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.

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.. CC-BY-NC-ND 4.0 International licenseIt is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . http://dx.doi.org/10.1101/253450 doi: bioRxiv preprint first posted online Jan. 27, 2018; 2 ;f/f+

Indigenous populations residing in low- and middle-income countries (LMICs) are highly underrepresented in medicine and public health research. Specifically, data on non-communicable diseases (NCDs) from indigenous populations remains scarce. Despite the increasing burden of NCDs in the Himalayan region, their prevalence in many indigenous populations remains understudied. The nationally representative public health surveys often do not include the indigenous communities, especially those that reside in rural areas or exist in small numbers. This observational cross-sectional survey study aimed to assess the prevalence of three NCD risk factors namely obesity, hypertension, and tachycardia and identify dietary and lifestyle variables associated with them across underrepresented indigenous populations of Nepal. A total of 311 individuals (53.3% women, 46.7% men) with mean age 43±15 years from 12 indigenous Nepali communities residing in rural (47.9%) or semi-urban (52.1%) areas volunteered to participate in this study. Univariate tests and multivariable logistic regressions were used to analyze the survey data. The mean systolic and diastolic blood pressures were 121.3±19.5 mmHg and 81.3±11.8 mmHg respectively. Overall, the prevalence of obesity and tachycardia was low (0.64% and 3.22%, respectively) but hypertension was prevalent at 23.8%. Hypertension was not significantly different across populations, but it was associated with age, BMI, and tobacco use, and collectively, these variables explained 13.9% variation in hypertension prevalence. Although we were unable to detect direct associations between individual determinants of hypertension identified in non-indigenous Nepalis, such as education levels, alcohol consumption, and smoking in this study, having one or more determinants increased the odds of hypertension in the indigenous participants. Furthermore, ~14% of the hypertensive individuals had none of the universally identified hypertension risk factors. The lack of association between previously identified risk factors for hypertension in these individuals indicates that the additional determinants of hypertension remain to be identified in indigenous Nepali populations.

Actions speak louder than words to prevent language extinctions Every two weeks a language becomes extinct, according to the United Nations Permanent Forum on Indigenous Issues (see http:// go.nature.com/RLfdzx). The Ethnologue linguistic resource lists 6,912 languages, 75% of which are spoken by a few indigenous peoples spread over more than 70 countries. The United Nation's 1996 Declaration of Linguistic Rights calls for linguists, governments and intergovernmental agencies to come up with policies to arrest this trend. In Nepal, for example, 70 indigenous languages are recognized; many of these have been represented in the media for more than a decade. Yet at least 11 have died out, 19 are almost extinct and 23 are endangered. More effort, increased funding, greater commitment and effective policies are all needed to preserve language diversity, particularly in developing countries.