The human milk oligosaccharide (HMO) 2'-fucosyllactose (2'FL) has shown potential in reducing body weight and fat mass gain, particularly in the context of high-fat diets. Here we explore how 2'FL achieves these effects by modulating the gut microbiota and intestinal mucus layer, offering promising insights for obesity prevention.
Content Outline
- Understanding the role of HMOs in preventing obesity
- How 2’FL reduced obesity and glucose intolerance
-
The role of intestinal mucus in modulating obesity
- How 2’FL modifies mucus composition and production
- 2’FL’s role in modulating the gut microbiota
- Fecal Proteome: Changes in metabolism-related proteins
- Conclusion: Is 2’FL a new frontier in obesity prevention?
Understanding the role of HMOs in preventing obesity
Obesity is a serious burden on healthcare providers across the world with more than 1 billion people living with the disease[i]. The problem is obesity is a gateway to many other metabolic conditions, including type 2 diabetes, heart disease, and changes in the gut microbiota.
The Western diet is a major contributor to the obesity pandemic thanks to its high fat and sugar content[ii], but it also leads to perturbations in the composition of the gut microbiome, compromising the integrity of the gut barrier, and causing inflammation[iii].
Weight loss through dietary changes and increased exercise are often the first port of call, but what if targeting the gut microbiome itself could prevent obesity? In recent years human milk oligosaccharides (HMOs) have gained particular scientific interest for their numerous health benefits.
Recent research has shown that a specific HMO, 2’fucosyllactose (2’FL) can induce positive changes in the metabolism and gut-brain signaling in mice fed high-fat diets[iv]. Yet, research into how 2’FL exerts its effects on obesity prevention is lacking. Recently, Paone and colleagues investigated how 2’FL influenced body weight and fat mass gain in mice fed a high-fat diet and whether there is a link between changes within the intestinal mucus production and secretion and microbiome shifts.
We’ll explore the results of the study in this article.
How 2’FL reduced obesity and glucose intolerance
One of the major results of the study published in the journal, Gut, was that supplementing a high-fat diet with 2’FL can lower the increase in body weight and fat mass and reduce glucose intolerance. Interestingly, 2’FL also modulates the hormones involved in appetite and energy homeostasis, in a similar way to weight loss injections like Wegovy.
For example, 2’FL increases the concentration of glucagon-like peptide-1 (GLP-1) and peptide YY, which tell the body it is full to curb hunger. The mice fed a high-fat diet alongside 2’FL supplementation also experienced reduced glucose intolerance and lower insulin levels during periods of fasting.
The role of intestinal mucus in modulating obesity
The mucus barrier in the gut is one of the first lines of defence for your gastrointestinal tract, but its integrity can be influenced by many factors including:
- High-fat diet
- Low-fibre/high-fibre diet
- Food additives
- Pre- and probiotic use[v]
The mucus layer of the gut lining is a gel-like covering across the epithelial cells which are responsible for allowing the transport of ions, molecules, and nutrients in and out. The thick gel made up of mucin proteins is like a sieve that absorbs and transports nutrients, keeps the tissues moist and protects the body from invading pathogens[vi].
However, changes in the mucus lining can affect your metabolic health. For example, increased numbers of mucus-degraders such as Ruminococcus gnavus are common in inflammatory bowel disease (IBD) patients. A damaged or dysfunctional mucus layer can allow bacterial lipopolysaccharide (LPS) to escape from the gut and into the bloodstream, leading to inflammation and the development of metabolic disease (figure 1).
Figure 1. How an IBD affected mucosal layer might look. There is likely to be an increase in mucus-degrading bacteria, inflammation, and LPS.
Yet, HMOs have been shown to have a positive effect on the expression of mucin glycoproteins in the mucus layer, helping to increase its integrity[vii].
How 2’FL modifies mucus composition and production
Paone et al demonstrated that 2’FL supplementation increased the expression of MUC2, the major gel-forming mucin in the colon responsible for forming the protective gel barrier.
These results are similar to earlier research by Yao et al, (2022) who found that after just 7 days of 2’FL supplementation, MUC2 secretion was increased in mice with colitis (figure 2).
Figure 2. Mice with colitis treated with 2’FL exhibited greater expression of MUC2 than mice without 2’FL treatment. Source: Yao et al (2022)
Interestingly, Paone et al also found that the HMO significantly impacted other mucins, glycosyl hydrolases, and glycosyltransferases, particularly in the colon where 9 out of 13 were upregulated and mucus secretion was increased, helping to thicken the protective gel layer.
This is significant because there is growing evidence that consuming a high-fat or Westernised diet can cause the development of metabolic disorders, including obesity, and the mucosal layer lining the gut is changed. For example, it is thinner and more porous, allowing toxins and pathogens to come within touching distance of the intestinal epithelial cells and setting off a cascade of inflammation[viii].
2’FL’s role in modulating the gut microbiota
Alongside exerting specific effects on the mucosal layer, 2’FL may also mediate these benefits through its ability to modulate the gut microbiota composition. For example, in the colitis-induced mice, the main bacteria genera present were Akkermansia and Bacteroides. Whereas the dominant bacteria in control and high-fat diet-fed mice belonged to the Desulfovibrionaceae (DSV) family. DSV are sulfate-reducing bacteria, which are usually a minority group in the gut, but have the potential to overgrow and become opportunistic pathobionts[ix].
It’s widely known that both of these mucin lovers can also use the same tools that they degrade colonic mucins with to metabolise HMOs like 2’FL and increase their numbers and activity. In turn, this has a positive effect on the mucosal layer, increasing its integrity and ensuring it doesn’t wear thin. In animal studies, Akkermansia muciniphila prevents high-fat diet-induced obesity because it stimulates the production of mucus, preventing it from thinning[x]. A. muciniphila is more prevalent in lean individuals and could offer targeted therapy for ameliorating metabolic diseases in the future[xi].
Did you know? You can further enrich you’re A. muciniphila colonies with our Akkermansia synbiotic which combines the beneficial powers of this extraordinary probiotic with 2’FL and resistant starch.
Fecal Proteome: Changes in metabolism-related proteins
A high-fat diet can impact the fecal proteome, affecting many of the proteins involved in metabolic processes which were shown in the high-fat diet-fed mice. However, 2’FL supplementation appeared to prevent the metabolic processes caused by the consumption of high-fat foods.
Conclusion: Is 2’FL a new frontier in obesity prevention?
Although it is widely known that a Westernised diet and obesity are linked to gut barrier dysfunction and that 2’FL may have protective benefits, it isn’t fully understood how this HMO does so. The research conducted by Paone and Co demonstrates that 2’FL may exert its benefits in preventing obesity by altering specific aspects of the mucus layer and diversifying and supporting the colonic ecosystem.
These results further confirm some of the positive benefits we already knew 2’FL, and other HMOs, could potentially exert in humans and are particularly pertinent as metabolic diseases, like obesity, become more prominent in our society.
Excited about the potential benefits of 2’FL for metabolic health? Get yours here.
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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