The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome

Nutrients. 2021 Oct 27;13(11):3836. doi: 10.3390/nu13113836.


Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2'-O-fucosyllactose and lacto-N-neotetraose (2'FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients.

Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2'FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined.

Results: Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2'FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2'FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance.

Conclusion: Supplementation with 2'FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2'FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.

Keywords: 2′-O-fucosyllactose; antibacterial response; gut microenvironment; human milk oligosaccharides; irritable bowel syndrome; lacto-N-neotetraose; metabolomics; microbiota.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bifidobacterium / drug effects
  • Dietary Supplements*
  • Double-Blind Method
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Intestinal Mucosa / drug effects
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / microbiology
  • Male
  • Middle Aged
  • Milk, Human / chemistry*
  • Oligosaccharides / pharmacology*
  • Treatment Outcome
  • Trisaccharides / pharmacology
  • Young Adult


  • Oligosaccharides
  • Trisaccharides
  • lacto-N-neotetraose
  • 2'-fucosyllactose