Chen Zhuo, Ge Xiaodong, Wang Yaolin, Zhang Jiawei, Sui Yinzi, Yin Xuemei, Wu Na, Yang Lei, Xu Jianda, Zhou Hongcheng, Wu Qin, Zeng Feng, Liu Liang, Shao Rong, Xu Wei
College of Marine and Bioengineering, Yancheng Institute of Technology, Yancheng, China.
Department of Orthopaedics, Changzhou Hospital Affiliated to Nanjing University of Chinese Medicine, Changzhou, China.
Mol Nutr Food Res. 2025 Apr;69(7):e202400996. doi: 10.1002/mnfr.202400996. Epub 2025 Feb 21.
Type 2 diabetes mellitus (T2DM), a widespread chronic metabolic disorder, presents a global challenge. Metformin hydrochloride, although widely prescribed, is associated with notable side effects. This study aims to explore safer, more effective alternatives by assessing the impact of Ruditapes philippinarum polysaccharides (RPPs) on glycemic control and modulation of microbiota in T2DM mice. A T2DM mouse model was established through a high-sucrose/high-fat diet and intraperitioneal streptozotocin injection. Glycometabolism indicators, histopathological features, and gut microbiota composition in caecum samples were assessed. Following 4 weeks of RPPs intervention, fasting blood glucose (FBG), glycated serum protein (GSP), area under the curve (AUC) of oral glucose tolerance test (OGTT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) levels were reduced in T2DM mice, while AKT-1 and GLUT-2 transcription levels were significant increased. Short-chain fatty acids (SCFAs) concentrations notably increased in the RPP-L group compared to the Model group, with improvements also observed in medium-chain fatty acids (MCFAs) and secondary bile acids (SBAs). Regarding gut microbiota, the Firmicutes-to-Bacteroidetes (F/B) ratio in RPP-L was substantially lower than in the Model group. At the genus level, beneficial bacteria, such as Akkermansia, Alloprevotella, Tidjanibacter, and Faecalibaculum demonstrated increased abundance. Correlation analysis identified Muribaculum, Paramuribaculum, Lacrimispora, and Turicibacter as microbial taxa associated with T2DM progression. RPPs significantly alleviated hyperglycemic symptoms in T2DM mice while enhancing the presence of beneficial gut bacteria, leading to a marked improvement in intestinal microbiota composition. This research offers foundational insights for the potential use of R. philippinarum in biomedical and nutraceutical applications.
2型糖尿病（T2DM）是一种广泛存在的慢性代谢紊乱疾病，构成了全球性挑战。盐酸二甲双胍虽然被广泛使用，但存在显著副作用。本研究旨在通过评估菲律宾蛤仔多糖（RPPs）对T2DM小鼠血糖控制和微生物群调节的影响，探索更安全、更有效的替代方案。通过高糖/高脂饮食和腹腔注射链脲佐菌素建立T2DM小鼠模型。评估盲肠样本中的糖代谢指标、组织病理学特征和肠道微生物群组成。RPPs干预4周后，T2DM小鼠的空腹血糖（FBG）、糖化血清蛋白（GSP）、口服葡萄糖耐量试验（OGTT）曲线下面积（AUC）、总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白胆固醇（LDL-c）水平降低，而AKT-1和GLUT-2转录水平显著升高。与模型组相比，RPP-L组的短链脂肪酸（SCFAs）浓度显著增加，中链脂肪酸（MCFAs）和次级胆汁酸（SBAs）也有所改善。关于肠道微生物群，RPP-L组的厚壁菌门与拟杆菌门（F/B）比值显著低于模型组。在属水平上，有益菌如阿克曼氏菌、别普雷沃氏菌、蒂贾尼氏菌和粪杆菌的丰度增加。相关性分析确定穆里杆菌属、副穆里杆菌属、泪孢菌属和Turicibacter为与T2DM进展相关的微生物分类群。RPPs显著减轻了T2DM小鼠的高血糖症状，同时增加了有益肠道细菌的数量，导致肠道微生物群组成显著改善。本研究为菲律宾蛤仔在生物医学和营养保健应用中的潜在用途提供了基础见解。
