慢性胰腺炎胰腺外分泌功能不全和肠道微生态及血清炎性指标水平的相关性

Correlation between pancreatic exocrine insufficiency and intestinal microecology and serum inflammatory index levels in chronic pancreatitis

目的 探讨胰腺外分泌功能不全和慢性胰腺炎(CP)患者肠道微生态及血清炎性指标变化的相关性。方法 选取2019年1月-2021年5月沧州市中心医院178例CP患者,根据是否伴有外分泌功能不全将其分为无外分泌功能不全组[粪弹力蛋白酶1(FE1)≥200μg/g,n=40]、轻中度外分泌功能不全组(100μg/g≤FE1<200μg/g,n=60),重度外分泌功能不全组(FE1<100μg/g,n=78),比较各组患者的肠道菌群、小肠细菌过度生长的差异情况以及血清降钙素原(PCT)、C反应蛋白(CRP)及肿瘤坏死因子-α(TNF-α)水平差异;Spearman相关分析肠道菌群、炎性因子与FE1的相关性。结果 重度外分泌功能不全组患者肠道杆菌科、肠道球菌科相对丰度[(0.032±0.004)、(0.049±0.011)]明显高于轻中度外分泌功能不全组[(0.024±0.003)、(0.036±0.008)]和无外分泌功能不全组[(0.011±0.001)、(0.020±0.005)],双歧杆菌科、乳酸杆菌科相对丰度[(0.012±0.002)、(0.015±0.002)]明显低于轻中度外分泌功能不全组[(0.025±0.006)、(0.020±0.004)]和无外分泌功能不全组[(0.046±0.009)、(0.031±0.006)],差异均有统计学意义(P均<0.05);轻中度外分泌功能不全组患者肠道杆菌科、肠道球菌科相对丰度明显高于无外分泌功能不全组,双歧杆菌科、乳酸杆菌科相对丰度明显低于无外分泌功能不全组,差异均有统计学意义(P均<0.05)。重度外分泌功能不全组小肠细菌过度生长阳性率(64.1%)高于轻中度外分泌功能不全组(30.0%)和无外分泌功能不全组(10.0%),差异均有统计学意义(P均<0.05);轻中度外分泌功能不全组小肠细菌过度生长阳性率高于无外分泌功能不全组,差异有统计学意义(P<0.05)。重度外分泌功能不全组PCT、CRP、TNF-α水平[(5.8±0.9)ng/L、(245.8±15.0)mg/L、(593.1±41.9)pg/mL]高于轻中度外分泌功能不全组[(4.3±0.6)ng/L、(201.0±13.8)mg/L、(512.5±35.6)pg/mL]和无外分泌功能不全组[(3.1±0.4)ng/L、(183.4±11.2)mg/L、(462.5±28.9)pg/mL],差异均有统计学意义(P均<0.05);轻中度外分泌功能不全组PCT、CRP、TNF-α水平高于无外分泌功能不全组,差异均有统计学意义(P均<0.05)。PCT、CRP、TNF-α、肠道杆菌科、肠道球菌科及小肠细菌过度生长阳性率均与FE1成负相关(r=-0.425、-0.518、-0.503、-0.619、-0.507、-0.511,P均<0.05),而双歧杆菌科、乳酸杆菌科与FE1成正相关(r=0.592、0.628,P均<0.05)。结论 CP外分泌功能不全患者的小肠细菌出现过度生长,且肠道益生菌减少,而有害菌增加,同时机体的炎性指标升高,此可能为CP外分泌功能不全患者的诊治提供有利依据。

Objective To explore the correlation between pancreatic exocrine insufficiency and changes in intestinal microbiota and serum inflammatory indicators in patients with chronic pancreatitis(CP).Methods A total of 178 CP patients were selected in the Cangzhou Central Hospital From January 2019 to May 2021 and were divided into no exocrine insufficiency group[faecal elastase 1(FE1)≥200 μg/g,n=40],mild-moderate exocrine insufficiency group(100 μg/g≤FE1<200 μg/g,n=60)and severe exocrine insufficiency group(FE1<100 μg/g,n=78)according to whether or not they were accompanied by exocrine insufficiency.The differences in intestinal flora,small intestinal bacterial overgrowth,and serum procalcitonin(PCT),C-reactive protein(CRP),tumour necrosis factor-α(TNF-α)levels were compared among the groups.The correlation between FE1 and intestinal flora,inflammatory factors were analyzed by Spearman correlation analysis.Results The relative abundance of Enterobacteriaceae and Enterococcaceae in patients in the severe exocrine insufficiency group[(0.032±0.004),(0.049±0.011)]were significantly higher than those in the mild-moderate exocrine insufficiency group[(0.024±0.003),(0.036±0.008)]and no exocrine insufficiency group[(0.011±0.001),(0.020±0.005)],and the relative abundance of Bifidobacteriaceae and Lactobacillaceae[(0.012±0.002),( 0.015±0.002)]were significantly lower than those in the mild-moderate exocrine insufficiency group[(0.025±0.006),(0.020±0.004)]and no exocrine insufficiency group[(0.046±0.009),(0.031±0.006)],and the differences were statistically significant(all P<0.05);the relative abundance of Enterobacteriaceae and Enterococcaceae in patients in the mild-moderate exocrine insufficiency group were significantly higher than that in the no exocrine insufficiency group,the relative abundance of Bifidobacteriaceae and Lactobacillaceae were significantly lower than that of the no exocrine insufficiency group,and the differences were statistically significant(all P<0.05).The positive rate of small intestinal bacterial overgrowth in the severe exocrine insufficiency group(64.1%)was higher than that in the mild-moderate exocrine insufficiency group(30.0%)and no exocrine insufficiency group(10.0%),and the differences were statistically significant(both P<0.05);the positive rate of small intestinal bacterial overgrowth in the mild-moderate exocrine insufficiency group was higher than that in the no exocrine insufficiency group,and the difference was statistically significant(P<0.05).The levels of PCT,CRP and TNF-αin the severe exocrine insufficiency group[(5.8±0.9)ng/L,(245.8±15.0)mg/L,(593.1±41.9)pg/mL] were higher than those in the mild-moderate exocrine insufficiency group[(4.3±0.6)ng/L,(201.0±13.8)mg/L,(512.5±35.6)pg/mL]and no exocrine insufficiency group[(3.1±0.4)ng/L,(183.4±11.2)mg/L,(462.5±28.9)pg/mL],and the differences were statistically significant(all P<0.05);the levels of PCT,CRP and TNF-α in the mild-moderate exocrine insufficiency group were higher than those in the no exocrine insufficiency group,and the differences were statistically significant(all P<0.05).The levels of PCT,CRP,TNF-α,Enterobacteriaceae,Enterococcaceae,and positive rate of small intestinal bacterial overgrowth were all negatively correlated with FE1(r=-0.425,-0.518,-0.503,-0.619,-0.507,-0.511;all P<0.05);while Bifidobacteriaceae and Lactobacillaceae were positively correlated with FE1(r=0.592,0.628;both P<0.05).Conclusions The small intestinal bacteria in patients with CP exocrine insufficiency overgrow,and intestinal probiotics were reduced,while harmful bacteria were increased,and the body ' s inflammatory indicators were increased.This might provide a favorable basis for the diagnosis and treatment of patients with CP exocrine insufficiency.