Interspecies variation in hominid gut microbiota controls host gene regulation

Amanda L. Muehlbauer, Allison L. Richards, Adnan Alazizi, Michael B. Burns, Andres Gomez, Jonathan B. Clayton, Klara Petrzelkova, Camilla Cascardo, Justyna Resztak, Xiaoquan Wen, Roger Pique-Regi, Francesca Luca, Ran Blekhman

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Article number110057
JournalCell reports
Issue number8
StatePublished - Nov 23 2021

Bibliographical note

Funding Information:
We would like to thank the primate zookeepers at the Ostrava Zoo, and especially Jana Pluhackova, for their help with chimpanzee fecal sample collection. We would also like to thank the primate zookeepers at the Como Park Zoo and Conservatory for their help with gorilla and orangutan fecal sample collection. Finally, we would like to thank Blekhman lab members, and especially Rich Abdill, Beth Adamovicz, Laura Grieneisen, and Sambhawa Priya, for their comments and advice on the manuscript. This work is supported by NIH ( R35-GM128716 to R.B. and R01-GM109215 to F.L. and R.P.-R.). Partial funding was provided by the Czech-American Scientific cooperation ( LH15175 ) supported by the Ministry of Education, Youth and Sports of the Czech Republic (to K.P.). This work was carried out, in part, by resources provided by the Minnesota Supercomputing Institute.

Publisher Copyright:
© 2021 The Author(s)


  • Gut microbiome, Primates, Hominids, Gene regulation

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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