Genetic and Transcriptional Analysis of Human Host Response to Healthy Gut Microbiota

Abstract

The study of host-microbiota interactions in humans is largely limited to identifying associations between microbial communities and host phenotypes. While these studies have generated important insights on the links between the microbiota and human disease, the assessment of cause-and-effect relationships has been challenging. Although this relationship can be studied in germfree mice, this system is costly, and it is difficult to accurately account for the effects of host genotypic variation and environmental effects seen in humans. Here, we have developed a novel approach to directly investigate the transcriptional changes induced by live microbial communities on human colonic epithelial cells and how these changes are modulated by host genotype. This method is easily scalable to large numbers of host genetic backgrounds and diverse microbiota and can be utilized to elucidate the mechanisms of host-microbiota interactions. Future extensions may also include colonic organoid cultures.