A microbiota-epigenetic circuit controls systematic circadian programs in the gut epithelium

Area of Science:

• Microbiology
• Epigenetics
• Chronobiology

Background:

• The intestinal microbiota influences host circadian rhythms and health.
• Histone deacetylase 3 (HDAC3) synchronizes lipid metabolism in the intestinal epithelium.
• The full extent of microbiota-circadian interactions in the gut remains unclear.

Purpose of the Study:

• To investigate the breadth and significance of microbiota-circadian crosstalk in the intestine.
• To understand how the gut microbiota programs rhythmic biological processes and epithelial functions.
• To elucidate the role of HDAC3 in microbiota-dependent circadian rhythms.

Main Methods:

• Comparison of gene expression patterns in conventional and germ-free mice.
• Analysis of microbiota-dependent circadian programs.
• Motif enrichment analysis to identify transcription factor involvement.

Main Results:

• The gut microbiota programs rhythmic expression of diverse biological processes (protein synthesis, cell proliferation, metabolism, immunity) in the intestinal epithelium.
• Gene expression rhythms are dampened in germ-free mice, indicating microbiota's role in structuring host gene expression timing.
• HDAC3 drives most microbiota-dependent circadian programs via rhythmic histone deacetylation, differentially controlling pathways by recruiting specific transcription factors.

Conclusions:

• The commensal microbiota programs "just-in-time" intestinal epithelial functions through epigenetic mechanisms.
• HDAC3 is a key mediator of microbiota-driven circadian rhythms in the gut.
• These findings offer a systematic view of microbiota-epigenetic interactions maintaining host homeostasis.