Human populations are evolving in close interaction with their environment, that they in turn shape. However, this intimate adequacy has been challenged many times during human evolutionary history, for example at the Neolithic revolution 10,000 years ago during the transition from a nomadic hunter-gatherer to a sedentary farming mode of subsistence, or more recently with the industrialization of human societies. While the influence of human activities on various ecosystems is largely recognized, little is know about the effect of ancient and recent changes in lifestyle, notably dietary regimes and access to medicine, on the symbiotic relationship we maintain with the microorganisms living in our guts, the gut microbiome. Our own gut microbial ecosystem is however currently considered to be essential for human health, and seems notably implicated in multiple metabolic and immune diseases. It also appears to be highly variable among individuals and populations, and at least partially heritable, making it a potential target for natural selection. The human gut microbiome therefore represents a phenotype of evolutionary, ecological and medical relevance. Although it appears that the gut microbiome interacts with its host (through e.g., diet, antibiotics use and the immune response) and with other intestinal communities (parasites, viruses), the respective influence of various environmental (whether ecological or cultural) and genetic factors on its composition is not clear. Notably, the loss of microbial biodiversity observed in urban industrialized populations (as compared to rural developing countries) could be due to their dietary specialization, hygiene practices, and/or other variables. This project aims at disentangling the interactions that exist between these different factors to understand (i) how the microbial ecosystem has coevolved in the long-term with humans dietary regimes and parasitism since the Neolithic revolution 10,000 years ago, (ii) how rapid changes in lifestyle, notably industrialisation, has impacted the gut microbial diversity and (iii) what is the influence of genetic determinants on the microbiome composition. To tackle these issues, we propose to sample and compare the gut microbiome of individuals from contrasted subsistence modes (hunter-gatherers versus farmers) and along a gradient of urbanisation (from African rural villages to African cities to a European city) in Cameroon and France. We will collect both anthropological data (nutritional, medical and ethnological questionnaires, and anthropometric measures) and biological data (intestinal parasitism, microbial and human genetic data), and jointly analyze the influence of variables of interest on the gut microbiome, using various statistical and bioinformatics tools. Bringing together classical biological anthropology approaches and next-generation sequencing technologies, this innovative project aims at dissecting how various ecological, cultural and genetic factors have impacted the gut microbial communities in the past, and likely continue to do so in the future, in the context of a rapid homogenization of food and hygiene practices across the World. This project will likely have an important impact in the fields of anthropology, ecology and evolution, as well as substantial implications in public health.