Science behind macroalgae activities

Modern broiler production has dramatically changed in the last years driven by an increasing consumer demand. The immune requirements vary throughout the production cycle depending on the physiological status and are also influenced by external factors. Among external factors, environmental stress such as temperature or stocking density, management stress such as vaccination programmes, feed stress such as transitions or presence of toxins can really impact the animals’ immune status and thus performance. Plus, sanitary pressure will greatly impact immunity and thus performance. This situation is aggravated if animals already present a low level of immunity.

The implementation of new regulations banning the inclusion of antibiotics in broilers diets as a routine means of growth promotion has led to an intensive research effort to identify alternative bioactive compounds that are able to promote animal health and performance. The modulation of the animal’s immune function is another approach leading to a higher resilience level against external aggressors such as infectious agents. The goal is to make animals able to better face daily challenges. Recent research has highlighted the potential of in-feed marine macroalgal polysaccharides as a reliable solution to strengthen animal defences. They are also a powerful tool to achieve performance potential in modern production systems, as well as good candidates as alternatives to in-feed antibiotics in animal husbandry.

Macroalgal extracts specificities

The cell wall of marine macroalgae is mainly composed of water-soluble sulphated polysaccharides which present a complex structure. The molecular weight and several structural specificities, including branched conformation, presence of several sugars and more particularly rare ones (xylose and rhamnose) and sulphation, confer to algal polysaccharides unique biological activities. Among other things, modulation of the immune response and reinforcement of the gut barrier function are being investigated. Sulphated polysaccharides are specific from marine macroalgae (they are not found in terrestrial plants, nor fresh water microalgae or yeast cell walls) as the marine environment is the only one where the sulphur chemical form can be integrated in the structure of organisms. Thanks to all these structural specificities, marine sulphated polysaccharides possess structural analogies with animal’s glycosaminoglycanes (GAG’s), like heparin. This explains their high degree of reactivity and specific biological activities when fed to animals.

Olmix Group innovative technology and marine bioactive ingredient extraction know-how led to the development of an in-feed product, Algimun, which is based on the combination of 2 biologically active macroalgal extracts:

1. MSP Immunity which constitutes an innovative modulating agent that reinforces innate and adaptive immune responses
2. MSP Barrier, which enhances the barrier function of the ­intestinal mucosa.

Photo: Olmix

Immunomodulating effects

Olmix has worked on such extracts and the immunomodulating activity of its MSP Immunity (extracted from green macroalgae Ulva sp) was first evident on porcine intestinal epithelial cells in vitro. MSP Immunity induced the transcription of several immune mediators involved in the activation, recruitment and migration of macrophages and dendritic cells (professional antigen-presenting cells), as well as differentiation and recruitment of lymphocytes, and induction of anti-inflammatory properties, thus raising interest for its use as an immunomodulating agent. This activation was shown to derive from the activation of the pattern recognition ­receptors (PRR) Toll-like receptors (TLR) 4 and 2.

Further research has been conducted in poultry models in order to demonstrate the ability of MSP Immunity to enhance innate and adaptive immune response of broilers through activation of heterophils and monocyte. Heterophils are functionally equivalent to mammalian neutrophils and are a critical component of innate immunity. Their activity can be evaluated by measuring the oxidative burst (release of reactive oxygen species (ROS) with bactericidal activity) and/or by conducting a degranulation assay, assessing the enzymatic activity of glucuronidase also able to degrade viruses and bacteria. Monocytes are important phagocytes in poultry, playing a critical role in both innate immunity (bactericidal activity via nitric oxide (NO) production) and initiation of the adaptive immune response via their role as antigen-presenting cell.

Figure 1 – Nitric oxide release by monocytes with different concentrations of MSP®IMMUNITY during 4 consecutive days.

The effect of this green algal extract (MSP Immunity) on birds’ monocytes and heterophils (purified from peripheral blood of 28 day-old broilers) was evaluated in vivo. 3 different concentrations of MSP Immunity (10, 25, 50mg/L) were given orally (per os) at day 0 (first day of the trial) for 24 hours and compared with the negative control. The experiments lasted 4 days in total. Results showed that MSP Immunity induced the activation of monocytes and heterophils. A dose and time response was observed for nitric oxide release by monocytes with a peak at day 1, swiftly declining, with values no longer statistically different from that of the negative control at day 3 (Figure 1). In parallel, the ability of MSP Immunity to induce glucuronidase activity in heterophils was also occurring in a time and dose-dependent manner (Figure 2). Additional in vitro experiments, using specific PRR inhibitors, showed that MSP Immunity activates monocytes and heterophils through recognition by TLR2 and TLR4 confirming the results obtained by Berri et al. (2017) in a porcine model.

Figure 2 – Glucuronidase activity by heterophils with different concentrations of MSP®IMMUNITY during 4 consecutive days.

Moreover, the study showed that the activation of monocytes and heterophils led to a transient increase of immune mediators transcription, including interleukin 1-β, interferon-α and interferon-γ. These cytokines are produced during innate immune responses and play an important role as activators of adaptive immune responses via the differentiation of Th1 cells that will determine cell-mediated immunity: antigen presentation activity of macrophages and induction of ­lymphocytes B to synthetise opsonizing antibodies.

Conclusion

The study highlights the potent role of MSP Immunity to support the development of adaptive immune response in broilers. This innovative bioactive compound can thus play an important role within the reduction of antibiotics in feed. Complementary trials in research centres or in the field have confirmed that when distributed continuously to broilers during starter and grower phases, MSP Immunity (associated with another Olmix MSP in a commercial product named Algimun), can accelerate the shift from innate to adaptive immunity (decreased heterophil to lymphocyte ratio), improve gut protection (higher plasmatic IgA levels) and improving technical performance.

References available upon request.