Human-identical milk oligosaccharides in infant formula products in Australia and New Zealand

Human milk oligosaccharides (HMOs), which account for the third largest component of human milk, transit to the large intestine where they are fermented by gastrointestinal microbiota, or excreted unchanged (1) . Recent advances in gene technology utilising microbial fermentation have allowed for the manufacture of human-identical milk oligosaccharides (HiMOs), which are chemically and structurally identical to the naturally occurring form. The HiMOs that have been manufactured are 2′-fucosyllactose (2′-FL), lacto-N-neotetraose, difucosyllactose, lacto-N-tetraose, 6′-sialyllactose and 3′-siallyllactose. The naturally occurring versions of these represent the most abundant in human milk, with 2′-FL identified in the greatest amounts (2) . A pre-market assessment by Food Standards Australia New Zealand (FSANZ) of these substances is required prior to inclusion in infant formula products. The assessment aimed to examine the safety and health effects of the addition of HiMOs to infant formula in Australia and New Zealand in place of currently permitted non-human identical oligosaccharides. Multidisciplinary teams assessed applications (n = 7) to permit six HiMOs in infant formula. Specifically, the safety assessment included the genetically modified microbiological matter for production, the adverse effects of consumption, and any impacts on infant growth. The health effects assessment identified the benefit of HiMO consumption for infants. Risk analysis was used to assess in vitro , ex vivo , animal and human studies, and to consider relevant Ministerial Policy Guidelines. No public health and safety risks were identified for the addition of HiMOs to infant formula, including when the substances are added cumulatively at the requested amounts. No safety concerns were identified for the gene donors or microbial sources for any of the manufactured HiMOs. No adverse effects to recipients that consumed HiMOs were identified in both clinical and laboratory settings, with a no observed adverse effect level of 2′-FL observed at 7500 mg/kg. No difference in growth outcomes was observed between infants who consumed formula with or without HiMO supplementation (p < 0.05), with no clinical significance observed (±3 g/day). Two substantiated health benefits for HMOs were identified; the promotion of a bifidogenic effect (reported in n = 39 studies), and limiting infection by pathogens including Campylobacter jejuni (reported in n = 25 studies). The development of a microbiota profile closer to that of breastfed infants is supported by the inclusion of a wider range of HiMOs in infant formula products. Based on these results, FSANZ permits the voluntary addition of six HiMOs to infant formula to create products that better reflect the oligosaccharide profile of human milk to support the normal growth and development of infants. Assessments of applications to expand these permissions are ongoing. This suggests that based on innovation and economies of scale, HiMOs could one day replace the previously used non-digestible oligosaccharides in infant formula products.