Gut microbiome transition across a lifestyle gradient in Himalaya

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. Whether shifts away from the foraging lifestyle that characterize much of humanity’s past influence the gut microbiome, and to what degree, remains unclear. Here, we characterize the stool bacterial composition of four Himalayan populations to investigate how the gut community changes in response to shifts in traditional human lifestyles. These groups led seminomadic hunting–gathering lifestyles until transitioning to varying levels of agricultural 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-associated microbes and find that differences in the lifestyles of Himalayan foragers and farmers are strongly correlated with microbial community variation. Furthermore, the gut microbiomes of all four traditional Himalayan populations are distinct from that of the Americans, indicating that industrialization may further exacerbate differences in the gut community. The Chepang foragers harbor an elevated abundance of taxa associated with foragers around the world. Conversely, the gut microbiomes of the 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. The gut microbiomes of Raute and Raji reveal an intermediate state between the Chepang and Tharu, indicating that divergence from a stereotypical foraging microbiome can occur within a single generation. Our results also show that environmental factors such as 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 lifestyles. 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 determining how large-scale gut microbiome reconfiguration impacts human biology.工业化人群的肠道微生物组（gut microbiome）组成与维持传统生活方式的人群存在显著差异。然而，要区分人类遗传、地理因素与生活方式各自对肠道微生物组的贡献，始终颇具难度。人类过往多数时期以觅食生活为典型特征，如今这种生活方式正在发生转变，这种转变是否会影响肠道微生物组？影响程度几何？目前仍不明确。本研究对四个喜马拉雅人群的粪便细菌组成进行了表征，旨在探究肠道菌群如何随人类传统生活方式的转变而发生改变。这些族群此前均过着半游牧的狩猎采集生活，之后不同程度地转向依赖农业的生活方式：塔鲁族（Tharu）于250至300年前开始农耕，劳特族（Raute）和拉吉族（Raji）的生活方式转型发生在30至40年前，而切庞族（Chepang）仍保留着诸多觅食生活方式的特征。我们评估了饮食与环境因素对其肠道相关微生物的影响，结果发现喜马拉雅地区的觅食者与农耕者的生活方式差异，与微生物群落变异呈现显著相关性。此外，四个喜马拉雅传统人群的肠道微生物组均与美国人群存在明显差异，这表明工业化可能进一步加剧肠道群落的差异。切庞族觅食者的肠道中，与全球各地觅食者相关的微生物类群丰度更高。与之相反，已转向农耕的人群其肠道微生物组与美国人群更为相似；农耕依赖程度以及若干相关生活方式与环境因素，与该人群肠道微生物组偏离觅食人群的程度显著相关。劳特族与拉吉族的肠道微生物组呈现出介于切庞族与塔鲁族之间的中间状态，这表明从典型觅食者微生物组的分化可在单一代际内完成。本研究结果还显示，饮用水源、固体烹饪燃料等环境因素与肠道微生物组显著相关。尽管不同人群的粪便细菌组成差异显著，但我们未发现不同生活方式下的α多样性（alpha diversity）存在明显差异。这项针对同一地理区域内遗传背景相似人群的研究，证实了生活方式在决定人类肠道微生物组组成方面的关键作用，并为后续研究指明了方向：即探明大规模肠道微生物组重构如何影响人类生物学特征。