Ma Yin-Hing, Islam Golam S, Wu Ying, Sabour Parviz M, Chambers James R, Wang Qi, Wu Shirley X Y, Griffiths Mansel W
Guelph Research and Development Centre, Agriculture and Agri-Food Canada, 93 Stone Road West, Guelph, Ontario N1G 5C9, Canada.
Graduate Department of Pharmaceutical Sciences, University of Toronto, 144 College Street West, Toronto, Ontario M5S 3M2, Canada.
Poult Sci. 2016 Dec 1;95(12):2911-2920. doi: 10.3382/ps/pew260. Epub 2016 Sep 1.
Encapsulation of bacteriophages ("phage") protects phage against environmental deactivation and provides a product that is easy to handle for storage and application with animal feed as an antibiotic alternative. The objective of this study was to evaluate an orally administered, encapsulated phage for efficient phage release in the gastrointestinal tract (GIT) of young chicks receiving feed. An optimized formulation that consisted of 0.8% low molecular weight (MW) alginate, 2% ultra-low molecular weight alginate and 3% whey protein completely released the encapsulated phage within 60 min under simulated intestinal conditions. This product was given to broiler chicks to determine passage time and distribution of the viable phage within the GIT. Following a single oral dose of 10 plaque-forming unit (PFU)/chick, the major portion (peak concentration) of the encapsulated phage passed through the chick's GIT and was detected in the feces within 4 h, with low levels being continuously excreted for up to 24 h. In comparison, the passage of free phage through the GIT occurred faster as indicated by a peak concentration in feces after 1.5 h. In assessing the temporal phage distribution, both encapsulated and free phage treatments showed no apparent difference, both having low levels of 10 to 10 PFU/g of contents along the entire GIT after 1, 2 and 4 h. These low concentrations recovered in vivo led us to examine various exposure conditions (with feed, fecal material, and buffer solutions) that were suspected to have affected phage viability/infectivity during oral delivery, sample recovery, and enumeration by plaque assay. Results showed that the exposure conditions examined did not significantly reduce phage viability and could not account for the observed low phage levels following oral administration in chicks that are on feed. In conclusion, an oral encapsulated phage dose can take more than 4 h to completely move through the GIT of young chicks. Thus, repeated or higher doses may be necessary to attain higher phage concentrations in the GIT.
噬菌体（“噬菌体”）的包囊化可保护噬菌体免受环境失活影响，并提供一种易于处理的产品，便于储存并作为抗生素替代品与动物饲料一起应用。本研究的目的是评估一种口服的、包囊化的噬菌体在接受饲料的幼雏胃肠道（GIT）中能否有效释放噬菌体。一种优化配方由0.8%的低分子量（MW）海藻酸盐、2%的超低分子量海藻酸盐和3%的乳清蛋白组成，在模拟肠道条件下，该配方能在60分钟内使包囊化的噬菌体完全释放。将该产品投喂给肉鸡雏鸡，以确定其在胃肠道内的通过时间和活噬菌体的分布。在每只雏鸡口服10个噬斑形成单位（PFU）的单次剂量后，包囊化噬菌体的主要部分（峰值浓度）通过雏鸡的胃肠道，并在4小时内于粪便中被检测到，低水平的噬菌体持续排泄长达24小时。相比之下，游离噬菌体通过胃肠道的速度更快，粪便中的峰值浓度出现在1.5小时后。在评估噬菌体的时间分布时，包囊化和游离噬菌体处理均未显示出明显差异，在1、2和4小时后，整个胃肠道内的内容物中噬菌体水平均较低，为10至10 PFU/g。体内回收的这些低浓度促使我们研究各种暴露条件（与饲料、粪便物质和缓冲溶液接触），这些条件被怀疑在口服给药、样品回收以及通过噬斑测定法计数过程中影响了噬菌体的活力/感染性。结果表明，所研究的暴露条件并未显著降低噬菌体的活力，也无法解释在采食饲料的雏鸡口服给药后观察到的低噬菌体水平。总之，口服包囊化噬菌体剂量需要超过4小时才能完全通过幼雏的胃肠道。因此，可能需要重复给药或给予更高剂量才能在胃肠道中达到更高的噬菌体浓度。
