12/30/2025
How your gut microbes help set your body’s internal clock
This figure shows how the gut and brain communicate through neural, immune, endocrine, and metabolic pathways that are influenced by the body’s internal clock. The microbiome, hormones, and light–dark cycles interact to coordinate sleep, metabolism, stress responses, and inflammation across the gut–brain axis.
1️⃣ Central and peripheral clocks
The brain’s master clock in the suprachiasmatic nucleus (SCN) aligns daily rhythms with environmental light through the retinohypothalamic tract. Peripheral clocks, including those in the gut, follow signals from the SCN but also respond to feeding times and microbial metabolites.
🟢 Example: Disrupted light exposure or irregular eating can desynchronize the gut’s circadian rhythm, altering microbial composition and metabolic regulation.
2️⃣ Endocrine pathway
The hypothalamic–pituitary–adrenal (HPA) axis links stress and circadian timing through hormone signaling. Gut microbes influence HPA activation by releasing metabolites and cytokines that affect cortisol release.
🟢 Example: Certain bacteria such as Actinobacteria and Streptococcus modulate HPA activity, contributing to changes in inflammation and stress hormone output.
3️⃣ Immune pathway
Microbial components interact with immune cells in the intestinal mucosa, producing cytokines that reach the brain through circulation or vagal signaling.
🟢 Example: Lipopolysaccharides (LPS) and pattern-associated molecules from gut bacteria trigger IL-1β and TNF-α release, linking dysbiosis to neuroinflammation and altered sleep quality.
4️⃣ Metabolic pathway
Microbes regulate lipid and glucose metabolism through production of short-chain fatty acids and other metabolites that follow circadian patterns.
🟢 Example: Species like Lactococcus chungangensis and Ruminococcus bromii affect lipid metabolism, aligning energy use with the body’s day–night cycle.
5️⃣ Neural pathway
The vagus nerve transmits microbial and immune signals bidirectionally between gut and brain. Neurotransmitters and microbial by-products influence mood, stress, and cognition through this circuit.
🟢 Example: Cytokines and bacterial metabolites act on vagal afferents, shaping neural activity in regions that regulate alertness and emotional balance.
Together, these pathways demonstrate how the microbiome acts as a peripheral clock that integrates environmental cues, diet, and stress signals with the brain’s circadian system. When alignment breaks down, it contributes to insomnia, metabolic dysfunction, and inflammation across multiple organ systems.
Source:
doi:10.3389/fpsyt.2025.1697200
