How the Gut-Brain-Sleep Axis May Affect Melatonin and Cortisol

Sleep, the gut, and stress are closely linked. Poor sleep can shift the gut, gut inflammation can affect how well you sleep, and stress pulls on both at once. These connections are real, and they are an active area of microbiome research. As a microbiome scientist, though, I think it helps to be clear about how strong the evidence is for each link, because a lot of what gets said about this online runs ahead of what the studies actually show.

This article walks through what the gut-brain-sleep axis is, what your microbes plausibly do to melatonin, cortisol, and deep sleep, and what the research does and does not support, so you can make practical decisions without overpromising yourself a fix.

Quick Answer: Can Your Gut Microbiome Affect Your Sleep?

Possibly, though the science is still early. The gut and brain communicate in both directions, and the microbiome appears to take part in that conversation through pathways like tryptophan metabolism, short-chain fatty acids, the immune system, and the vagus nerve. Human studies have linked a more diverse microbiome to better sleep, but most of the direct cause-and-effect evidence comes from animal work, and much of it measures deep, non-REM sleep rather than the whole night. So supporting your gut is a reasonable part of good sleep habits, alongside morning light, a consistent schedule, and stress management, not a proven treatment for insomnia. If you have ongoing sleep problems, it is worth seeing a clinician, since some sleep disorders need specific care.

If you haven’t yet read the foundational blog, start here:
Circadian Rhythm & Gut Microbiome: Sleep and Energy Guide

What the Research Actually Shows

Akkermansia is often studied for its role in helping support the gut lining, supporting metabolic health, and may also support weight balance within a healthier microbiome ecosystem.

What the Gut-Brain-Sleep Axis Is

The gut and brain stay in near-constant contact, and the microbiome sits in the middle of that exchange. The main channels researchers point to are:

• The vagus nerve, a direct communication line between the gut and the brain.

• Neurotransmitter-related signaling. Gut microbes can influence molecules such as serotonin, GABA, and dopamine, or the precursors used to make them.

• Hormones. Cortisol, melatonin, and appetite hormones like GLP-1, ghrelin, and leptin all respond to gut and metabolic signals.

• Immune signaling. Inflammation can affect both sleep and the stress response.

• Short-chain fatty acids, the compounds gut bacteria make from fiber, which have been studied for effects on the gut barrier, metabolism, and sleep.

This map of communication routes is well supported (Cryan et al., 2019). What is less settled is exactly how much each route shapes a given night's sleep in a healthy person, which is where careful reading matters.

Serotonin, Tryptophan, and Melatonin: What the Gut Actually Does

About 90 percent of the body's serotonin is made in the gut, which is true and often repeated. It is worth being precise about what it means. That gut serotonin acts locally, in the digestive tract, and does not cross the blood-brain barrier, so it does not travel up and become the serotonin or melatonin your brain uses for sleep. Brain serotonin, and the melatonin your pineal gland makes from it, are produced separately inside the central nervous system.

So the honest version of the microbiome-to-melatonin story is indirect. Gut microbes help shape how tryptophan, the shared building block for serotonin and melatonin, is used and routed through the body (O'Mahony et al., 2015; Cryan et al., 2019). In mice, gut bacteria have also been shown to nudge the host's own melatonin production through the metabolites they release (Liu et al., 2024). That is a plausible and interesting link, but it is early and largely from animal work, not a proven pipeline from a probiotic to a better night's sleep.

Cortisol, Your Body Clock, and the Gut

Cortisol is not only a stress hormone. It is also a circadian one, and its daily curve is part of how your body wakes and winds down (So et al., 2009). In a typical rhythm, cortisol is higher in the morning, supporting wakefulness, and lower at night, which makes room for melatonin to rise.

Short-Chain Fatty Acids and Deep Sleep

Short-chain fatty acids, especially butyrate, are among the more interesting gut compounds for sleep. In a mouse study, oral butyrate increased deep, non-REM sleep, the restorative stage, without acting as a stimulant (Szentirmai et al., 2019). Two things are worth being clear about: this was an animal study, and the effect was on non-REM sleep specifically, not REM. Claims that short-chain fatty acids reorganize REM or run brainstem dream circuits go beyond what that work showed.

Butyrate is produced by fiber-fermenting bacteria such as Faecalibacterium prausnitzii, Roseburia species, and Clostridium butyricum. The practical takeaway that holds up is a food-first one: feeding those bacteria with fiber and a varied plant diet is a sensible way to support short-chain fatty acid production, whether or not it measurably changes your sleep.

Melatonin and Melatonin-Free Approaches

Melatonin supplements are widely used and, for many adults, are generally considered reasonable for short-term situations such as easing jet lag or shifting a sleep schedule. Because melatonin is a hormone, the data on long-term daily use are more limited, so it makes sense to be thoughtful about extended use and to check with a clinician, especially for children, during pregnancy, or alongside other medications.

Melatonin-free approaches take a different angle. Instead of adding the sleep hormone directly, they aim to support the body's own circadian rhythm through habits like consistent light exposure and meal timing, and, in some formulas, through calming ingredients rather than hormones. Neither approach is a cure for insomnia, and responses vary from person to person.

How to Support the Gut-Brain-Sleep Axis

None of the steps below is a guaranteed fix, but each is low-risk, reasonably supported for sleep or gut health, and worth building into a routine.

• Get morning light. Daylight early in the day helps anchor your circadian clock.

• Dim screens and lights at night. Lower evening light helps protect your natural melatonin rise.

• Keep a consistent schedule and try to eat earlier. Regular timing supports both sleep and the daily rhythm of your gut microbes.

• Eat a variety of plants and fiber. This feeds the bacteria that make short-chain fatty acids. Polyphenol-rich foods like berries, cocoa, pomegranate, and green tea, plus prebiotic fibers like inulin and resistant starch, are good additions.

• Manage stress. Because stress, cortisol, and sleep are linked, practices that lower stress can help the whole system settle.

A few foods often mentioned for sleep, such as kiwifruit and tart cherries, have small human studies behind them, and fermented foods support the microbiome more broadly. Treat these as helpful habits rather than remedies.

Where a Supplement Fits

Habits come first. Light, schedule, stress, and a fiber-rich diet do more for sleep and the gut than any capsule. If you want to add a supplement as a complement, here is how the two Next-Microbiome options fit, framed honestly.

Sleepy-Biome is a melatonin-free sleep formula. It combines probiotic strains with calming botanicals and ingredients such as L-theanine and GABA, and it is designed to support relaxation and the body's own rhythm rather than to override it with the sleep hormone. Treat it as a complement to good sleep habits, not a treatment for insomnia.

Akkermansia Chewable is built around Akkermansia muciniphila, a mucus-associated species studied for its links to the gut barrier and metabolic health (Cani and de Vos, 2017). It is aimed at gut-barrier support rather than sleep specifically, so it fits here as a broader microbiome option.

Treat either as one part of a routine, and check with a clinician before starting a supplement if you are pregnant, nursing, immunocompromised, managing a condition, or taking medication.

Common Questions About Sleep and the Gut Microbiome

1. Can the gut microbiome affect sleep?

It appears to play a role. The gut and brain communicate both ways, and a more diverse microbiome has been linked to better sleep in people, though most direct cause-and-effect evidence is still from animal studies (Matenchuk et al., 2020).

2. What disrupts the gut-brain-sleep axis?

Common factors include chronic stress, gut inflammation, an imbalanced microbiome, late-night eating, bright light at night, and irregular sleep timing. Most of these affect the circadian rhythm, the gut, or both.

3. Is it safe to take melatonin long term?

Short-term melatonin use is generally considered reasonable for many adults, but long-term daily data are more limited, and because it is a hormone it is worth being thoughtful about extended use. Check with a clinician before long-term use, and especially for children, during pregnancy, or alongside other medications.

4. Which probiotics have been studied for sleep?

Some short-chain-fatty-acid-producing strains, such as Clostridium butyricum, have early signals in mostly animal research for sleep-related pathways. Human evidence is still limited, so no specific strain can be called a proven sleep aid yet.

5. How does gut inflammation affect deep sleep?

Inflammation can influence stress signaling, vagus nerve tone, and sleep quality, and poor sleep and inflammation can reinforce each other. The relationship runs in both directions rather than one way.

6. Can cortisol problems cause insomnia?

A disrupted cortisol rhythm, such as cortisol staying elevated in the evening, is associated with trouble falling asleep and lighter sleep. If you suspect a persistent issue, a clinician can help identify the cause rather than leaving you to guess.

7. Does poor sleep affect the gut microbiome?

It can. In one human study, several nights of restricted sleep reduced microbial diversity, although it did not measurably change gut barrier permeability (Karl et al., 2023). Short-term effects appear real but modest.

8. Which foods support better sleep and a healthy gut?

A varied, fiber-rich diet with plenty of plants feeds the bacteria that produce short-chain fatty acids. Foods sometimes linked to sleep in small studies include kiwifruit and tart cherries, and fermented foods support the microbiome more broadly. Think of these as supportive habits, not remedies.

Related Reading

• Circadian Rhythm and Gut Microbiome: Sleep and Energy Guide, the foundational piece on daily rhythm and the microbiome.
  

• Akkermansia Microbiome Guide, on the keystone gut-barrier species.

• The Oral Microbiome: The Missing Half of Gut Health, for the mouth-to-gut connection.

• Prebiotics vs Probiotics, to see how each supports the microbiome.

Scientific References:

1. Cryan JF, O'Riordan KJ, Cowan CSM, et al.
   The microbiota-gut-brain axis
   Physiol Rev 2019;99(4):1877-2013
   doi:10.1152/physrev.00018.2018 (Review)

2. O'Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF.
   Serotonin, tryptophan metabolism and the brain-gut-microbiome axis
   Behav Brain Res 2015;277:32-48
   doi:10.1016/j.bbr.2014.07.027 (Review)

3. Liu B, et al.
   Gut microbiota regulates host melatonin production through epithelial cell MyD88. Gut Microbes 2024;16(1):2313769
   doi:10.1080/19490976.2024.2313769 (Animal study)

4. So AY, Bernal TU, Pillsbury ML, Yamamoto KR, Feldman BJ.
   Glucocorticoid regulation of the circadian clock modulates glucose homeostasis 
   PNAS 2009;106(41):17582-17587 
   doi:10.1073/pnas.0909733106 (Mechanistic study of glucocorticoids and clock genes; it does not show microbes control cortisol)

5. Szentirmai E, Millican NS, Massie AR, Kapas L.
   Butyrate, a metabolite of intestinal bacteria, enhances sleep
   Sci Rep 2019;9(1):7035
   doi:10.1038/s41598-019-43502-1 (Animal study, non-REM sleep)

6. Karl JP, Whitney CC, Wilson MA, et al.
   Severe, short-term sleep restriction reduces gut microbiota community richness but does not alter intestinal permeability in healthy young men
   Sci Rep 2023;13:213 
   doi:10.1038/s41598-023-27463-0 (Human study)

7. Matenchuk BA, Mandhane PJ, Kozyrskyj AL.
   Sleep, circadian rhythm, and gut microbiota
   Sleep Med Rev 2020;53:101340
   doi:10.1016/j.smrv.2020.101340 (Human review)

8. Cani PD, de Vos WM.
   Next-generation beneficial microbes: the case of Akkermansia muciniphila.
   Front Microbiol 2017;8:1765
   doi:10.3389/fmicb.2017.01765 (Review)

Written by Ali Rıza Akın

Microbiome Scientist, Author & Founder of Next-Microbiome

Ali Rıza Akın is a microbiome scientist with nearly 30 years of experience in translational biotechnology, systems biology, and applied microbiome research, spanning discovery, preclinical development, and clinical-stage translation.

His work focuses on how microbial ecosystems interact with human physiology, including:

• Gut barrier function and intestinal permeability

• Mucus-associated microbiota (Akkermansia-related systems)

• Oral–gut microbiome axis

• Short-chain fatty acids (SCFAs) and metabolic signaling

• Circadian rhythm–microbiome interactions

• Clinical Research Contributions

He has contributed to multiple clinical-stage microbiome programs, supporting bacterial strain discovery, optimization, and formulation design across different therapeutic areas, including:

Active Ulcerative Colitis (Inflammatory Bowel Disease)

Hyperoxaluria (Oxalate Metabolism Disorder)

Microbiome-driven gut health and inflammatory conditions

These studies were part of broader clinical development programs evaluating microbiome-based approaches. His contributions focused on the early-stage scientific and translational pipeline, including strain discovery, functional optimization, and multi-strain formulation design.

Scientific Contributions:

Ali Rıza Akın is the discoverer of Christensenella californii, a bacterial species associated with microbiome diversity and metabolic health.

He is a contributing author to scientific publications and Bacterial Therapy of Cancer (Springer), and the author of Bakterin Kadar Yaşa: İçimizdeki Evren: Mikrobiyotamız.

Approach:

His work emphasizes evidence-based microbiome science, long-term safety, and a systems-based understanding of how microbes influence human health.

Review and Sources

This article is written and reviewed by a microbiome scientist and is based on the peer-reviewed studies listed in the References. It is reviewed periodically against current research.

Medical Disclaimer

This content is for educational and informational purposes only and is not medical advice. It is not intended to diagnose, treat, cure, or prevent any disease, including insomnia or other sleep disorders. If you have ongoing sleep problems, or symptoms such as loud snoring, gasping during sleep, or heavy daytime sleepiness, see a qualified healthcare professional, since these can point to a treatable condition. Dietary supplements are not reviewed or approved by the US Food and Drug Administration for safety before they are sold, and products containing Akkermansia muciniphila are intended for adults; the international regulatory clearances that exist cover adults and adolescents aged 12 and over. Talk to a clinician before starting any new supplement, including melatonin, especially if you are pregnant, nursing, immunocompromised, managing a health condition, or taking medication.

Last reviewed: July 2026