β-Glucan successfully stimulated the immune system in different jawed vertebrate species
Introduction
A variety of natural polysaccharides have shown the ability to stimulate the immune system of invertebrate and vertebrate species. Among these compounds, the glucans stand out and their role as a biologically active immunomodulator has been well documented for more than 40 years. ‘Glucans’ is the common name given to a group of polysaccharide polymers, classified based on interchain linkages as either α- or β-linked. They are widely distributed in bacteria, algae, fungi and plants, with different structural types [(see Barsanti et al. [1]]. Their structure is comprised of a main chain of β-(1,3)- and/or β-(1,4)-D-glucopyranosyl units in non-repeating but non-random order, with side chains of varying lengths [2].
Specifically, the β-glucans are the most well-known ‘glucans’ and their benefits have been investigated in a wide range of vertebrates such as humans [3], dogs [4,5], pigs [6], cattle [7], horses [8], sheep [9], chickens [10], frogs [11], fish [12] and invertebrates such as shrimp [13], crab [14], and insects such as bees [15] and drosophila [16]. These benefits include lower stress [17], anti-cancer [18], anti-allergies [19], regulate blood sugar levels [20], prebiotics [21,22], reduce serum cholesterol in hypercholesterolemic animals [23], increase wound healing [24], immune adjuvant [25] and they are extensively used to improve health, growth and general performance in farm animals. In a recent review, Petit and Wiegertjes [26] provided evidence that β-glucans are also able to stimulate a new concept called trained immunity or innate immune memory, which allows macrophages, monocytes, and natural killer cells to show enhanced responsiveness when they reencounter pathogens [27]. In addition, β-glucans have also been successfully used in diverse administration routes such as oral [12], injection or bath [28].
In a review, Soltanian et al. [29] suggested that β-glucan is an immunostimulant that is active across the evolutionary spectrum. Although it is plausible, the studies referred to in the review and also on the current literature did not have the appropriate experimental design to reach this conclusion. The effects of β-glucan are influenced by their molecular weight, degree of branching [2,30], purity, source and extraction process as demonstrated by Pilarski et al. [12]. In addition, the diversity of experimental designs, methods, and administration routes as mentioned before is an aggravating factor for comparing/extrapolating β-glucans’ effects across species. Thus, in this study, we fed four different vertebrate species: mice, dog, piglets and chicks, with two β-glucan molecules (BG01 and BG02) and control diet for 28 days. We measured the serum IL-2 production as an indicator of innate immune response, the neutrophils and monocytes phagocytosis index as a cellular immune response and anti-body production against ovoalbumin as an adaptive immune response. This is the first report of this nature on jawed vertebrates.
Section snippets
Experimental animals and welfare statement
Male and female dogs (average age 2.5 ± 0.5 years, average weight 14.5 ± 2.1 kg, 61% males, and different breeds) were purchased from Marshall Farms, North Rose, NY, USA. Piglets (all white Yorkshire x Landrace; age 3 weeks, average weight 6.3 ± 0.7 kg, 54% males) were obtained from Oak Hill Genetics (Ewing, IL, USA) and leghorn chickens (age 10 days, average weight 65 ± 17.1 g, 50% males) from Hy-Line International, Bryan, TX, USA. All mice used were 8-week-old females of the BALB/c strain
Results
As shown in Table 1, purity of BG01 is 77%, whereas purity of BG02 is 55%. In order to use similar doses of glucan, we used different dose (15 mg/kg or 25 mg/kg) to make the treatments more comparable regard glucan level, since that it is the major active compound. Although it not to be the exactly same glucan level, the small difference between glucan levels in the diet (11.5 mg for BG01 and 13.7 mg for BG02) are really biologically irrelevant and not responsible to trigger the quite different
Discussion
So far, no published study has investigated the effects of β-glucan molecules on different vertebrate species using the same experimental protocol. Here, we show that both β-glucan molecules stimulate four individual immune responses in similar patterns in mice, dogs, piglets and chicks, but with different magnitudes of responses between individual β-glucan samples. Pilarski et al. [12] using the same two β-glucan molecules from this study also showed that the β-glucan samples exhibited
Conclusions
The current literature recognizes more than 31,000 papers that discuss the immunological and other physiological activities of glucans. However, scientific reports directly comparing individual glucans are limited [12,[67], [68], [69]], and a direct comparison of the effects of glucan in several species is completely absent. Therefore, this report is not important because it describes the biological activity of two samples of glucan, but because it is the first report demonstrating that two
Acknowledgments
The authors would like to thank Biorigin for their β-glucan donation and financial support. The funders had no role in the study design, data collection and analysis, or decision to publish. The authors have no competing interests to declare.
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