Interspecies Variation in Hominid Gut Microbiota Controls Host Gene Regulation

ABSTRACT Variation in gut microbiome is associated with wellness and disease in humans, and yet the molecular mechanisms by which this variation affects the host are not well understood. A likely mechanism is that of 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. Using ATAC-seq, we showed that a subset of these changes in gene expression are associated with changes in host chromatin accessibility and transcription factor binding induced by exposure to gut microbiota. We then created a manipulated microbial community with titrated doses of Collinsella, demonstrating that manipulation of the composition of the microbiome under both natural and controlled conditions leads to distinct and predictable gene expression profiles in host cells. Taken together, our results suggest that specific microbes play an important role in regulating expression of individual host genes involved in human complex traits. The ability to fine-tune the expression of host genes by manipulating the microbiome suggests future therapeutic routes. IMPORTANCE The composition of the gut microbiome has been associated with various aspects of human health, but the mechanism of this interaction is still unclear. We utilized a cellular system to characterize the effect of the microbiome on human gene expression. We showed that some of these changes in expression may be mediated by changes in chromatin accessibility. Furthermore, we validate the role of a specific microbe and show that changes in its abundance can modify the host gene expression response. These results show an important role of gut microbiota in regulating host gene expression and suggest that manipulation of microbiome composition could be useful in future therapies.

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Microbial control of host gene regulation and the evolution of host–microbiome interactions in primates

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0598 ◽

2020 ◽

Vol 375 (1808) ◽

pp. 20190598 ◽

Cited By ~ 1

Author(s):

Laura Grieneisen ◽

Amanda L. Muehlbauer ◽

Ran Blekhman

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Host Species ◽

Evolutionary Dynamics ◽

Microbial Control ◽

Host Gene ◽

Primate Species ◽

Microbiome Composition ◽

Wide Range ◽

Species Specific

Recent comparative studies have found evidence consistent with the action of natural selection on gene regulation across primate species. Other recent work has shown that the microbiome can regulate host gene expression in a wide range of relevant tissues, leading to downstream effects on immunity, metabolism and other biological systems in the host. In primates, even closely related host species can have large differences in microbiome composition. One potential consequence of these differences is that host species-specific microbial traits could lead to differences in gene expression that influence primate physiology and adaptation to local environments. Here, we will discuss and integrate recent findings from primate comparative genomics and microbiome research, and explore the notion that the microbiome can influence host evolutionary dynamics by affecting gene regulation across primate host species. This article is part of the theme issue ‘The role of the microbiome in host evolution’.

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Host Gene Regulation by Transposable Elements: The New, the Old and the Ugly

Viruses ◽

10.3390/v12101089 ◽

2020 ◽

Vol 12 (10) ◽

pp. 1089 ◽

Cited By ~ 2

Author(s):

Rocio Enriquez-Gasca ◽

Poppy A. Gould ◽

Helen M. Rowe

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Transposable Elements ◽

Essential Gene ◽

Expression Patterns ◽

Genetic Material ◽

Endogenous Retroviruses ◽

Host Gene ◽

New Genes ◽

Host Genes

The human genome has been under selective pressure to evolve in response to emerging pathogens and other environmental challenges. Genome evolution includes the acquisition of new genes or new isoforms of genes and changes to gene expression patterns. One source of genome innovation is from transposable elements (TEs), which carry their own promoters, enhancers and open reading frames and can act as ‘controlling elements’ for our own genes. TEs include LINE-1 elements, which can retrotranspose intracellularly and endogenous retroviruses (ERVs) that represent remnants of past retroviral germline infections. Although once pathogens, ERVs also represent an enticing source of incoming genetic material that the host can then repurpose. ERVs and other TEs have coevolved with host genes for millions of years, which has allowed them to become embedded within essential gene expression programmes. Intriguingly, these host genes are often subject to the same epigenetic control mechanisms that evolved to combat the TEs that now regulate them. Here, we illustrate the breadth of host gene regulation through TEs by focusing on examples of young (The New), ancient (The Old), and disease-causing (The Ugly) TE integrants.

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