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Gut microbiota has a widespread and modifiable effect on host gene regulation

By Allison Richards, Amanda L. Muehlbauer, Adnan Alazizi, Michael B. Burns, Anthony Findley, Francesco Messina, Trevor J. Gould, Camilla Cascardo, Roger Pique-Regi, Ran Blekhman, Francesca Luca

Posted 27 Oct 2017
bioRxiv DOI: 10.1101/210294

Variation in gut microbiome is associated with wellness and disease in humans, yet the molecular mechanisms by which this variation affects the host are not well understood. A likely mechanism is through changing gene regulation in interfacing host epithelial cells. Here, we treated colonic epithelial cells with live microbiota from five healthy individuals and quantified induced changes in transcriptional regulation and chromatin accessibility in host cells. We identified over 5,000 host genes that change expression, including 588 distinct associations between specific taxa and host genes. The taxa with the strongest influence on gene expression alter the response of genes associated with complex traits. Further, using ATAC-seq, we show that these changes in gene expression are likely the result of changes in host chromatin accessibility induced by exposure to gut microbiota. We then created a manipulated microbial community with titrated doses of Collinsella, demonstrating that both natural and controlled microbiome composition leads to distinct, and predictable, gene expression profiles in the host. Together, our results suggest that specific microbes play an important role in regulating expression of individual host genes involved in human complex traits. Our work also supports the hypothesis that one of the mechanisms by which the microbiome regulates host gene expression is through changes in chromatin accessibility in host cells. Finally, the ability to fine tune the expression of host genes by manipulating the microbiome suggests future therapeutic routes for human wellness.

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