Study on Helicobacter pylori-positive gastric ulcer with gastric bleeding based on metagenomics changes of intestinal flora after omeprazole combined with thrombin treatment
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摘要: 目的 基于宏基因组学探讨幽门螺杆菌(Helicobacter pylori，HP)阳性胃溃疡伴胃出血患者用奥美拉唑联合凝血酶治疗后肠道菌群的变化。方法 选取2022年1月—2023年10月收治的106例HP阳性胃溃疡伴胃出血患者为研究对象，随机分为奥美拉唑组(n=53)和联合组(n=53)。比较两组患者的临床资料，收集患者肠道粪便标本，进行宏基因组检测，分析两组患者肠道菌群变化情况。结果 治疗前，两组患者肠道菌群中普雷沃菌属(Alloprevotella)占比最大(分别为14.86%和15.03%)，其次为螺杆菌属(Helicobacter)，两组患者肠道菌群均差异无统计学意义(P>0.05)。治疗后，两组患者肠道菌群中Alloprevotella、布劳特菌属(Blautia)、普氏菌属(Prevotella)、罗氏菌属(Roseburia)、罗斯菌属(Rothia)占比均提高，且联合组患者的Alloprevotella、Blautia、Prevotella和Rothia均高于奥美拉唑组，Helicobacter低于奥美拉唑组，均差异有统计学意义(P < 0.05)。治疗前，两组患者肠道菌群多样性均差异无统计学意义(P>0.05)；治疗后，联合组肠道菌群α多样性及β多样性均小于奥美拉唑组，两组之间差异有统计学意义(P < 0.05)。Lefse法分析两组患者的肠道优势菌显示，治疗前两组患者的肠道优势菌群均为Alloprevotella、Helicobacter和Veillonella；治疗后奥美拉唑组患者的肠道优势菌群为Alloprevotella和Helicobacter，联合组为Alloprevotella、Blautia、Prevotella和Rothia。功能富集差异分析结果显示，两组患者肠道菌群的KEGG功能主要富集在氨基酸代谢、碳水化合物代谢、细胞的生殖过程和信号传导以及能量代谢等26个功能类别上，治疗前两组患者各功能类别均差异无统计学意义(P>0.05)；治疗后，相较于联合组，奥美拉唑组患者肠道菌群上述26个KEGG功能异常，两组间差异有统计学意义(P < 0.05)。结论 HP阳性胃溃疡患者经奥美拉唑联合凝血酶治疗后，肠道菌群发生变化，治疗后肠道菌群多样性降低，Alloprevotella、Blautia、Prevotella和Rothia为肠道优势菌群，且菌群功能有所好转。Abstract: Objective To investigate the changes of intestinal flora in Helicobacter pylori(HP)-positive gastric ulcer patients with gastric bleeding after omeprazole combined with thrombin treatment based on metagenomics.Methods A total of 106 patients with HP-positive gastric ulcer accompanied by gastric bleeding admitted to our hospital from January 2022 to October 2023 were selected as the study objects. They were randomly divided into omeprazole group(n=53) and combined group(n=53). Clinical data of the two groups were compared, intestinal stool samples were collected, and metagenomic detection was performed to analyze the changes of intestinal flora of the two groups.Results Before treatment, Alloprevotella accounted for the largest proportion of intestinal flora in the two groups(14.86% and 15.03%, respectively), followed by Helicobacter, and there were no statistically significant differences in intestinal flora between the two groups(P>0.05). After treatment, the proportion of Alloprevotella, Blautia, Prevotella, Roseburia and Rothia in intestinal flora of patients in both groups increased. Alloprevotella, Blautia, Prevotella and Rothia in combination group were higher than omeprazole group, while Helicobacter was lower than omeprazole group, statistically significant(P < 0.05). Before treatment, there was no significant difference in intestinal flora diversity between the two groups(P>0.05). After treatment, α diversity and β diversity of intestinal flora in combination group were lower than those in omeprazole group, and the difference between the two groups was statistically significant(P < 0.05). Lefse analysis of intestinal dominant bacteria in the two groups showed that the intestinal dominant bacteria in the two groups before treatment were Alloprevotella, Helicobacter and Veillonella. After treatment, the dominant bacterial groups of omeprazole group were Alloprevotella and Helicobacter, and the combined group were Alloprevotella, Blautia, Prevotella and Rothia. The results of functional enrichment difference analysis showed that the KEGG function of intestinal flora between the two groups was mainly concentrated in 26 functional categories, including amino acid metabolism, carbohydrate metabolism, cell reproductive process and signal transduction, and energy metabolism, and there was no statistical significance in all functional categories between the two groups before treatment(P>0.05). After treatment, compared with the combined group, the intestinal flora of omeprazole group was abnormal with the above 26 KEGG functions, and the difference between the two groups was statistically significant(P < 0.05).Conclusion After treatment with omeprazole combined with thrombin, intestinal flora of HP-positive gastric ulcer patients changed, and the diversity of intestinal flora decreased. Alloprevotella, Blautia, Prevotella and Rothia were the dominant intestinal flora, and the flora function was improved.
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Key words:
- gastric ulcer /
- stomach bleeding /
- macrogene sequencing /
- intestinal flora /
- Helicobacter pylori
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表 1 两组患者的临床资料比较
例(%)，X±S 临床资料 奥美拉唑组(n=53) 联合组(n=53) t/χ2 P 性别 1.140 0.286 男 21(39.62) 26(49.06) 女 32(60.38) 27(60.94) 年龄/岁 0.729 0.393 < 45 30(56.60) 34(64.15) ≥45 23(43.40) 19(35.85) BMI 21.30±3.57 21.86±3.44 0.822 0.413 病程/月 17.34±4.11 17.19±3.86 0.194 0.847 吸烟史 0.182 0.669 是 29(54.72) 31(58.49) 否 24(45.28) 22(41.51) 饮酒史 2.234 0.135 是 25(47.17) 32(60.38) 否 28(52.83) 21(39.62) 高血压 0.410 0.522 是 20(37.74) 17(32.08) 否 33(62.26) 36(67.92) 糖尿病 0.729 0.393 是 16(30.19) 12(22.64) 否 37(69.81) 41(77.36) 婚姻状况 1.641 0.200 已婚 33(62.26) 27(60.94) 未婚 20(37.74) 26(49.06) 饮食偏好 2.234 0.135 硬 36(67.92) 31(58.49) 软 17(32.08) 22(41.51) 饮食习惯 2.918 0.088 规律 22(41.51) 30(56.60) 不规律 31(58.49) 23(43.40) 胃溃疡分期 1.641 0.200 A1 33(62.26) 39(73.58) A2 20(37.74) 14(26.42) 胃溃疡直径/mm 9.86±1.33 9.52±1.46 1.253 0.213 临床症状 1.031 0.597 胃部疼痛 13(24.53) 16(30.19) 食欲不振 16(30.19) 19(35.85) 餐后腹胀/胃部不适 23(43.40) 18(33.96) 实验室指标 PT/s 13.86±3.55 14.03±2.98 0.267 0.790 TT/s 23.05±1.67 22.76±1.71 0.883 0.379 APTT/s 46.43±5.30 45.82±5.24 0.596 0.553 GAS/(ng/L) 138.54±20.11 134.69±21.73 0.947 0.346 SS/(ng/L) 32.36±5.25 31.08±4.96 1.290 0.200 FIB/(g/L) 2.51±0.64 2.55±0.47 0.367 0.715 D-二聚体/(μg/L) 2.10±0.28 2.07±0.32 0.514 0.609 MOT/(ng/L) 313.42±40.17 316.58±39.18 0.410 0.683 PG/(μg/L) 105.35±16.64 107.40±15.75 0.651 0.516 VEGF/(pg/mL) 208.66±23.57 211.45±24.08 0.603 0.548 TFF1/(ng/mL) 7.84±1.05 7.90±1.22 0.271 0.787 EGF/(pg/mL) 103.37±14.16 100.08±13.35 1.231 0.221 
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表 2 患者治疗前后肠道菌群比较
% 菌群种类 治疗前 治疗后 奥美拉唑组 联合组 奥美拉唑组 联合组 Alloprevotella 14.86 15.03 19.22 29.31 Bacteroides 1.89 1.77 1.65 1.43 Blautia 1.36 1.47 4.84 6.06 Faecalibacterium 2.57 2.46 2.32 1.98 Haemophilus 6.21 6.03 3.46 2.07 Helicobacter 12.69 11.25 6.37 4.10 Neisseria 7.52 7.14 3.22 3.05 Porphyromonas 1.12 1.03 1.01 0.98 Prevotella 1.35 1.69 4.57 8.98 Pseudomonas 8.87 8.12 3.50 3.26 Roseburia 1.07 1.35 1.28 1.79 Rothia 1.28 1.30 4.32 9.30 Streptococcus 7.84 6.31 4.18 3.74 Veillonella 10.39 9.20 4.91 4.63
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