Longo Miriam, Rubio Teresa, Lamelas Araceli, Jericó Daniel, Rodenes-Gavidia Andrea, Cervero Jordi, Martínez-Blanch Juan, Chenoll Empar, Martorell Patricia, Paolini Erika, Meroni Marica, Riezu-Boj José Ignacio, Solares Isabel, Sampedro Ana, Urigo Francesco, Collantes María, Battistin Michele, Gatti Stefano, Quincoces Gemma, Peñuelas Ivan, Moreno-Aliaga María Jesús, Ávila Matías A, Di Pierro Elena, Ramón Daniel, Milagro Fermín I, Dongiovanni Paola, Fontanellas Antonio
Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, 20122, Italy.
ADM Research Center-Valencia, University of Valencia Science Park (Parc Científic de La Universitat de València), Paterna, 46980, Spain.
J Physiol Biochem. 2025 Sep 26. doi: 10.1007/s13105-025-01124-4.
Acute intermittent porphyria (AIP) is a genetic metabolic disorder characterized by neurovisceral attacks. Although high-carbohydrate diets or intravenous glucose administration can help alleviate incipient attacks in patients, these interventions may also promote insulin resistance and increase metabolic risk. This study explored targeted dietary interventions to manage hyperinsulinemia and to enhance glucose uptake in insulin-sensitive organs under high-carbohydrate diet. Body composition and fecal microbiota profile were also investigated in a murine model of the disease. Wild-type and AIP mice (n = 6/group) were supplemented with tapioca maltodextrin in drinking water for 12 weeks, alongside heat-treated Bifidobacterium animalis subsp. lactis CECT-8145 (BPL1®HT), its by-product lipoteichoic acid (LTA), or the insulin-sensitizing agent α-lipoic acid (α-LA). Liver-targeted therapies, previously assessed in AIP mice, were also included in this study. AIP mice on a high-carbohydrate diet exhibited hyperinsulinemia and tissue-specific differences in glucose uptake compared to wild-type mice. Dysbiosis, marked by reduced fecal Dorea spp. and Adlercreutzia muris, alongside higher abundance of Escherichia coli, was also showed. Supplementation with α-LA and LTA revealed superior ability to improve glucose tolerance test and skeletal muscle glucose uptake, reduce hyperinsulinemia, and enhance body composition by increasing lean mass relative to fat, compared to gene therapy or liver-targeted insulin administration. Notably, LTA restored fecal microbiota profiles resembling those of wild-type mice. In conclusion, supplementation with LTA from BPL1®HT and α-LA may represent promising dietary interventions to manage glucose tolerance, improve insulin sensitivity in muscle and adipose tissues, and potentially ameliorate body composition in AIP patients under a high-carbohydrate diet.
急性间歇性卟啉病（AIP）是一种以神经内脏发作症状为特征的遗传性代谢紊乱疾病。尽管高碳水化合物饮食或静脉注射葡萄糖可帮助缓解患者的初期发作症状，但这些干预措施也可能会促进胰岛素抵抗并增加代谢风险。本研究探索了在高碳水化合物饮食情况下，通过有针对性的饮食干预来控制高胰岛素血症，并增强胰岛素敏感器官对葡萄糖的摄取。同时，还在该疾病的小鼠模型中研究了身体组成和粪便微生物群特征。野生型小鼠和AIP小鼠（每组n = 6）在饮水中补充木薯麦芽糊精12周，同时补充经过热处理的动物双歧杆菌乳亚种CECT - 8145（BPL1®HT）、其副产物脂磷壁酸（LTA）或胰岛素增敏剂α-硫辛酸（α-LA）。本研究还纳入了之前在AIP小鼠中评估过的肝脏靶向治疗方法。与野生型小鼠相比，采用高碳水化合物饮食的AIP小鼠表现出高胰岛素血症以及葡萄糖摄取的组织特异性差异。还观察到肠道菌群失调，表现为粪便中多雷亚菌属和鼠阿德勒克雷茨菌减少，同时大肠杆菌丰度增加。与基因治疗或肝脏靶向胰岛素给药相比，补充α-LA和LTA显示出更优的能力，能够改善葡萄糖耐量试验和骨骼肌对葡萄糖的摄取，降低高胰岛素血症，并通过增加瘦体重相对于脂肪的比例来改善身体组成。值得注意的是，LTA恢复了类似于野生型小鼠的粪便微生物群特征。总之，补充来自BPL1®HT的LTA和α-LA可能是有前景的饮食干预措施，可用于控制葡萄糖耐量，改善肌肉和脂肪组织中的胰岛素敏感性，并可能改善高碳水化合物饮食下AIP患者的身体组成。
