The gut microbiome exhibits extreme compositional variation between hominid hosts. However, it is unclear how this variation impacts host physiology across species and whether this effect can be mediated through microbial regulation of host gene expression in interacting epithelial cells. Here, we characterize the transcriptional response of human colonic epithelial cells in vitro to live microbial communities extracted from humans, chimpanzees, gorillas, and orangutans. We find that most host genes exhibit a conserved response, whereby they respond similarly to the four hominid microbiomes. However, hundreds of host genes exhibit a divergent response, whereby they respond only to microbiomes from specific host species. Such genes are associated with intestinal diseases in humans, including inflammatory bowel disease and Crohn's disease. Last, we find that inflammation-associated microbial species regulate the expression of host genes previously associated with inflammatory bowel disease, suggesting health-related consequences for species-specific host-microbiome interactions across hominids.

Center for Molecular Medicine and Genetics Wayne State University Detroit MI 48201 USA

Center for Molecular Medicine and Genetics Wayne State University Detroit MI 48201 USA; Department of Obstetrics and Gynecology Wayne State University Detroit MI 48201 USA

Department of Animal Science University of Minnesota Saint Paul MN USA

Department of Biology Loyola University Chicago IL 60660 USA

Department of Biology University of Nebraska at Omaha Omaha NB USA; Department of Food Science and Technology University of Nebraska Lincoln Lincoln NB USA

Department of Biostatistics University of Michigan Ann Arbor MI USA

Department of Genetics Cell Biology and Development University of Minnesota Minneapolis MN USA; Department of Ecology Evolution and Behavior University of Minnesota Minneapolis MN USA

The Czech Academy of Sciences Institute of Vertebrate Biology Brno Czech Republic; Liberec Zoo Liberec Czech Republic; The Czech Academy of Sciences Institute of Parasitology Ceske Budejovice Czech Republic

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