Light Exposure at Night and Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) Modulate the Gut Microbiota in Mice

It has long been revealed that the environmental light signals influence non-image forming physiological functions, such as pupillary light reflex and phototaxis. It has been shown that these physiological functions were mediated through the melanopsin –expressing intrinsically photosensitive retina ganglion cells (ipRGCs). The ipRGCs also synchronize numerous physiological homeostasis and behaviors, including circadian rhythm, activity cycle, hormone release, and body temperature, to the external light dark cycle. Recent studies suggests that the circadian rhythm is involved in modulation of physiological regeneration and storage of energy. The disrupted circadian rhythm in mammals is also found to be related to higher risks of acquiring metabolic disorders, such as insulin resistance, obesity and hyperlipidemia, which could further develop into severe diseases including type II diabetes. However, the mechanism responsible for the manipulation of metabolism by light signals remains unknown. There are evidences showing that the gut microbiota has a direct impact on the metabolic status of mammals. Thus, we want to determine whether the ipRGC -mediated light signal transduction from the retina would affect body metabolism through the alterations of gut microbiota. By constructing a metagenomics library of gut microbiota from wild-type and melanopsin knock-out (MKO) mice and performing next generation sequencing(NGS), our findings shows distinct microbial categories in different compartments of digestive track in mice. This finding indicates the importance of investigating gut microtiota along the total digestive track instead of examining stool. Also, we discover distinct gut microbiota in wild-type and MKO mice that are exposed to dim light during the night time, comparing to the mice living in normal light-dark cycle. This finding indicates that the gut microbiota being a critical modulator of the bidirectional relationships between metabolism and light signal transduction. In addition, we find diverse composition of gut microbiota in the MKO mice when compared to wildtype mice even in the normal light-dark cycle. It also provides evidence for a new phenotype of MKO mice. Furthermore, we investigate the correlation between dim-light-exposure-at-night (dLAN) induced obesity and the altered gut microbiota. We show the diversified amount of some specific gut microbes may contribute to dLAN induced obesity. To sum up, our results suggest that the gut microbiota is a critical modulator of the dLAN induced metabolic disorder, and we provide possible mechanisms of the circadian-metabolic converges.