In a recent study published in the journal, molecular metabolismResearchers studied the effect of environmental and genetic disorders on circadian rhythms on peripheral circadian synchronization and oscillations of the gastrointestinal microbiome.
Stady: Original Article Biological genetic and environmental disturbances lead to weight gain through changes in the gut microbiome. Image Credit: Alpha Tauri 3D Graphics / Shutterstock
The central biological clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is known to regulate sleep and other rhythmic activities and modulate humoral and neural signals that synchronize peripheral biological clocks to adapt to changes in the environment. In addition, different organs have peripheral clocks, which are essentially clock genes that regulate physiological activity through tissue-specific genes that are controlled by the clock.
Disturbances in the central clock due to intrinsic and extrinsic temporal mismatch, such as jet lag or night shift work, result in asynchrony between different peripheral clocks, which is thought to alter metabolism in general. Studies have found associations between disturbances in the circadian rhythm and metabolic disorders such as diabetes and obesity. Furthermore, associations between circadian disruptions and changes in the composition and rhythms of the gut microbiome have also been observed. However, the role of central and peripheral circadian disruption and subsequent imbalances in the gut microbiome in metabolic disorders remains unclear.
In this study, researchers determined clock gene expression in different gastrointestinal tissues using quantitative real-time polymerase chain reaction (qRT-PCR) in different mouse models.
Genetic circadian disruption has been explored using mice with brain-specific SCN and muscle Arnt-1-like protein (with money 1( saa )with money 1SCNfl / –), while wild-type mice that underwent stimulated transformation (SSW) were used to test for daily environmental disturbances. All mice were on a schedule of 12 h of light and 12 h of dark. The SSW group rats then underwent altered light, dark, and jet lag schedules, while the with money 1SCNfl / – Mice were transferred to continuous darkness for various periods.
Activity profiles were calculated based on running wheel activity. A food intake monitor was used for feeding profiles, and stool samples were analyzed to assess energy uptake efficiency. Stool samples were also analyzed for bile acid composition and short-chain fatty acid composition.
Nuclear magnetic resonance (NMR) measurements identified fat, free fluid, and lean body mass composition. Tissue and blood samples from sacrificed mice were then used to measure intestinal permeability, triglycerides, and plasma glucose levels. High-throughput sequencing of 16S ribosomal ribosomal acid (rRNA) and enzymatic gene profiling were performed to determine microbiome composition and function.
Gene expression of a group of genes including with 1 money, daily period 2 (Bear 2)nuclear receptors, family 1, group D, member 1NR1D1 or Rev-erb), and the D site of the albumin promoter binding protein (dB) using qRT-PCR. Germ-free microbiome transfers from circadian-ruptured mice to wild-type mice were also performed to understand the impact of an altered microbiome on physiological function.
The results reported desynchronization of peripheral biological clocks in GI tissue and microbiome arrhythmias from genetic and environmental circadian disruption models. Disparities were observed especially in the microbial taxa involved in lipid and sugar metabolism and short chain fatty acid fermentation.
In the with money 1SCNfl / – In mice, arrhythmias in the microbiome were associated with obesity, disruption of glucose homeostasis, and weight gain. Similarly, SSW mice showed increases in body weight and plasma glucose levels associated with disruption of microbiome oscillation patterns.
In addition to, with money 1SCNfl / – Mice showed intermittent rhythms of eating when switched to continuous darkness, while the eating patterns of SSW rats persisted in rhythm but their phases were altered. The authors believe that the loss of microbiome rhythms in both sets of circadian disruption could be due to a change in feeding behaviour, a loss of synchronization between peripheral GI clocks, or both.
The with money 1SCNfl / – The mice showed a more severe loss of the microbiome rhythm, with microbial diversity changes at the family and asylum levels. However, a few taxa remarkably maintained the rhythm, which can be attributed to variable but functional peripheral clocks or other intrinsic factors in bacteria.
Transfer experiments indicated perturbation of gastrointestinal balance and increased body weight in wild-type mice colonized with a dysregulated microbiome of clock-inactivated mice. Wild-type mice also showed altered gene expression of CCGs and peripheral clock genes.
Overall, the results indicated that genetic or environmental disruption of central biological clocks and subsequent peripheral gastrointestinal clock asynchrony are closely related to intestinal microbiome arrhythmias and functional changes that lead to metabolic abnormalities.
The study highlights the role of lifestyles that disrupt circadian rhythms in the development of metabolic disorders such as obesity and diabetes and emphasizes the importance of microbiome rhythms in metabolic health.
- Altaha, B., Heddes, M., Pilorz, V., Niu, Y., Gorbunova, E., Gigl, M., Kleigrewe, K., Oster, H., Haller, D., & Kiessling, S. (2022). Genetic and environmental circadian disruption leads to weight gain through changes in the gut microbiome. molecular metabolism101628. https://doi.org/10.1016/j.molmet.2022.101628And the https://www.sciencedirect.com/science/article/pii/S2212877822001971