幽门螺杆菌根除治疗导致肠道微生物组的显著变化,包括对肠道微生物组功能潜力的影响。益生菌是研究最多的减少抗生素微生物群相关后果的潜在方法之一。然而,益生菌的有益作用仍在讨论中。此外,有人担心益生菌的安全性,强调需要研究其他治疗干预措施。我们研究的目的是评估丁酸菊粉补充剂对肠道微生物群变化的影响(肠道微生物群组成,丰富的代谢途径,和肠道耐药组)由幽门螺杆菌根除疗法引起。
方法:22例幽门螺杆菌阳性患者,19至64岁,被纳入研究并随机分为两个治疗组,如下:(1)ECAB-14(n=11),埃索美拉唑20毫克,克拉霉素500毫克,阿莫西林1000毫克,和二柠檬酸三钾240毫克,每天两次,每个操作系统,14天,(2)、ECAB-Z-14(n=11),埃索美拉唑20毫克,克拉霉素500毫克,阿莫西林1000毫克,和二柠檬酸三钾240毫克,每天两次,随着丁酸+菊粉(Zacofalk),每日两片,每个含有250毫克的丁酸,和250毫克菊粉,每个操作系统,14天。在根除治疗之前(时间点I)从每个受试者收集粪便样本。根除治疗结束后(时间点II),和根除治疗结束后一个月(时间点III)。使用IlluminaNextSeq500平台分离来自粪便样品的总DNA用于全基因组测序。评估了肠道微生物群的定性和定量变化,包括阿尔法和贝塔多样性,功能潜力和抗生素抗性基因分析。
结果:两个治疗组(ECAB-14和ECAB-Z-14)根除治疗后立即与基线相比,肠道菌群α多样性显著降低。根除治疗结束后一个月,ECAB-Z-14治疗组的这种多样性达到了基线。然而,在ECAB-14治疗臂中,在根除幽门螺杆菌治疗结束后1个月内观察到Shannon指数降低.在ECAB-Z-14治疗组中观察到较少的肠道微生物群功能潜能改变。仅在ECAB-14治疗组中,负责与丁酸盐产生相关的代谢途径的基因的丰度降低。到治疗结束时,两个治疗组的肠道微生物群中抗生素抗性基因的患病率均显着增加。然而,在ECAB-14治疗组中观察到更严重的改变.
结论:H.幽门螺杆菌根除治疗导致分类学变化,阿尔法多样性指数的降低,以及肠道微生物群和肠道耐药性的功能潜力改变。在根除幽门螺杆菌治疗期间服用丁酸+菊粉补充剂可以帮助维持肠道微生物群处于初始状态,并促进其在根除幽门螺杆菌后的恢复。
H. pylori eradication therapy leads to significant changes in the gut microbiome, including influence on the gut microbiome\'s functional potential. Probiotics are one of the most studied potential methods for reducing the microbiota-related consequences of antibiotics. However, the beneficial effects of probiotics are still under discussion. In addition, there are some concerns about the safety of probiotics, emphasizing the need for research of other therapeutic interventions. The aim of our study was to evaluate the influence of butyric acid+inulin supplements on gut microbiota changes (the gut microbiota composition, abundance of metabolic pathways, and gut resistome) caused by H. pylori eradication therapy.
METHODS: Twenty two H. pylori-positive patients, aged 19 to 64 years, were enrolled in the study and randomized into two treatment groups, as follows: (1) ECAB-14 (n = 11), with esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, per os, for 14 days, and (2), ECAB-Z-14 (n = 11), with esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, along with butyric acid+inulin (Zacofalk), two tablets daily, each containing 250 mg of butyric acid, and 250 mg of inulin, per os, for 14 days. Fecal samples were collected from each subject prior to eradication therapy (time point I), after the end of eradication therapy (time point II), and a month after the end of eradication therapy (time point III). The total DNA from the fecal samples was isolated for whole genome sequencing using the Illumina NextSeq 500 platform. Qualitative and quantitative changes in gut microbiota were assessed, including alpha and beta diversity, functional potential and antibiotic resistance gene profiling.
RESULTS: Gut microbiota alpha diversity significantly decreased compared with the baseline immediately after eradication therapy in both treatment groups (ECAB-14 and ECAB-Z-14). This diversity reached its baseline in the ECAB-Z-14 treatment group a month after the end of eradication therapy. However, in the ECAB-14 treatment arm, a reduction in the Shannon index was observed up to a month after the end of H. pylori eradication therapy. Fewer alterations in the gut microbiota functional potential were observed in the ECAB-Z-14 treatment group. The abundance of genes responsible for the metabolic pathway associated with butyrate production decreased only in the ECAB-14 treatment group. The prevalence of antibiotic-resistant genes in the gut microbiota increased significantly in both treatment groups by the end of treatment. However, more severe alterations were noted in the ECAB-14 treatment group.
CONCLUSIONS: H. pylori eradication therapy leads to taxonomic changes, a reduction in the alpha diversity index, and alterations in the functional potential of the gut microbiota and gut resistome. Taking butyric acid+inulin supplements during H. pylori eradication therapy could help maintain the gut microbiota in its initial state and facilitate its recovery after H. pylori eradication.