Ji Wangli, Yang Daoxin, Zhang Wenjing, Wang Yuan, Hao Zhenzhen, Guo Kairui, Sun Xianhua, Wang Shuai, Yang Shuyan, Ma Jianshuang, Luo Huiying, Yao Bin, Zhang Meiling, Zhang Honglian, Huang Huoqing, Su Xiaoyun
State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, No. 2 West Yuanmingyuan Road, Beijing, 100193, China.
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Probiotics Antimicrob Proteins. 2025 Jul 16. doi: 10.1007/s12602-025-10664-6.
Intestinal alkaline phosphatase (AP) detoxifies lipopolysaccharides, which has been exploited in treating infection of Gram-negative bacterial pathogens such as Escherichia coli. Orally administered AP has the potential to modulate the gut microbiota, which is in part ascribed to its ability to degrade ATP, a well-known inhibitor of gut commensal bacteria. In addition, AP can fortify the gut barrier. Therefore, we hypothesized that the enzyme might also be used to control intestinal Gram-positive pathogens such as Clostridium perfringens. Herein, broiler chickens were challenged with 3 × 10 colony-forming units of C. perfringens daily from 14 to 20 days. Low (1000 U/kg of feed) and high (5000 U/kg of feed) doses of a recombinant bovine intestinal AP (bIAP) were orally administered to the chickens throughout the study. bIAP could indeedalleviate the gut lesion and diarrhea symptom in chickens challenged with C. perfringens and reversed the decline in their growth performance. 16S rRNA gene sequencing and non-targeted metabolomics analyses revealed that bIAP could modulate the gut microbiota, which was accompanied with a change of the gut metabolites profile, the improved intestinal integrity and immunity, and an ultimate protection of the animals from C. perfingens infection. Strikingly, the RT-qPCR assay showed that the transcript levels of key tight junction proteins zonula occludens-1, Mucin 2, claudin-1, and occludin in the duodenum, jejunum, and ileum were even superior in the high dose group than those in the unchallenged group, suggestive of enhanced integrity of the intestinal barrier. Enzymes such as bIAP are, therefore, a powerful tool in modulating the gut microbiota for better health of the host animals.
肠道碱性磷酸酶（AP）可解毒脂多糖，这一特性已被用于治疗革兰氏阴性细菌病原体感染，如大肠杆菌感染。口服AP有调节肠道微生物群的潜力，部分原因是其具有降解ATP的能力，ATP是一种已知的肠道共生细菌抑制剂。此外，AP可以强化肠道屏障。因此，我们推测这种酶也可用于控制肠道革兰氏阳性病原体，如产气荚膜梭菌。在此，从14日龄至20日龄，每天用3×10个产气荚膜梭菌菌落形成单位对肉鸡进行攻毒。在整个研究过程中，给鸡口服低剂量（1000 U/kg饲料）和高剂量（5000 U/kg饲料）的重组牛肠道AP（bIAP）。bIAP确实可以减轻产气荚膜梭菌攻毒鸡的肠道损伤和腹泻症状，并逆转其生长性能的下降。16S rRNA基因测序和非靶向代谢组学分析表明，bIAP可以调节肠道微生物群，同时伴随着肠道代谢物谱的变化、肠道完整性和免疫力的改善，以及最终对动物免受产气荚膜梭菌感染的保护。令人惊讶的是，RT-qPCR分析表明，十二指肠、空肠和回肠中关键紧密连接蛋白闭合蛋白-1、黏蛋白2、紧密连接蛋白-1和闭合蛋白的转录水平在高剂量组甚至高于未攻毒组，提示肠道屏障完整性增强。因此, 像bIAP这样的酶是调节肠道微生物群以促进宿主动物健康的有力工具。
