The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3

Abstract

Microbial entrainment of metabolism The metabolism of mammals is synchronized to daily cycles relating to sleep and mealtimes. It is not surprising that the gut microbiota, which aids in digestion, should also display daily cycling. Kuang et al. found that the gut microbiota can mediate daily cycles epigenetically (see the Perspective by Bishehsari and Keshavarzian). The microbiota induces rhythmic expression of histone deacetylase 3 (HDAC3) in epithelial cells of the small intestine, but not those of the colon. HDAC3 expression drives oscillations in intestinal metabolic gene expression, especially for nutrient transport and lipid metabolism. HDAC3 also directly activates estrogen-related receptor α, which promotes lipid absorption. Consequently, mice that lack a gut microbiota lack daily regulation of their metabolism and become obese on high-fat chow. Disruption of HDAC3 cycling could be an explanation for human obesity associated with antibiotic damage to the microbiota and with sleep disruption caused by jet lag and nighttime working. Science , this issue p. 1428 ; see also p. 1379