Editors' ChoiceCIRCADIAN REGULATION

Could gut flora cycles be key to treating diabetes?

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Science Translational Medicine  22 Jul 2020:
Vol. 12, Issue 553, eabd3618
DOI: 10.1126/scitranslmed.abd3618

Abstract

Gut microbiota abundance rhythms are ablated in patients with type 2 diabetes.

Disruption of the circadian clock plays a significant role in the development and severity of metabolic diseases such as type 2 diabetes (T2D). Along with this, the clock is known to influence gut microbial homeostasis, and changes in the gut microbiota have been correlatively linked to metabolic health. However, previous investigations of the gut microbiota have not included temporal information, leading to a dearth of data on which components of the microbiome are under circadian regulation. This absence of temporal information has hampered mechanistic insights into the influence of circadian rhythms on metabolic disease.

To determine which components of the microbiome are under circadian regulation, Reitmeier et al. interrogated three major gut flora datasets that had captured temporal information as part of their sampling protocols. They found that there were many operational taxonomic units (OTUs) whose abundances were rhythmic over a 24-hour period. A subset of these rhythmic OTUs were disrupted in patients with T2D, with intermediate phenotypes seen in patients who were prediabetic. Not only were the arrhythmic taxa in patients with T2D predictive of T2D in an independent cohort, but the functional changes that would occur due to the dysregulation of gut microbiota rhythms suggested that the loss of metabolic oscillation plays a mechanistic role in the development of T2D. This implies that chronotherapeutic treatment modalities could be effective for T2D.

Two major caveats to this study are that there is regional variation in the rhythmicity of the oscillatory gut microbiota that is affected by T2D and that the correlative link between the arrhythmic taxa and T2D does not confer causation. Nevertheless, the strong connection between T2D and the clock in this work emphasizes the need to take into account sampling time in all microbiome studies as this research demonstrates yet another avenue where the circadian clock influences an essential physiological function.

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