Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL.
Gnubiotics Sciences SA, Epalinges, Switzerland.
J Anim Sci. 2021 Jan 1;99(1). doi: 10.1093/jas/skab014.
Milk oligosaccharides (MO) are bioactive compounds in mammalian milk that provide health benefits to neonates beyond essential nutrients. GNU100, a novel animal MO biosimilar, was recently tested in vitro, with results showing beneficial shifts in microbiota and increased short-chain fatty acid (SCFA) production, but other effects of GNU100 were unknown. Three studies were conducted to evaluate the safety, palatability, and gastrointestinal (GI) tolerance of GNU100. In study 1, the mutagenic potential of GNU100 was tested using a bacterial reverse mutation assay and a mammalian cell micronucleus test. In study 2, palatability was assessed by comparing diets containing 0% vs. 1% GNU100 in 20 adult dogs. In study 3, 32 adult dogs were used in a completely randomized design to assess the safety and GI tolerance of GNU100 and explore utility. Following a 2-wk baseline, dogs were assigned to one of four treatments and fed for 26 wk: 0%, 0.5%, 1%, and 1.5% GNU100. On weeks 2, 4, and 26, fresh fecal samples were collected to measure stool quality, immunoglobulin A, and calprotectin, and blood samples were collected to measure serum chemistry, inflammatory markers, and hematology. On weeks 2 and 4, fresh fecal samples were collected to measure metabolites and microbiota. On week 4, total feces were collected to assess apparent total tract macronutrient digestibility. Although revertant numbers were greater compared with the solvent control in tester strain WP2uvrA(pKM101) in the presence of metabolic activation (S9) in the initial experiment, they remained below the threshold for a positive mutagenic response in follow-up confirmatory tests, supporting that GNU100 is not mutagenic. Similarly, no cytotoxicity or chromosome damage was observed in the cell micronucleus test. The palatability test showed that 1% GNU100 was strongly preferred (P < 0.05; 3.6:1 consumption ratio) over the control. In study 3, all dogs were healthy and had no signs of GI intolerance or illness. All diets were well accepted, and food intake, fecal characteristics, metabolite concentrations, and macronutrient digestibilities were not altered. GNU100 modulated fecal microbiota, increasing evenness and Catenibacterium, Megamonas, and Prevotella (SCFA producers) and reducing Collinsella. Overall, the results suggest that GNU100 is palatable and well-tolerated, causes no genotoxicity or adverse effects on health, and beneficially shifts the fecal microbiota, supporting the safety of GNU100 for the inclusion in canine diets.
牛奶低聚糖（MO）是哺乳动物乳中的生物活性化合物，除了提供必需营养素外，还能为新生儿提供健康益处。最近，一种新型动物 MO 生物类似物 GNU100 在体外进行了测试，结果显示微生物群发生有益变化，短链脂肪酸（SCFA）产量增加，但 GNU100 的其他作用尚不清楚。进行了三项研究来评估 GNU100 的安全性、适口性和胃肠道（GI）耐受性。在研究 1 中，使用细菌回复突变试验和哺乳动物细胞微核试验测试了 GNU100 的致突变潜力。在研究 2 中，通过比较 20 只成年犬的 0%和 1% GNU100 含量的饮食来评估适口性。在研究 3 中，使用 32 只成年犬进行完全随机设计，以评估 GNU100 的安全性和 GI 耐受性，并探索其用途。在 2 周的基线后，将犬分为四组中的一组，并喂养 26 周：0%、0.5%、1%和 1.5% GNU100。在第 2、4 和 26 周时，收集新鲜粪便样本以测量粪便质量、免疫球蛋白 A 和钙卫蛋白，并采集血液样本以测量血清化学、炎症标志物和血液学。在第 2 和 4 周时，收集新鲜粪便样本以测量代谢物和微生物群。在第 4 周时，收集总粪便以评估全肠道宏量营养素消化率的表观值。尽管在初始实验中存在代谢激活（S9）时，WP2uvrA(pKM101)测试菌株中的回复突变数与溶剂对照相比增加，但在后续确认试验中仍低于阳性致突变反应的阈值，这表明 GNU100 没有致突变性。同样，在细胞微核试验中也未观察到细胞毒性或染色体损伤。适口性试验表明，1% GNU100 比对照物（3.6:1 的消耗比）更受青睐。在研究 3 中，所有犬均健康，无任何 GI 不耐受或疾病迹象。所有饮食均被很好地接受，食物摄入量、粪便特征、代谢物浓度和宏量营养素消化率均未改变。GNU100 调节粪便微生物群，增加均匀度和 Catenibacterium、Megamonas 和 Prevotella（SCFA 产生菌），减少 Collinsella。总体而言，结果表明 GNU100 适口性好，耐受性良好，不会引起遗传毒性或对健康产生不良影响，并且有益地改变了粪便微生物群，支持 GNU100 可安全用于犬类饮食。
