Homeostatic crosstalk among gut microbiome, hypothalamic and hepatic circadian clock oscillations, immunity and metabolism in response to different light-dark cycles: A multiomics study

文献类型： 外文期刊

第一作者： Zhen, Yongkang

作者： Zhen, Yongkang;Wang, Yifan;He, Feiyang;Chen, Yifei;Ge, Ling;Wang, Yusu;Wei, Wenjun;Rahmat, Ali;Wang, Mengzhi;Wang, Yifan;Wang, Mengzhi;Hu, Liangyu;Loor, Juan J.;Loor, Juan J.;Wang, Mengzhi

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关键词： circadian clock; gut microbiome; host-microbes interaction; innate immune; light-dark cycles; tryptophan metabolism

期刊名称：JOURNAL OF PINEAL RESEARCH （ 影响因子：10.3； 五年影响因子：12.4 ）

ISSN： 0742-3098

年卷期： 2023 年 75 卷 2 期

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收录情况： SCI

摘要： The accelerated pace of life at present time has resulted in tremendous alterations in living patterns. Changes in diet and eating patterns, in particular, coupled with irregular light-dark (LD) cycles will further induce circadian misalignment and lead to disease. Emerging data has highlighted the regulatory effects of diet and eating patterns on the host-microbe interactions with the circadian clock (CC), immunity, and metabolism. Herein, we studied how LD cycles regulate the homeostatic crosstalk among the gut microbiome (GM), hypothalamic and hepatic CC oscillations, and immunity and metabolism using multiomics approaches. Our data demonstrated that central CC oscillations lost rhythmicity under irregular LD cycles, but LD cycles had minimal effects on diurnal expression of peripheral CC genes in the liver including Bmal1. We further demonstrated that the GM could regulate hepatic circadian rhythms under irregular LD cycles, the candidate bacteria including Limosilactobacillus, Actinomyces, Veillonella, Prevotella, Campylobacter, Faecalibacterium, Kingella, and Clostridia vadinBB60 et al. A comparative transcriptomic study of innate immune genes indicated that different LD cycles had varying effects on immune functions, while irregular LD cycles had greater impacts on hepatic innate immune functions than those in the hypothalamus. Extreme LD cycle alterations (LD0/24 and LD24/0) had worse impacts than slight alterations (LD8/16 and LD16/8), and led to gut dysbiosis in mice receiving antibiotics. Metabolome data also demonstrated that hepatic tryptophan metabolism mediated the homeostatic crosstalk among GM-liver-brain axis in response to different LD cycles. These research findings highlighted that GM could regulate immune and metabolic disorders induced by circadian dysregulation. Further, the data provided potential targets for developing probiotics for individuals with circadian disruption such as shift workers.

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