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

Abstract

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.

New Awareness of the Interplay Between the Gut Microbiota and Circadian Rhythms

“…Furthermore, the study demonstrated that GM could influence immune and metabolic disorders caused by circadian dysregulation. These insights offer potential targets for developing probiotics specifically tailored for individuals with circadian disruption, such as shift workers ( Zhen et al 2023 ).…”

“…In the study conducted by Zhen et al (2023), the researchers explored the impact of different LD cycles (LD light hour/dark hour) on the interconnected rhythms of GM, hypothalamic, and hepatic clock genes, as well as immunity and metabolism. They employed multi-omics approaches to investigate four irregular LD cycles (LD0/24, LD24/0, LD8/16, LD16/8) along with a normal LD cycle (LD12/12).…”

Lactobacillus johnsonii Improves Intestinal Barrier Function and Reduces Post-Weaning Diarrhea in Piglets: Involvement of the Endocannabinoid System

“…However, previous studies and our recent studies have shown that the mechanism of probiotic intervention on host physiology is extremely complex, and the gut microbiome enhances intestinal health by playing a direct or indirect regulatory role [10,12,[19][20][21]. These regulatory mechanisms involve complex systems to control various aspects of intestinal homeostasis (intestinal barrier function and immune regulation, etc.…”

Dietary Lactobacillus delbrueckii Affects Ileal Bacterial Composition and Circadian Rhythms in Pigs

“…These microbial diurnal rhythms synchronize with feeding rhythms to anticipate host gut function and can be affected by dietary nutrients [14,16]. Circadian transcription factor NFIL3, histone deacetylase, gut-microbe-generated short-chain fatty acids, and rhythmic hormone melatonin were recruited rhythmically, and produced synchronized diurnal oscillations in histone acetylation, metabolic gene expression, and nutrient uptake [17][18][19][20]. Choi et al systemically reviewed microbial oscillators that are generally promoted by dietary nutrients, such as plant-based, low-fat (lean) diets, and most were abolished by low-fiber, high-sugar, high-fat (Western) diets [16].…”