High Sugar & Fat Diet Influences the Brain circRNA Profiles in Murine by Regulating the Gut-Brain Axis

Recent studies showed that the gut microbiota metabolites could modulate the host physiology, and circRNAs could be degraded by induced with poly(I:C) or virus. Here, we aim to find some more connections between circRNAs and gut microbiome using direct and indirect evidences. For that, a diet with increased amounts of sugar and fat (high-sugar and high-fat, HSHF diet) to disturb the gut microbiome, then monitored the effect on pathology, metabolism, transcription and brain circRNAs in mice. Results showed that the HSHF diet induced dysbacteriosis, damaged the intestinal tract and caused changes in circRNA sequence profiles in brain, there were 88 circRNAs were up-regulated while more than 199 circRNAs were down-regulated, which indicated that the HSHF diet degrade the brain circRNAs. We also found that gut microbiota byproduct of TMAO or microbiota (Kombucha tea) could deteriorate these changes. These findings demonstrate a link between circRNA and gut microbiome, enlarge the 'microbiome- transcriptome' linkage library and provide more information on gut-brain axis, which would provide more information on the interplay between gut and brain to aid in the identification of potential therapeutic markers and mechanistic solutions to complex problems commonly encountered in pathology, toxicology, and drug development studies, while those complex interaction system still need much more study. Funding Statement: The present work was supported by the financial support from the National Natural Science Foundation of China (81701086), the Guangzhou Science and Technology Plan Projects ((201604016050，201707020022), Natural Science Foundation of Hunan (2019JJ50631), GDAS' Project of Science and Technology Development (2019GDASYL- 0104007). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The animal protocols used in this work were approved by the Institutional Animal Care and Use committee of the Center of Laboratory Animals of the Guangdong Institute of Microbiology.