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

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 (ß-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.

Human milk oligosaccharide supplementation in irritable bowel syndrome patients: A parallel, randomized, double-blind, placebo-controlled study.

OBJECTIVES: Human milk oligosaccharides safely and beneficially impact bifidobacteria abundance in healthy adults, while their effects in patients with irritable bowel syndrome (IBS) are unknown. Hence, we aimed to determine the dose of 4:1 mix of 2'-O-fucosyllactose and Lacto-N-neotetraose (2'FL/LNnT) that increases fecal bifidobacteria abundance without aggravating overall gastrointestinal symptoms in IBS patients in a randomized, double-blind, controlled study. Additionally, the impact of 2'FL/LNnT on the fecal bacterial profile was assessed. METHODS: Irritable bowel syndrome patients diagnosed according to the Rome IV criteria received placebo (glucose), or 5 g or 10 g 2'FL/LNnT for 4 weeks followed by a four-week follow-up period. Gastrointestinal Symptom Rating Scale-IBS was used to assess gastrointestinal symptom severity; fecal microbiota composition was evaluated by GA-map™ Dysbiosis Test. RESULTS: Of the included 60 patients, two (one placebo and one 10 g) discontinued prematurely. Fecal bifidobacteria abundance was increased at week 4, but not at week 8, in the 10 g group compared to the other groups. Severity of overall or individual gastrointestinal symptoms did not differ between the groups at week 4 or 8, and no symptom deterioration was seen in any of the groups. The 10 g dose influenced overall fecal microbiota composition, and responders-defined as bifidobacteria increase ≥50%-could be discriminated from non-responders based on fecal microbiota modulation. CONCLUSIONS: The 10 g dose of 2'FL/LNnT induced an increase in the beneficial Bifidobacterium spp. without aggravating gastrointestinal symptoms in patients with IBS. This approach may be worthwhile to modulate gut microbiota of IBS patients toward a healthier profile.

Feruloylated and nonferuloylated arabino-oligosaccharides from sugar beet pectin selectively stimulate the growth of Bifidobacterium spp. in human fecal in vitro fermentations.

The side chains of the rhamnogalacturonan I fraction in sugar beet pectin are particularly rich in arabinan moieties, which may be substituted with feruloyl groups. In this work the arabinan-rich fraction resulting from sugar beet pulp based pectin production was separated by Amberlite XAD hydrophobic interaction and membrane separation into four fractions based on feruloyl substitution and arabino-oligosaccharide chain length: short-chain (DP 2-10) and long-chain (DP 7-14) feruloylated and nonferuloylated arabino-oligosaccharides, respectively. HPAEC, SEC, and MALDI-TOF/TOF analyses of the fractions confirmed the presence of singly and doubly substituted feruloylated arabino-oligosaccharides in the feruloyl-substituted fractions. In vitro microbial fermentation by human fecal samples (n = 6 healthy human volunteers) showed a selective stimulation of bifidobacteria by both the feruloylated and the nonferuloylated long-chain arabino-oligosaccharides to the same extent as the prebiotic fructo-oligosaccharides control. None of the fractions stimulated the growth of the potential pathogen Clostridium difficile in monocultures. This work provides a first report on the separation of potentially bioactive feruloylated arabino-oligosaccharides from sugar beet pulp and an initial indication of the potentially larger bifidogenic effect of relatively long-chain arabino-oligosaccharides as opposed to short-chain arabino-oligosaccharides.

Maximal release of highly bifidogenic soluble dietary fibers from industrial potato pulp by minimal enzymatic treatment.

Potato pulp is a poorly utilized, high-volume co-processing product resulting from industrial potato starch manufacturing. Potato pulp mainly consists of the tuber plant cell wall material and is particularly rich in pectin, notably galactan branched rhamnogalacturonan I type pectin which has previously been shown to exhibit promising properties as dietary fiber. The objective of this study was to solubilize dietary fibers from potato pulp by a one-step minimal treatment procedure and evaluate the prebiotic potential of the fibers. Statistically designed experiments were conducted to investigate the influence of enzyme type, dosage, substrate level, incubation time, and temperature on the enzyme catalyzed solubilization to define the optimal minimal enzyme treatment for maximal fiber solubilization. The result was a method that within 1 min released 75% [weight/weight (w/w)] dry matter from 1% (w/w) potato pulp treated with 1.0% (w/w) [enzyme/substrate (E/S)] pectin lyase from Aspergillus nidulans and 1.0% (w/w) E/S polygalacturonase from Aspergillus aculeatus at pH 6.0 and 60 °C. Molecular size fractionation of the solubilized fibers revealed two major fractions: one fraction rich in galacturonic acid of 10-100 kDa indicating mainly homogalacturonan, and a fraction >100 kDa rich in galactose, presumably mainly made up of ß-1,4-galactan chains of rhamnogalacturonan I. When fermented in vitro by microbial communities derived from fecal samples from three healthy human volunteers, both of the solubilized fiber fractions were more bifidogenic than fructo-oligosaccharides (FOS). Notably the fibers having molecular masses of >100 kDa selectively increased the densities of Bifidobacterium spp. and Lactobacillus spp. 2-3 times more than FOS.