Ask any astronaut about life in orbit and, sooner or later, the conversation turns to practicalities. There is the floating toothpaste and the sleeping bags strapped to walls. Less glamorously, there is a gut that doesn't always keep to schedule.
Constipation is a well-known complaint among space travellers, but the reason has never been clear. Researchers at the University of Copenhagen, working with NASA, now think they have found an important clue. They found it in the blood rather than in the gut.
Reading the gut through the blood
The team's findings are published in Nature Communications. They analysed 488 blood plasma samples from 52 astronauts, 41 men and 11 women. The samples were taken before, during and after missions of two to nine months aboard the International Space Station between 2006 and 2018, and came from three earlier NASA studies.
The researchers did not hunt for particular substances. They used an "untargeted" approach instead, measuring hundreds of small molecules called metabolites at once to see which ones changed in space. Around 40 compounds did.
The clearest signal came from a group of molecules that includes p-cresol sulfate, phenylacetylglutamine and 4-ethylphenol sulfate. Gut bacteria make these when they break down protein in the large intestine, and the liver then processes them before they circulate in the blood. Their levels rose during flight.
It is worth being precise here. The study did not sample the astronauts' gut bacteria directly. The blood metabolites act as a chemical fingerprint of what the bacteria are doing.
"We see changes in astronauts' blood samples that indicate that the gut bacteria begin to ferment protein to a greater extent than usual within weeks after the astronauts arrive in space, and this change continues until they are back on Earth," said joint first author Giorgia La Barbera, associate professor at the university's Department of Nutrition, Exercise and Sports.
According to the paper, the changes appeared shortly after launch. They did not grow stronger the longer crews stayed in orbit, and they faded within a few days of landing.
When the fibre runs out
Protein fermentation is normal and happens on Earth too. Gut bacteria prefer fibre. When the fibre is used up, typically because food lingers longer in the intestine, they turn to protein instead.
The researchers suspect this is what happens in weightlessness. "The lack of gravity in space probably causes food to move more slowly through the intestine, and this fits with the fact that we are seeing signs of increased protein fermentation. This may also help explain constipation in astronauts," said co-author Henrik Roager.
That remains a hypothesis. The study did not measure how quickly food moved through the astronauts' guts, and it did not record their bowel symptoms.
The other joint first author, Jan Stanstrup, said the result was strikingly consistent given that the samples came "from a total of 52 different astronauts, on different missions and across many years". Three of the same metabolites were also flagged in NASA's earlier Twins Study.
Why it matters for Mars
The byproducts of protein fermentation matter for health. "We know that products of protein fermentation are often associated with negative health consequences, such as kidney damage, potential effects on mood or reduced ability to focus, among others," said senior author Lars Ove Dragsted. The study itself did not measure those outcomes in astronauts.
Missions to the Moon and Mars will last far longer than a stay on the space station, and La Barbera said "countermeasures may be needed". Roager suggested more dietary fibre, prebiotics, or treatments that help keep the gut moving. The paper specifically proposes more slow-fermented carbohydrates on board the station, an idea that has not yet been tested.
Lessons for patients on Earth
The researchers also see a possible parallel closer to home. "You can use this knowledge to help bedridden patients. They also experience constipation and likely also have increased protein fermentation that may aggravate health conditions," Dragsted said.
That link is a suggestion rather than a finding, because no bedridden patients were studied. A separate critical review also urges caution. Published on 20 August in Frontiers in Physiology by gastroenterologists at the Aerospace Center Hospital in Beijing, it says direct measurements of human gut motility in space remain sparse. It also notes that bed-rest studies used to mimic weightlessness have produced contradictory results, with some reporting faster transit rather than slower.
Still, the Copenhagen study offers something rare: a clear, repeatable signal from a very unusual group of people. For crews bound for Mars, part of the answer may turn out to be on the menu.
