幽门螺杆菌感染对溃疡性结肠炎患者炎性细胞因子水平和肠道菌群含量的影响
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摘要
目的 观察幽门螺杆菌(helicobacter pylori,Hp)感染对溃疡性结肠炎(ulcerative colitis,UC)患者血清炎性细胞因子水平和肠道菌群含量的影响,探讨Hp在UC发病的作用机制。方法 选择于2017年9月至2018年9月在我科住院的36例UC患者作为研究对象,ELISA法检测其血清TNF-α、IL-1、IL-6及IL-10水平,Real-time PCR法检测粪便中长双歧杆菌、嗜酸乳杆菌及大肠埃希菌16SrDNA含量。~(14)C呼气试验检测Hp感染情况,分析Hp感染对患者血清炎性细胞因子水平和肠道菌群含量的影响,并与同期在我院进行体检的44名健康体检者进行比较。结果 UC组Hp感染率(22.22%)显著低于对照组(45.45%),UC组血清中IL-1(288.52±122.72 pg/ml)、IL-6(88.24±75.82 ng/L)及TNF-α(575.50±254.81 pg/ml)水平均高于对照组(163.64±48.23 pg/ml)、(25.70±8.79 ng/L)及(328.65±96.64 pg/ml),但IL-10水平(86.73±18.55 pg/ml)却明显低于对照组(141.17±62.85 pg/ml);此外,UC组粪便大肠埃希菌含量(10.33±1.221 9)高于对照组(9.33±1.40),嗜酸乳杆菌(9.49±1.29)及长双歧杆菌(10.56±0.69)含量低于对照组(9.68±1.26)及(10.82±1.62)。Hp阳性的UC患者血清IL-1(205.88±54.90 pg/ml)、IL-6(40.53±26.99 ng/L)和TNF-α(402.75±104.60 pg/ml)水平均低于Hp阴性的UC患者(312.13±127.04 pg/ml)、(101.88±79.97 ng/L)及(624.85±264.51 pg/ml),但是其IL-10水平(110.38±25.74 pg/ml)高于Hp阴性的UC患者(86.73±18.55),粪便中长双歧杆菌含量(11.66±1.17)高于Hp阴性的UC患者(10.44±0.53),且以上差异均有统计学意义(均P <0.05)。余肠道菌群含量差异均无统计学意义(均P> 0.05)。结论 UC患者Hp感染率明显低于健康人群,且Hp阳性UC患者血清促炎性炎细胞因子水平明显下调,抗炎性细胞因子及肠道有益菌种相应上调,这可能与UC的发病和进展有关。
Objective To study the effect of Helicobacter pylori(Hp) on serum inflammatory cytokines and intestinal flora in patients with ulcerative colitis(UC), and to explore the role of Hp in the pathogenesis of UC. Methods Blood samples and fecal specimens of the total 36 patients with UC were collected in our hospital from September 2017 to September 2018. Serum proinflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), IL-6 and anti-inflammatory cytokine IL-10 were detected by ELISA. The content of 16 SrDNA of Bifidobacterium longicarum,Lactobacillus acidophilusand Escherichia coli in feces were detected by real-time PCR. Comparing the patients with 44 healthy people who underwent physical examination in our hospital during the same period, we analyze the effect of Hp infection on serum inflammatory cytokines and intestinal flora in patients with UC, and the Hp infection was detected by ~(14)C breath test. Results The infection rate of Hp in UC group(22.22%) was significantly lower than that in control group(45.45%). The serum levels of IL-1(288.52+122.72 pg/ml), IL-6(88.24+75.82 ng/L), TNF-α(575.50+254.81 pg/ml) in UC group were significantly higher than those in control group(163.64+48.23 pg/ml),(25.70+8.79 ng/L),(328.65+96.64 pg/ml), but the levels of IL-10(86.73+18.55 pg/ml) were significantly lower than those in control group(163.64+48.23 pg/ml). In addition, the fecal escherichia coli content(10.33+1.22) in UC group was higher than that in control group(9.33+1.40), and the contents of Lactobacillus acidophilus(9.49+1.29) and Bifidobacterium longum(10.56+0.69) were lower than those in control group(9.68+1.26),(10.82+1.62). The serum levels of IL-1(205.88+54.90 pg/ml), IL-6(40.53+26.99 ng/L), and TNF-α(402.75+104.60 pg/ml) in Hp-positive UC patients were lower than those in Hp-negative UC patients(312.13+127.04 pg/ml),(101.88+79.97 ng/L),(624.85+264.85 pg/ml), but their levels of IL-10(110.38+25.74 pg/ml) was higher in Hppositive UC patients, the contents of Bifidobacterium in Hp-positive UC patients(11.66+1.17) was higher than that in Hpnegative UC patients(10.44+0.53), and the differences were statistically significant(P<0.05). There was no significant difference in the content of bacteria in the residual intestine(P>0.05).Conclusion The infection rate of Hp in UC patients was significantly lower than that in healthy people, and the level of proinflammatory cytokines in serum of Hp-positive UC patients was significantly decreased, while anti-inflammatory cytokines and beneficial intestinal bacteria were increased accordingly, which may be related to the pathogenesis and progress of UC.
Objective To study the effect of Helicobacter pylori(Hp) on serum inflammatory cytokines and intestinal flora in patients with ulcerative colitis(UC), and to explore the role of Hp in the pathogenesis of UC. Methods Blood samples and fecal specimens of the total 36 patients with UC were collected in our hospital from September 2017 to September 2018. Serum proinflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), IL-6 and anti-inflammatory cytokine IL-10 were detected by ELISA. The content of 16 SrDNA of Bifidobacterium longicarum,Lactobacillus acidophilusand Escherichia coli in feces were detected by real-time PCR. Comparing the patients with 44 healthy people who underwent physical examination in our hospital during the same period, we analyze the effect of Hp infection on serum inflammatory cytokines and intestinal flora in patients with UC, and the Hp infection was detected by ~(14)C breath test. Results The infection rate of Hp in UC group(22.22%) was significantly lower than that in control group(45.45%). The serum levels of IL-1(288.52+122.72 pg/ml), IL-6(88.24+75.82 ng/L), TNF-α(575.50+254.81 pg/ml) in UC group were significantly higher than those in control group(163.64+48.23 pg/ml),(25.70+8.79 ng/L),(328.65+96.64 pg/ml), but the levels of IL-10(86.73+18.55 pg/ml) were significantly lower than those in control group(163.64+48.23 pg/ml). In addition, the fecal escherichia coli content(10.33+1.22) in UC group was higher than that in control group(9.33+1.40), and the contents of Lactobacillus acidophilus(9.49+1.29) and Bifidobacterium longum(10.56+0.69) were lower than those in control group(9.68+1.26),(10.82+1.62). The serum levels of IL-1(205.88+54.90 pg/ml), IL-6(40.53+26.99 ng/L), and TNF-α(402.75+104.60 pg/ml) in Hp-positive UC patients were lower than those in Hp-negative UC patients(312.13+127.04 pg/ml),(101.88+79.97 ng/L),(624.85+264.85 pg/ml), but their levels of IL-10(110.38+25.74 pg/ml) was higher in Hppositive UC patients, the contents of Bifidobacterium in Hp-positive UC patients(11.66+1.17) was higher than that in Hpnegative UC patients(10.44+0.53), and the differences were statistically significant(P<0.05). There was no significant difference in the content of bacteria in the residual intestine(P>0.05).Conclusion The infection rate of Hp in UC patients was significantly lower than that in healthy people, and the level of proinflammatory cytokines in serum of Hp-positive UC patients was significantly decreased, while anti-inflammatory cytokines and beneficial intestinal bacteria were increased accordingly, which may be related to the pathogenesis and progress of UC.
引文
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[12]张欣,李洺,杨嫣华,等.炎症性肠病患者血清TNF-α、IL-35水平变化及其临床意义[J].内科急危重症杂志,2017,23(5):400-402.
[13]谢华,何良梅,刘瑶,等.肠道菌群与炎症性肠病[J].赣南医学院学报,2017,37(4):659-663.
[14]Ram M,Barzilai O,Shapira Y,et al.Helicobacter pylori serology in autoimmune diseases-fact or fiction[J].Clin Chem Lab Med,2013,51(5):1075-1082.
[15]Higgins PDR,Johnson LA,Luther J,et al.Prior Helicobacter pylori infection ameliorates salmonella typhimuriuminduced colitis:mucosal crosstalk between stomach and distal intestine[J].Inflamm Bowel Dis,2011,17(6):1398-1408.
[16]褚源.溃疡性结肠炎患者腔菌群及膜菌群变化的研究[D].安徽:安徽医科大学,2014.
[2]Man SM,Zhang L,Day AS,et al.Detection of enterohepatic and gastric Helicobacter species in fecal specimens of children with Crohn's disease[J].Helicobacter,2008,13(4):234-238.
[3]Bartels LE,Jepsen P,Christensen LA,et al.Diagnosis of helicobacter pylori infection is associated with lower prevalence and subsequent incidence of crohn's disease[J].JCrohns Colitis,2016,10(4):443-448.
[4]Shah A,Talley NJ,Walker M,et al.Is there a link between H-Pylori and the epidemiology of Crohn's disease[J].Digest Dis Sci,2017,62(9):2472-2480.
[5]Zhang SH,Zhong BH,Chao K,et al.Role of Helicobacter species in Chinese patients with inflammatory bowel disease[J].Eur J CLin Microbiol,2011,49(5):1987-1989.
[6]卢晓敏,王振宁,杨军.溃疡性结肠炎合并幽门螺杆菌感染患者清除幽门螺杆菌治疗对预后的影响[J].山西医药杂志,2015,(1):60-62.
[7]贾宝会.炎症性肠病与幽门螺杆菌感染关系的Meta分析[D].山西:山西医科大学,2018.
[8]Rokkas T,Gisbert JP,Niv Y,et al.The association between Helicobacter pylori infection and inflammatory bowel disease based on meta-analysis[J].United Eur Gastroent,2015,3(6):539-550.
[9]Roka K,Roubani A,Stefanaki K,et al.The prevalence of Helicobacter pylori gastritis in newly diagnosed children with inflammatory bowel disease[J].Helicobacter,2014,19(5):400-405.
[10]Wu YZ,Tan G,Wu F,et al.H.pylori attenuates TNBS-induced colitis via increasing mucosal Th2 cells in mice[J].Oncotarget,2017,8(43):73810-73816.
[11]Wedrychowicz A,Tomasik P,Zajac A,et al.Prognostic value of assessment of stool and serum IL-1 beta,IL-1ra and IL-6concentrations in children with active and inactive ulcerative colitis[J].Arch Med Sci,2018,14(1):107-114.
[12]张欣,李洺,杨嫣华,等.炎症性肠病患者血清TNF-α、IL-35水平变化及其临床意义[J].内科急危重症杂志,2017,23(5):400-402.
[13]谢华,何良梅,刘瑶,等.肠道菌群与炎症性肠病[J].赣南医学院学报,2017,37(4):659-663.
[14]Ram M,Barzilai O,Shapira Y,et al.Helicobacter pylori serology in autoimmune diseases-fact or fiction[J].Clin Chem Lab Med,2013,51(5):1075-1082.
[15]Higgins PDR,Johnson LA,Luther J,et al.Prior Helicobacter pylori infection ameliorates salmonella typhimuriuminduced colitis:mucosal crosstalk between stomach and distal intestine[J].Inflamm Bowel Dis,2011,17(6):1398-1408.
[16]褚源.溃疡性结肠炎患者腔菌群及膜菌群变化的研究[D].安徽:安徽医科大学,2014.