It's all down to the chemical Linkage – some Prebiotics can stimulate Immune Cells

16 / 2021

Prebiotics are often used to make foods richer in fibre. Certain prebiotics – polysaccharides consisting of many monosaccharides (mannoses) linked in a specific way (β-1→4-glycosidic) – exhibit immunostimulatory effects alongside these properties. This is the conclusion of an international team of scientists with the involvement of the Paul-Ehrlich-Institut. The new findings could be important for the development of immunostimulatory foodstuffs as well as new adjuvants for vaccines. "Cells" reports on the results in its online edition dated 14 July 2021.

Mannose molecule 3D illustration (Source: Irina Anosova/

A research team coordinated by PD Dr Stefan Schülke from the Molecular Allergology Department at the Paul-Ehrlich-Institut collaborated with a team led by Professor Masako Toda of Tohoku University and the Hokkaido University in Japan to investigate the immunological properties of certain sugar structures, so-called manno-oligosaccharides. For this purpose, they used immune cells (dendritic cells) from mice.

Stimulation of these immune cells with manno-oligosaccharides caused only mannoses with β-(1→4)-linkages to significantly induce production of cytokines, messenger substances of immune cells. This affected, among other things, the cytokines interleukin 6 and 10 (IL-6, IL-10), tumor necrosis factor-α (TNF-α), and interferon-β (IFN-β). In addition, the sugar structures increased the breakdown of sugar (glycolysis) of immune dendritic cells as well as their ability to activate cells of the acquired immune system, so-called CD4+-T helper cells.

These results suggest that mannoses with β-(1→4)-linkages are immunostimulatory molecules. Fostering glycolysis may be involved in the production of pro-inflammatory cytokines in dendritic cells stimulated by β-Man-(1→4).

"Our results could contribute to the development of immune-enhancing functional foodstuffs," said PD Dr Stefan Schülke, explaining the significance of the findings. Furthermore, they may also provide an approach for the development of innovative vaccine adjuvants.


Mannans are polysaccharides. Polysaccharides are carbohydrates that are made up of a larger number of simple sugars (monosaccharides). They are connected by various so-called glycosidic linkages. Some mannans consist of β-1→4-glycosidic-linked mannose units (β-Man-(1→4) and are found in plants as accompanying substances of cellulose. This is how they are found in coffee beans and soybeans, among others. These kinds of manno-oligosaccharides could also have immunological functions in addition to their prebiotic effect. Prebiotics are non-digestible components of food that foster the growth and activity of bacteria in the intestine.

Original Publication

Cheng TY, Lin YJ, Saburi W, Vieths S, Scheurer S, Schülke S, Toda M (2021): β-(1→4)-Mannobiose Acts as an Immunostimulatory Molecule in Murine Dendritic Cells by Binding the TLR4/MD-2 Complex.
Cells 10: 1774.

Updated: 22.07.2021