Immune modulation by non-digestible and non-absorbable beta-1,3/1,6-glucan

Chemistry of beta-1,3/1,6-glucans Beta-glucans comprise a very diverse group of polysaccharides (even paper) in which glucose molecules as the only building block are linked together by beta-linkages. Only very few beta-glucan structures, notably beta-1,3/ 1,6-glucans, are bioactive in the sense that they interact with receptors on immune cells and elicit specific biological responses. Beta-1,3/1,6-glucans are branched chains of glucose molecules connected by beta-1,3-glycosidic bonds, and in which the branching points are beta-1,6 linkages, as shown in the schematic diagram for the beta-glucan found in yeast. This net-like molecular structure constitutes the inner layer of the cell wall of baker’s yeast, providing mechanical strength to the cells. In live cells, the beta-1,3/1,6glucan structure is attached to a surface layer of complex proteoglycans (mainly proteomannans) and chitin. Many published studies on biological effects of ‘betaglucans’ have been carried out with poorly defined products and created misconceptions regarding mode of action of beta-1,3/1,6-glucans. A reference product like Zymosan contains, for instance, mannose-rich proteoglycans attached to the beta-1,3/1,6-glucan structure. Since these mannose-proteins are very potent allergens and antigens, whereas the pure beta-1,3/1,6-glucan component counteracts allergy and does not elicit any antibody production against itself, it is difficult to interpret experimental results on biological effects of Zymosan. Poor chemical description holds true also for extracts from mycelial fungi used in experimental studies. The beta-1,3/ 1,6-glucan component in crude fungal extracts has therefore incorrectly been held responsible for allergenic and pro-inflammatory effects of such extracts and of molds. The ability of beta-1,3/1,6-glucans to activate innate immune cells depends on its branched structure. A beta1,3-glucan without any side chains (branches) does not activate macrophages. Products with only one single glucose molecule in the ‘side chain’, as in most mushroom beta-1,3/ 1,6-glucans (e.g. lentinan), have lower macrophage activating activity than yeast cell-wall beta-1,3/1,6-glucan. In addition to chain length, the frequency of side chains is essential for immune-stimulating and immunemodulating ability of beta-1,3/1,6-glucans (1, 2). These molecular structures may change or be destroyed during extraction, hence affecting the biological activity of the extracted product. The materials section of papers on biological effects of ‘beta-glucans’ should therefore be studied carefully.