Circadian rhythmicity is a defining feature of mammalian metabolism that synchronizes metabolic processes to day-night light cycles. Here, we show that the intestinal microbiota programs diurnal metabolic rhythms in the mouse small intestine through histone deacetylase 3 (HDAC3). The microbiota induced expression of intestinal epithelial HDAC3, which was recruited rhythmically to chromatin, and produced synchronized diurnal oscillations in histone acetylation, metabolic gene expression, and nutrient uptake. HDAC3 also functioned noncanonically to coactivate estrogen-related receptor α, inducing microbiota-dependent rhythmic transcription of the lipid transporter gene Cd36 and promoting lipid absorption and diet-induced obesity. Our findings reveal that HDAC3 integrates microbial and circadian cues for regulation of diurnal metabolic rhythms and pinpoint a key mechanism by which the microbiota controls host metabolism.

SAAving vitamin A–mediated immunity The vitamin A metabolite retinol is critical for B and T cell development and homing to the gut. Intestinal myeloid cells such as dendritic cells and macrophages take up retinol and process it into retinoic acid (RA), which in turn initiates RA-dependent gene expression programs in lymphocytes. Bang et al . identified LDL receptor-related protein 1 (LRP1) as a myeloid cell surface receptor for retinol. LRP1 binds retinol chaperoned by serum amyloid A (SAA) proteins, and SAA–retinol complexes are then endocytosed and metabolized by myeloid cells. Mice lacking either Saa or myeloid-specific Lrp1 exhibited profound impairments in vitamin A–mediated immunity. B and T cell trafficking to the intestine, immunoglobulin A production by B cells, and protection from enteric Salmonella Typhimurium infection were all diminished when either of these crucial players was missing. —STS

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