目的 探讨营养干预对肝硬化代偿期合并糖尿病患者肠道微生物的影响。方法 收集2022年9月-2023年9月本院收治的80名肝硬化代偿期合并糖尿病患者，随机分为对照组和观察组，每组40例。对照组使用常规降糖药物治疗，观察组在对照组基础上，进行营养干预，根据1。5g/kg的体重剂量摄入乳清蛋白质粉，接受常规饮食咨询和营养建议。每4周收集空腹血清样本，在干预前和营养干预后12周收集粪便样本，使用全自动生化分析仪、ELISA法检测血清葡萄糖、总胆固醇、高密度脂蛋白(HDL-c)胆固醇和低密度脂蛋白胆固醇(LDL-c)胆固醇水平等临床参数。使用Illumina Nova Seq平台对粪便基因组DNA测序。结果 对照组患者12周后临床各项指标与基线比较，差异均无统计学意义(P＞0。05)。观察组患者营养干预后空腹血糖(t=2。862，P=0。005)、空腹胰岛素(t=5。926，P＜0。001)、HOMA-IR(t=2。680，P=0。009)、hs-CRP(t=3。386，P=0。001)、蛋白质氧化率(t=7。762，P=0。001)均显著降低，呼吸商显著增加(t=2。958，P=0。004)。营养干预后6个菌种的相对丰度发生了显著变化，分别属于厚壁菌门、拟杆菌门和变形菌门。属于拟杆菌属和梭菌目的菌种在营养干预后产生了显著的菌株基因组变化。基于HOMA-IR的相对改善，将观察组患者分为响应者(R)亚组和非响应者(NR)亚组。两个亚组之间肠道微生物群的动态变化差异有统计学意义(P=0。008)。结论 肠道微生物群在营养干预对肝硬化代偿期合并糖尿病患者胰岛素敏感性影响中发挥重要作用，可能有助于临床实施个体化生活方式干预。
Effect of nutritional intervention on gut microbiota of patients with compensated cirrhosis and diabetes
Objective To observe the effect of nutritional intervention on the gut microbiota of patients with com-pensated cirrhosis and diabetes.Methods Eighty patients with compensated cirrhosis and diabetes admitted to our hospit-al from September 2022 to September 2023 were collected and randomly divided into a control group and an observation group,with 40 cases in each group.The control group received conventional antidiabetic medication,while the observation group underwent nutritional intervention in addition to the conventional antidiabetic medication,including intake of whey protein powder at a dose of 1.5 g/kg,routine dietary counseling,and nutritional advice.Fasting serum samples were collec-ted every 4 weeks,and fecal samples were collected before and 12 weeks after nutritional intervention.Clinical indexes such as blood glucose,total cholesterol,high-density lipoprotein cholesterol(HDL-c),and low-density lipoprotein choles-terol(LDL-c)were measured using an automatic biochemical analyzer and ELISA method.Fecal genomic DNA was se-quenced on the Illumina Nova Seq platform.Results After 12 weeks,there were no statistically significant differences in clinical indexes compared to baseline in the control group(P＞0.05).In the observation group,fasting blood glucose(t=2.862,P=0.005),fasting insulin(t=5.926,P＜0.001),HOMA-IR(t=2.680,P=0.009),hs-CRP(t=3.386,P=0.001),and protein oxidation rate(t=7.762,P=0.001)significantly decreased,while the respiratory quotient significantly increased(t=2.958,P=0.004)after nutritional intervention.The relative abundance of six species belonging to Firmicutes,Bacteroid-etes and Proteobacteria changed significantly after nutritional intervention.The species within Bacteroides and Clostridiales showed significant genomic changes after nutritional intervention.Based on the relative improvement in HOMA-IR,the observation group participants were divided into responder(R)and non-responder(NR)subgroups.The dy-namic changes in gut microbiota between the two subgroups were statistically significant(P=0.008).Conclusion The gut microbiota plays a crucial role in the effect of nutritional intervention on insulin sensitivity in patients with compensated cirrhosis and diabetes.This may contribute to the implementation of personalized lifestyle interventions in clinical practice.
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