Constipation has been an unglamorous constant of human spaceflight, and nobody could say exactly why. An analysis of 488 blood samples drawn from 52 astronauts before, during, and after long stays aboard the International Space Station now offers a biochemical answer, and it points squarely at the colon.
Within weeks of launch, the bacteria living in astronauts' large intestines appear to change what they eat. Instead of fermenting fiber, they break down more protein. The chemical fingerprint of that shift showed up reliably in the bloodstream, faded within days of landing, and matched a pattern researchers on Earth already associate with food moving too slowly through the gut.
The work, from the University of Copenhagen in collaboration with NASA, was published in Nature Communications at the end of June and reached its final version of record in mid-August, when the university released the findings publicly.
Forty Compounds Changed, and Nearly All Roads Led to the Colon
The samples came from 11 female and 41 male astronauts, average age 48, who flew missions lasting two to nine months between 2006 and 2018. Blood had been banked through three NASA protocols run out of the Nutritional Biochemistry Laboratory at Johnson Space Center: the Nutritional Status Assessment study, the Biochemical Profile study, and the ProK dietary trial.
Using untargeted liquid chromatography and high-resolution mass spectrometry, the team found roughly 40 circulating compounds that changed with spaceflight. The most consistent signal came from molecules produced when gut bacteria ferment amino acids. Levels of p-cresol sulfate, phenylacetylglutamine and 4-ethylphenol sulfate all rose during flight, alongside 3-indoxyl sulfate and phenol sulfate. Tyrosine, the amino acid those bacteria feed on to make several of them, went down.
A statistical model built on 81 chemical features could identify which samples had been drawn in orbit with an error rate of 2.6 percent. Notably, the metabolites did not drift further as missions went on. What the data captured was a change tied to launch and to landing, not a slow accumulation.
Why a Slower Gut Changes What Bacteria Eat
Gut microbes prefer fiber. When intestinal contents move at a normal pace, there is enough carbohydrate to go around. When transit slows, the fiber runs out first, and the bacteria switch to the next available fuel, which is protein.
Henrik Roager, an associate professor at Copenhagen's Department of Nutrition, Exercise and Sports and a co-author, said in a statement from the university that the absence of gravity probably slows food through the intestine, which fits the fermentation signal the team observed. "This may also help explain constipation in astronauts," he said.
Diet explained only part of the picture. About 27.5 percent of the changing chemical features tracked with food intake, mostly reduced caffeine, along with lower levels of a fish intake marker among the women and minor shifts in fats. That left most of the signal unexplained by what the crews were eating.
The same group has previously shown that these proteolytic markers rise when intestinal contents pass more slowly in people on the ground, which is the basis for reading the astronaut data the way they do. Protein fermentation also generates ammonia and hydrogen sulfide, and several of the metabolites that rose in orbit have been linked elsewhere to problems beyond the digestive tract. Phenylacetylglutamine was recently implicated in cellular senescence. Indoxyl sulfate and p-cresol sulfate are associated with worse outcomes in people whose kidney function is already compromised. Senior author Lars Ove Dragsted noted that products of protein fermentation are often linked to kidney damage and to possible effects on mood and concentration.
What the Study Could Not Measure
The central limitation is worth stating plainly: nobody measured how fast anything actually moved through these astronauts' intestines. Transit time is an inference drawn from blood chemistry, not a direct observation, and the authors present prolonged transit as a possible explanation rather than a demonstrated one, wording their own abstract keeps deliberately hedged.
The study was observational. It shows an association between spaceflight and a shift in microbial metabolism. It does not prove that slower transit caused the shift, and it did not assess whether any crew member's kidneys, mood or concentration were affected. Those concerns come from separate research on the same compounds in other populations.
The design also has real strengths. Repeated sampling of the same individuals before, during, and after flight makes each astronaut serve as their own comparison, and the pattern held across three studies, multiple crews, and more than a decade of missions. The original sample collections were funded by NASA's Human Research Program, the analysis by the Novo Nordisk Foundation, and the authors reported no competing interests. The raw data sit with NASA's Life Sciences Data Archive.
From the Space Station to the Hospital Bed
The practical suggestion coming out of the paper is not a drug. It is fiber. The researchers propose increasing the availability of slowly fermented carbohydrates aboard the station so microbes have something other than protein to work on, with prebiotics or measures that speed transit as alternatives.
Whether that works has not been tested in orbit. For missions to the Moon or Mars, where resupply is limited, and crews are aloft far longer than nine months, it is a question with a deadline attached.
There is a terrestrial version of the same problem. Dragsted suggested the findings may apply to bedridden patients, who also experience constipation and may carry the same elevated fermentation products. That has not been confirmed. Plasma uric acid also fell about 10 percent during flight and rebounded after landing, a change the authors attribute mainly to fluid shifts rather than to the gut.
Anyone with persistent constipation or unexplained digestive changes should raise it with a clinician rather than drawing conclusions from astronauts.
Key Questions Answered
What did the researchers actually find?
In 488 blood samples from 52 astronauts, markers of bacterial protein fermentation rose during spaceflight and returned toward baseline within days of landing.
Does this prove microgravity slows digestion?
No. Transit time was never measured directly. Slower transit is the explanation the authors consider most likely, because the same chemical pattern appears in people with slow gut transit on Earth.
Could the change simply be the space food?
Diet accounted for roughly 27.5 percent of the affected compounds, mainly less caffeine and less fish among the women. That leaves most of the signal unexplained by diet alone.
Were the astronauts harmed?
The study did not assess kidney function, mood, or cognition. Concerns about these metabolites come from research in other populations, not from measurements in this crew.
What is being proposed as a countermeasure?
More slowly fermented carbohydrates, meaning fiber, plus prebiotics or measures that speed transit. None of this has been tested in orbit.
Does any of this apply on Earth?
Possibly to bedridden patients, who share the constipation and, the authors suspect, the fermentation shift. That has not been confirmed.
