Zhang Quanzheng, Zhou Jinhua, Zhang Xiaoxiao, Mao Rui, Zhang Chuan
Department of Critical Care Medicine, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China.
West China Fourth Hospital, Sichuan University, Chengdu, China.
Front Microbiol. 2023 Aug 16;14:1243811. doi: 10.3389/fmicb.2023.1243811. eCollection 2023.
Observational studies have provided evidence of a close association between gut microbiota and the progression of chronic hepatitis B (CHB). However, establishing a causal relationship between gut microbiota and CHB remains a subject of investigation.
Genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of CHB came from the Medical Research Council Integrative Epidemiology Unit (IEU) Open GWAS project. Based on the maximum likelihood (ML), Mendelian randomization (MR)-Egger regression, inverse variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and weighted-mode and weighted-median methods, we conducted a bidirectional, two-sample, MR analysis to explore the causal relationship between the gut microbiota and CHB. Additionally, we evaluated the genetic associations between individual gut microbes and CHB using the Linkage disequilibrium score regression (LDSC) program.
According to the IVW method estimates, genetically predicted class Alphaproteobacteria (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.34-0.96; false discovery rate [FDR] = 0.046), genus group (OR = 0.60; 95% CI, 0.39-0.91; FDR = 0.026), genus (OR = 0.73; 95% CI, 0.56-0.94; FDR = 0.022) exhibited a protective effect against CHB. On the other hand, family Family XIII (OR = 1.79; 95% CI, 1.03-3.12; FDR = 0.061), genus group (OR = 1.34; 95% CI, 1.04-1.74; FDR = 0.043), genus group (OR = 1.59; 95% CI, 1.01-2.51; FDR = 0.056), genus (OR = 1.35; 95% CI, 1.00-1.82; FDR = 0.049), and genus group (OR = 1.69; 95% CI, 1.10-2.61; FDR = 0.076) were associated with an increased risk of CHB. The results from LDSC also indicated a significant genetic correlation between most of the aforementioned gut microbiota and CHB. Our reverse MR analysis demonstrated no causal relationship between genetically predicted CHB and gut microbiota, and we observed no significant horizontal pleiotropy or heterogeneity of instrumental variables (IVs).
In this study, we identified three types of gut microbiota with a protective effect on CHB and five types with an adverse impact on CHB. We postulate that this information will facilitate the clinical prevention and treatment of CHB through fecal microbiota transplantation.
观察性研究已提供证据表明肠道微生物群与慢性乙型肝炎（CHB）进展之间存在密切关联。然而，确定肠道微生物群与CHB之间的因果关系仍是一个研究课题。
肠道微生物群的全基因组关联研究（GWAS）汇总数据来自MiBioGen联盟，而CHB的GWAS汇总数据来自医学研究理事会综合流行病学单位（IEU）开放GWAS项目。基于最大似然法（ML）、孟德尔随机化（MR）-Egger回归、逆方差加权法（IVW）、MR多效性残差和异常值法（MR-PRESSO）以及加权模式和加权中位数方法，我们进行了双向、两样本MR分析，以探讨肠道微生物群与CHB之间的因果关系。此外，我们使用连锁不平衡评分回归（LDSC）程序评估了个体肠道微生物与CHB之间的遗传关联。
根据IVW方法估计，基因预测的α-变形菌纲（优势比[OR]=0.57；95%置信区间[CI]，0.34-0.96；错误发现率[FDR]=0.046）、属组（OR=0.60；95%CI，0.39-0.91；FDR=0.026）、属（OR=0.73；95%CI，0.56-0.94；FDR=0.022）对CHB具有保护作用。另一方面，XIII科（OR=1.79；95%CI，1.03-3.12；FDR=0.061）、属组（OR=1.34；95%CI，1.04-1.74；FDR=0.043）、属组（OR=1.59；95%CI，1.01-2.51；FDR=0.056）、属（OR=1.35；95%CI，1.00-1.82；FDR=0.049）和属组（OR=1.69；95%CI，1.10-2.61；FDR=0.076）与CHB风险增加相关。LDSC的结果还表明，上述大多数肠道微生物群与CHB之间存在显著的遗传相关性。我们的反向MR分析表明，基因预测的CHB与肠道微生物群之间不存在因果关系，并且我们未观察到显著的水平多效性或工具变量（IVs）的异质性。
在本研究中，我们鉴定出三种对CHB具有保护作用的肠道微生物群类型和五种对CHB具有不利影响的类型。我们推测，这些信息将有助于通过粪便微生物群移植对CHB进行临床预防和治疗。
