Observed: In Drosophila (Iso31 and a per01 clock mutant), microbiome presence versus sterility changes gut gene expression programs that track circadian “cycling.” The microbiome dampens the amplitude and alters the phase distribution of gut transcript cycling, whereas sterile flies show broader and higher-amplitude gut transcriptional cycling.
Observed + mechanistic: Time-restricted feeding increases host rhythmic gene expression partly through histone acetylation; HDAC inhibition increases H4ac and upregulates cycling genes, consistent with microbiome–chromatin modulation of stress-coupled transcription.
Observed: The microbiome stabilizes gut clock responses to LD shifts, reducing rapid remodeling of clock gene expression compared with sterile conditions.
The provided evidence specifically resolves gut-circadian gene expression under feeding/LD perturbations and associated microbiome presence/absence, but it does not (i) map gene expression changes across diverse stress modalities, (ii) quantify which microbial taxa drive specific host pathways, or (iii) test causal host regulatory logic genome-wide beyond gut clock/transcription-factor and histone-acetylation mediation.
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