Sleep and the Gut: What the Microbiome Has to Do With Your Sleep
The gut produces the largest part of the body's own serotonin and has its own melatonin pool. Via the gut-brain axis, tryptophan metabolism and the microbiome-serotonin-melatonin axis, the gut may help shape sleep. What of this is solidly proven, what sounds plausible but remains speculation, and what you can actually do in everyday life.
Hardly any topic is as hyped and at the same time as overstretched as the gut. On the internet you read that the microbiome is the secret conductor of sleep, that you only have to feed the right bacteria and then sleep comes by itself. That is too simple. What is true: the gut produces the majority of the body's own serotonin, it has its own melatonin pool, and the microbiome intervenes in tryptophan metabolism (Yano 2015 in Cell, Konturek 2007). What is also true: microbiome diversity and sleep measures are correlated in early studies (Smith 2019 in PLOS ONE). What is false is the claim that this implies a simple lever. The serotonin produced in the gut does not reach the brain. Probiotics, according to meta-analyses, work only to a small degree (Yu 2024). The gut-sleep connection is real, but it is a web, not a switch. In this spoke I separate what the evidence supports from what goes beyond it.
This spoke is the microbiome lens of the sleep cluster. We go through the gut-brain axis (how gut and brain communicate at all), tryptophan metabolism and the serotonin-melatonin axis, the role of gut bacteria in serotonin production, the microbiome's own day-night rhythm, what the observational studies on microbiome and sleep show, what probiotics achieve according to meta-analyses, the PNI lenses and three concrete levers for everyday life. And we clearly mark where the evidence ends.
The Gut-Brain Axis: How Gut and Brain Talk
The gut and the brain are not separate worlds. They constantly exchange signals, in both directions. This connection is called the gut-brain axis, and ever since the microbiome was recognized as a player, people speak of the microbiome-gut-brain axis. The major review by Cryan and colleagues 2019 in Physiological Reviews mapped this axis comprehensively.
Communication runs through several channels in parallel. First, the vagus nerve, a direct nerve connection between the gut and the brainstem. Second, the immune system, via messengers such as cytokines. Third, metabolism, above all via the tryptophan pathway and via short-chain fatty acids that gut bacteria produce from dietary fiber. Fourth, hormonal signals. Sleep is reachable through several of these channels, which is why the idea that the gut may help shape sleep has real biological substance.
The Microbiome-Gut-Brain Axis, Comprehensively Mapped
Review John Cryan and the team at APC Microbiome Ireland published in 2019 in Physiological Reviews one of the most cited reviews on the microbiome-gut-brain axis. They describe that microbiome and brain communicate via the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, with the involvement of microbial metabolites such as short-chain fatty acids. Factors such as mode of birth, antibiotics, diet, stress and age shape the microbiome composition. The work classifies the axis as relevant for a range of neuropsychiatric and age-related conditions, but emphasizes that many findings come from animal models and that translation to humans is still in progress.
Cryan JF, O'Riordan KJ, Cowan CSM, et al. Physiol Rev. 2019;99(4):1877-2013. doi:10.1152/physrev.00018.2018 · PMID: 31460832
For sleep, the metabolism channel is particularly interesting, because here lies the biochemical bridge between gut bacteria and the sleep hormone melatonin. We look at this next. Anyone wanting to go deeper into the vagus pathway will find it covered in detail in the gut cluster under Gut-Brain Axis and Vagus Stimulation.
Tryptophan Metabolism and the Serotonin-Melatonin Axis
At the center is a protein building block from food: tryptophan. Several important signaling substances arise from it, and which pathway is taken depends in part on the microbiome.
The pathway decisive for sleep is the serotonin-melatonin axis. Tryptophan is converted via the enzyme tryptophan hydroxylase first to 5-hydroxytryptophan and then to serotonin. Serotonin can subsequently be converted via two further enzymes to melatonin, the hormone that helps set the sleep-wake rhythm in motion. This pathway classically runs in the pineal gland in the brain, but the same enzyme machinery is also found in the enteroendocrine cells of the gut (Konturek 2007 in Journal of Physiology and Pharmacology).
The microbiome intervenes at several points. It competes for tryptophan, it can divert a portion via the so-called kynurenine pathway, and it can influence serotonin production via its metabolic products. The review by Grifka-Walk 2021 in Frontiers in Immunology explicitly describes tryptophan as a signaling molecule that acts back and forth between host and microbiome.
A common misconception: that more serotonin in the gut means better mood and better sleep. That is not the case. The serotonin produced in the gut does not cross the blood-brain barrier. The serotonin pool in the gut and the one in the brain are anatomically separate and serve different functions (Jones 2020). The gut pool mainly controls intestinal movement, secretion and metabolism. If the gut helps shape sleep, then not by sending serotonin into the brain, but via the indirect routes of the gut-brain axis: immune signals, the vagus nerve, metabolites and circadian timing.
Do Gut Bacteria Really Produce Serotonin?
Yes, and this is one of the best-documented findings in the whole field. About 90 to 95 percent of the body's own serotonin is produced in the gut, by the enterochromaffin cells. Two animal-model studies have shown that gut bacteria actively help control this production.
Spore-Forming Gut Bacteria Regulate Serotonin Production
In vivo Jessica Yano and the team around Elaine Hsiao at Caltech published in 2015 in Cell a much-cited work. In germ-free mice, serotonin production in the colon was markedly reduced. When the animals were colonized with certain spore-forming bacteria from the mouse and human microbiome, serotonin production in the enterochromaffin cells rose again. The effect was mediated by certain bacterial metabolic products. The study shows that the microbiome is an important regulator of the gut's own serotonin, with consequences for intestinal movement and platelet function.
Yano JM, Yu K, Donaldson GP, et al. Cell. 2015;161(2):264-276. doi:10.1016/j.cell.2015.02.047 · PMID: 25860609
Butyrate and Co. Boost the Key Serotonin Enzyme
In vivo Christopher Reigstad and colleagues at the Mayo Clinic showed in 2014 in FASEB Journal that short-chain fatty acids are the key. In mice with a human microbiome, the production of the enzyme tryptophan hydroxylase 1, which limits serotonin synthesis, was markedly increased. In a cell model of human enterochromaffin cells, short-chain fatty acids directly stimulated the activity of this enzyme. This names a concrete mechanism: dietary fiber is fermented by bacteria into short-chain fatty acids, and these crank up the gut's own serotonin production.
Reigstad CS, Salmonson CE, Rainey JF, et al. FASEB J. 2014;29(4):1395-1403. doi:10.1096/fj.14-259598 · PMID: 25550456
That this mechanism also has a downside is shown by a more recent work: Zhai 2022 in Cell Host Microbe found that the bacterium Ruminococcus gnavus, via certain tryptophan breakdown products, can stimulate serotonin production so strongly that in an animal model it triggers diarrhea-predominant irritable bowel symptoms. More gut-derived serotonin is therefore not automatically better. It is about balance, not maximization.
Does the Gut Have Its Own Sleep-Wake Rhythm?
Surprisingly, yes. The microbiome is not a static resident but follows a daily rhythm of its own, and this rhythm is interlinked with the host's circadian system.
The Microbiome Oscillates in a Daily Rhythm and Helps Time the Host
In vivo Christoph Thaiss and the team around Eran Elinav showed in 2016 in Cell that the composition and metabolism of the gut microbiome fluctuate rhythmically over the course of the day. Even the spatial distribution of the bacteria at the gut wall changes over the day. This microbial rhythmicity in turn helps program the host's daily rhythms, that is its gene activity in gut and liver. When the microbiome rhythm was disturbed, the host rhythms also became disordered. The work links the microbiome directly to the internal clock.
Thaiss CA, Levy M, Korem T, et al. Cell. 2016;167(6):1495-1510.e12. doi:10.1016/j.cell.2016.11.003 · PMID: 27912059
In practice this is a strong argument for regular meal times. When you eat is not only a question of calories but a zeitgeber that helps align the microbiome and, via this route, also your internal clock. Irregular eating late at night or a chronic social jet lag can disturb this order. Light biology remains the strongest zeitgeber, but meal timing is an underrated second lever.
What Does Research Show on Microbiome and Sleep in Humans?
Here the air gets thinner. The mechanisms above stem predominantly from animal models. In humans there are so far mainly observational studies, and these show associations, not causes.
Higher Microbiome Diversity, Better Sleep Measures
Human · Observation Robert Smith and colleagues published in 2019 in PLOS ONE a study that used actigraphy to collect objective sleep measures and at the same time analyzed the microbiome. Higher overall microbiome diversity was positively correlated with sleep efficiency and total sleep time, and negatively with wake time after sleep onset. Diversity was also positively correlated with the cytokine interleukin-6. Individual bacterial groups such as Lachnospiraceae, Corynebacterium and Blautia were negatively linked to certain sleep measures. The authors explicitly emphasize that these are correlations that point to possible connections but do not prove causation. The sample was also small and limited to men.
Smith RP, Easson C, Lyle SM, et al. PLoS One. 2019;14(10):e0222394. doi:10.1371/journal.pone.0222394 · PMID: 31589627
The finding is interesting, but it allows no simple conclusion. It could be that a diverse microbiome favors better sleep. It could equally be that good sleep, good nutrition and a healthy lifestyle bring about both a diverse microbiome and good sleep, without one causing the other. Observational studies cannot disentangle this.
Probiotics for Sleep: What the Meta-Analyses Say
If the microbiome influences sleep, then probiotics should be able to improve it, so the logic goes. The randomized studies give a cautious, mixed answer to this.
Probiotics and Sleep Quality, 11 Randomized Trials
Meta-Analysis Bei Yu and colleagues analyzed in 2024 in Frontiers in Neurology 11 randomized controlled trials. Probiotics and paraprobiotics significantly improved sleep quality in adults with sleep disorders and in healthy people with stress-related sleep problems, but the effect was small (standardized mean difference minus 0.34). Subgroup analyses showed that the result depended on health status, intervention duration, bacterial strain and the measurement criteria used. The authors note that additional studies are needed.
Yu B, Wang KY, Wang NR, Zhang L, Zhang JP. Front Neurol. 2024;15:1477533. doi:10.3389/fneur.2024.1477533 · PMID: 39479010
A second meta-analysis by Ito 2024 in Clinical Nutrition ESPEN included 15 randomized studies and found that probiotics significantly reduced the Pittsburgh Sleep Quality Index after 4 to 16 weeks, that is improved sleep quality. Here too there were methodological limitations and a risk of bias in some studies. In addition, the randomized study by Lee 2021 in Nutrients with 156 adults showed that a specific probiotic over 8 weeks improved sleep quality as well as depressive and anxious symptoms and lowered the inflammatory marker interleukin-6.
The signals point in a positive direction, but the effects are small and inconsistent. A probiotic can be a sensible supplementary attempt in some people, especially when gut symptoms or elevated stress exist in parallel. But it is not a reliable sleep aid and no substitute for the fundamentals. Anyone with sleep problems should first address light biology, rhythm, stress regulation and sleep hygiene before a probiotic is added as fine-tuning. Which strain, which dose and for whom exactly it helps is still scientifically open.
The PNI Lenses: Four Perspectives on Gut and Sleep
In Clinical Psychoneuroimmunology we do not look at one organ but at the connections between the systems. Four lenses help to sort the gut-sleep connection.
Neuro-Endocrine Lens
Tryptophan, serotonin and melatonin form an axis that runs in the gut as in the brain. The gut supplies building blocks and its own melatonin pool, the brain steers via the internal clock. Both depend on the same raw material, tryptophan.
Immunological Lens
Messengers such as interleukin-6 connect microbiome and sleep (Smith 2019, Lee 2021). Low-grade inflammation can disturb sleep, and disturbed sleep can fuel inflammation. A diverse microbiome and short-chain fatty acids have a dampening effect here.
Circadian Lens
Microbiome and host oscillate in a daily rhythm and time each other (Thaiss 2016). Meal times thus become a zeitgeber. Irregular, late eating can disturb this order, regular meals and overnight fasting support it.
Metabolic Lens
Dietary fiber is fermented by bacteria into short-chain fatty acids that stimulate serotonin production and support the gut barrier (Reigstad 2014). A varied, plant-forward diet is the lever with the broadest effect.
What Does Not Work: The Typical Overstatements
"My microbiome test tells me which bacteria disturb my sleep." The data do not support that. There is no validated sleep marker in stool. Commercial tests deliver a snapshot, but the translation of patterns into concrete sleep recommendations is not established. Such a test without a clear medical question creates mainly uncertainty.
"More serotonin from the gut makes you happy and sleepy." The serotonin produced in the gut does not reach the brain (Jones 2020). Tryptophan-rich foods or bacteria that raise the gut serotonin level do not automatically improve mood or sleep. More is not better here, as the irritable bowel example of Zhai 2022 shows.
"A probiotic replaces the sleeping pill." No. The meta-analyses show small effects (Yu 2024, Ito 2024). Probiotics can complement, but the sleep fundamentals and work on root causes carry the larger part.
Three Levers With the Best Rationale
Use Meal Rhythm as a Zeitgeber
Eat at regular times and keep an overnight window of about 12 hours in which you eat nothing. Because microbiome and internal clock follow a daily rhythm and time each other (Thaiss 2016), it makes sense not to have the last large meal too late in the evening. This supports the circadian order that carries good sleep.
Variety and Fiber on the Plate
A plant-forward, varied diet with many different fiber sources promotes a diverse microbiome and the production of short-chain fatty acids (Reigstad 2014). Higher diversity was associated with better sleep measures in Smith 2019. This is the broadest lever, and it has many further benefits.
The Sleep Fundamentals First
Light in the morning, darkness in the evening, a fixed rhythm and stress regulation have the strongest and best-documented effect on sleep. The gut is a supplementary player, not the lead actor. A probiotic can be a supplementary attempt but does not replace this foundation.
The Gut Is a Player, Not a Switch
The connection between sleep and the gut is real and biologically well founded. But it is a web of nervous system, immune system, metabolism and internal clock, not a single button you press. Anyone who tends gut and sleep together, with rhythm, variety and good fundamentals, works with biology instead of against it.
Safety Note
This article is for information and does not replace a medical examination. Persistent sleep problems lasting more than three to four weeks, pronounced daytime sleepiness, suspected sleep apnea, as well as new or stubborn gut symptoms such as chronic diarrhea, blood in the stool, unintended weight loss or nighttime complaints should be medically evaluated. Probiotics and dietary supplements can have side effects and interact with illnesses or medications, especially with a weakened immune system. Existing therapies should not be discontinued or changed without medical consultation.
Frequently Asked Questions
Can a disturbed gut affect sleep?
There is a plausible biological pathway and early signals from observational studies, but no proof of a simple cause-and-effect chain. Smith 2019 in PLOS ONE found in healthy men that higher overall microbiome diversity was correlated with better sleep efficiency and longer total sleep time, and negatively with wake time after sleep onset. That is a correlation, not causation. The theoretical bridge is the gut-brain axis: gut bacteria influence tryptophan metabolism, serotonin production in the gut, the immune system and, via the vagus nerve, the brain (Cryan 2019). Whether a disturbed gut worsens sleep, poor sleep worsens the gut, or both reinforce each other is not yet clarified. In practice it makes sense to consider both sides.
Does the gut really produce serotonin and melatonin?
Yes, both. About 90 to 95 percent of the body's own serotonin is produced by enterochromaffin cells in the gut, not in the brain. Yano 2015 in Cell showed in an animal model that certain spore-forming gut bacteria stimulate serotonin production. Reigstad 2014 in FASEB Journal added that short-chain fatty acids such as butyrate increase the key enzyme tryptophan hydroxylase 1. Melatonin is also produced in the gut: according to Konturek 2007, the gastrointestinal tract contains considerably more melatonin than the pineal gland, where it may act mainly locally and protect tissue. Important caveat: the serotonin produced in the gut does not cross the blood-brain barrier and is not the same as the serotonin in the brain (Jones 2020).
What is the serotonin-melatonin axis?
It is the biochemical pathway from the protein building block tryptophan via serotonin to melatonin. Tryptophan is converted via the enzyme tryptophan hydroxylase to 5-hydroxytryptophan and then to serotonin. Serotonin can be converted via two further enzymes to melatonin, the sleep hormone. This pathway runs in the pineal gland, but also in the enteroendocrine cells of the gut (Konturek 2007). The microbiome intervenes at several points: it competes for tryptophan, diverts a portion via the kynurenine pathway and can influence serotonin production via short-chain fatty acids (Grifka-Walk 2021). What is not proven: that targeted microbiome manipulation can reliably ramp up melatonin production for falling asleep.
Do probiotics help with sleep?
The evidence points to a small but measurable effect, but is not yet strong. Yu 2024 in Frontiers in Neurology analyzed 11 randomized controlled trials and found a significant but small benefit on sleep quality (standardized mean difference minus 0.34). Ito 2024 in Clinical Nutrition ESPEN included 15 studies and found a significant reduction in the Pittsburgh Sleep Quality Index after 4 to 16 weeks. Lee 2021 in Nutrients showed in an 8-week RCT with 156 adults that a specific probiotic improved sleep quality and depressive and anxious symptoms and lowered interleukin-6. The effects are small, depending on the strain, the duration and the baseline state. Probiotics may have a supportive effect in some people, but they are not a reliable sleep aid.
What is evidence-based and what is speculative regarding sleep and the gut?
Well established: the gut produces the majority of the body's own serotonin and harbors its own melatonin pool (Yano 2015, Konturek 2007). The microbiome influences tryptophan metabolism and communicates via the gut-brain axis (Cryan 2019). Microbiome and host show daily rhythmic fluctuations (Thaiss 2016). Early observational studies link microbiome diversity to sleep measures (Smith 2019). Still speculative or weak: that a particular bacterial signature causes sleep disorders, that commercial microbiome tests deliver reliable sleep recommendations, that probiotics are a dependable sleep aid, that you can deliberately steer melatonin production through diet. Many conclusions on the internet go beyond the data.
What role do short-chain fatty acids play for sleep?
Short-chain fatty acids such as butyrate, propionate and acetate are produced when gut bacteria ferment dietary fiber. Reigstad 2014 in FASEB Journal showed that these fatty acids increase serotonin production in the enterochromaffin cells by upregulating the enzyme tryptophan hydroxylase 1. Through this there is an indirect link to the serotonin-melatonin axis. Short-chain fatty acids are also anti-inflammatory and can strengthen the gut barrier. Whether a fiber-rich diet measurably improves sleep via this pathway is not directly proven in humans. What can be said: a varied, fiber-rich diet promotes a diverse microbiome, and higher diversity was associated with better sleep measures in Smith 2019.
Does the microbiome have its own day-night rhythm?
Yes. Thaiss 2016 in Cell showed in an animal model that the composition and metabolism of the gut microbiome fluctuate rhythmically over the course of the day and that even the spatial distribution of the bacteria at the gut wall changes. This microbial rhythmicity in turn helps time the host's daily rhythms. If the microbiome rhythm is disturbed, for example by irregular eating or jet lag, the host rhythms also become disordered. In practice this means: meal times and meal rhythm are not only relevant for weight but part of the circadian order that supports good sleep. That is a strong argument for regular meal times and overnight fasting, even if the direct sleep studies in humans here are still thin.
Should I do a microbiome test for sleep problems?
In the vast majority of cases no, at least not as a first step. Commercial microbiome tests deliver a descriptive snapshot, but the translation of patterns into concrete sleep therapies is not established. There is no validated sleep marker in stool. It makes more sense to first address the known causes: sleep hygiene, light biology and circadian rhythm, stress and cortisol, sleep apnea screening, and where appropriate cognitive behavioral therapy for insomnia. A stool test is indicated when relevant gut symptoms exist in parallel, for example chronic diarrhea, suspected inflammatory bowel disease or irritable bowel syndrome. Then it is about gut diagnostics in three pillars, not about a sleep test.
What can I practically do to support gut and sleep?
Three levers with the best rationale. First, regular meal times and a consistent overnight window of about 12 hours, because microbiome and host follow a daily rhythm (Thaiss 2016). Second, a varied, fiber-rich diet that promotes a diverse microbiome and short-chain fatty acids (Reigstad 2014, Smith 2019). Third, the sleep fundamentals first, that is light in the morning, darkness in the evening, a fixed rhythm and stress regulation. A probiotic can be a supplementary attempt but according to meta-analyses works only to a small degree (Yu 2024, Ito 2024). If sleep problems persist for more than three to four weeks or gut symptoms are added, this should be medically evaluated. This article does not replace a medical examination.
All Articles in the Sleep Cluster
- Pillar: Treating Sleep Disorders Holistically
- Spoke 1: Staying Asleep
- Spoke 2: Trouble Falling Asleep
- Spoke 3: Waking at 3 a.m.
- Spoke 4: Magnesium for Sleep Problems
- Spoke 5: Melatonin Effect and Dosage
- Spoke 6: Herbal Sleep Aids
- Spoke 7: Menopause and Sleep
- Spoke 8: Implementing Sleep Hygiene Correctly
- Spoke 9: CBT-I for Insomnia
- Spoke 10: Recognizing Sleep Apnea
- Spoke 13: Sleep and the Gut Microbiome (you are here)
Connections to Other Topics
The pillar article of the cluster. Where the gut-sleep connection fits into the overall strategy of light biology, rhythm, metabolism and work on root causes.
The spoke from the gut cluster that goes deeper into the nerve connection between gut and brain. Here the axis underlying this article is explained.
The sleep hormone in detail. Why the gut has its own melatonin pool and what really matters with melatonin as a supplement.
How cortisol, the internal clock and nighttime wake phases are connected and why meal rhythm plays a role as a zeitgeber.
Sources and Further Reading
- 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 · PMID: 31460832 [Review]
- Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264-276. doi:10.1016/j.cell.2015.02.047 · PMID: 25860609 [In vivo]
- Reigstad CS, Salmonson CE, Rainey JF, et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 2014;29(4):1395-1403. doi:10.1096/fj.14-259598 · PMID: 25550456 [In vivo]
- Thaiss CA, Levy M, Korem T, et al. Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations. Cell. 2016;167(6):1495-1510.e12. doi:10.1016/j.cell.2016.11.003 · PMID: 27912059 [In vivo]
- Smith RP, Easson C, Lyle SM, et al. Gut microbiome diversity is associated with sleep physiology in humans. PLoS One. 2019;14(10):e0222394. doi:10.1371/journal.pone.0222394 · PMID: 31589627 [Real-World]
- Grifka-Walk HM, Jenkins BR, Kominsky DJ. Amino Acid Trp: The Far Out Impacts of Host and Commensal Tryptophan Metabolism. Front Immunol. 2021;12:653208. doi:10.3389/fimmu.2021.653208 · PMID: 34149693 [Review]
- Jones LA, Sun EW, Martin AM, Keating DJ. The ever-changing roles of serotonin. Int J Biochem Cell Biol. 2020;125:105776. doi:10.1016/j.biocel.2020.105776 · PMID: 32479926 [Review]
- Zhai L, Huang C, Ning Z, et al. Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis. Cell Host Microbe. 2022;31(1):33-44.e5. doi:10.1016/j.chom.2022.11.006 · PMID: 36495868 [In vivo]
- Lee HJ, Hong JK, Kim JK, et al. Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2021;13(8):2660. doi:10.3390/nu13082660 · PMID: 34444820 [RCT]
- Yu B, Wang KY, Wang NR, Zhang L, Zhang JP. Effect of probiotics and paraprobiotics on patients with sleep disorders and sub-healthy sleep conditions: a meta-analysis of randomized controlled trials. Front Neurol. 2024;15:1477533. doi:10.3389/fneur.2024.1477533 · PMID: 39479010 [Meta-Analysis]
- Ito H, Tomura Y, Kitagawa Y, et al. Effects of probiotics on sleep parameters: A systematic review and meta-analysis. Clin Nutr ESPEN. 2024;63:623-630. doi:10.1016/j.clnesp.2024.07.006 · PMID: 39094854 [Meta-Analysis]
- Konturek SJ, Konturek PC, Brzozowska I, et al. Localization and biological activities of melatonin in intact and diseased gastrointestinal tract. J Physiol Pharmacol. 2007;58(3):381-405. PMID: 17928638 [Review]