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 characterizes 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 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）组成与传统生活方式人群存在差异。然而，要将人类遗传、地理因素与生活方式对肠道微生物组的影响区分开来，一直颇具挑战。人类过往多数时期所依赖的觅食生活方式的转变是否会影响肠道微生物组，以及影响程度如何，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，以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。这些人群此前均以半游牧式的狩猎采集生活方式为主，随后不同程度地转向依赖农业的生产模式。塔鲁（Tharu）人群于250至300年前开始从事农业生产，劳特（Raute）与拉吉（Raji）人群则在30至40年前完成转型，而切庞（Chepang）人群仍保留了诸多觅食生活方式的特征。本研究评估了饮食与环境因素对其肠道相关微生物的影响，发现喜马拉雅觅食人群与农耕人群的生活方式差异，与微生物群落组成的变化显著相关。此外，四个传统喜马拉雅人群的肠道微生物组均与美国人群存在显著差异，这表明工业化可能会进一步加剧肠道菌群组成的差异。切庞觅食人群体内与全球范围内觅食人群相关的微生物类群丰度更高。与之相反，已转型从事农业的人群的肠道微生物组与美国人群更为相似；农业依赖程度以及若干相关生活方式与环境因素，均与该人群肠道微生物组相较于觅食人群的分化程度显著相关。劳特与拉吉人群的肠道微生物组呈现出介于切庞人群与塔鲁人群之间的中间状态，这表明从典型觅食者肠道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存在显著差异，但我们未发现不同生活方式人群的肠道菌群α多样性（alpha diversity）存在明显差异。针对生活在同一地理区域、遗传背景相似的人群开展的本研究结果，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，并指出了下一阶段的研究挑战：即探明大规模肠道微生物组重构如何影响人类生物学机能。