November 02, 2023 7 min read
Current scientific research has identified human milk oligosaccharides (HMOs) as having many benefits for human health. There are over 200 of these glycans (sugars), and they are the third most abundant part of human breast milk[i].
One of the handful is lacto-N-tetraose (LNT), one of the most abundant HMOs present in human breast milk, and the one we are going to observe in this article. So, join us as once again we enter this fantastic world of biological magic.
Lacto-N-tetraose or LNT has noteworthy importance in the HMO world. In research studies, it has been seen to have multiple functions, as a prebiotic (food) for the gut microbiota, antiadhesive properties that ultimately protect the gut cells from attachment by pathogenic bacteria, anti-viral protection, and immune-modulating processes that enhance the immune system against disease[ii].
LNT is composed of four monosaccharides, meaning it is classed as a tetra-saccharide. The monosaccharide units are galactose, N-acetylglucosamine, an additional galactose, and glucose. Being the least soluble of the glycans, and because of its binding pattern, LNT components can combine and create an almost solid structure, a composition that has been seen to have immunomodulatory and metabolic properties, these processes may help fight disease[iv].
LNT and LNnT are isomers. That means they have the same molecular formula, but their atoms are arranged in different formations. LNT and its derivatives constitute more than half of HMOs. LNT is classified as a type I HMO and LNnT is a type II HMO. They are identical except for their glycosidic linkage, β1-3 vs β1-4. Interestingly, it is this structural difference that is hypothesised as the reason for the differential phenotypes in bifidobacterial utilisation in these two HMOs. We’ll explore LNnT in more depth shortly.
Lacto-N-tetraose is a prebiotic because it encourages the growth of healthy gut bacteria. Its presence in human breast milk means that LNT is one of the first functional foods you encounter as babies, feeding the first colonisers of your gut microbiome, including Bifidobacteria.
Bifidobacterium longum infantis (B. infantis) is particularly fond of LNT. B. infantisis a typical resident of the infant gut, taking full advantage of HMOs like LNT to bolster its abundance. Being present in large numbers is of uppermost importance for your good gut microbes. Once in your colon, it thrives and contributes to an optimum environment where good gut bacteria can become abundant.
Research shows that B. infantis grows more efficiently while utilising LNT rather than LNnT. A further study by Li et al (2023) also demonstrated that B. infantiscan use N-acetylglucosamine-containing HMOs, including LNT, as nitrogen sources[v].
The metabolism of LNT by strains such as B. infantisyields SCFAs like acetate and lactate, powerful postbiotics that have been shown to regulate the immune system and improve the integrity of the gut barrier function[vi]. For example, Groeger et al., (2013) found that oral administration of B. infantissignificantly reduced plasma C-reactive protein (CRP) levels in patients with both gastrointestinal and non-gastrointestinal inflammatory disorders (ulcerative colitis, chronic fatigue syndrome, and psoriasis). CRP is an inflammatory biomarker produced by the liver and increases when there’s inflammation in the body.
The results of the study revealed that B. infantisfeeding reduced CRP levels in all three inflammatory states and lowered other pro-inflammatory messenger levels in healthy subjects, including TNF-α and IL-6. Therefore, demonstrating that this microbial strain could have positive benefits on the systemic immune system[vii].
Furthermore, a literature review by Clarke et al., (2012) found that B. infantismay also help to relieve the symptoms of irritable bowel syndrome (IBS), like abdominal pain, bloating, and gas.
B. infantisinteraction sees its genome encode a series of hydrolases (set of enzymes) that lead to additional enzyme and oligosaccharide transporters, initiating LNT into the chain of chemical events, and feeding it into the Bifidobacteriumfermentation pathway. This means B. infantisgenerates ATP (energy) and other substrates required for anabolic processes such as lactate (muscle energy), NAD+ crucial coenzymes found in every cell, and acetate, another energy producer, through the utilisation of HMOs like LNT[viii].
It is the production of these metabolites that may reduce the circulation of pro-inflammatory messengers and cytokines. Whereas SCFAs such as acetate may benefit specific cardio-metabolic diseases by lowering visceral fat levels[ix].
Acetate is also the preferred energy source of the butyrate producer Faecalibacterium prausnitzii.So, B.infantismay inadvertently help increase butyrate production by feeding on LNT, transforming it into acetate, and cross-feeding other beneficial gut microbes.
As well as its interaction with beneficial gut microbes, LNT offers other health benefits through its anti-microbial, anti-adhesion, and anti-viral properties[x].
In studies with other HMOs, LNT has been shown to interact with the cells that line the gut, called epithelial cells. Here, LNT becomes a decoy for potential pathogenic bacteria, drawing pathogens away from binding to the colon cells via a process of secretions that almost compel these pathogens to bind elsewhere. This action renders the pathogen unable to establish itself let alone a colony. Without numbers, the risk of disease is reduced, thus providing much-needed protection, important at any stage of life, but probably none more so when we are in our infancy[xi][xii].
With the gut cells left to go about their intended duties, HMOs like LNT then go even further, being a source of food for the gut microbiota comes with a rich reward, the production of postbiotics. These are the result of probiotics (bacteria) consuming prebiotics (food). All of these participate in day-to-day chemical reactions that keep us ticking along and include:
LNT is a complex carbohydrate molecule that is an important constituent of human breast milk. It is an example of a human milk oligosaccharide (HMO). As we’ve witnessed in this article, LNT has several important functions for human health, including nourishing and supporting the growth of important health-promoting bacteria, particularly Bifidobacteria, and protecting the body from potential pathogens.
LNT is one of the first functional foods we encounter as babies. Like other HMOs, LNT isn’t digested by our digestive system, instead, the good gut bacteria do it for us, transforming it into useful postbiotic molecules that help to maintain, regulate, and promote our health. But emerging research shows that HMOs are not just important in our infancy, but throughout our lifetime. Why not explore our range of HMO products to see how you can support your gut microbiome and beyond?
Written by: Leanne 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.
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[vi] Chichlowski M, Shah N, Wampler JL, Wu SS, Vanderhoof JA. Bifidobacterium longum Subspecies infantis (B. infantis) in Pediatric Nutrition: Current State of Knowledge. Nutrients. 2020 May 28;12(6):1581. doi: 10.3390/nu12061581. PMID: 32481558; PMCID: PMC7352178.
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[ix] Nogal A, Louca P, Zhang X, Wells PM, Steves CJ, Spector TD, Falchi M, Valdes AM, Menni C. Circulating Levels of the Short-Chain Fatty Acid Acetate Mediate the Effect of the Gut Microbiome on Visceral Fat. Front Microbiol. 2021 Jul 15;12:711359. doi: 10.3389/fmicb.2021.711359. PMID: 34335546; PMCID: PMC8320334.
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[xi] Wiciński M, Sawicka E, Gębalski J, Kubiak K, Malinowski B. Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology. Nutrients. 2020 Jan 20;12(1):266. doi: 10.3390/nu12010266. PMID: 31968617; PMCID: PMC7019891.
[xii] Cheng L, Kong C, Wang W, Groeneveld A, Nauta A, Groves MR, Kiewiet MBG, de Vos P. The Human Milk Oligosaccharides 3-FL, Lacto-N-Neotetraose, and LDFT Attenuate Tumor Necrosis Factor-α Induced Inflammation in Fetal Intestinal Epithelial Cells In Vitro through Shedding or Interacting with Tumor Necrosis Factor Receptor 1. Mol Nutr Food Res. 2021 Apr;65(7):e2000425. doi: 10.1002/mnfr.202000425. Epub 2021 Mar 3. PMID: 33465830; PMCID: PMC8047892.
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