Life’s Timekeepers: Brain and Gut Microbiome in Conversation

Article by Iris Cheang

Circadian rhythm is the biological 24-h master clock, keeping everything in the body on schedule by orchestrating sleep-wake cycle, digestion and hormone secretion, hence regulation of gut barrier function and appetite.

But the modern lifestyle has thrown a few wrenches into the gears. Ultra-processed foods, artificial lights, irregular meals and night life can all disrupt this delicate clockwork. 

An often-overlooked player in this story is the gut microbiome. Turns out that bacteria may also have their own internal clocks (according to emerging research - but more is needed!), acting like small cogs that keep the body’s bigger clock ticking on time.

Despite our brain and gut being physically far apart, a bidirectional communication between them has been well established, involving immune cells acting as postmen or the vagus nerve as a high-speed railway, shuttling small molecules as signals and information influencing brain function, sleep quality and stress responses.

What makes you an ‘Early Bird’ or ‘Night Owl’?

Individuals have different internal clocks that guide them when to be awake, active and sleep, known as circadian phenotypes. About 40% of the population falls into either the ‘early bird’ or ‘night owl’ chronotypes, while the rest have a flexible sleeping and activity schedules. ‘Early birds’ tend to wake up and sleep early, they are more energetic and efficient in the morning. On the other hand, ‘night owls’ works better in the second half of the day,

Surprisingly, your gut microbiome might be partly behind this. Having more of a certain type of bacteria may be why someone finds it harder to get out of bed in the early morning for school, or for someone to need more sleep than others.

Decoding: Host circadian rhythm and the gut microbiome crosstalk

Regular mealtimes are an important factor in keeping the clock on time. The composition, location and functioning of gut microbiome shift between day and night, dependent on host feeding cycle. In obese mice, disrupted feeding cycles led to loss of rhythmic gut bacterial changes, and time-restricted eating only partly restore their microbiome, suggesting that irregular eating could impact circadian function over time through microbiome manipulation.

Certain probiotic strains produce metabolites — such as GABA and short-chain fatty acids — that may influence the host’s circadian system and support sleep regulation. A lack in GABA-producing bacteria like Lactobacillus and Bifidobacterium has been shown to positive correlate with higher rates of sleep disorder.

1.Short chain fatty acids (SCFAs)

Short-chain fatty acids (SCFAs) are produced when gut bacteria ferment complex carbohydrates—mainly dietary fibers—in the large intestine. While many dietary fibers act as prebiotics by promoting beneficial gut bacteria, not all fibers have prebiotic properties, and some prebiotics include other compounds beyond fibers. Foods rich in complex carbohydrates and fibre include whole grains, vegetables, fruits, nuts, seeds, and legumes.

The ‘Big Three’ of SCFAs, acetate, propionate and butyrate, can reach the brain, maintaining brain homeostasis and integrity of the blood brain barrier (BBB), hence brain health. They also support gut barrier integrity to prevent ‘leaky’ gut, reducing inflammation, promote mucus, serotonin and GABA production, which may aid sleep by calming arousal systems.

Research shows that insomnia patients have lower gut microbial diversity and richness than healthy people, including fewer butyrate-producing bacteria. In mice, butyrate increased deep sleep by 70%, suggesting its influence in sleep quality and potential links to insomnia.

2.Tryptophan and Serotonin

Tryptophan, an essential amino acid and precursor to serotonin, is mostly absorbed in the small intestine, though some reaches the colon and used by gut bacteria. Serotonin, one of the happy hormones, involved in mood and circadian rhythm regulation, is also the precursor to melatonin, implicating its role in sleep regulation.

Higher abundance of beneficial microbes supports the conversion of tryptophan to serotonin, while harmful bacteria like enteropathogenic E. coli may suppress serotonin production and favor disease development.

Although tryptophan is mainly found in protein-rich foods, diet may not be the most effective way to boost brain serotonin. As the least abundant amino acid in protein, tryptophan competes with other amino acids for transport to cross the BBB, making it less likely to reach the brain. Unfortunately, serotonin itself cannot cross the BBB. However, α-Lactalbumin, a milk protein with a relatively higher tryptophan content has been associated with improved mood and cognition, suggesting higher brain serotonin levels. Despite its limited effect on brain levels, it is still important to produce serotonin for peripheral circadian rhythm regulation in organs like the liver. 

Interestingly, regular aerobic exercise has been shown to increase brain serotonin by increasing blood tryptophan levels and enhancing its transport to the brain—an effect that may persist post-exercise. 

3. Melatonin

Melatonin, the sleep-promoting hormone, is synthesised in response to darkness and helps synchronise the biological clock with light-dark cycle. It modulates sleep-wake cycles and regulates the release of neurotransmitters like serotonin, GABA and glutamate (GABA precursor), hence affecting different brain regions involve in sleep regulation. 

The microbiome modulates cells that produce melatonin from serotonin, hence changes in microbial composition and function may affect sleep and circadian rhythm. Increase in some bacteria have been linked to higher insomnia risk. In return, melatonin may impact the biological clocks in certain intestinal bacteria hence their overall function.

Melatonin supplements over the counter could be used for short-term insomnia and jet-lags, while specialist prescription is required for long-term use.

4.Gamma-Aminobutyric Acid (GABA)

GABA is the main inhibitory neurotransmitter to calm the brain, playing a key role in stress relief and sleep regulation by suppressing neural activity. GABA supplementation for four weeks was associated with improved sleep efficiency and reduced time to fall asleep in insomnia patients.

GABA also acts through the vagus nerve, a key gut-brain axis pathway. In mice, administration of GABA-producing bacteria, Lactobacillus, reduced depressive markers and anxiety-like behavior, which is not observed in mice with their vagus nerve removed.

While GABA supplementation is only medically prescribed, it is also found in foods like bean sprouts, rice, vegetables and potatoes, or produced by GABA-producing bacteria like Lactobacillus, Bifidobacterium and Bacteroides which are present in a probiotic supplement.

How can we do our internal timekeeping naturally?

Diet

  • Regular mealtimes: Consistent eating schedules help synchronise peripheral clocks in organs such as the liver and gut, which support the overall circadian system. Irregular eating patterns can disrupt these rhythms and negatively affect metabolism and sleep quality.

  • Balanced diet including complex carbohydrates: Complex carbs (found in whole grains, vegetables, legumes) influence circadian rhythms by modulating the gut microbiome and supporting stable blood glucose levels. Stable blood sugar helps avoid nighttime awakenings related to hypoglycemia. Additionally, complex carbs can increase tryptophan availability to the brain, which may support melatonin production and promote sleep onset.

Exercise

  • Regular moderate to vigorous exercise (150 minutes per week): Physical activity is a strong zeitgeber (time cue) that helps regulate the central circadian clock in the suprachiasmatic nucleus (SCN). Studies show that exercise can advance or delay circadian phase depending on timing, improving sleep onset and quality.

  • Consistency: Exercising regularly, ideally at similar times each day, reinforces circadian entrainment.

  • Outdoor activity and sunlight exposure: Natural light is the primary environmental cue for circadian rhythms. Outdoor exercise increases exposure to morning or afternoon light, which helps regulate melatonin secretion and improves sleep timing.

Sleep schedule

  • Digital detox 1-2 hours before bedtime: Exposure to blue light from screens suppresses melatonin production, delaying sleep onset and disrupting circadian rhythm. Minimising screen time before bed can improve sleep latency and quality.

  • Reducing artificial light in the evening supports the natural rise of melatonin, preparing the body for sleep.

Meditation/Yoga

  • Potential improvements in sleep: Mind-body practices such as meditation and yoga may reduce stress and lower sympathetic nervous system activity, which can facilitate sleep onset and improve sleep quality.

  • While some studies show promising results, further high-quality research is needed to confirm consistent benefits and to clarify mechanisms.

References

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Iris is a final-year nutrition student at University College London (UCL) with a huge passion in nutrition and the gut microbiome, especially the gut-brain axis. She is very excited to discover the interplay between nutrition and neuroscience/psychiatry through evidence-based research, actively investigating dietary interventions in brain and mental health management. She is also very keen to bridge the gap between scientific research and real world application through blog writing and potentially clinical involvement.

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