The use of probiotics in the management of necrotising enterocolitis in HIV exposed premature and very-low birth weight infants

The heavy burden of maternal HIV infection has resulted in a high prevalence of premature birth and associated necrotizing enterocolitis (NEC). Human milk oligosaccharides (HMOs) were recently associated with HIV infection and transmission through breastfeeding and were also shown to reduce NEC in an animal model, particularly the HMO disialyllacto-Ntetraose (DSLNT). The primary aim of this study was to verify differences in HMO composition between HIV-infected and HIV-uninfected women. The secondary aim was to assess whether the HMO composition in the milk of mothers whose infants were diagnosed with NEC differs from that of mothers whose infants did not develop NEC. This study forms part of a larger clinical trial conducted at the Tygerberg Children's Hospital, Cape Town, South Africa, which recruited HIV-infected and HIV-uninfected mothers and their preterm infants (<34 wk gestation; $500 and #1250 g). Eighty-two mother-infant pairs were selected for the substudy. Mother-infant pairs were stratified according to the mother's HIV (infected/ uninfected) and secretor status (secretor/nonsecretor). HMOs in 4and 28-d postpartum milk samples were analyzed by HPLC and compared between groups. Our results confirm previous reports that HIV-infected mothers have higher relative abundances of 3#-sialyllactose in their milk compared with HIV-uninfected mothers (10.7% vs. 6.8%; P < 0.01). Most intriguingly, the data also indicated that low concentrations of DSLNT in the 4-d milk samples in the mother's milk increased the infant's risk of NEC (200 6 126 vs. 345 6 186 mg/mL; P < 0.05), which is in accordance with results from previously published animal studies and warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01868737. J. Nutr. 144: 1227–1233, 2014. Introduction The heavy burden of maternal HIV infection has contributed to the prevalence of premature birth and necrotizing enterocolitis (NEC) (1,2), one of the most common intestinal disorders in preterm infants (3). Human milk oligosaccharides (HMOs) 1 Supported by various sources; the main sources were National Research Foundation, Nestlé Nutrition Institute Africa, the Medical Research Council, and Faculty of Medicine and Health Sciences, Stellenbosch University. 2 Author disclosures: E. Van Niekerk, C. A. Autran, D. G. Nel, G. F. Kirsten, R. Blaauw, and L. Bode, no conflicts of interest. 3 Supplemental Figure 1 is available from the ‘‘Online Supporting Material’’ link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition. org. 8 Abbreviations used: DFLNH, difucosyllacto-N-hexaose; DSLNT, disialyllactoN-tetraose; FUT2, fucosyltransferase 2; HMO, human milk oligosaccharide; LNFP, lacto-N-fucopentaose; NEC, necrotizing enterocolitis; Se, secretor; TBCH, Tygerberg Children's Hospital; 3#SL, 3#-sialyllactose. * To whom correspondence should be addressed. E-mail: evettev@sun.ac.za. (4,5), complex carbohydrates that are highly abundant in breast milk but not in infant formula (6), were recently associated with HIV infection and transmission through breastfeeding (7) and were also shown to reduce NEC in an animal model (8). More than 100 structurally distinct HMOs have been identified (9). Concentrations of individual oligosaccharides vary with gestation (term vs. preterm), over the course of lactation, and from one mother to another (5). Interpersonal HMO variations are most pronounced for a1-2-fucosylated HMO. a1-2-Fucosylation of milk oligosaccharides is catalyzed by the enzyme fucosyltransferase 2 (FUT2), encoded by the secretor (Se), which also affects a person's Se blood group status (10,11). Women with an active Se locus (secretors) express a functional FUT2 enzyme, and their milk contains high concentrations of a1-2-fucosylated HMOs [e.g., 2#fucosyllactose or lacto-N-fucopentaose (LNFP) 1]. Nonsecretors lack a functional FUT2 enzyme, and their milk does not contain a12-fucosylated HMOs. Given the accumulating evidence in support ã 2014 American Society for Nutrition. Manuscript received November 4, 2013. Initial review completed November 29, 2013. Revision accepted May 16, 2014. 1227 First published online June 11, 2014; doi:10.3945/jn.113. 187799. Stellenbosch University http://scholar.sun.ac.za