Ali Muhsin, Ullah Hidayat, Farooqui Nabeel Ahmed, Deng Ting, Siddiqui Nimra Zafar, Ilyas Muhammad, Ali Sharafat, Rahman Mujeeb Ur, Rehman Ata Ur, Alioui Yamina, Wang Liang, Yi Xin
Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, China.
Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, China.
Heliyon. 2024 Sep 24;10(19):e38370. doi: 10.1016/j.heliyon.2024.e38370. eCollection 2024 Oct 15.
Cyclophosphamide (CTX) is an anticancer medication that suppresses host immunity as well as adversely affects mucosal inflammation and gut microflora dysbiosis. The gut microflora is recognized as a substantial factor in host metabolism and immunological homeostasis. To improve immunity and inhibit cytotoxic and homeostatic imbalances triggered by CTX, it is essential to monitor immunoregulators. In this research, we assessed the impact of Octopus peptide hydrolysate (OPH) on immune modulation, intestinal integrity, and gut microbial composition in CTX-induced immune-deficient mice. The results revealed that OPH increased body weight, and immunological organ indices, and improved the histological changes in the colon, thymus, and spleen. The OPH stimulated the secretion of cytokines (IL-1β, IL-6, and TNF-α) and antibodies (IgM and IgA) while reducing the ratio of lipopolysaccharide LPS) and diamine oxidase (DAO) in the serum. OPH further enhanced goblet cell and mucus production, upregulated the expression of gut tight-junction proteins (Occludin, Zonula Occludin-1, Mucin-2, and Claudin-1), and activated the TLR4/NF-κB cascade (p-IκBα, P65/p-p65). In addition, OPH treatment declined the Bacteroidetes/Firmicutes ratio, enhanced the relative ratio of /, and reversed the ecological equilibrium of the gut microflora. The findings revealed that OPH serves as a prebiotic to prevent CTX-mediated disruption in the intestinal barrier and boosts gut mucosal immunity by attenuating gut microflora imbalance, implying that OPH could be used as an immunological ingredient in nutritious foods to regulate the immune system and protect the gut from inflammatory diseases.
环磷酰胺（CTX）是一种抗癌药物，它会抑制宿主免疫力，并对黏膜炎症和肠道微生物群失调产生不利影响。肠道微生物群被认为是宿主代谢和免疫稳态的一个重要因素。为了提高免疫力并抑制CTX引发的细胞毒性和稳态失衡，监测免疫调节因子至关重要。在本研究中，我们评估了章鱼肽水解物（OPH）对CTX诱导的免疫缺陷小鼠的免疫调节、肠道完整性和肠道微生物组成的影响。结果显示，OPH增加了体重和免疫器官指数，并改善了结肠、胸腺和脾脏的组织学变化。OPH刺激了细胞因子（IL-1β、IL-6和TNF-α）和抗体（IgM和IgA）的分泌，同时降低了血清中脂多糖（LPS）和二胺氧化酶（DAO）的比例。OPH进一步增强了杯状细胞和黏液的产生，上调了肠道紧密连接蛋白（紧密连接蛋白、闭合蛋白-1、黏蛋白-2和Claudin-1）的表达，并激活了TLR4/NF-κB级联反应（p-IκBα、P65/p-p65）。此外，OPH处理降低了拟杆菌门/厚壁菌门的比例，提高了/的相对比例，并逆转了肠道微生物群的生态平衡。研究结果表明，OPH作为一种益生元，可预防CTX介导的肠道屏障破坏，并通过减轻肠道微生物群失衡来增强肠道黏膜免疫力，这意味着OPH可作为营养食品中的一种免疫成分，用于调节免疫系统并保护肠道免受炎症性疾病的侵害。
