Environment dominates over host genetics in shaping human gut microbiota

Abstract

Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

Host genetics and microbiome associations from the lens of genome wide association studies

“…Additionally, several recent studies have identified a significant heritability of bacterial α-diversity [28,30,39]. In contrast, a recent analysis of 1,046 Israeli individuals from different ancestral origins but a relatively shared environment did not replicate any of the above results, and did not identify statistically significant host-genomics associations with either the overall microbiome composition or individual taxa [8]. Another recent study identified significant co-occurrence of bacterial taxa among 270 family members [28], and several other studies identified a significantly different microbiome composition between individuals from different populations [20,40], but it is not possible to tease apart the roles of genetics and environment in such studies.…”

“…Recent studies employing these technologies have uncovered evidence for both environmental and host genetic association with the microbiome composition [8,11,20,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. However, to date there is no consensus regarding how and to what extent does host genetics shapes the gut microbiome, as compared to environmental factors.…”

“…The estimated heritability of these taxa was typically 10%-30%, which is substantially lower than several wellknown human complex traits, such as height, body mass index (BMI), and even education attainment [38]. A recent re-analysis of the largest reported twin study to date (2,252 twins) found that the average heritability of gut bacterial taxa likely lies between 1.9% and 8% [8]. Taken together, these results indicate that there are several genetically heritable bacterial taxa, but that the overall gut microbiome heritability is relatively small.…”

“…First, there is an excessive bacterial similarity among individuals sharing a household, but no such similarity was observed across family members without a history of household sharing [8,20,22,35]. Second, over 20% of gut microbiome β-diversity variance can be inferred via several measured environmental factors, such as answers to food frequency and drug use questionnaires [8,33,34], whereas no statistically significant result was obtained when applying a similar methodology to genetic variants [8]. These results further demonstrate that the gut microbiome is predominantly shaped by environmental factors.…”

“…In recent years the importance of the gut microbiome in human metabolism and health is increasingly gaining recognition [1][2][3][4][5][6][7][8][9][10][11][12]. Recent studies have associated the microbiome with various health parameters including obesity, diabetes mellitus, cancer, and inflammatory, metabolic and neurodegenerative disorders [13][14][15][16][17].…”