Glucose Oligosaccharide and Long-Chain Glucomannan Feed Additives Induce Enhanced Activation of Intraepithelial NK Cells and Relative Abundance of Commensal Lactic Acid Bacteria in Broiler Chickens

Abstract

Restrictions on the use of antibiotics in the poultry industry stimulate the development of alternative nutritional solutions to maintain or improve poultry health. This requires more insight in the modulatory effects of feed additives on the immune system and microbiota composition. Compounds known to influence the innate immune system and microbiota composition were selected and screened in vitro, in ovo, and in vivo. Among all compounds, 57 enhanced NK cell activation, 56 increased phagocytosis, and 22 increased NO production of the macrophage cell line HD11 in vitro. Based on these results, availability and regulatory status, six compounds were selected for further analysis. None of these compounds showed negative effects on growth, hatchability, and feed conversion in in ovo and in vivo studies. Based on the most interesting numerical results and highest future potential feasibility, two compounds were analyzed further. Administration of glucose oligosaccharide and long-chain glucomannan in vivo both enhanced activation of intraepithelial NK cells and led to increased relative abundance of lactic acid bacteria (LAB) amongst ileum and ceca microbiota after seven days of supplementation. Positive correlations between NK cell subsets and activation, and relative abundance of LAB suggest the involvement of microbiota in the modulation of the function of intraepithelial NK cells. This study identifies glucose oligosaccharide and long-chain glucomannan supplementation as effective nutritional strategies to modulate the intestinal microbiota composition and strengthen the intraepithelial innate immune system.

Long-chain glucomannan supplementation modulates immune responsiveness, as well as intestinal microbiota, and impacts infection of broiler chickens with Salmonella enterica serotype Enteritidis

“…GM supplemented chickens showed increased relative abundance of lactic acid bacteria (LAB) including Streptococcus species, Lactobacillus species and Bifidobacterium gallinarum in the ileum and caeca compared to the ones fed the standard diet. This observation was in agreement with a previous study using GM supplementation [ 31 ] and may indicate that these LAB preferentially benefit from GM. Before SE infection, the relative abundance of only Streptococci was increased in the caeca of chickens receiving GM supplementation.…”

“…A distinct population of IL-2Rα + 20E5 + cells was not observed, although the possibility that these cells exist at a very low frequency cannot be excluded. The stimulatory impact of GM affecting numbers and function of intraepithelial NK and T cells before infection is similar to observations in uninfected chickens of the same age supplemented with GM [ 31 ]. Whether the distinct increase in 20E5 + intraepithelial NK cells is a result of recruitment of 20E5 + NK cells or development of IL-2Rα + into 20E5 + NK cells needs to be investigated in future experiments.…”

“…Higher numbers of intraepithelial CD8αα + and CD8αβ + cytotoxic T cells were observed in GM supplemented chickens compared to the standard diet post-infection, although only significant in the CD8αβ + subset, suggesting a role in the defense against SE. Interestingly, the stimulatory effects of GM on the numbers of intraepithelial T cells is stronger under SE challenge as compared to non-challenged GM-supplemented chickens [ 31 ]. The stimulatory effects of GM on NK and T cells may be facilitated by the cytosolic aryl hydrocarbon receptor (AHR) or G-protein coupled receptors (GPCRs) that recognize diet-derived ligands as was shown in humans and mice [ 53 – 55 ].…”

“…The correlation between SE-CFUs and SE-specific antibody titers was analyzed using the Spearman’s rank correlation test. The procedure to analyze the microbiota composition using the microarray chip has been described elsewhere [ 31 ]. Correlations between immune parameters and microbial taxa were analyzed using the Pearson product-moment correlation procedure.…”

“…Furthermore, administration of probiotics to embryos by in ovo inoculation has shown to reduce SE infection incidence after hatch [ 44 , 45 ]. In a previous study we showed that long-chain glucomannan (GM), a water-soluble polysaccharide that acts as a prebiotic, increased numbers and activation of NK cells in the IEL population as well as the relative abundance of lactic acid bacteria (LAB) in the intestine [ 31 ]. However, it is not known yet whether and how the increased numbers and function of NK cells and the effects on microbiota composition upon GM supplementation increase the resistance to infections such as SE.…”