Gut Microbiota Has a Widespread and Modifiable Effect on Host Gene Regulation

Area of Science:

• Microbiology
• Genomics
• Human Health

Background:

• Gut microbiome variation impacts human health, but molecular mechanisms remain unclear.
• Host epithelial cell gene regulation is a potential mechanism linking microbiome and health.
• Understanding these interactions is crucial for developing microbiome-based therapies.

Purpose of the Study:

• To investigate how live gut microbiota influences gene expression and chromatin accessibility in colonic epithelial cells.
• To identify specific microbial taxa associated with host gene expression changes.
• To explore the therapeutic potential of manipulating the microbiome for host gene regulation.

Main Methods:

• Treatment of colonic epithelial cells with live microbiota from healthy individuals.
• Quantification of transcriptional regulation and chromatin accessibility changes (ATAC-seq).
• Manipulation of a microbial community with specific taxa (e.g., *Collinsella*) to assess dose-dependent effects.

Main Results:

• Over 5,000 host genes showed altered expression, with 588 specific microbe-gene associations identified.
• Microbial taxa significantly influenced genes related to complex human traits.
• Microbiota-induced gene expression changes were linked to alterations in host chromatin accessibility and transcription factor binding.

Conclusions:

• Specific gut microbes actively regulate host gene expression, including those involved in complex traits.
• Microbiome composition directly influences host cell gene expression profiles.
• Targeted manipulation of the gut microbiome offers a promising avenue for future therapeutic interventions.