{
  "abstract": "Introduction Prebiotics are an emerging therapeutic option in ulcerative colitis (UC), which can modulate the gut microbiota and improve outcomes. 1 2’-fucosyllactose (2’-FL) is a human milk oligosaccharide (HMO) with in vitro prebiotic potential in UC.2Methods This adequately powered, randomised double-blind placebo-controlled crossover design clinical trial assessed the effect of 2’-FL in mild-to-moderate UC (PRInCE-UC, NCT06050811).38 patients were randomised to consume either 5g per day of 2’-FL or 5g per day of maltodextrin placebo for 28 days. This was followed by a 21 day washout period, before crossing over for a further 28 days, then a final washout.Validated patient-reported outcome measures, faeces, serum and urine were collected at weeks 0, 4, 7, 11, and 14. In addition to clinical outcomes, microbiota changes in 16S sequencing, and cross-biofluid metabolomic changes using 1H nuclear magnetic resonance spectroscopy were analysed.Results 2’-FL significantly modulated the gut microbiota, with the most marked changes being an increase in Bifidobacterium (effect size 4.3%, 95% CI 2.03%-6.55%, p = 0.000313) [figure 1].A shift towards oxidative metabolism was seen in faecal metabolites with 2’FL, with increased tricarboxylic acid cycle intermediates and decreased lactate. Cross-biofluid short chain fatty acid trends, including an increase in urinary acetate and butyrate, were consistent with microbiota-associated acetate production with 2’-FL, with downstream cross-feeding of butyrate producing taxa and higher systemic butyrate.These changes were accompanied by a significant improvement in IBD-Control-8 score during 2’-FL exposure (1.44 point increase, p = 0.025) and a downward trend in faecal calprotectin (46.1 μg/g drop with 2’-FL, p = 0.4).Clinical responders to 2’-FL exhibited a different SCFA profile to non-responders with lower isobutyrate and valerate, suggesting a shift from proteolytic to saccharolytic activity. Increased age and reduced baseline Bifidobacterium abundance were associated with 2’-FL response.Conclusions In this world-first clinical trial of an HMO in UC, 2’-FL significantly modulated the gut microbiota and modified cross-compartmental metabolic profiles.References Kennedy JM, et al. A review on the use of prebiotics in ulcerative colitis. Trends Microbiol. 2024.Kennedy JM, et al. Comparison of prebiotic candidates in ulcerative colitis using an in vitro fermentation model. J Appl Microbiol. 2024.Abstract FP9 Figure 1Top 10 microbiome taxa showing treatment effects with 2’FL versus control",
  "authors": [
    {
      "affiliations": [
        "University of Reading, Reading, United Kingdom",
        "Royal Berkshire NHS Foundation Trust, Reading, United Kingdom"
      ],
      "name": "James Kennedy"
    },
    {
      "affiliations": [
        "University of Reading, Reading, United Kingdom"
      ],
      "name": "Patricia Sanz Morales"
    },
    {
      "affiliations": [
        "University of Reading, Reading, United Kingdom"
      ],
      "name": "Carlos Poveda"
    },
    {
      "affiliations": [
        "University of Reading, Reading, United Kingdom"
      ],
      "name": "Gemma Walton"
    },
    {
      "affiliations": [
        "Royal Berkshire NHS Foundation Trust, Reading, United Kingdom"
      ],
      "name": "Aminda De Silva"
    },
    {
      "affiliations": [
        "University of Reading, Reading, United Kingdom"
      ],
      "name": "Glenn Gibson"
    }
  ],
  "title": "FP9 2'-fucosyllactose modulates gut microbiota and metabolic profiles in ulcerative colitist",
  "uid": "3778a347-70d1-5e27-8e66-21d2026be06b"
}