOI: 10.1111/j.1651-2227.1996.tb14095.x. View

14.

Kumazaki T, Yoshida A . Biochemical evidence that secretor gene, Se, is a structural gene encoding a specific fucosyltransferase. Proc Natl Acad Sci U S A. 1984; 81(13):4193-7. PMC: 345395. DOI: 10.1073/pnas.81.13.4193. View

15.

Johnson P, WATKINS W . Purification of the Lewis blood-group gene associated alpha-3/4-fucosyltransferase from human milk: an enzyme transferring fucose primarily to type 1 and lactose-based oligosaccharide chains. Glycoconj J. 1992; 9(5):241-9. DOI: 10.1007/BF00731136. View

16.

Kunz C, Rudloff S, Baier W, Klein N, Strobel S . Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr. 2000; 20:699-722. DOI: 10.1146/annurev.nutr.20.1.699. View

17.

Erney R, Malone W, Skelding M, Marcon A, Kleman-Leyer K, ORyan M . Variability of human milk neutral oligosaccharides in a diverse population. J Pediatr Gastroenterol Nutr. 2000; 30(2):181-92. DOI: 10.1097/00005176-200002000-00016. View

18.

McGuire M, Meehan C, McGuire M, Williams J, Foster J, Sellen D . What's normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically. Am J Clin Nutr. 2017; 105(5):1086-1100. PMC: 5402033. DOI: 10.3945/ajcn.116.139980. View

19.

Azad M, Robertson B, Atakora F, Becker A, Subbarao P, Moraes T . Human Milk Oligosaccharide Concentrations Are Associated with Multiple Fixed and Modifiable Maternal Characteristics, Environmental Factors, and Feeding Practices. J Nutr. 2018; 148(11):1733-1742. DOI: 10.1093/jn/nxy175. View

20.

Han S, Derraik J, Binia A, Sprenger N, Vickers M, Cutfield W . Maternal and Infant Factors Influencing Human Milk Oligosaccharide Composition: Beyond Maternal Genetics. J Nutr. 2021; 151(6):1383-1393. DOI: 10.1093/jn/nxab028. View