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Review
. 2025 Oct 29:18:17562848251386319.
doi: 10.1177/17562848251386319. eCollection 2025.

Microbiota-targeted strategies in IBD: therapeutic promise of 2'-fucosyllactose and beyond

Nicholas Fanous  1 , Nicholas J Talley  2   3 , Thanaboon Chaemsupaphan  4   5 , Esther Lee  6 , Binod Rayamajhee  7   8 , Shaghayegh Baradaran Ghavami  9 , Nesa Kazemifard  9 , Hamid Asadzadeh Aghdaei  9   10 , Emil Chuang  11 , Rupert W Leong  12
Affiliations
Review

Microbiota-targeted strategies in IBD: therapeutic promise of 2'-fucosyllactose and beyond

Nicholas Fanous et al. Therap Adv Gastroenterol. .

Abstract

Inflammatory bowel diseases (IBD) are chronic and recurrent conditions of the gastrointestinal tract. IBD is often challenging to manage due to the complex etiology and involvement of multiple dysregulated immune pathways. Current treatments, including biologics and immunosuppressants, are associated with significant risks and side effects, highlighting the need for safer alternatives. Human milk oligosaccharides (HMOs), a group of bioactive carbohydrates found in human breast milk, play a crucial role in shaping the infant gut microbiome, modulating microbial metabolism and immune responses, and reducing inflammation. Notably, HMOs have no nutritional value for the infant and travel undigested through the upper gastrointestinal tract, serving as selective substrates for beneficial gut bacteria and supporting intestinal epithelial health. Among these, 2'-fucosyllactose (2'-FL) is the most abundant and well-studied HMO, functioning as a trisaccharide prebiotic. Emerging evidence suggests that the benefits of HMOs extend beyond infancy, with potential therapeutic applications in modulating immune responses, promoting epithelial health, and reducing inflammation in IBD. This review summarizes current research on the role of 2'-FL in inflammation and colitis, exploring its potential role in treating IBD.

Keywords: 2′-Fucosyllactose (2′-FL); dietary fibers; dysbiosis; gut microbiota; gut permeability; inflammatory bowel diseases (IBD); prebiotics.

Plain language summary

A natural sugar from breast milk may help treat inflammatory bowel disease Inflammatory bowel diseases (IBD) like Crohn’s disease and ulcerative colitis cause chronic gut inflammation and can be difficult to treat. Current medicines don’t work for everyone and may have side effects, so researchers are looking for safer ways to improve gut health. One option is to target the gut microbiome; the community of microbes that support digestion, immunity, and gut lining integrity. In IBD, this microbiome is often out of balance. 2′-fucosyllactose (2′-FL), a natural sugar found in breast milk, feeds beneficial bacteria such as Bifidobacterium. In infants, it helps protect the gut lining and regulate immune function. Studies in animals and laboratory models show that 2′-FL can boost helpful bacteria, reduce harmful species, lower inflammation, and strengthen the gut barrier. Early research in ulcerative colitis suggests that 2′-FL may improve microbiome balance, gut health, and quality of life. Ongoing clinical trials are exploring its use in IBD, alone or combined with other treatments like faecal microbiota transplantation. If proven effective, 2′-FL could offer a safe, natural addition to standard therapies, helping more people with IBD achieve better symptom control.

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Conflict of interest statement

R.W.L.: Professor R.W.L. has served on advisory boards for AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, and Takeda. He has also received research grants from Joanna Tiddy, USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, the Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, and MRFF. E.C.: Dr E.C. is employed by Intrinsic Medicine, a company developing 2′-FL as a drug to treat IBD. E.L.: Works with Professor R.W.L. N.J.T.: A formal conflict of interest disclosure is currently pending confirmation. To maintain transparency, we have included publicly available information on Professor Talley’s affiliations, as previously reported in the literature: Professor Talley has participated in national and international committees, including the MBS Review Taskforce (2016–2020), NHMRC Principal and Research Committees (2016–2021), NHMRC Council (2021–2024), and is currently President of the Asia Pacific Association of Medical Journal Editors (APAME). He also contributes to community and advocacy work through the International Foundation for Functional GI Disorders (IFFGD). N.F., T.C., B.R., S.B.G., N.K., and H.A.A.: None to disclose.

Figures

Figure 1.
Figure 1.
Classification of HMOs into three main types: neutral fucosylated HMOs, neutral nonfucosylated HMOs, and acidic sialylated HMOs. Examples of each category include 2′-FL and 3′-FL, LNT and LNnT, and 3′-SL and 6′-SL, respectively. This categorization highlights the structural diversity of HMOs and their key components. 2′-FL, 2′-fucosyllactose; 3′-FL, 3′-fucosyllactose; 3′-SL, 3′-sialyllactose; 6s′-SL, 6′-sialyllactose; HMO, human milk oligosaccharides; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetraose.
Figure 2.
Figure 2.
Pathophysiological alterations in IBD: dysbiosis of the gut microbiota, disruption of the gut barrier, and inflammation, can be improved by 2′-FL through different pathways. 2′-FL, 2′-Fucosyllactose; GSH-Px, glutathione peroxidase; SCFA, short-chain fatty acid; SOD, superoxide dismutase.
See this image and copyright information in PMC

References

    1. Guan Q. A comprehensive review and update on the pathogenesis of inflammatory bowel disease. J Immunol Res 2019; 2019: 7247238. - PMC - PubMed
    1. Thurl S, Munzert M, Boehm G, et al. Systematic review of the concentrations of oligosaccharides in human milk. Nutr Rev 2017; 75(11): 920–933. - PMC - PubMed
    1. Zhang S, Li T, Xie J, et al. Gold standard for nutrition: a review of human milk oligosaccharide and its effects on infant gut microbiota. Microb Cell Fact 2021; 20(1): 108. - PMC - PubMed
    1. Suligoj T, Vigsnaes LK, Abbeele PVD, et al. Effects of human milk oligosaccharides on the adult gut microbiota and barrier function. Nutrients 2020; 12(9): 2808. - PMC - PubMed
    1. Khorsand B, Asadzadeh Aghdaei H, Nazemalhosseini-Mojarad E, et al. Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn’s disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets. Front Cell Infect Microbiol 2022; 12: 1015890. - PMC - PubMed

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