The Human Milk Oligosaccharide - 2'-Fucosyllactose (2'-FL) Prevents Intestinal Inflammation, Study Finds

July 12, 2024 7 min read

The Human Milk Oligosaccharide - 2'-Fucosyllactose (2'-FL) Prevents Intestinal Inflammation Cover Image

Human milk oligosaccharides (HMOs) are the first taste of sweetness you get once you arrive on this beautiful planet. HMOs are the sugar component of mum’s milk, scientifically known as glycans. As well as providing that first sweet experience, these glycans supply you with energy and then go on to help establish the abundance of your gut bacteria.

Over the past decade, studies into HMOs have revealed several benefits they offer for your current health and beyond. Research has shown how HMOs help establish your good gut flora by restricting the growth of potential pathogens that chance their luck in a takeover of the gut space. They achieve this by preventing the pathogen from binding to your gut cells, this action halts the establishment of potential disease whilst also promoting good bacteria like, Bifidobacteria  and Lactobacillus  to flourish.

HMOs also help to establish and teach the immune system to protect you, a biological system that if kept fully serviced should last a lifetime[i]. But the benefits of HMOs don’t appear to be stopping there. In February 2024, Schalich et al. published a study investigating the role of a specific HMO in the prevention and treatment of adult colitis, a study that would enter a field of (so far) uncharted research. So, why not kick back, and pull up a pew, as the results are in.

What was the purpose of the study?

The study entitled, A human milk oligosaccharide prevents intestinal inflammation in adulthood via modulating gut microbial metabolism, analysed the role of 2’-Fucosyllactose (2’-FL) in the prevention of colitis in adult mice.

The researchers used 2’-FL as a food source for the bacteria Bifidobacterium infantis and assessed how the secreted metabolites from B. infantis  go on to offer protection[ii].

HMOs have come a long way since their very early days of first being recognized in the 1930s. There are a few with growing notoriety, but only one is known as the repair HMO, and that’s 2’-FL. It has been used in many studies and is evolving as a formidable force in working magic in the gut ecosystem. Through its efforts to help establish an abundant and diverse microbiota, 2’-FL appears to be offering the foundations for health, not only for the gut but throughout the body.

The study aimed to establish if 2’-FL could modulate the human gut microbiome in such a way that it could prevent intestinal inflammation in acute colitis mouse models.

What is colitis?

Colitis is a form of inflammatory bowel disease that results in the formation of ulcers and the presence of chronic inflammation in the lining of the colon. Approximately 5 million people are living with ulcerative colitis globally, and this number is growing[iii].

Colitis is caused by various factors, including:

  • Genetic predisposition
  • Infection e.g., food poisoning
  • Dysregulated immune response
  • Dysbiosis
  • Epithelial barrier defects

The disease results in painful inflammation in the gut that can lead to severe bleeding, dehydration, swollen colon, perforated colon, increased risk of cancer, inflammation in other areas of the body, and, in severe cases emergency surgery[iv][v][vi].

What have previous studies shown us about 2’-FL and its interaction with the gut microbiota?

Previous studies have helped to establish some of the benefits of 2’-FL and how it can interact and shape the gut microbiota.

A review by Walsh et al (2020), explained how HMO-consuming bacteria, resulted in the secretion of metabolites and increased production of essential biological components, like short-chain fatty acids (SCFAs).

SCFAs are the result of the fermentation of dietary fibers by your gut bacteria, such as Bifidobacterium infantis. SCFAs are often found to be low in many diseases, explaining that disease can flourish due to interruption of the pathway that leads to SCFA production or the low numbers of SCFAs in general.

The review also demonstrated that HMOs play a role in modulating gut epithelial cells. These cells are integral to the immune responses that repel pathogens and their binding, thus offering protection from potential diseases.

2’-FL and its protective effects against aging

In January 2022, Wang et al investigated the protective properties offered by 2’-FL in the aging process. While much research has been conducted in infants and concludes that 2’-FL possesses important anti-inflammatory and immunity benefits, there is little research into its effects within the elderly population.

The results showed that the use of 2’-FL reduced oxidative stress damage in the intestines of the D-galactose-induced accelerated mouse model, reducing intestinal inflammation through the regulation of sirtuin1 [SIRT1] related and nuclear factor E2-related factor 2 (Nrf2) pathways.

The study also found that 2’-FL promoted the production of SCFAs, including acetate, propionate, and butyrate.

Furthermore, the study saw a rise in the abundance of the bacterial strain, Akkermansia muciniphila.  A. muciniphila is a relatively newfound strain and has already been pinpointed as a next-generation probiotic. The strain promotes the growth of good bacteria, inhibits the development of several chronic diseases, and may have important therapeutic properties, as noted by Pellegrino et al[vii][viii].

How does 2’-FL protect intestinal homeostasis?

Over the past decade, several studies have demonstrated that for almost all chronic illnesses, there has been a presence of oxidative stress and a low abundance of SCFAs. This has concluded that to limit the risk of disease, there must be a balance between oxidants and antioxidants and a good production of SCFAs. For this to happen, the gut flora must also be balanced and diverse, which can be supported by nourishment from prebiotics, like HMOs.

The current study by Schalich et al., (2024) found that adult mice who consumed 2’-FL had an increased abundance of several health-promoting bacterial species in their gut, including Bifidobacteria and Lactobacillus.

Furthermore, this microbial community, enriched by the HMO, could utilize beneficial effects in acute colitis mouse models, suggesting that 2’-FL could balance the gut microbiome to prevent intestinal inflammation. Some of the possible mechanisms by which 2’FL helped include:

  • Mitigating inflammation, ulceration and crypt damage in the colon
  • Reducing the expression of pro-inflammatory cytokines
  • Protecting the intestinal barrier

Could pantothenol be the secret behind 2’-FLs success?

Using B. infantisas a bacterial model because it loves to consume HMOs and is also present in low numbers in healthy adults, the researchers turned their attention to investigating how 2’-FL exerts its protective benefits through gut microbiome regulation.

They found three secreted metabolites unique to HMO consumption by B. infantis,one of which was pantothenol. If you’re thinking you’ve heard of this before, you likely have, pantothenol is an alcohol derivative of vitamin B5. In some organisms, pantothenol is converted to pantothenate, serving as a provitamin.

The study showed that the metabolism of 2’-FL by B. infantis increased the production of pantothenol. It suggested there might be a pantothenate biosynthesis mechanism by Bifidobacterium pseudolongum which was also enriched after 28 days of 2’-FL consumption.

Overall Schalich et al., (2024) found that pantothenate reduces the oxidative response, protects the intestinal lining, and can prevent colitis. Therefore, pantothenate production could be critical in the 2’-FL-mediated prevention of intestinal inflammation.

What does this mean for the future?

The study helped to shed some light on the potential for 2’-FL to be a safe and tolerable therapeutic approach for preventing colitis and maintaining intestinal barrier integrity in inflammatory bowel disease patients.

This research further demonstrates 2’-FL’s ability to modulate the composition of the gut microbiome and promote beneficial bacterial strains, including members of the Bifidobacteria  genus. These species collectively strengthen the gut barrier and reduce the risk of intestinal inflammation by upregulating the production of beneficial metabolites, including pantothenol. This builds on previous research that identified that 2’-FL could play an important role in the aging process in mice by attenuating inflammation within the gut environment.

2’-FL is the most abundant human milk oligosaccharide accounting for almost 30% of the total HMOs in secreting mothers, perhaps highlighting its significance in building the foundations for human health.

Emerging research demonstrates, HMOs, including 2’-FL, may also have important roles in adult gut health. You can get ahead of the trend by supporting the balance of your gut with the PureHMO® Prebiotic Powder from Layer Origin.

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] 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.

[ii] Schalich KM, Buendia MA, Kaur H, Choksi YA, Washington MK, Codreanu GS, Sherrod SD, McLean JA, Peek RM Jr, Acra SA, Townsend SD, Yan F. A human milk oligosaccharide prevents intestinal inflammation in adulthood via modulating gut microbial metabolism. mBio. 2024 Apr 10;15(4):e0029824. doi: 10.1128/mbio.00298-24. Epub 2024 Mar 5. PMID: 38441000; PMCID: PMC11005405.

[iii] Le Berre, C., Honap, S. and Peyrin-Biroulet, L. (2023) ‘Ulcerative colitis’, The Lancet, 402(10401), pp. 571–584. doi:10.1016/s0140-6736(23)00966-2.

[iv] Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet. 2017 Apr 29;389(10080):1756-1770. doi: 10.1016/S0140-6736(16)32126-2. Epub 2016 Dec 1. PMID: 27914657; PMCID: PMC6487890.

[v] Porter RJ, Kalla R, Ho GT. Ulcerative colitis: Recent advances in the understanding of disease pathogenesis. F1000Res. 2020 Apr 24;9:F1000 Faculty Rev-294. doi: 10.12688/f1000research.20805.1. PMID: 32399194; PMCID: PMC7194476.

[vi] Slonovschi E, Kodela P, Okeke M, Guntuku S, Lingamsetty SSP. Surgical Treatment in Ulcerative Colitis, Still Topical: A Narrative Review. Cureus. 2023 Jul 16;15(7):e41962. doi: 10.7759/cureus.41962. PMID: 37588306; PMCID: PMC10427119.

[vii] Wang J, Hu JQ, Song YJ, Yin J, Wang YY, Peng B, Zhang BW, Liu JM, Dong L, Wang S. 2'-Fucosyllactose Ameliorates Oxidative Stress Damage in d-Galactose-Induced Aging Mice by Regulating Gut Microbiota and AMPK/SIRT1/FOXO1 Pathway. Foods. 2022 Jan 7;11(2):151. doi: 10.3390/foods11020151. PMID: 35053883; PMCID: PMC8774504.

[viii] Pellegrino A, Coppola G, Santopaolo F, Gasbarrini A, Ponziani FR. Role of Akkermansia in Human Diseases: From Causation to Therapeutic Properties. Nutrients. 2023 Apr 8;15(8):1815. doi: 10.3390/nu15081815. PMID: 37111034; PMCID: PMC10142179.


1 Response

Ellie Williams
Ellie Williams

August 14, 2024

Hi, I have long covid which has wiped my bifidobacteria and so I’m trying to increase numbers with inulin and lots of plant whole foods. They seem to be very difficult to increase due to Covid. Having long covid also means having very strong reactions to milk products including lactoferrin and GOS. I’m contemplating on trying HMO’s however I’m worried even this will make me react. Do you have any knowledge of this or suggestions? I’m desperate to increase my bifidos. Many thanks

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