The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn's disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae-previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy.

中文翻译：

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肠道微生物群组成的属性及其与炎症性肠病患者对抗 TNF-α 药物临床原发性无反应的相关性。

人体内最大的微生物聚集体存在于胃肠道。宿主胃肠道中的微生物群包括一个多样化的生态系统，肠道微生物群在维持肠道稳态方面起着至关重要的作用。本研究旨在检查肠道微生物群是否会影响原发性无反应患者对抗 TNF-α 治疗的无反应性，从而确定负责任的微生物作为无反应性的生物标志物。在完成抗 TNF 治疗的诱导期后，从一组确诊为 IBD（溃疡性结肠炎 (UC) 或克罗恩病 (CD)）的患者中收集粪便样本。16S rRNA 测序分析用于检查粪便样本中微生物群落的模式。比较抗 TNF-α 治疗后有反应者和原发性无反应者 IBD 患者粪便微生物群的质量和数量。根据我们的假设，观察到两个患者亚组之间的肠道微生物组组成存在差异。在无反应的患者中检测到产生短链脂肪酸 (SCFA) 的细菌数量减少，包括厌氧菌属、粪球菌属、毛螺菌属、罗斯氏菌属和瘤胃球菌属，这是生态失调的标志。被确定为临床无反应预测因子的生态失调的生物标志物包括克雷伯氏菌、真杆菌科、RF32、动物双歧杆菌和穆氏杆菌科（以前称为 S24-7）。标志性生物标志物显示，在对抗 TNF-α 药物表现出原发性无反应的患者中，肠道微生物群的组成发生了显着变化。生态失调，