scholarly journals Associations of Human Milk Oligosaccharides and Bioactive Proteins with Infant Morbidity and Inflammation Among Malawian Mother-Infant Dyads

Author(s):  
Josh M Jorgensen ◽  
Rebecca Young ◽  
Per Ashorn ◽  
Ulla Ashorn ◽  
David Chaima ◽  
...  

ABSTRACT Background Human milk oligosaccharides (HMOs) and bioactive proteins likely benefit infant health, but information on these relationships is sparse. Objective We aimed to examine associations of milk content of HMOs and bioactive proteins with incidence and longitudinal prevalence of infant morbidity (any illness, fever, diarrhea, acute respiratory infection, and loss of appetite) and markers of inflammation [C-reactive protein (CRP) and α-1-acid glycoprotein (AGP)]. These are secondary analyses of a randomized controlled trial. Methods Breast milk samples at 6 mo postpartum (n = 659) were analyzed to quantify absolute abundance of HMOs, relative abundance of fucosylated HMOs, sialylated HMOs, and 51 individual HMOs, and concentrations of 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of these constituents with infant morbidity from 6 to 7 and 6 to 12 mo, and CRP and AGP at 6 and 18 mo, considering maternal secretor status (FUT2 gene positive) and adjusting for covariates and multiple hypothesis testing. Results Among secretors there were positive associations between total HMOs and longitudinal prevalence of fever (p = 0.032), fucosylated HMOs and incidence of diarrhea (p = 0.026), and lactoferrin and elevated CRP at 18 mo (p = 0.011). Among non-secretors, there were inverse associations between lactoferrin and incidence of fever (p = 0.007), osteopontin and longitudinal prevalence of lost appetite (p = 0.038), and fucosylated HMOs and incidence of diarrhea (p = 0.025), lost appetite (p = 0.019), and concentrations of AGP and CRP at 6 mo (p = 0.001 and 0.010); and positive associations between total HMOs and incidence of lost appetite (p = 0.024) and elevated CRP at 18 mo (p = 0.026), lactalbumin and incidence of diarrhea (p = 0.006), and lactoferrin and elevated CRP at 18 mo (p = 0.015). Conclusion Certain HMOs and bioactive proteins were associated with infant morbidity and inflammation, particularly among non-secretors. Further research is needed to elucidate causality of these relationships. Registered at clinicaltrials.gov as NCT01239693. This trial was registered at clinicaltrials.gov as NCT01239693.

2019 ◽  
Vol 14 (2) ◽  
pp. 635-648 ◽  
Author(s):  
Melissa A. E. Lawson ◽  
Ian J. O’Neill ◽  
Magdalena Kujawska ◽  
Sree Gowrinadh Javvadi ◽  
Anisha Wijeyesekera ◽  
...  

AbstractDiet-microbe interactions play an important role in modulating the early-life microbiota, with Bifidobacterium strains and species dominating the gut of breast-fed infants. Here, we sought to explore how infant diet drives distinct bifidobacterial community composition and dynamics within individual infant ecosystems. Genomic characterisation of 19 strains isolated from breast-fed infants revealed a diverse genomic architecture enriched in carbohydrate metabolism genes, which was distinct to each strain, but collectively formed a pangenome across infants. Presence of gene clusters implicated in digestion of human milk oligosaccharides (HMOs) varied between species, with growth studies indicating that within single infants there were differences in the ability to utilise 2′FL and LNnT HMOs between strains. Cross-feeding experiments were performed with HMO degraders and non-HMO users (using spent or ‘conditioned’ media and direct co-culture). Further 1H-NMR analysis identified fucose, galactose, acetate, and N-acetylglucosamine as key by-products of HMO metabolism; as demonstrated by modest growth of non-HMO users on spend media from HMO metabolism. These experiments indicate how HMO metabolism permits the sharing of resources to maximise nutrient consumption from the diet and highlights the cooperative nature of bifidobacterial strains and their role as ‘foundation’ species in the infant ecosystem. The intra- and inter-infant bifidobacterial community behaviour may contribute to the diversity and dominance of Bifidobacterium in early life and suggests avenues for future development of new diet and microbiota-based therapies to promote infant health.


2020 ◽  
Vol 113 (1) ◽  
pp. 209-220
Author(s):  
Josh M Jorgensen ◽  
Rebecca Young ◽  
Per Ashorn ◽  
Ulla Ashorn ◽  
David Chaima ◽  
...  

ABSTRACT Background Human milk oligosaccharides (HMOs) and bioactive breast milk proteins have many beneficial properties. Information is sparse regarding associations between these milk constituents and infant growth and development in lower-income countries. Objectives We aimed to examine associations of milk content of HMOs and bioactive proteins at 6 mo postpartum with infant growth and motor and cognitive development. These are secondary analyses of a randomized controlled trial in rural Malawi. Methods Breast milk samples were analyzed at 6 mo (n = 659) for general categories of HMOs (total HMOs, fucosylated HMOs, and sialylated HMOs), 51 individual HMOs, and 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of the relative abundances of HMOs and concentrations of bioactive proteins with infant growth from 6 to 12 mo [change in length-for-age (ΔLAZ), weight-for-age, weight-for-length, and head circumference z-scores] as well as ability to stand or walk alone at 12 mo, and motor and language skills, socioemotional development, executive function, and working memory at 18 mo. Analyses were adjusted for covariates and multiple hypothesis testing. Results Among all participants, there were inverse associations of IgA and lactoferrin concentrations with motor skills (P = 0.018 and P = 0.044), and a positive association of lactalbumin concentration with motor skills (P = 0.038). Among secretors only [fucosyltransferase 2 gene (FUT2) positive], there were positive associations of absolute abundance of HMOs with ΔLAZ (P = 0.035), and relative abundance of fucosylated and sialylated HMOs with language at 18 mo (P < 0.001 and P = 0.033, respectively), and inverse associations of osteopontin with standing and walking at 12 mo (P = 0.007 and 0.002, respectively). Relative abundances of several individual HMOs were associated with growth and development, mostly among secretors. Conclusions Certain bioactive breast milk proteins and HMOs are associated with infant growth and motor and cognitive development. Further studies are needed to determine if a causal relation exists. This trial was registered at clinicaltrials.gov as NCT01239693.


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