Salomonsson E., Vigsnaes L., Sommer M., Hennet T., Bytzer P.
Department of Medicine, Zealand University Hospital, Denmark

Intensive research over the past decade has established the gut microbiota as an important player influencing many aspects of human physiology including energy metabolism, hormonal balance and immunity. Breast milk, the first diet for an infant, contains human milk oligosaccharides (HMOs) that shape the infant’s gut microbiota by selectively stimulating the growth of specific bacteria, especially bifidobacteria. After weaning, diet, together with genetics and environmental influences, is one of the main factors contributing to the composition of the human gut microbiota. Hence, dietary manipulation represents a strategy to promote a beneficial gut microbiota. In addition to their bifidogenic activity, the ability of HMOs to modulate immune function and the gut barrier make them prime candidates to restore a beneficial microbiota in dysbiotic adults and provide health benefits. However, the effects of HMOs on the adult gut microbiota and gastrointestinal tract have never been examined.

We conducted a parallel, double-blind, randomized, placebo-controlled, HMO supplementation study in 100 adult healthy volunteers. Participants were randomized into 10 groups, each consuming chemically produced HMOs at various daily doses (5, 10 or 20 grams), or 2 grams of glucose as placebo for 2 weeks. Safety was assessed through physical examination, hematology and blood chemistry analysis. Tolerance was recorded by a self-administered Gastrointestinal Symptoms Rating Scale (GSRS) questionnaire covering symptoms related to abdominal pain, indigestion, reflux, diarrhea and constipation, and stool consistency by the Bristol Stool Form Scale (BSFS). Adverse events were monitored from intake of first dose and throughout the intervention period. The composition of the intestinal microbiota was determined by 16S rRNA sequencing of faecal samples before and during HMO intervention.

All participants completed the study without premature discontinuation. Physical parameters, including pulse rate and blood pressure, remained unchanged during and after HMO uptake. Routine clinical chemistry and haematology analyses also remained stable over the course of the study. The GSRS scores were low at baseline, and remained low after intervention, and only a minor change was observed for stool frequency and consistency. Adverse events recorded throughout the intervention period were all characterized as mild. The 16S rRNA sequencing analysis revealed that HMO supplementation specifically modified the adult gut microbiota with the primary impact being substantial increases in abundance of Actinobacteria and Bifidobacterium in particular, and a reduction of Firmicutes and Proteobacteria. The increase in Bifidobacterium, reaching more than 25% in some individuals, was dose-dependent but was not dependent on the initial Bifidobacterium abundance.

This study provides the first data on safety, tolerance and impact of HMOs on the gut microbiota of healthy adult subjects. Collectively, the results from this study show that supplementing the diet with HMOs is a valuable strategy to shape the gut microbiota and specifically promote the growth of beneficial bifidobacteria and health.

Keywords: HMOs, Safety, Tolerance, Sequencing, Bifidobacterium, Probiotics

Salomonsson E., et al. (2016). Human milk oligosaccharides; Now as substantial modulators of the adult gut microbiota.  Conference Proceedings of IPC2016. Paper presented at the International Scientific Conference on Probiotics and Prebiotics, Budapest (p. 114.). IPC2016

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