Although previous research has shown that host genetics (i.e., some human genes related to diet, metabolism, taste and immunity) are associated with the abundance of several gut bacterial taxa, the degree to which human genetics shape gut microbiome composition remains elusive.
A new study, led by Prof. Eran Segal from the Department of Computer Science and Applied Mathematics and the Department of Molecular Cell Biology at the Weizmann Institute of Science (Rehovot, Israel), has found that environmental factors are major determinants of the human gut microbiome and several human phenotypes are as strongly associated with the gut microbiome as with host genetics.
Genotype and microbiome data from 1,046 healthy Israeli adults -consisting of Ashkenazi (n = 508), North African (n = 64), Middle Eastern (n = 34), Sephardi (n = 19), Yemenite (n = 13) and ‘admixed/other’ (n = 408) ancestries- were analysed in order to determine whether genetics play a major role in determining gut microbiome variation among people. Blood samples were collected for genotyping and phenotyping and stool samples for metagenome sequencing and 16S ribosomal ribonucleic acid (rRNA) gene sequencing. In addition to genetic data and gut microbiome composition, anthropometric measurements and food frequency and lifestyle questionnaires (including dietary habits, lifestyle, medications, and additional measurements) were collected for each study participant.
The researchers first verified that genetic differences were easily detected across individuals of different ancestries. However, no differences were seen in the gut microbiomes of individuals of different ancestries. The researchers found that the host’s genetics only accounted for about 2% of the variation between populations, showing that the host’s genetics may play a minor role in shaping the human gut microbiome composition.
Evidence that the gut microbiome was shaped largely by environmental factors comes from significant similarities found in the compositions of the gut microbiomes of genetically unrelated individuals who shared a household, whereas no significant gut microbiome similarity was found among relatives who did not have a history of household sharing. Besides this, over 20% of the inter-person gut microbiome variability was associated with factors related to diet, drugs and anthropometric measurements. Limited evidence was found for gut microbiome associations with specific single nucleotide polymorphisms. The fact that variance in gut microbiome b-diversity can be inferred from diet and lifestyle was previously reported in humans.
On the other hand, the researchers investigated how gut microbial communities interact with human genes to influence several anthropometric and clinical parameters. It was found that both host genetics and gut microbiome data improved the prediction accuracy of glucose (fasting glucose levels and glycaemic status) and obesity measures (body mass index, levels of high-density lipoprotein cholesterol, waist circumference, hip circumference, and waist-hip ratio), compared to models that used only host genetic and environmental data. These results suggested that the gut microbiome can be used to infer a significant fraction of the variance of several human phenotypes.
Finally, the researchers replicated their results in 836 Dutch individuals from the LifeLines DEEP cohort.
In conclusion, diet and lifestyle may be the primary dominant factors that shape the human gut microbiome composition. Thus, gut microbiome composition is predominantly shaped by non-genetic factors. Further studies in other cohorts from different genetic backgrounds and that occupy different environments will allow validation of these findings and will explore in much more detail the relationship between the gut microbiome, genetics and human health.
Rothschild D, Weissbrod O, Barkan E, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018; 555(7695):210-5. doi: 10.1038/nature25973.