非酒精性脂肪性肝病肠道菌群变化及其与胰岛素抵抗的关系

Changes of intestinal flora and correlation with insulin resistance in nonalcoholic fatty liver disease

目的探讨非酒精性脂肪性肝病(NAFLD)患者肠道菌群变化及其与胰岛素抵抗(IR)的关系。方法选择非酒精性脂肪性肝病患者60例(NAFLD组)和健康体检者30例(对照组),对肠道中的4种细菌进行培养和计数,计算肠道定植抗力指标双歧杆菌与大肠埃希菌数值之比(B/E值)以反映肠道菌群变化状态,比较2组间细菌数量及B/E值的变化;同时测定各临床指标,采用稳态模型IR指数(HOMA-IR)评估IR程度。结果 (1)细菌数量及B/E值变化:与对照组相比,NAFLD组大肠埃希菌数量增加,双歧杆菌和乳杆菌数量均减少(P<0.05),肠球菌2组间差异无统计学意义;B/E值明显降低(P<0.05)。(2)NAFLD组各临床指标及HOMA-IR明显增高(P<0.05)。(3)相关分析:B/E值与体质量指数、收缩压、舒张压、血清丙氨酸氨酸转移酶、天门冬氨酸氨酸转移酶、三酰甘油、总胆固醇、空腹血糖、空腹胰岛素、HOMA-IR均呈显著负相关(r分别为-0.741、-0.829、-0.932、-0.440、-0.405、-0.611、-0.878、-0.628、-0.817、-0.846,P<0.01)。(4)多元线性回归分析:在控制血压、血糖和血脂等因素后,B/E值是HOMA-IR的独立影响因素(R2=0.716,P<0.01)。结论 NAFLD患者存在肠道菌群失调、肠道定植抗力受损,其程度与IR程度密切相关,提示肠道菌群失调可能通过参与IR而在NAFLD的发生、发展过程中发挥作用。

Objective To investigate changes of intestinal flora and correlation with insulin resistance（IR） in nonalcoholic fatty liver disease patients. Methods Sixty patients with nonalcoholic fatty liver disease（NAFLD group） and 30 normal subjects（Control group） were selected and their intestinal bacteria were cultured and counted routinely. We counted intestinal colonization resistance index B/E value which can be used to reflecting changes of intestinal flora and compared changes of bacteria number and B/E value between the two groups. Clinical indexes were measured and insulin resistance was evaluated using steady-state model HOMA-IR. Results First,Bacteria number and B/E value： compared with control group,NAFLD group Enterobacteriaceae increased s ignificantly,Bifid bacteria and Lactobacilli decreased significantly（P 〈0.05）,B/E value lowered significantly（P 〈0.05）,and Enterococcus difference was not statistically significant. Second,Clinical indexes and HOMA-IR of NAFLD group increased significantly（ P 〈0.05）. Third,Correlation analysis：the B/E value was negatively correlated with BMI,SBP,DBP,ALT,AST,TG,TC, FPG,FINS,and HOMA-IR（r =- 0.741,- 0.829,- 0.932,- 0.440,- 0.405,- 0.611,- 0.878,- 0.628,- 0.817and- 0.846,P 0.01）. Fourth,Multiple linear regression analysis：in the control of blood pressure,blood glucose and blood lipid and other factors,B/E value was independent risk factor of HOMA-IR（R^2= 0.716,P〈 0.01）. Conclusion Patients with NAFLD show intestinal flora imbalance and intestinal colonization resistance damage,which is closely related to IR. Intestinal flora imbalance may be involved in IR and play a role in the occurrence and development of NAFLD.