This project undertakes a groundbreaking exploration of the distinct and rich microbiota of the Brazilian Yanomami people, using advanced functional assays both in vitro and in vivo through gnotobiotic mouse models, and specialized microbiological techniques. Our objective is to decipher the regulatory roles of the Yanomami microbiota—markedly different from that found in industrialized societies—on intestinal epithelial and immune cell functions. We hypothesize that specific strains unique to the Yanomami may positively influence intestinal barrier integrity, maintain immune balance, and reduce susceptibility to colorectal cancer (CRC), a disease prevalent in industrialized settings. This collaborative research, involving the Vereecke and Paulino labs, will identify and analyze Yanomami-specific bacterial strains and examine how their diet impacts microbiota stability and subsequent physiological responses. Importantly, we ensure that all aspects of our research adhere to the highest ethical standards in studying indigenous populations. By studying how the Yanomami microbiota modulates immune responses and CRC risk using sophisticated gnotobiotic mouse models, we aim to uncover the mechanisms through which indigenous microbiota maintain intestinal health and prevent disease. This comprehensive analysis could lead to novel preventative and therapeutic strategies for health issues commonly associated with industrialized lifestyles, including CRC.