Postoperative insulin resistance (IR) is a metabolic disorder characterized by decreased insulin sensitivity and elevated blood glucose levels following major surgery. Our previous clinical study identified a notable correlation between postoperative IR and gut microbiota, particularly butyrate-producing bacteria, yet the mechanisms remain unclear. In this study, we established gastric resection SD rat models to evaluate the impact of Clostridium butyricum NCU-27 (butyrate-producing bacteria) on postoperative IR. The results demonstrated significant reductions in fasting blood glucose (FBG), fasting insulin (FIns) levels, and HOMA-IR (6.64 ± 0.76 vs. 11.47 ± 1.32; 4.27 ± 0.59 vs. 7.40 ± 0.54) in the postoperative period compared to the control group (P < 0.05). Additionally, glucose tolerance and hepatic glycogen content were markedly improved (P < 0.001). Further exploration of butyrate demonstrated effects similar to C. butyricum NCU-27, potentially mediated through the gut-liver axis by inhibiting mTORC1 expression in liver cells, activating the IRS1/AKT pathway, enhancing glucose uptake and glycogen synthesis, suppressing gluconeogenesis, increasing insulin sensitivity, and improving IR. Finally, the use of mTORC1 agonists and inhibitors further confirmed the critical role of the mTORC1 pathway in mediating the beneficial effects of C. butyricum NCU-27 and butyrate on postoperative IR. In conclusion, this study elucidated that C. butyricum NCU-27 improves postoperative IR by regulating butyrate metabolism and inhibiting the mTORC1 pathway, offering new insights for preventing and treating post-gastrectomy IR.

Keywords: Butyrate; Gut microbiota; Gut-liver axis; MTORC1; Postoperative insulin resistance.

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术后胰岛素抵抗（IR）是一种代谢障碍，特征是大手术后胰岛素敏感性降低和血糖水平升高。我们之前的一项临床研究发现，术后胰岛素抵抗与肠道微生物群之间存在显著关联，特别是产丁酸菌，但其机制尚不清楚。在这项研究中，我们建立了胃切除SD大鼠模型，以评估产丁酸梭状芽孢杆菌NCU-27（一种产丁酸菌）对术后胰岛素抵抗的影响。结果显示，在术后期间，实验组的空腹血糖（FBG）、空腹胰岛素（FIns）水平和HOMA-IR指数显著低于对照组（P < 0.05），具体数值分别为6.64 ± 0.76 vs. 11.47 ± 1.32，以及4.27 ± 0.59 vs. 7.40 ± 0.54。此外，葡萄糖耐量和肝脏糖原含量也明显改善（P < 0.001）。进一步探讨丁酸发现其作用类似于产丁酸梭状芽孢杆菌NCU-27，可能通过抑制肝细胞mTORC1表达、激活IRS1/AKT通路、增强葡萄糖摄取和糖原合成、抑制糖异生、提高胰岛素敏感性以及改善IR等方式介导。最后，使用mTORC1激动剂和抑制剂进一步证实了mTORC1途径在调节产丁酸梭状芽孢杆菌NCU-27和丁酸对术后胰岛素抵抗的有益作用中的关键角色。总之，本研究阐明了产丁酸梭状芽孢杆菌NCU-27通过调节丁酸代谢及抑制mTORC1通路改善术后胰岛素抵抗，为预防和治疗胃切除后胰岛素抵抗提供了新的见解。

关键词：
丁酸；肠道微生物群；肠肝轴；MTORC1；术后胰岛素抵抗。