Human milk oligosaccharides (HMO) receive a lot scientific interest in the field of infant nutrition. Novel technologies enable to produce isolated HMO isoforms at large scale, enabling their use as food ingredient. In the European Union first HMO are permitted as novel food for addition to infant formula.
Publications on HMO have quadrupled since 2010 (National Library of Medicine https://pubmed.ncbi.nlm.nih.gov/). This is because novel processing techniques allow production of certain HMO isoforms on industrial scale (Faijes et al. 2019; Sprenger et al. 2017). Until the turn of this millennium, human milk oligosaccharides could only be extracted from mother's milk, their function tested small scale and limited to laboratory settings (Bode et al. 2016; Furuike et al. 2003). Cow's or goat's milk are poor sources for milk oligosaccharides because concentrations are low and lack the diversity of those in human milk (Zeuner et al. 2019).
These generated molecules are structurally identical to those isolated from mother's milk. Four of these – 2'‑fucosyllactose (2'‑FL) – lacto‑N‑neotetraose (LNnT) – the mixture of 2'‑fucosyllactose with difucosyllactose (DiFL) – and as of April 2020, lacto‑N‑tetraose (LNT) are permitted on the European market and in food for infants (EU/2016/375; EU/2016/376; EU/2019/1979; EU/2020/484).
As part of the novel food application process in Europe, a safety evaluation is made by the European Food Safety Agency (EFSA) on behalf of the European Commission. Novel food applications are currently ongoing for 3'‑ and 6'-sialyllactose (3'‑SL and 6'‑SL, respectively) [https://ec.europa.eu/food/safety/novel_food/authorisations/summary-applications-and-notifications_en]. As a consequence, communication on these components in foods is increasing in parallel to the novel scientific insights on their function and potential health benefits generated at high pace.
HMO addition to infant food may be benficial and they may be prebiotic, reduce infection risk, promote the immune system and cognitive development, and provide sialic acid, needed for brain development.
Bode L, Contractor N, Barile D, Pohl N, Prudden AR, Boons G-J, Jin Y-S, Jennewein S. Overcoming the limited availability of human milk oligosaccharides: challenges and opportunities for research and application. Nutrition reviews 2016; 74(10):635–44. at: www.ncbi.nlm.nih.gov/pubmed/27634978
Commission Implementing Decision (EU) 2016/375 of 11 March 2016 authorising the placing on the market of lacto-N-neotetraose as a novel food ingredient under Regulation (EC) No 258/97 of the European Parliament and of the Council (notified under document C(2016) 1419): EU CELEX_32016D0375. at: https://eur-lex.europa.eu/legal-content/GA/TXT/?uri=CELEX:32016D0375
Commission Implementing Decision (EU) 2016/376 of 11 March 2016 authorising the placing on the market of 2′-O-fucosyllactose as a novel food ingredient under Regulation (EC) No 258/97 of the European Parliament and of the Council (notified under document C(2016) 1423): CELEX_32016D0376 [status of: 2020 Feb 24]. at: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32016D0376
Commission implementing Regulation (EU) 2019/1979 of 26 November 2019 authorising the placing on the market of 2'-Fucosyllactose/Difucosyllactose mixture as a novel food under Regulation (EU) 2015/2283 of the European Parliament and of the Council and amending Commission Implementing Regulation (EU) 2017/2470 (Text with EEA relevance): CELEX_32019R1979. at: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32019R1979
Commission Implementing Regulation (EU) 2020/484 of 2 April 2020 authorising the placing on the market of lacto-N-tetraose as a novel food under Regulation (EU) 2015/2283 of the European Parliament and of the Council and amending Commission Implementing Regulation (EU) 2017/2470 (Text with EEA relevance): EUR-Lex - 32020R0484 - EN - EUR-Lex [status of: 2020 May 19]. at: https://eur-lex.europa.eu/legal-content/EN/TXT/?qid=1518461535841&uri=CELEX:32020R0484
EFSA NDA. Safety of 2′‐O‐fucosyllactose as a novel food ingredient pursuant to Regulation (EC) No 258/97. EFSA Journal 2015a; 13(7):1313. at: https://www.efsa.europa.eu/en/efsajournal/pub/4184
EFSA NDA. Safety of lacto‐N‐neotetraose and 2′‐O‐fucosyllactose as novel food ingredients in food supplements for children. EFSA Journal 2015b; 13(11):32. at: https://www.efsa.europa.eu/en/efsajournal/pub/4299
EFSA NDA. Safety of lacto‐N‐neotetraose as a novel food ingredient pursuant to Regulation (EC) No 258/97. EFSA Journal 2015c; 13(7). at: https://www.efsa.europa.eu/en/efsajournal/pub/4183
EFSA NDA. Safety of 2’‐fucosyllactose/difucosyllactose mixture as a novel food pursuant to Regulation (EU) 2015/2283: EFSA-Q-2018-00374. EFSA Journal 2019a [status of: 2020 May 19]; 17(6). at: https://www.efsa.europa.eu/en/efsajournal/pub/5717
EFSA NDA, Turck D, Castenmiller J, Henauw S de, Hirsch‐Ernst KI, Kearney J, Maciuk A, Mangelsdorf I, McArdle HJ, Naska A, Pelaez C, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Cubadda F, Engel K‐H, Frenzel T, Heinonen M, Marchelli R, Neuhäuser‐Berthold M, Poulsen M, Sanz Y, Schlatter JR, van Loveren H, Colombo P, Knutsen HK. Safety of lacto‐N‐tetraose (LNT) as a novel food pursuant to Regulation (EU) 2015/2283. EFSA Journal 2019b; 17(12). at: https://www.efsa.europa.eu/en/efsajournal/pub/5907
Faijes M, Castejón-Vilatersana M, Val-Cid C, Planas A. Enzymatic and cell factory approaches to the production of human milk oligosaccharides. Biotechnology advances 2019; 37(5):667–97. at: https://pubmed.ncbi.nlm.nih.gov/30935964
Sprenger GA, Baumgärtner F, Albermann C. Production of human milk oligosaccharides by enzymatic and whole-cell microbial biotransformations. Journal of biotechnology 2017; 258:79–91. at: https://pubmed.ncbi.nlm.nih.gov/28764968
Zeuner B, Teze D, Muschiol J, Meyer AS. Synthesis of Human Milk Oligosaccharides: Protein Engineering Strategies for Improved Enzymatic Transglycosylation. Molecules (Basel, Switzerland) 2019; 24(11). at: https://pubmed.ncbi.nlm.nih.gov/31141914back