Human milk oligosaccharides


A substrate needs to meet three criteria for acknowledged as prebiotic. The most challenging of these is the demonstration of a health benefit (or reduction of disease) in the host mediated by some but not all microorganisms that ferment the substrate. Health benefits of dietary prebiotic candidates are direct through binding of pathogens (decoy-effect) or indirect and associated with short-chain fatty acids as product of selective fermentation. Human milk oligosaccharide isoforms, galacto- and fructooligosaccharides, and lipophilic substances are under investigation for their classification as prebiotics.


The International Association for Probiotics and Prebiotics (ISAPP) defines a prebiotic as "a substrate that is selectively utilized by host microorganisms conferring a health benefit" (Gibson et al. 2017). Accordingly, prebiotics are not limited to carbohydrates nor is their effect limited to the gastrointestinal tract. Also, the nasal or oral cavities, vagina, skin, bone health, brain function or the cardiovascular are seen as organ systems beneficially affected by prebiotics (Gibson et al. 2017).

A prebiotic substrate has to reach the localised microbiota intact, is specifically selected as food source by certain microbiota species, and the health benefit (enhancing health or reducing disease symptoms) is mediated through specific – not all – resident microbiota species (Gibson et al. 2017; Krumbeck et al. 2016). A prebiotic that encourages growth of Bifidobacterium subspecies is called "bifidogenic" i.e. it exerts "bifidogenic effects" or supports "bifidogenesis" which is positive because the growing bifidobacteria population is considered a sign of intestinal health (Ríos-Covián et al. 2016; Roberfroid et al. 2010​​​​​​​). Together with Lactobacillus subspecies, these were the first intestinal microbiota species associated with health benefits. With progress in analytical methods other possibly beneficial microbiota species are being identified (Hutkins et al. 2016).

Potential prebiotic-associated health benefits include but are not limited to the reduction of infantile colic, risk for atopic disease, infection, mucosal inflammation or gas production and stimulation of peristaltic and softer stool consistency leading to increased defaecation frequency (Krumbeck et al. 2016). These health benefits are most likely mediated by prebiotic modes of action that include

  • the increased growth or activity of beneficial microbiota species,
  • reduction or inhibition of pathogens,
  • decreased bacterial gut barrier translocation via promotion of colonic mucin production
  • stimulation of the immune system and regulation of signalling pathways,
  • regulation of plasma lipid concentrations,
  • increasing sensitivity to insulin and other hormones, and
  • changes in bioavailability of substances affecting other organs beneficially such as brain function and cognition or bone mineralisation (Gibson et al. 2017​​​​​​​; Krumbeck et al. 2016).

Prebiotics stimulate growth or activity of bacteria that produce short-chain fatty acids (SCFA) – acetate, butyrate, propionate and other volatile variants – and a subsequent reduction in intestinal pH. The reduced pH creates a difficult growth environment for many pathogens and thus protects against infections (Gibson et al. 2017​​​​​​​; Ríos-Covián et al. 2016). In addition, butyrate serves as preferred fuel for many intestinal cells, promotes barrier function, and – together with acetate – reduces inflammation (Krumbeck et al. 2016).

Pathogen inhibition can also occur by binding of the prebiotic substrate to the pathogen or receptor sites and thus preventing "docking" to cell surfaces. This is called "decoy-effect" by which for example certain human milk oligosaccharide (HMO) isoforms bind to potential pathogens (Gibson et al. 2017​​​​​​​).

Some bacteria genera induced by prebiotics substrates modulate the expression of pro- and anti-inflammatory cytokines and thus regulate gut inflammation. Bifidobacterium subspecies increase expression of secretory immunoglobulin A, a key player in the complement immune system (Krumbeck et al. 2016).

Establishing such a health benefit is difficult but the ISAPP suggests that a study in the target population should demonstrate a change in health markers or symptoms mediated by specific microbiota populations that are affected by the prebiotic substrate.(Gibson et al. 2017​​​​​​​). The most extensive body of evidence has accumulated on oligosaccharides (OS) such as inulin and oligofructose (from inulin), fructooligosaccharides (FOS) and galactooligosaccharides (GOS). These indigestible carbohydrates are bifidogenic (Hutkins et al. 2016). The investigation of their health benefits is ongoing. Other prebiotic candidates are natural and synthetic human milk oligosaccharide isoforms, bovine milk oligosaccharides, some poly-unsaturated fatty acids (PUFA), conjugated linoleic acid (CLA), lactulose, resistant starch, pectin, bile acids, and plant polyphenols (Gibson et al. 2017​​​​​​​; Hutkins et al. 2016).


  • References

    Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, Scott K, Stanton C, Swanson KS, Cani PD, Verbeke K, Reid G. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nature reviews. Gastroenterology & hepatology 2017; 14(8):491–502. at:

    Hutkins RW, Krumbeck JA, Bindels LB, Cani PD, Fahey G, Goh YJ, Hamaker B, Martens EC, Mills DA, Rastal RA, Vaughan E, Sanders ME. Prebiotics: why definitions matter. Current opinion in biotechnology 2016; 37:1–7. at: 

    Krumbeck JA, Maldonado-Gomez MX, Ramer-Tait AE, Hutkins RW. Prebiotics and synbiotics: dietary strategies for improving gut health. Current opinion in gastroenterology 2016; 32(2):110–9. at: 

    Ríos-Covián D, Ruas-Madiedo P, Margolles A, Gueimonde M, Los Reyes-Gavilán CG de, Salazar N. Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health. Frontiers in microbiology 2016; 7:185. at:

    Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, Wolvers D, Watzl B, Szajewska H, Stahl B, Guarner F, Respondek F, Whelan K, Coxam V, Davicco M-J, Léotoing L, Wittrant Y, Delzenne NM, Cani PD, Neyrinck AM, Meheust A. Prebiotic effects: metabolic and health benefits. The British journal of nutrition 2010; 104 Suppl 2:S1-63. at: