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Gut ( IF 23.0 ) Pub Date : 2021-04-01 , DOI: 10.1136/gutjnl-2021-324449
Philip J Smith

### Large-scale association analyses identify host factors influencing human gut microbiome composition Kurilshikov A, Medina-Gomez C, Bacigalupe R et al . Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat Genet 2021; 53:156–165. doi: 10.1038/s41588-020-00763-1 Multiple genome-wide association studies (GWAS) have identified host genetic loci associated with gut microorganisms. However, many signals are weak and cohorts are highly variable. Kurilshikov et al report the largest genome-wide meta-analysis of associations between host genetic variants and gut microbiota. 16S ribosomal RNA (rRNA) sequence data from 18 340 participants within 24 cohorts were analysed. Core microbiota consisted of nine genera present in >95% of individuals, the most abundant being Bacteroides , Faecalibacterium , Blautia and Alistipes . Variation in microbiome richness, diversity and composition was influenced by multiple factors including DNA extraction and 16S rRNA gene profiling methodology, ancestry, age and body mass index. Only a subset of gut bacteria was heritable. Two GWAS meta-analysis approaches identified 31 loci affecting the microbiome. Only the Lactase ( LCT ) locus, encoding the enzyme, passed strict correction for the number of taxa tested and showed age-dependent association (weaker effect in children and adolescents) with Bifidobacterium abundance. Biological interpretation of genetic traits through a phenome-wide association study identified overlap between host genetic variants affecting the microbiome and host characteristics including metabolic and immune traits, and dietary preferences. Mendelian randomisation suggested higher abundance of Actinobacteria and its genus Bifidobacterium may have a protective effect on UC, and higher abundance of Oxalobacteraceae may have a protective effect on rheumatoid arthritis. These potential causal links between gut microbial taxa and disease may indicate a potential for future microbiome-based therapies and more generally this study supports the concept of personalised nutrition and medical strategies based on host genetics and the gut microbiome. ### The future of cancer-targeted immunotherapy needs the approval of the hepatic tumour microenvironment Heinrich B, Brown Z, Diggs L et al. Steatohepatitis impairs T-cell-directed immunotherapies against liver tumors in mice. Gastroenterology 2021; 160(1): …

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文献中的GI亮点

大规模关联分析确定了影响人类肠道微生物组组成的宿主因素Kurilshikov A,Medina-Gomez C,Bacigalupe R等。大规模关联分析确定了影响人类肠道微生物组组成的宿主因素。Nat Genet 2021;53:156–165。DOI:10.1038 / s41588-020-00763-1多项全基因组关联研究(GWAS)已确定与肠道微生物相关的宿主遗传基因座。但是,许多信号微弱,并且队列变化很大。Kurilshikov等人报告了宿主基因变异与肠道菌群之间关联的最大的全基因组荟萃分析。分析了来自24个队列中18 340名参与者的16S核糖体RNA(rRNA)序列数据。核心菌群由9个属组成,存在于> 95%的个体中,其中最丰富的是拟杆菌,费氏杆菌,Blautia和Alistipes。微生物组丰富度,多样性和组成的变化受多种因素影响,包括DNA提取和16S rRNA基因谱分析方法,血统,年龄和体重指数。只有一部分肠道细菌是可遗传的。两种GWAS荟萃分析方法确定了影响微生物组的31个基因座。仅编码该酶的乳糖酶(LCT)基因座通过了对受测分类单元数量的严格校正,并显示出年龄依赖性与双歧杆菌丰度的关联(对儿童和青少年有较弱的影响)。通过全基因组关联研究对遗传性状进行生物学解释,发现影响微生物组的宿主遗传变异与宿主特征(包括代谢和免疫特征以及饮食偏爱)之间存在重叠。孟德尔随机化表明,放线菌及其双歧杆菌属的丰度较高,可能对UC有保护作用,而草杆菌科的丰度较高,可能对类风湿关节炎具有保护作用。肠道微生物分类群和疾病之间的这些潜在因果关系可能表明未来基于微生物组的治疗方法的潜力,并且更广泛的说,这项研究支持基于宿主遗传学和肠道微生物组的个性化营养和医学策略的概念。###靶向癌症的免疫疗法的未来需要肝肿瘤微环境的批准Heinrich B,Brown Z,Diggs L等。脂肪性肝炎损害了针对小鼠肝肿瘤的T细胞定向免疫疗法。胃肠病学2021; 160(1):… 以及较高的草酸杆菌科细菌含量可能对类风湿关节炎具有保护作用。肠道微生物分类群和疾病之间的这些潜在因果关系可能表明未来基于微生物组的治疗方法的潜力,并且更广泛的说,这项研究支持基于宿主遗传学和肠道微生物组的个性化营养和医学策略的概念。###靶向癌症的免疫疗法的未来需要肝肿瘤微环境的批准Heinrich B,Brown Z,Diggs L等。脂肪性肝炎损害了针对小鼠肝肿瘤的T细胞定向免疫疗法。胃肠病学2021; 160(1):… 以及较高的草酸杆菌科细菌含量可能对类风湿关节炎具有保护作用。肠道微生物分类群和疾病之间的这些潜在因果关系可能表明未来基于微生物组的治疗方法的潜力,并且更广泛地说,本研究支持基于宿主遗传学和肠道微生物组的个性化营养和医学策略的概念。###靶向癌症的免疫疗法的未来需要肝肿瘤微环境的批准Heinrich B,Brown Z,Diggs L等。脂肪性肝炎损害了针对小鼠肝肿瘤的T细胞定向免疫疗法。胃肠病学2021; 160(1):… 肠道微生物分类群和疾病之间的这些潜在因果关系可能表明未来基于微生物组的治疗方法的潜力,并且更广泛的说,这项研究支持基于宿主遗传学和肠道微生物组的个性化营养和医学策略的概念。###靶向癌症的免疫疗法的未来需要肝肿瘤微环境的批准Heinrich B,Brown Z,Diggs L等。脂肪性肝炎损害了针对小鼠肝肿瘤的T细胞定向免疫疗法。胃肠病学2021; 160(1):… 肠道微生物分类群和疾病之间的这些潜在因果关系可能表明未来基于微生物组的治疗方法的潜力,并且更广泛地说,本研究支持基于宿主遗传学和肠道微生物组的个性化营养和医学策略的概念。###靶向癌症的免疫疗法的未来需要肝肿瘤微环境的批准Heinrich B,Brown Z,Diggs L等。脂肪性肝炎损害了针对小鼠肝肿瘤的T细胞定向免疫疗法。胃肠病学2021; 160(1):… 脂肪性肝炎损害了针对小鼠肝肿瘤的T细胞定向免疫疗法。胃肠病学2021; 160(1):… 脂肪性肝炎损害了针对小鼠肝肿瘤的T细胞定向免疫疗法。胃肠病学2021; 160(1):…
更新日期:2021-03-05
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