PT - JOURNAL ARTICLE AU - Aashish R. Jha AU - Emily R. Davenport AU - Yoshina Gautam AU - Dinesh Bhandari AU - Sarmila Tandukar AU - Katharine Ng AU - Susan Holmes AU - Guru Prasad Gautam AU - Jeevan Bahadur Sherchand AU - Carlos D. Bustamante AU - Justin L. Sonnenburg TI - Gut microbiome transition across a lifestyle gradient in Himalaya AID - 10.1101/253450 DP - 2018 Jan 01 TA - bioRxiv PG - 253450 4099 - http://biorxiv.org/content/early/2018/01/27/253450.short 4100 - http://biorxiv.org/content/early/2018/01/27/253450.full AB - The composition of the gut microbiome in industrialized populations differs from those living traditional lifestyles. However, it has been difficult to separate the contributions of human genetic and geographic factors from lifestyle/modernization. Here, we characterize the stool bacterial composition of four Himalayan populations to investigate how the gut community changes in response to shifts in human lifestyles. These groups led seminomadic hunting-gathering lifestyles until transitioning to varying dependence upon farming. The Tharu began farming 250-300 years ago, the Raute and Raji transitioned 30-40 years ago, and the Chepang retain many aspects of a foraging lifestyle. We assess the contributions of dietary and environmental factors on their gut microbiota and find that the gut microbiome composition is significantly associated with lifestyle. The Chepang foragers harbor elevated abundance of taxa associated with foragers around the world. Conversely, the gut microbiomes of populations that have transitioned to farming are more similar to those of Americans, with agricultural dependence and several associated lifestyle and environmental factors correlating with the extent of microbiome divergence from the foraging population. For example, our results show that drinking water source and solid cooking fuel are significantly associated with the gut microbiome. Despite the pronounced differences in gut bacterial composition across populations, we found little differences in alpha diversity across populations. These findings in genetically similar populations living in the same geographical region establish the key role of lifestyle in determining human gut microbiome composition and point to the next challenging steps of isolating dietary effects from other factors that change during modernization.