Our digestive tract is home to trillions of microbes forming a complex community important to our health. Recent literature has revealed the essential role of gut microbiome to our physiology, especially that of the digestive system including GI cancers. Using colorectal cancer as an example, I will illustrate how metagenomics and animal transplant experiments can enhance our understanding of the host-microbial interaction in diseases, providing novel mechanistic insights and providing translational potentials. I will also discuss how we can harness these research findings to improve patient care, on disease diagnosis and treatment enhancement. This inter-disciplinary approach has provided an unprecedented opportunity for translational research and will take us into a new realm of precision medicine in the near future.