| Background and purpose:Helicobacter pylori(Hp)infection can cause many intragastric and extra gastric diseases.China is a developing country with a high rate of Hp infection and gastric cancer.Studies have confirmed that eradication of Hp can not only reduce the recurrence of peptic ulcer,but also the risk of gastric cancer.Although the guidelines have already recommend bismuth quadruple therapy,concomitant therapy,sequential therapy,etc.,3% ～ 24% of patients still failed initial treatment due to antibiotic resistance,patient compliance,and drug metabolism differences caused by individual gene polymorphism of patients.Recent research has found that eradication of Hp can induce an imbalance of gut microbiota and probiotics can reduce gut microbiota imbalance caused by eradication.But the effect of probiotics on rescue eradication and its regulation of on gut microbiotas are still unclear.The research is divided into two parts including observational research and interventional research,in order to initially explore the effects of pretreatment with probiotics on eradication rate and adverse effects,as well as the compositional alternations of gut microbiota.Method:The first part of the observational study: we included patients who came to our hospital for eradication from August 2018 to December 2020 because of previous failure to eradicate Hp.We obtained clinical data from the outpatient data system and questionnaire surveys of patients,including baseline data,past eradication history,gastroscopy performance,antibiotic susceptibility result,CYP2C19 gene polymorphism,this treatment plan and treatment outcome.Eradication failure is defined as: one or more failures to eradicate Hp in the past.According to whether probiotic preparations have been prescribed before eradication,it is divided into probiotic group and non-probiotic group.The secondary drug susceptibility rate and eradication rate were counted,and adverse reactions during were recorded via telephone return visit,and then analyze the risk factors affecting the eradication rate of rescue treatment.The second part of the interventional study: prospectively included 40 patients who came to our hospital for eradication due to previous failure to eradicate Hp.Eradication failure is defined as: patients have failed ≥1 times with standard bismuth quadruple eradication that recommended by the Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection or the rest of the regime failed ≥2 times;according to the random number,they were treated with or without Birid Triple Viable(Bifico)pretreated for 30-days and followed with esomeprazole(Nexium)40mg Bid + Bismuth Potassium Citrate(Lizhu Dele)220mg Bid +Amoxicillin Capsules(Amoxicillin)1g Bid+ furazolidone 100 mg Bid for 14 days.Adverse reactions and eradication efficacy of the patients were followed up.During the treatment,we collected the stool before the probiotics(T0),before the eradication(T1),after the eradication(T2)and 4 weeks after the eradication(T3)and stored them in a refrigerator at-80°C.At the end of the experiment,the stool specimens were sent to Shanghai Meiji Biomedical Technology Co.,Ltd.for 16 S r RNA high-throughput sequencing.Results:The first part of observational study: 143 patients who were experienced eradication failure were included from the Gastroenterology Clinic of the First Affiliated Hospital of Nanchang University.There are 53 cases in the probiotic group,and 90 cases in the non-probiotic group.66 cases underwent Hp susceptibility testing,and 34 patients conducted CYP2C19 gene polymorphism testing.The resistance rates of rescue therapy patients on metronidazole,clarithromycin,levofloxacin,amoxicillin,rifampicin,furazolidone,and tetracycline were 95.7%,80.3%,60.6%,3.0%,3.0%,0,0,respectively,and the most common resistance mode was clarithromycin +metronidazole + levofloxacin multi-resistant(48.5%),followed by clarithromycin +metronidazole dual-resistant(24.2%),metronidazole single-resistant(12.1%),metronidazole + levofloxacin dual-resistant(6.1 %).Most of the patients showed fast or moderate metabolites,accounting for 50%(17/34)and 47.1%(16/34)respectively.The eradication rate of furazolidone combined with amoxicillin/ tetracycline treatment for 14-days was respectively 89.5%(85/95),89.6%(43/48)for rescue therapy.The eradication was not significantly affected whether probiotics were pretreated(92.5%vs.87.8%,p=0.378).The side effects incidence in the probiotic group was lower than that of the non-probiotic group(5.7%vs.14.7%,p=0.019).The second part of interventional study: A total of 40 patients were enrolled and divided into probiotics group(n = 22)and non-probiotics group(n = 18)according to random number method.They were treated with amoxicillin-furazolidone bismuth quadruple therapy for 14-days with or without Birid Triple Viable(Bifico)pretreated.The total eradication rate was 87.5% by ITT analysis,and 89.7% by PP analysis.There was no significant difference in the eradication rate between the two groups(p=1.000).In probiotic group,the relative abundance of Parabacteroides and Flavonifractor in the gut of increased significantly after taking Bifico for 1 month.At the end of eradication,the alpha diversity index of the probiotic group and the non-probiotic group included the Chao1 index and Sobs.Both the index and Shannon index showed a downward trend,and both recovered to the pre-eradication level 4weeks after eradication.PLS-DA analysis showed that the composition of the intestinal flora at the end of eradication was significantly different between the probiotic group and the non-probiotic group than before the eradication,but the probiotic group was closer to the state before eradication than the non-probiotic group at 4 weeks after eradication.Species composition analysis showed that the relative abundance of Escherichia-Shigella,Klebsiella,and Enterobacter in the intestines of the two groups of patients at the end of eradication was higher than before eradication,and decreased after 4 weeks of eradication,while beneficial bacteria such as Bifidobacterium,Blautia and Romboutsia was significantly reduced at the end of eradication,and increased after 4 weeks of eradication;among them,the change of beneficial bacteria in the probiotic group was more significant than that in the non-probiotic group.Conclusion:The supplementation of probiotics before the eradication of rescue therapy can not improve the efficacy,but can reduce the incidence of adverse reactions.14-days of furazolidone combined with amoxicillin/tetracycline bismuth quadruple therapy has a good efficacy and safety in the remedial treatment of Hp.The secondary resistance rates of amoxicillin,rifapentine,furazolidone and tetracycline in Jiangxi Provence remained stable at a low level.The most common pattern of resistance in patients with failed eradication was clarithromycin + metronidazole + levofloxacin multiple resistance. |
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