In the 1960s, at Harvard Medical School, the physiologist John Pappenheimer and his colleagues kept goats awake. The idea behind it was old and slightly unfashionable: that a tired body brews something — a substance that builds up the longer we stay awake and, past some threshold, pulls us under. So the team drew cerebrospinal fluid from sleep-deprived goats and infused a tenth of a millilitre of it into the brains of well-rested rats. The rats slept more and moved less for at least six hours [1][2]. Whatever was in the fluid, there was more of it the longer the goats had been kept up, rising steadily across the first 48 hours [2]. They called it Factor S.

It took until 1982 to learn what Factor S was made of. By then the hunt had moved from goats to human urine, and when the purified molecule was finally taken apart it turned out to be a small glycopeptide whose ingredients included muramic acid and diaminopimelic acid. A few trillionths of a mole per kilogram of body weight, infused into a rabbit's brain, raised deep slow-wave sleep by about half [3]. Muramic acid and diaminopimelic acid are the signature building blocks of peptidoglycan — the mesh that bacterial cell walls are made of.

The team was careful about what that meant. Later work filled it in: when immune cells digest bacteria they release exactly this kind of fragment, and the body reads it as a signal to sleep [4]. One of the first sleep substances ever purified from a tired animal carried the fingerprints of bacteria.

This article is about that hint, and how far it has been followed since. We tend to think of sleep as something the brain does, alone, in the dark. The research keeps pointing lower down.

The other nervous system

The gut has a nervous system of its own. Anatomists call it the enteric nervous system: a continuous web of 400–600 million neurons embedded in the gut wall — roughly as many as in the spinal cord [5]. It can run digestion without instruction from the head, which is why the neurobiologist Michael Gershon's nickname for it, the second brain, has stuck.

What matters for sleep is the chemistry it shares with the first one. More than 90% of the body's serotonin is made in the gut, not the brain, and in mice much of that production depends on the residents: spore-forming gut bacteria prompt the cells of the colon lining to make it, germ-free mice have markedly less, and giving them those bacteria restores it [6]. Serotonin is the molecule the body turns into melatonin, the hormone of darkness — and the gut is full of that, too. By one widely repeated estimate, the digestive tract contains at least 400 times more melatonin than the pineal gland that is supposed to be its headquarters [7].

Gut serotonin and melatonin do local work — moving food along, keeping time — and do not simply float up to the brain. The line upward is the vagus nerve, a cable running from the gut to the brainstem. In one much-cited experiment, mice fed a Lactobacillus strain became calmer, with smaller stress-hormone surges and altered receptors for GABA, the brain's main quietening signal — and none of it happened in mice whose vagus nerve had been cut [8]. The message was travelling by wire.

So: a second nervous system, sharing the sleep chemistry of the first, connected to it by a direct line, and — this is the part Pappenheimer could not have known — permanently inhabited.

What the night shift eats

The inhabitants are the trillions of microbes of the large intestine, and like any workforce they are shaped by what they are fed. They are not fed what we are fed. Sugar, starch, fat and protein are absorbed high up, in the small intestine; what reaches the colon is what we could not digest ourselves. That means fibre — and it means colour.

Fibre first. Gut bacteria ferment it into short-chain fatty acids, of which butyrate is the best studied. In 2019 researchers gave mice a butyrate-releasing compound by mouth and watched their deep, non-REM sleep rise by almost 50% for four hours. When butyrate was delivered straight into the portal vein of rats — the vessel that carries everything absorbed from the gut to the liver — non-REM sleep rose by 70% for six hours. Injected under the skin instead, it had no significant effect [9]. The signal, in other words, is read on the way out of the gut. A bacterial product, made from the remains of dinner, telling the body to sleep more deeply: Factor S again, half a century on.

People are harder to study than mice, but the human data lean the same way. In a sleep-laboratory study of 26 adults, days with more fibre were followed by nights with less of the lightest stage of sleep and more slow-wave sleep; more saturated fat predicted less slow-wave sleep, and more sugar predicted more awakenings [10].

Then the colour. The pigments and tannins that make berries dark and tart — polyphenols — are large, awkward molecules. Only an estimated 5–10% of what we swallow is absorbed in the small intestine; the remaining 90–95% travels on to the colon, where bacteria take it apart [11]. For a long time that looked like waste. It now looks like delivery.

The best-studied northern example is aronia, Aronia melanocarpa. In a 12-week double-blind trial in 66 healthy men, a daily aronia extract supplying 116 mg of polyphenols — the equivalent of 75 g of berries — increased Anaerostipes, a butyrate-producing genus, by 10.6%, while whole aronia fruit powder increased Bacteroides by 193%; blood-vessel function improved in both groups [12]. A second 12-week trial, in 102 middle-aged men and women, found that aronia polyphenols increased the gene richness of the gut microbiome and the abundance of two butyrate-producing species [13]. Those trials were designed around arteries rather than sleep, but they show the first half of the chain in people: dark berries change who is on the night shift. And in a cross-sectional study of 1,936 Italian adults, those whose diets supplied the most of certain polyphenols were less likely to report poor sleep [14].

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A clock in the dark

The microbes do not only eat. They keep time. Sample a gut every few hours and the population is never the same twice: species rise and fall across the day, and so does the work they are doing — a rhythm found in both mice and people, and set largely by when the host eats. Shift the light cycle of mice as if flying them back and forth across time zones, and the rhythm falls apart [15].

The same paper contains one of the more memorable small experiments in the field. Two people gave stool samples before, during and after a flight from the United States to Israel. Germ-free mice that received the mid-jet-lag samples had higher blood sugar after a glucose challenge and put on more body fat than mice given samples from the same travellers once they had recovered [15]. Two travellers make an anecdote rather than a trial, but a striking one: something about a disrupted night had been written into the microbes, and could be handed on.

Take the microbes away altogether and sleep itself loses its shape. Mice given broad-spectrum antibiotics for four weeks, until their gut bacteria were all but gone, slept less in their rest phase and more in their active phase, and slipped between sleep stages more often; the contents of their gut were depleted of serotonin and vitamin B6 [16]. They still slept. They just no longer slept like animals that knew what time it was.

The gut, then, is a clock as well as a kitchen — one that is set by mealtimes and that, in turn, helps tell the rest of the body where in the 24 hours it is.

What a short night does downstream

The line runs both ways. If the gut shapes the night, the night shapes the gut — and quickly.

In a Swedish crossover experiment, 9 healthy young men slept roughly four hours a night for two nights and, on another occasion, roughly eight. After just two short nights the balance of their gut bacteria had shifted — the ratio of Firmicutes to Bacteroidetes rose — and their insulin sensitivity after a meal was about a fifth lower [17]. (We followed what that does to the next afternoon in The 3 p.m. Collapse.)

Mice show where a longer run of bad nights leads. Four weeks of fragmented sleep — woken again and again, never fully deprived — changed their gut communities, appeared to make the gut wall leakier, and brought on inflammation in fat tissue and a slide in insulin sensitivity. Transplanting the microbes of the sleep-disturbed mice into germ-free mice reproduced the findings. And after two weeks of normal sleep, the microbial changes had reversed [18].

That last detail is the hopeful one, and it fits what is seen in people living ordinary lives. When 26 young men wore sleep trackers for 30 days, those with the most diverse gut microbiomes slept most efficiently and spent the least time awake during the night [19]. A correlation cannot say which came first. The loop suggests it hardly matters: sleep better and the gut community recovers; feed the gut community and sleep has more to work with. It is a circle, and a circle can be entered anywhere.

The housekeeper that only works on an empty stomach

There is one more night worker to meet, and it is mechanical rather than microbial. When the stomach and small intestine have been empty for a while, a wave of strong contractions begins in the stomach and travels the length of the small bowel, sweeping leftovers ahead of it. Physiologists call it the migrating motor complex. In humans the sweep recurs every 90–120 minutes for as long as the fast lasts, and it stops the moment we eat [20][21]. When it fails, bacteria overgrow in the small intestine, where they do not belong [20].

Night is the longest fast most of us manage, which makes it the housekeeper's main shift — unless dinner arrives late. And a late meal does more than delay the sweep. In a crossover trial, 20 healthy volunteers ate the same dinner at either 18:00 or 22:00 and went to bed at 23:00. After the late dinner their blood sugar peaked about 18% higher, they burned about 10 percentage points less of the meal's fat overnight, and their cortisol ran higher [22]. (Cortisol at midnight is a subject of its own; we wrote about it in The Tiger That Never Leaves.)

The stomach has an opinion as well. In a Japanese study of 147 people with reflux disease and 294 without, going to bed within three hours of dinner carried more than seven times the odds of reflux compared with waiting four hours or more [23]. Lying down on a full stomach is, quite literally, an uphill job.

How fast the stomach clears is not fixed, either. In a double-blind trial in 24 healthy volunteers, 1,200 mg of ginger taken an hour before a meal halved the time the stomach needed to half-empty — 13.1 minutes against 26.7 with placebo [24]. That was dried ginger in capsules rather than juice, but it is the old kitchen logic of ginger with the evening meal, measured.

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What to do this week

None of this asks for a new life. It asks for a slightly different evening, held steady for seven days.

1. Close the kitchen three hours before bed. If lights-out is 23:00, dinner ends by 20:00. Of everything here, this is the change with the most human evidence behind it.
2. Put fibre on the dinner plate. Rye bread, barley, oats, lentils, beans, cabbage. Juice is not where fibre lives — the whole plant is.
3. Add something dark every day. Polyphenols are what a berry juice does carry. Aronia is tart and tannic, so we start with 100 ml of Moon Berry with lunch or dinner rather than a full glass on an empty stomach.
4. Eat at the same times, weekends included. The microbial clock is set by meals, and it prefers a regular schedule.
5. Give the night a real fast. Twelve hours between the end of dinner and breakfast leaves the housekeeper time for several full sweeps.
6. Have the ginger with dinner, not after it. A glass of Golden Blend at the table, or a spoonful of Root Boost in warm water just before it.

Sleep and the gut, in short

Sleep and the gut regulate each other. Gut bacteria turn fibre into signals such as butyrate, which deepens sleep in animal studies, and they keep a daily rhythm set by mealtimes. Short nights disturb them within days. Fibre, dark berries, regular mealtimes and a dinner that ends three hours before bed support both.

One caution: if you take anticoagulants, live with reflux or a diagnosed gut or sleep condition, or are pregnant, check with your doctor or pharmacist before adding ginger or tart juices to your evenings.

Back to the goats

Pappenheimer went looking for the substance of tiredness in the brain, and what his team held in their hands fifteen years later was built like a fragment of a bacterium. It took another generation for the rest to come into view: the second nervous system, the microbes that keep time, the butyrate read at the liver's door, the housekeeper waiting for the kitchen to close.

Sleep is not something the head does while the body waits. It is a shift change. The day crew clocks off; another, far older workforce clocks on. Our part is small and unglamorous — feed them well, finish dinner early, turn off the light — and then let the night shift get on with it. If sleep itself is the struggle, the wider picture is in When Sleep Won’t Come.

Frequently asked questions

Does gut health really affect sleep?

The evidence says the two are linked in both directions. In mice, removing gut bacteria with antibiotics blurs the normal day–night sleep pattern [16], and butyrate, a product of gut bacteria, increases deep sleep [9]. In people, a more diverse gut microbiome goes with more efficient sleep [19], and two short nights are enough to shift the balance of gut bacteria [17].

What should we eat in the evening to sleep better?

A dinner built around fibre — whole grains, pulses, vegetables — and light on saturated fat and sugar. In a sleep-laboratory study of 26 adults, more fibre predicted more slow-wave sleep, while more sugar predicted more awakenings [10]. Add polyphenol-rich dark berries during the day, and finish eating about three hours before bed.

Do probiotics help with sleep?

Modestly, by people's own account. A 2020 meta-analysis of 14 studies found that probiotics improved self-rated sleep by 0.78 points on the Pittsburgh Sleep Quality Index, while objective sleep measurements did not change [25]. We would start by feeding the bacteria already there: fibre and polyphenols, every day.

How long before bed should we stop eating?

Three hours at least; four is better. Going to bed within three hours of dinner was linked to more than seven times the odds of reflux compared with waiting four hours or more [23], and a 22:00 dinner raised the overnight blood-sugar peak by about 18% compared with the same meal at 18:00 [22].

References

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This article is for education and is not medical advice. If you have a diagnosed condition, are pregnant or take regular medication, talk to your doctor or pharmacist before changing your diet.