Department of Pediatric Hematology Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Front Immunol. 2024 May 7;15:1397485. doi: 10.3389/fimmu.2024.1397485. eCollection 2024.
Previous studies have indicated a potential link between the gut microbiota and lymphoma. However, the exact causal interplay between the two remains an area of ambiguity.
We performed a two-sample Mendelian randomization (MR) analysis to elucidate the causal relationship between gut microbiota and five types of lymphoma. The research drew upon microbiome data from a research project of 14,306 participants and lymphoma data encompassing 324,650 cases. Single-nucleotide polymorphisms were meticulously chosen as instrumental variables according to multiple stringent criteria. Five MR methodologies, including the inverse variance weighted approach, were utilized to assess the direct causal impact between the microbial exposures and lymphoma outcomes. Moreover, sensitivity analyses were carried out to robustly scrutinize and validate the potential presence of heterogeneity and pleiotropy, thereby ensuring the reliability and accuracy.
We discerned 38 potential causal associations linking genetic predispositions within the gut microbiome to the development of lymphoma. A few of the more significant results are as follows: Genus (OR = 0.619, 95% CI 0.438-0.873, = 0.006) demonstrated a potentially protective effect against Hodgkin's lymphoma (HL). Genus (OR = 0.473, 95% CI 0.278-0.807, = 0.006) was a protective factor for diffuse large B-cell lymphoma. Genus (OR = 0.541, 95% CI 0.341-0.857, = 0.009) exhibited suggestive protective effects against follicular lymphoma. Genus (OR = 0.354, 95% CI 0.198-0.631, = 0.0004) showed protective properties against T/NK cell lymphoma. The test indicated an absence of heterogeneity, and the MR-Egger test did not show significant horizontal polytropy. Furthermore, the leave-one-out analysis failed to identify any SNP that exerted a substantial influence on the overall results.
Our study elucidates a definitive causal link between gut microbiota and lymphoma development, pinpointing specific microbial taxa with potential causative roles in lymphomagenesis, as well as identifying probiotic candidates that may impact disease progression, which provide new ideas for possible therapeutic approaches to lymphoma and clues to the pathogenesis of lymphoma.
先前的研究表明肠道微生物群与淋巴瘤之间存在潜在联系。然而，两者之间的确切因果关系仍存在不确定性。
我们进行了两样本孟德尔随机化（MR）分析，以阐明肠道微生物群与五种类型淋巴瘤之间的因果关系。该研究利用了来自 14306 名参与者的微生物组数据和包含 324650 例病例的淋巴瘤数据。根据多项严格标准，精心选择单核苷酸多态性作为工具变量。采用五种 MR 方法，包括逆方差加权法，评估微生物暴露与淋巴瘤结局之间的直接因果关系。此外，进行敏感性分析以稳健地检查和验证潜在的异质性和多效性，从而确保可靠性和准确性。
我们发现了 38 种潜在的因果关联，这些关联将肠道微生物组中的遗传易感性与淋巴瘤的发生联系起来。以下是一些更显著的结果：属（OR=0.619，95%CI 0.438-0.873，=0.006）对霍奇金淋巴瘤（HL）具有潜在的保护作用。属（OR=0.473，95%CI 0.278-0.807，=0.006）是弥漫性大 B 细胞淋巴瘤的保护因素。属（OR=0.541，95%CI 0.341-0.857，=0.009）对滤泡性淋巴瘤具有提示性保护作用。属（OR=0.354，95%CI 0.198-0.631，=0.0004）对 T/NK 细胞淋巴瘤具有保护作用。MR-Egger 检验未显示出显著的水平多效性。此外，逐一剔除分析未能确定任何 SNP 对整体结果产生重大影响。
本研究阐明了肠道微生物群与淋巴瘤发展之间的明确因果关系，确定了特定的微生物类群在淋巴瘤发生中的潜在因果作用，并确定了可能影响疾病进展的益生菌候选物，为淋巴瘤的可能治疗方法提供了新的思路，并为淋巴瘤的发病机制提供了线索。
