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GI highlights from the literature

BASIC SCIENCE Large-scale association analyses identify host factors influencing human gut microbiome composition Kurilshikov A, MedinaGomez C, Bacigalupe R et al. Largescale association analyses identify host factors influencing human gut microbiome composition. Nat Genet 2021; 53:156–165. doi: 10.1038/s41588-020-00763-1 Multiple genomewide 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 genomewide metaanalysis 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 metaanalysis 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 agedependent association (weaker effect in children and adolescents) with Bifidobacterium abundance. Biological interpretation of genetic traits through a phenomewide 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 microbiomebased therapies and more generally this study supports the concept of personalised nutrition and medical strategies based on host genetics and the gut microbiome.