Disrupting the daily routine of gut microbes in mice impacts their metabolism, increasing the risk for metabolic dysfunction, according to a new study. The results may inform a link between microbiota damage and human obesity, for example, in our modern environment, the authors say. "Our findings suggest how modern lifestyle factors, such as antibiotics or long-distance jet travel, might disrupt microbiota-clock interactions and thus worsen metabolic disease," said study coauthor, Lora Hooper. Many aspects of mammalian metabolism, including the gut microbiome, are tied to circadian cycles. However, the relationship between the microbiome and circadian pathways, as well as the underlying molecular mechanisms that link day-night light cycles and metabolic gene expression, aren't well-known. In a mouse model, Zheng Kuang and colleagues investigated the microbiota's role in regulating the daily rhythms of metabolic gene expression by altering histone acetylation, which is known to be an important circadian-epigenetic mechanism. Kuang et al. found that certain bacteria initiated expression of the histone deacetylase 3 (HDAC3) in epithelial cells in the small intestines of mice, in turn leading to synchronized daily oscillations in the expression of metabolic genes related to nutrient transport and lipid metabolism. Germ-free mice that lacked a gut microbiota didn't exhibit this rhythmic regulation of their metabolism, the authors showed. The authors also discovered that HDAC3 was involved in promoting lipid adsorption and obesity. In further studies in the mice, chronic disruptions to the circadian light cycle and the rhythm of HDAC3 expression worsened diet-induced obesity. "In our current 'modern' environment characterized by light pollution, and 'Western diet', the cross talk between host circadian clock and the microbiota may allow promotion of metabolic dysfunction and obesity," write Faraz Bishehsari and Ali Keshavarzian in a related Perspective.
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Journal
Science