非酒精性脂肪性肝病患者肠道菌群与胰高血糖素样肽1的相关性分析

Correlation of intestinal flora with serum glucagon-like peptide-1 level in patients with nonalcoholic fatty liver disease

目的探讨非酒精性脂肪性肝病(NAFLD)患者肠道菌群失调与血清胰高血糖素样肽(GLP)1水平的相关性。方法选取2018年1月-2018年12月在武汉市汉口医院就诊的NAFLD患者116例为NAFLD组,另选取同期在本院体检的96例健康者为对照组。收集所有患者的新鲜粪便标本进行细菌培养,分析肠道菌群变化,评估肠道菌群定植抗力(B/E比值)。比较2组之间BMI、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FPG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、血清GLP-1水平、肠道菌群的数量及B/E比值的变化。计量资料2组间比较采用t检验;计数资料2组间比较采用χ~2检验;相关性分析采用Pearson相关分析和偏相关分析。结果NAFLD组BMI[(24.76±2.93)kg/m^2vs(22.35±2.54)kg/m^2]、TG[(1.15±0.65)mmol/L vs(0.93±0.62)mmol/L]、TC[(4.06±1.02)mmol/L vs(3.71±1.15)mmol/L]、LDL-C[(2.76±0.93)mmol/L vs(2.33±0.87)mmol/L]、FINS[(15.17±7.39)m IU/L vs(12.74±6.81)m IU/L]、HOMA-IR[(2.58±1.38)vs(2.14±1.25)]、肠杆菌[(9.56±1.85)log cfu/g vs(8.38±1.92)log cfu/g]、肠球菌[(8.12±1.47)log cfu/g vs(7.66±1.54)log cfu/g]及葡萄球菌[(7.54±1.22)log cfu/g vs(7.03±1.18)log cfu/g]高于对照组,而血清GLP-1水平[(6.95±2.74)pmol/L vs(8.06±2.86)pmol/L]、双歧杆菌[(8.87±1.76)log cfu/g vs(9.71±1.86)log cfu/g]、乳酸杆菌[(8.31±1.55)log cfu/g vs(8.97±1.57)log cfu/g]、拟杆菌[(8.66±1.21)log cfu/g vs(9.23±1.34)log cfu/g]及B/E比值[(0.96±0.17)vs(1.15±0.15)]低于对照组(t值分别为6.327、2.504、2.347、3.450、2.469、2.411、4.544、2.219、3.075、-2.878、-3.371、-3.068、-3.251、-8.539,P值均<0.05)。血清GLP-1水平与B/E比值呈正相关(r=0.604,P<0.05),而与BMI、TG、TC、LDL-C、HOMA-IR呈负相关(r值分别为-0.551、-0.424、-0.386、-0.445、-0.503,P值均<0.05);控制BMI、TG、TC、LDL-C、HOMA-IR等因素后,GLP-1与B/E比值仍然呈正相关(r=0.576,P<0.05)。结论NAFLD患者血清GLP-1水平降低与肠道菌群失调存在相关性。

Objective To investigate the correlation of intestinal dysbacteriosis with serum glucagon-like peptide-1(GLP-1)level in patients with nonalcoholic fatty liver disease(NAFLD).Methods A total of 116 patients with NAFLD who attended Wuhan Hankou Hospital from January to December 2018,were enrolled as NAFLD group,and 96 healthy individuals who underwent physical examination in our hospital during the same period of time were enrolled as control group.Fresh feces samples were collected from all subjects and bacterial culture was performed;the change in intestinal flora was analyzed,and the Bifidobacterium-Escherichia coli(B/E)ratio was calculated to evaluate the colonization resistance of intestinal flora.The two groups were compared in terms of the changes in body mass index(BMI),triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),fasting plasma glucose(FPG),fasting insulin(FINS),Homeostasis Model Assessment of Insulin Resistance(HOMA-IR),serum GLP-1 level,number of intestinal bacteria,and B/E ratio.The t-test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Pearson correlation analysis and partial correlation analysis were performed.Results Compared with the control group,the NAFLD group had significantly higher levels of BMI(24.76±2.93 kg/m^2 vs 22.35±2.54 kg/m^2,t=6.327,P<0.05),TG(1.15±0.65 mmol/L vs 0.93±0.62 mmol/L,t=2.504,P<0.05),TC(4.06±1.02 mmol/L vs 3.71±1.15 mmol/L,t=2.347,P<0.05),LDL-C(2.76±0.93 mmol/L vs 2.33±0.87 mmol/L,t=3.450,P<0.05),FINS(15.17±7.39 m IU/L vs 12.74±6.81 m IU/L,t=2.469,P<0.05),HOMA-IR(2.58±1.38 vs 2.14±1.25,t=2.411,P<0.05),Enterobacter(9.56±1.85 log cfu/g vs 8.38±1.92 log cfu/g,t=4.544,P<0.05),Enterococcus(8.12±1.47 log cfu/g vs 7.66±1.54 log cfu/g,t=2.219,P<0.05),and Staphylococcus(7.54±1.22 log cfu/g vs 7.03±1.18 log cfu/g,t=3.075,P<0.05),as well as significantly lower levels of serum GLP-1(6.95±2.74 pmol/L vs 8.06±2.86 pmol/L,t=-2.878,P<0.05),Bifidobacterium(8.87±1.76 log cfu/g vs 9.71±1.86 log cfu/g,t=-3.371,P<0.05),Lactobacillus(8.31±1.55 log cfu/g vs 8.97±1.57 log cfu/g,t=-3.068,P<0.05),Bacteroides(8.66±1.21 log cfu/g vs 9.23±1.34 log cfu/g,t=-3.251,P<0.05),and B/E ratio(0.96±0.17 vs 1.15±0.15,t=-8.539,P<0.05).Serum GLP-1 level was positively correlated with B/E ratio(r=0.604,P<0.05)and was negatively correlated with BMI,TG,TC,LDL-C,and HOMA-IR(r=-0.551,-0.424,-0.386,-0.445,and-0.503,all P<0.05).After the control for BMI,TG,TC,LDL-C,and HOMA-IR,serum GLP-1 level was still positively correlated with B/E ratio(r=0.576,P<0.05).Conclusion The reduction in serum GLP-1 level is correlated with intestinal dysbacteriosis in patients with NAFLD.