What is Lacto-N-neotetraose (LNnT)?

November 19, 2023 7 min read

LNNT, human milk oligosaccharides, SuperHMO prebiotic mix

Human milk is fundamental to the development of the neonate. There is, of course, the option of formula, but even then, this has to contain the many bioactive ingredients that human milk delivers, if successful development is going to be achieved.

Amongst these bioactive ingredients are human milk oligosaccharides (HMOs), the sugar or energy part of mums’ milk. Scientific research shows that human milk consists of many components, and each appears to have a special role. You could think of them as specific keys for specific locks. HMOs are no different and for this reason, have gathered lots of traction in the scientific research world.

One such HMO is lacto-N-neotetraose (LNnT). and science is showing this HMO could hold many keys to human health, and that is exactly what we will be investigating in this article. So, please join us as we unlock the many gifts LNnT has to offer.

What is Lacto-N-neotetraose?

LNnT has been identified as one of the most abundant HMOs present in human breast milk. In recent years, scientific research has identified LNnT as a prebiotic or food for good gut bacteria. Alongside this, LNnT has other benefits such as antiadhesive properties, enabling this HMO to interact with your intestinal cells, making it difficult for potential pathogenic bacteria to attach and cause serious damage.  

LNnT also possesses anti-viral protection. This protective mechanism sees the HMO mirror specific structures of the viral receptors, rendering the ability of viruses to attach to the host cell useless[i].

Also, in this line of defence, LNnT provides you with immune-modulating processes that enhance the immune system against disease[ii]. This is achieved via cell-to-cell binding and comes as a result of cell event recognition, a process that enhances overall communication and defence[iii].

It’s these important properties that have thrust LNnT into the scientific spotlight, and we’ll be taking a closer look later in this article.  

Structure of Lacto-N-neotetraose

LNnT is an isomer of lacto-N-tetraose (LNT). That means they contain the same number of atoms but are arranged in different ways. LNT represents the core structure of type 1 HMOs while LNnT represents type 2.

Structurally, LNnT consists of D-galactose, N-acetyl-D-glucosamine, D-galactose and D-glucose making it a four-monosaccharide unit or a tetrasaccharide[iv].

Structure of LNnT 

 

Figure 1. Structure of Lacto-N-neotetraose[v].

What are the benefits of Lacto-N-neotetraose?

As we began to allude to earlier, LNnT is a prebiotic that helps to build a robust gut microbiome, nourishing good bacteria and stimulating their growth and activity. But that’s not all, LNnT also plays pivotal roles in human immunity and may potentially alleviate some intolerable gastrointestinal symptoms.

Building Bifidobacteriacommunities

LNnT has an important role in promoting and building the initial gut microbiota in the infant. Its interaction assists in the building of Bifidobacteriastrains, one of the first species to populate the human intestine. Bifidobacteriaare essential for promoting the growth and health of the microbiome, and continued protection from invading pathogens.

Our first set of bacteria, including Bifidobacteriaand Lactobacilli strains, are provided by mum during birth and breastfeeding[vi]. From the moment we begin to feed on HMO-infused human milk, LNnT and others feed these bacterial strains, leading to an increased abundance of these colonies. By doing so, Bifidobacteriastrains become a more dominating class, producing beneficial metabolites like short-chain fatty acids (SCFAs) and cross-feeding other members of the microbial community.

Immune system

As our microbiota world is being established, so is our immune system. The human immune system is like an internal shield of protection, an important cascading network of communication. Your immune system is a pretty clever piece of kit, boasting a photographic memory that means it remembers the germs it has previously been exposed to. So, if you encounter it again, your immune system knows exactly how to react and rid them from your body.

HMOs including LNnT teach the immune system how to operate and function[vii]. As our immune system advances so do we. For example, during our early years, as we take our first steps, we become prone to falls, cuts, and grazes. This is just a natural part of growing up, and our immune system swings into action to deal with inflammation and infection. Interestingly, some studies have shown that LNnT specifically accelerates the wound healing process and also holds anti-inflammatory properties[viii].

Furthermore, LNnT also induces type 2 immune responses, including the:

  • production of T helper cells
  • activation of B cells
  • activation of cytokine T cells[ix][x]

Dysbiosis

Establishing a healthy bacterial community promotes the activity and health of your gut and beyond. For many of us, this begins to be established from birth but other lifestyle factors, such as a poor diet, lack of exercise, stress, and even illness can lead to your microbiome becoming imbalanced, a state commonly referred to as dysbiosis[xi]

Dysbiosis can cause a whole array of side effects, some can be very painful, uncomfortable, or embarrassing. However, to date there have been numerous studies, where coupled with                2’-fucosyllactose (2’FL), LNnT assists in the relief of symptoms and improves the quality of life of irritable bowel syndrome patients[xii].

Hope for Inflammatory Bowel Disease and other chronic conditions

Because of their ability to shape the human gut, particularly through the stimulation of Bifidobacteria,HMOs are often investigated for their effects on gut barrier function. A leaky gut or compromised barrier function is often seen in conditions including IBS, IBD, and more generally in the ageing process.

In a study by Suligoi, et al (2020), the effects of HMOs on gut barrier function were investigated using a 4-1 mix of 2’FL and LNnT using a Simulated Human Intestinal Microbial Ecosystem (SHIME) model.

The results showed that introducing a mix of 2’FL and LNnT stimulated the growth of Bifidobacteria. In turn, this boosted SCFA production, specifically butyrate. In many studies, butyrate has been shown to have positive effects on the human immune function, and on chronic diseases, such as:

Overall, the results of the study show promise for HMOs being able to modulate the immune system, strengthen the gut lining, which is implicated in IBD and IBS, and promote overall good health.

Summary

Overall, LNnT is an important and abundant constituent of human breast milk, being one of the 200+ HMOs identified so far. An isomer of LNT, LNnT supports our growth and development, and that of our gut microbiome, from the initial stages of life.

Research shows that it has an integral role in establishing a solid foundation for our microbial communities, bolsters their abundance, and helps to modulate our immune system.

Why not explore our range of HMO products, including LNnT, to find out how you can support your own gut microbiota?        

Written byLeanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome. 

Sources

[i] Morozov V, Hansman G, Hanisch FG, Schroten H, Kunz C. Human Milk Oligosaccharides as Promising Antivirals. Mol Nutr Food Res. 2018 Mar;62(6):e1700679. doi: 10.1002/mnfr.201700679. Epub 2018 Mar 1. PMID: 29336526.

[ii] Hu M, Miao M, Li K, Luan Q, Sun G, Zhang T. Human milk oligosaccharide lacto-N-tetraose: Physiological functions and synthesis methods. Carbohydr Polym. 2023 Sep 15;316:121067. doi: 10.1016/j.carbpol.2023.121067. Epub 2023 May 25. PMID: 37321746.

[iii] Obrink B, Ocklind C. Cell-cell recognition: relation to cell adhesion with special reference to adhesion of hepatocytes. Blood Cells. 1983;9(2):209-19. PMID: 6661558.

[iv] Chen X. Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis. Adv Carbohydr Chem Biochem. 2015;72:113-90. doi: 10.1016/bs.accb.2015.08.002. Epub 2015 Nov 11. PMID: 26613816; PMCID: PMC9235823.

[v] EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA); Turck D, Castenmiller J, De Henauw S, 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, Frenzel T, Heinonen M, Marchelli R, Neuhäuser-Berthold M, Poulsen M, Maradona MP, Schlatter JR, van Loveren H, Colombo P, Knutsen HK. Safety of lacto-N-neotetraose (LNnT) produced by derivative strains of E. coli BL21 as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 2020 Nov 19;18(11):e06305. doi: 10.2903/j.efsa.2020.6305. PMID: 33240437; PMCID: PMC7676322.

[vi] Yassour M, Jason E, Hogstrom LJ, Arthur TD, Tripathi S, Siljander H, Selvenius J, Oikarinen S, Hyöty H, Virtanen SM, Ilonen J, Ferretti P, Pasolli E, Tett A, Asnicar F, Segata N, Vlamakis H, Lander ES, Huttenhower C, Knip M, Xavier RJ. Strain-Level Analysis of Mother-to-Child Bacterial Transmission during the First Few Months of Life. Cell Host Microbe. 2018 Jul 11;24(1):146-154.e4. doi: 10.1016/j.chom.2018.06.007. PMID: 30001517; PMCID: PMC6091882.

[vii] Plaza-Díaz J, Fontana L, Gil A. Human Milk Oligosaccharides and Immune System Development. Nutrients. 2018 Aug 8;10(8):1038. doi: 10.3390/nu10081038. PMID: 30096792; PMCID: PMC6116142.

[viii] Farhadihosseinabadi B, Gholipourmalekabadi M, Salimi M, Abdollahifar MA, Bagheri M, Samadikuchaksaraei A, Ghanbarian H, Mozafari M, Kazemi B, Niknejad H. The in vivo effect of Lacto-N-neotetraose (LNnT) on the expression of type 2 immune response involved genes in the wound healing process. Sci Rep. 2020 Jan 22;10(1):997. doi: 10.1038/s41598-020-57860-8. PMID: 31969618; PMCID: PMC6976585.

[ix] Farhadihosseinabadi B, Gholipourmalekabadi M, Salimi M, Abdollahifar MA, Bagheri M, Samadikuchaksaraei A, Ghanbarian H, Mozafari M, Kazemi B, Niknejad H. The in vivo effect of Lacto-N-neotetraose (LNnT) on the expression of type 2 immune response involved genes in the wound healing process. Sci Rep. 2020 Jan 22;10(1):997. doi: 10.1038/s41598-020-57860-8. PMID: 31969618; PMCID: PMC6976585.

[x] Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Helper T Cells and Lymphocyte Activation. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26827/

[xi] Khan I, Ullah N, Zha L, Bai Y, Khan A, Zhao T, Che T, Zhang C. Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome. Pathogens. 2019 Aug 13;8(3):126. doi: 10.3390/pathogens8030126. PMID: 31412603; PMCID: PMC6789542.

[xii] Palsson OS, Peery A, Seitzberg D, Amundsen ID, McConnell B, Simrén M. Human Milk Oligosaccharides Support Normal Bowel Function and Improve Symptoms of Irritable Bowel Syndrome: A Multicenter, Open-Label Trial. Clin Transl Gastroenterol. 2020 Dec;11(12):e00276. doi: 10.14309/ctg.0000000000000276. PMID: 33512807; PMCID: PMC7721220.

[xiii] Palsson OS, Peery A, Seitzberg D, Amundsen ID, McConnell B, Simrén M. Human Milk Oligosaccharides Support Normal Bowel Function and Improve Symptoms of Irritable Bowel Syndrome: A Multicenter, Open-Label Trial. Clin Transl Gastroenterol. 2020 Dec;11(12):e00276. doi: 10.14309/ctg.0000000000000276. PMID: 33512807; PMCID: PMC7721220.

[xiv] Vigsnaes LK, Ghyselinck J, Van den Abbeele P, McConnell B, Moens F, Marzorati M, Bajic D. 2'FL and LNnT Exert Antipathogenic Effects against C. difficile ATCC 9689 In Vitro, Coinciding with Increased Levels of Bifidobacteriaceae and/or Secondary Bile Acids. Pathogens. 2021 Jul 22;10(8):927. doi: 10.3390/pathogens10080927. PMID: 34451391; PMCID: PMC8402123.

[xv] Šuligoj T, Vigsnæs LK, Abbeele PVD, Apostolou A, Karalis K, Savva GM, McConnell B, Juge N. Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function. Nutrients. 2020 Sep 13;12(9):2808. doi: 10.3390/nu12092808. PMID: 32933181; PMCID: PMC7551690.

[xvi] Recharla N, Geesala R, Shi XZ. Gut Microbial Metabolite Butyrate and Its Therapeutic Role in Inflammatory Bowel Disease: A Literature Review. Nutrients. 2023 May 11;15(10):2275. doi: 10.3390/nu15102275. PMID: 37242159; PMCID: PMC10221771.


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