Xie Ya, Cao Qiongjiao, Huang Zhen, Zou Xin
Department of Gastroenterology, The First People's Hospital of Loudi, Loudi, China.
Intensive Care Unit, The First People's Hospital of Loudi, Loudi, China.
Mediators Inflamm. 2025 Jun 5;2025:8181816. doi: 10.1155/mi/8181816. eCollection 2025.
Previous observational studies have suggested an association between the composition of the intestinal microbiome and lactose intolerance (LI). However, the causal direction remains unclear. This study utilized Mendelian randomization (MR) to rigorously evaluate the potential causal link between the gut microbiome and LI. Genome-wide association studies (GWASs) summary statistics for gut microbiota and LI were sourced from previously published GWAS studies. Multiple methods, such as Simple mode, MR-Egger regression, weighted median, inverse variance-weighted (IVW), and weighted model, were used to determine the causal relationship between gut microbiota and LI. To validate the primary findings from the MR analyses, several sensitivity analyses were conducted. Furthermore, a reverse MR analysis was executed on bacterial taxa previously identified to have a potential causal link with LI risk, aiming to evaluate the possibility of reverse causation. The IVW results revealed that the genus (OR = 0.584, 95%CI 0.356-0.958, =0.0330), genus group (OR = 0.467, 95% CI 0.242-0.899, =0.023), and genus group (OR = 0.506, 95% CI 0.2653-0.968, =0.039) have a protective effect against LI. In contrast, the genus (OR = 1.86, 95% CI 1.105-3.131, =0.0194) displayed a predisposing effect. Sensitivity analyses did not detect any outlier single-nucleotide polymorphisms (SNPs). Further analyses reinforced the association between specific gut microbiota compositions and LI. No evidence suggested reverse causality between LI and the bacterial taxa identified in the reverse MR analysis. From a genetic standpoint, this MR study indicates a causal relationship between variations in gut microbiota composition and LI. This not only underscores the potential of gut microbiota-centric treatments for LI but also provides a foundation for exploring the role of gut microbiota in LI development. Further study of the mechanism of Lachnospiraceae in the treatment of IL is conducive to the discovery of new therapeutic targets for IL.
先前的观察性研究表明肠道微生物群的组成与乳糖不耐受（LI）之间存在关联。然而，因果关系仍不明确。本研究利用孟德尔随机化（MR）来严格评估肠道微生物群与LI之间的潜在因果联系。肠道微生物群和LI的全基因组关联研究（GWASs）汇总统计数据来自先前发表的GWAS研究。使用了多种方法，如简单模式、MR-Egger回归、加权中位数、逆方差加权（IVW）和加权模型，来确定肠道微生物群与LI之间的因果关系。为了验证MR分析的主要结果，进行了几项敏感性分析。此外，对先前确定与LI风险有潜在因果联系的细菌类群进行了反向MR分析，旨在评估反向因果关系的可能性。IVW结果显示，属（OR = 0.584，95%CI 0.356 - 0.958，P = 0.0330）、属组（OR = 0.467，95%CI 0.242 - 0.899，P = 0.023）和属组（OR = 0.506，95%CI 0.2653 - 0.968，P = 0.039）对LI有保护作用。相比之下，属（OR = 1.86，95%CI 1.105 - 3.131，P = 0.0194）表现出易患作用。敏感性分析未检测到任何异常单核苷酸多态性（SNP）。进一步分析加强了特定肠道微生物群组成与LI之间的关联。没有证据表明LI与反向MR分析中确定的细菌类群之间存在反向因果关系。从遗传学角度来看，这项MR研究表明肠道微生物群组成的变化与LI之间存在因果关系。这不仅强调了以肠道微生物群为中心的LI治疗的潜力，也为探索肠道微生物群在LI发展中的作用提供了基础。进一步研究毛螺菌科在治疗IL中的机制有助于发现IL的新治疗靶点。
