Scientists demonstrate how microbiome and feeding patterns impact circadian rhythms in the gut

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Research published in journals PNAS We have shown that the gut microbiota stabilizes the synchronization of circadian rhythms in the gut and brain.

study: The microbiome stabilizes circadian rhythms in the gutImage Credit: Vovantarakan/Shutterstock

Background

The gut microbiota is the community of microorganisms present in the human/animal gastrointestinal tract. It plays an important role in regulating various physiological processes, including metabolism, immune response, and neuronal function.

The gut microbiota is stable in the long term, but diet can induce temporary changes in its composition. Similarly, the gut microbiota exhibits rhythmic changes in composition and localization throughout the day-night cycle.

In the current study, scientists investigated the interplay between gut microbiota, time-restricted eating patterns, and circadian rhythms. Drosophila (Common Drosophila) intestine.

Circadian regulation of gut microbiota

Drosophila with unlimited food supply (freely) was used to study whether the composition and diversity of the gut microbiota changed during the course of the day-night cycle. This finding revealed a lack of circadian cycling of the gut microbiota in wild-type flies and flies lacking circadian clock genes.

We also revealed that wild-type flies exposed to rhythmic feeding patterns at specific time points had no circadian variation in gut microbiota composition and diversity. However, in flies lacking circadian clock genes, the circadian clock was found to interfere with the effects of time-restricted feeding patterns on the gut microbiota.

Effects of time-restricted feeding on the circadian transcriptome

Analysis of circadian gene expression was performed in studies using flies with and without the microbiome. The findings revealed that both time-restricted feeding and microbiome loss have profound effects on the gut circadian transcriptome.

Host genes encoding metabolic proteins showed increased cycles in flies without a microbiome (germ-free). In contrast, genes associated with development and differentiation showed decreased circulation.

Loss of periodic expression of genes related to oxidative phosphorylation and energy metabolism was observed in flies reared under time-restricted feeding conditions (food provided at specific time points).

Induction of circular gene expression was observed under time-limited feeding conditions. Changes in transcription factor activity were found to be responsible for global changes in circulating expression. Similar to time-limited feeding, microbiome loss was found to affect cyclical gene expression.

Effects of time-restricted feeding on cycle gene expression appeared to be mediated by increases in histones AcetylationThe findings revealed that restricted feeding conditions induced a strong rhythm of histone acetylation and that many genes affected by these conditions responded to histone acetylation.

The gut microbiota of Drosophila is nearly stable in daily cycles.  (A and B) Microbiome diversity shows no diurnal oscillations in the gut of wild-type Iso31 or clock mutant per01 flies under ad libitum (AF) or TF conditions.  I used JTK_cycle to evaluate rhythm.  (C and D) Certain bacterial species circulate under TF conditions, but only per01.  The JTK_cycle value is displayed.The gut microbiota of Drosophila is nearly stable in daily cycles. (A and B) Microbiome diversity shows no diurnal variation in wild-type Iso31 or clock mutants01 Throw guts under ad-lib (AF) or TF conditions. I used JTK_cycle to evaluate rhythm. (C and D) Certain bacterial species cycle under TF conditions, whereas01. JTK_cycle value is displayed.

Functional impact of time-limited feeding and the microbiome

Flies maintained on time-restricted feeding were exposed to different stressors (starvation, bacterial injection, heat shock) to determine the effects of restricted feeding on health and fitness.

Findings revealed that restricting feeding reduced fly survival in stressful conditions. In other words, restricted feeding increases the susceptibility of flies to stressors despite beneficial metabolic effects.

Microbiome functional impacts were determined using a circadian phase shift paradigm (a modified course of the day-night cycle). Experiments used flies with and without the microbiome.

Findings revealed that the presence of the microbiome increased circadian clock gene circulation in the fly brain. Overall, we observed that sterile flies reset more rapidly due to changes in the day/night cycle compared to flies with a microbiome.

In other words, the gut microbiota modulates the response of the gut clock to changes in the day-night cycle and promotes synchronization of gut-brain circadian rhythms.

Significance of research

This study reveals that the fly gut microbiota is not circulating. However, it regulates the circadian rhythm of gene expression in the gut and prevents sharp fluctuations in response to different environmental conditions.

As the journal’s scientist noted, “These findings have important implications for the general state of the modern world.”

sauce:

Zhang Y. 2023. The microbiome stabilizes circadian rhythms in the gut. PNAS, https://www.pnas.org/doi/10.1073/pnas.2217532120

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