Green algal sulfated polysaccharides: a natural alternative to antibiotics via modulation of the intestinal immune response

Alternative prophylactic strategies are needed to limit the use of antibiotics in animal husbandry. One potential solution is to limit the level of infections via stimulation of the innate immune response. Green algae have emerged as a rich source of bioactive natural compounds that can be used as a new generation of growth enhancers capable to potentiate the immune function and improve animal health. Recently, a crude extract of marine sulfated polysaccharides (MSP) prepared from the green macroalgae Ulva armoricana harvested from the shores of northern Brittany (France) was evaluated, in vitro, as an antibacterial compound against bacterial strains found in livestock animals as well as for its immunomodulatory activity on differentiated porcine intestinal epithelial cell line IPEC-1. We showed that this MSP extract was able to inhibit the bacterial growth of several pathogenic bacteria and stimulate mRNA expression of intestinal immune response mediators such as IL1α, IL1β, L-6, IL-8, TNFα, TGFβ, CCL20, PPAR-γ, a ligand-activated anscription factor, and the TLR2 receptor. The MSP extract was further purified and the low molecular weight water-soluble sulfated polysaccharides fraction (ulvan) confirmed its capacity to stimulate the expression of cytokines such as CCL20, IL8, and TNFα, both at mRNA and protein levels. By using human embryonic kidney HEK 293 reporter cell lines for pattern recognition receptors, we found that this ulvan fraction act mainly via interaction with the TLR4 receptor. In addition, western blot analysis of ulvan-treated HEK 293-TLR4 cells showed an increase in the Akt signaling pathway and nuclear factor-γB (NFγB) phosphorylation, able to induce cytokine gene expression. Used as a feed additive, the MSP may constitute a new prophylactic strategy to increase intestinal health of livestock animals, and thereby reducing the subsequent use of antibiotic treatment. Furthermore, the ulvan fraction could be used, in vaccination strategies, as an immunostimulating adjuvant compound to effectively complex and deliver TLR ligands to relevant immune cells