腸道菌群與十二指腸潰瘍的因果關系：雙樣本孟德爾隨機化研究

背景：腸道菌群的多樣性和功能已被認為是影響人類健康的重要因素。遺傳學和流行病學方法的進步，尤其是孟德爾隨機化分析的應用，為深入揭示腸道菌群與十二指腸潰瘍之間的因果關系提供了新的視角。目的：使用雙樣本孟德爾隨機化分析研究腸道菌群與十二指腸潰瘍之間的因果關系。方法：從MiBioGen數據庫中篩選腸道菌群的遺傳變異樣本。從全基因組關聯研究中篩選出與十二指腸潰瘍相關的遺傳位點作為工具變量。使用逆方差加權法、加權中位數法、MR?Egger回歸分析法等評估腸道菌群與十二指腸潰瘍之間的因果關系。同時行異質性和水平多效性檢驗以保證結果的穩定性。結果：擬桿菌屬（Bacteroides；OR=0.998，95% CI： 0.996～1.000，P=0.014）、普雷沃菌屬_7（Prevotella_7；OR=0.999，95% CI： 0.998～1.000，P=0.043）和土孢桿菌屬（Terrisporobacter；OR=0.998，95% CI： 0.997～1.000，P=0.029）與十二指腸潰瘍之間呈負向因果關系，而雙歧桿菌屬（Bifidobacterium；OR=1.001，95% CI： 1.000～1.003，P=0.046）、拉克梭狀芽孢桿菌屬（Lachnoclostridium；OR=1.002，95% CI： 1.001～1.004，P=0.007）和歐陸森菌屬（Olsenella；OR=1.001，95% CI： 1.000～1.002，P=0.018）與十二指腸潰瘍之間呈正向因果關系。敏感性分析顯示可以剔除異質性和水平多效性對因果效應產生的影響。結論：雙樣本孟德爾隨機化分析顯示Bacteroides、Prevotella_7、Terrisporobacter可能是十二指腸潰瘍的保護因素，而Bifidobacterium、Lachnoclostridium、Olsenella可能是危險因素。

關鍵詞 腸道菌群； 十二指腸潰瘍； 因果關系； 孟德爾隨機化分析

Causal Relationship Between Gut Microbiota and Duodenal Ulcer： A Two?sample Mendelian Randomization Study HOU Yaqi1，2， LI Yuan1，2， YAN Lixuan1，2， GONG Wanli1，2， WANG Yang1，2， LU Xuechun3， HE Peifeng1，2， YU Qi1，2." 1School of Management， Shanxi Medical University， Jinzhong， Shanxi Province （030600）; 2Shanxi Key Laboratory of Big Data for Clinical Decision Research， Taiyuan; 3Department of Hematology， the Second Medical Center amp; National Clinical Research Center for Geriatric Diseases， Chinese PLA General Hospital， Beijing

Correspondence to： YU Qi， Email： yuqi@sxmu.edu.cn

Background： The diversity and function of gut microbiota have been regarded as crucial factors affecting human health. With the advances in genetics and epidemiology， especially the application of Mendelian randomization analysis， a novel perspective has been provided for profoundly uncovering the causal relationship between gut microbiota and duodenal ulcer. Aims： To investigate the causal relationship between gut microbiota and duodenal ulcer through two?sample Mendelian randomization analysis. Methods： Genetic variation samples of the gut microbiota were screened from the MiBioGen database. Genetic loci related to duodenal ulcer were selected as instrumental variables from genome?wide association study. The inverse?variance weighted method， weighted median method， and MR?Egger regression analysis were used to assess the causal relationship between gut microbiota and duodenal ulcer. Tests for heterogeneity and horizontal pleiotropy were conducted to ensure the stability of the results. Results： Bacteroides （OR=0.998， 95% CI： 0.996?1.000， P=0.014）， Prevotella_7 （OR=0.999， 95% CI： 0.998?1.000， P=0.043） and Terrisporobacter （OR=0.998， 95% CI： 0.997?1.000， P=0.029） exhibited negative causal relationship with duodenal ulcer， while Bifidobacterium （OR=1.001， 95% CI： 1.000?1.003， P=0.046）， Lachnoclostridium （OR=1.002， 95% CI： 1.001?1.004， P=0.007） and Olsenella （OR=1.001， 95% CI： 1.000?1.002， P=0.018） presented positive causal relationship with duodenal ulcer. The sensitivity analysis indicated that the influences of heterogeneity and horizontal pleiotropy on the causal relationship could be excluded. Conclusions： The two?sample Mendelian randomization analysis revealed that Bacteroides， Prevotella_7 and Terrisporobacter were protective factors for duodenal ulcer， while Bifidobacterium， Lachnoclostridium and Olsenella were risk factors.

Key words Gut Microbiota; Duodenal Ulcer; Causal Relationship; Mendelian Randomization Analysis

十二指腸潰瘍是我國人群中的常見病、多發病，是臨床消化系統疾病的常見類型，其病因復雜，一般認為是由于大腦皮質接受外界的不良刺激后，胃和十二指腸壁血管和肌肉發生痙攣，胃腸黏膜的抵抗力降低，致使胃腸黏膜易受胃液消化而形成潰瘍?！?br>