Yuan Xiuxia, Zhang Yu, Pang Lijuan, Zhang Xiaoyun, Kang Yulin, Hei Gangrui, Li Xue, Song Xueqin
Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China.
Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Psychiatry, Shandong Daizhuang Hospital, Jining, Shandong, China.
Psychoneuroendocrinology. 2025 Feb;172:107255. doi: 10.1016/j.psyneuen.2024.107255. Epub 2024 Dec 12.
This study aimed to explore the relationship among gut microbiota imbalance, the homeostasis model of assessment of insulin resistance (HOMA-IR) and cognitive impairments in patients with schizophrenia (SCZ). We conducted a case-control study involving 189 first-episode, drug-naïve SCZ patients and 115 healthy controls (HCs). Main methods adopted included metagenomics analysis, glucose metabolism assessment, and cognitive function evaluation using the MATRICS Consensus Cognitive Battery (MCCB). Fecal microbiota composition was analyzed via high-throughput sequencing of 16S ribosomal RNA. Patients with SCZ showed a higher likelihood of developing IR (23 %), compared to HCs (12 %). The IR group exhibited significantly higher levels of fasting blood glucose (FBG), fasting insulin (FINS), HOMA-IR, and homeostasis model assessment-β (HOMA-β), while showing lower insulin sensitivity index (ISI) levels (all p < 0.05). Patients with IR demonstrated lower scores in working memories (WM), verbal learning (HVLT) and reasoning and problem solving (RPS), compared to those without IR. Additionally, microbiota analysis revealed that IR patients had higher abundance of Negativicutes, Streptococcaceae, Enterobacteriaceae, Lachnoclostridium, Dialister, Klebsiella, and Enterobacter, and lower abundance of Flavonifractor and Rikenellaceae. Notably, Negativicutes, Streptococcaceae, Lachnoclostridium, Flavonifractor, and Rikenellaceae were shared between SCZ and IR conditions. Mediation analysis indicated that the relative abundance of Streptococcaceae have an indirect effect on WM through HOMA-IR (β=-0.148, SE=0.067, 95 %CI=-0.280 to -0.020). The study suggests that IR may play a mediating role in the relationship between gut microbiota dysbiosis and cognitive impairments in patients with SCZ, which could point to potential new avenues for therapeutic interventions.
本研究旨在探讨精神分裂症（SCZ）患者肠道微生物群失衡、胰岛素抵抗稳态模型评估（HOMA-IR）与认知障碍之间的关系。我们进行了一项病例对照研究，纳入了189例首发、未用药的SCZ患者和115例健康对照（HCs）。采用的主要方法包括宏基因组学分析、葡萄糖代谢评估以及使用MATRICS共识认知成套测验（MCCB）进行认知功能评估。通过对16S核糖体RNA进行高通量测序分析粪便微生物群组成。与HCs（12%）相比，SCZ患者发生胰岛素抵抗（IR）的可能性更高（23%）。IR组的空腹血糖（FBG）、空腹胰岛素（FINS）、HOMA-IR和稳态模型评估-β（HOMA-β）水平显著更高，而胰岛素敏感性指数（ISI）水平更低（所有p<0.05）。与无IR的患者相比，IR患者在工作记忆（WM）、言语学习（HVLT）以及推理和解决问题（RPS）方面的得分更低。此外，微生物群分析显示，IR患者中Negativicutes、链球菌科、肠杆菌科、拉克诺梭菌属、戴阿利斯特菌属、克雷伯菌属和肠杆菌属的丰度更高，而黄酮分解菌属和理研菌科的丰度更低。值得注意的是，Negativicutes、链球菌科、拉克诺梭菌属、黄酮分解菌属和理研菌科在SCZ和IR状态之间存在共性。中介分析表明，链球菌科的相对丰度通过HOMA-IR对WM有间接影响（β=-0.148，SE=0.067，95%CI=-0.280至-0.020）。该研究表明，IR可能在SCZ患者肠道微生物群失调与认知障碍之间的关系中起中介作用，这可能为治疗干预指出潜在的新途径。
