Scientists have found a new clue linking the gut to the brain.
A chemical made by certain intestinal bacteria may increase the risk of Alzheimer’s disease and may also be connected with faster loss of memory and thinking abilities.
The chemical is called imidazole propionate, or ImP. Researchers at the University of Wisconsin–Madison found that people with higher levels of ImP in their blood were more likely to show biological signs associated with dementia.
The research was published in Nature Communications. It was led by University of Wisconsin–Madison professors Barbara Bendlin and Federico Rey together with their collaborators.
The discovery builds on work the researchers began almost a decade ago. Their earlier studies found that the collection of bacteria living in the intestines of people with Alzheimer’s disease differs from that of people without the disease.
These bacteria and other tiny organisms make up what is commonly called the gut microbiome. They help digest food and produce many chemicals that can enter the bloodstream and travel throughout the body.
Scientists have become increasingly interested in the possibility that some of these substances may influence the brain. This connection is often described as the gut-brain relationship because signals can travel between the digestive system, immune system, nervous system and brain.
In the new study, the researchers focused on ImP, which is produced when certain gut bacteria process histidine. Histidine is an amino acid that the human body needs and is found naturally in many protein-rich foods.
Not everyone produces the same amount of ImP. Some people carry ImP-producing bacteria but have relatively low levels, while others appear to produce much larger amounts.
Rey noted that a bacterium does not need to be common in the gut to have a meaningful effect. Even microbes present in small numbers can produce chemicals that spread through the body and influence human cells.
ImP has previously attracted attention outside dementia research. Higher levels have been linked in earlier studies with conditions including type 2 diabetes and coronary artery disease.
The Wisconsin researchers wanted to know whether the compound could also affect the brain. In experiments with mice, they found that ImP reaching the brain increased the buildup of two abnormal proteins closely associated with Alzheimer’s disease.
These proteins are beta-amyloid and tau. In Alzheimer’s disease, beta-amyloid can collect into plaques between nerve cells, while abnormal tau can form tangled structures inside cells.
Both changes are major features of Alzheimer’s disease and are associated with damage to neurons. As increasing numbers of brain cells become unhealthy or die, memory, reasoning and other mental abilities can gradually decline.
The researchers then examined blood samples and other health information from almost 1,200 people participating in the Wisconsin Registry for Alzheimer’s Prevention and studies at the Wisconsin Alzheimer’s Disease Research Center.
People with high ImP levels were much more likely to have biological signs of abnormal brain proteins and nerve cell problems. Because many participants had taken repeated thinking and memory tests over time, researchers could also compare ImP levels with changes in mental performance.
Those with the highest ImP levels experienced faster cognitive decline. This strengthened the evidence that the gut-produced chemical may be connected with processes involved in Alzheimer’s disease rather than simply appearing alongside them.
The team also identified a genetic variation found in about 43% of participants that was linked with much higher ImP levels. The researchers believe this variation may affect how efficiently the kidneys remove ImP from the blood.
Interestingly, the same genetic region had previously been connected with Alzheimer’s risk in large genetic studies. The new findings may offer a possible biological explanation for that older observation.
The research raises the possibility of treating high ImP levels in the future. Bendlin compared the idea with cholesterol treatment, where doctors can use medicines such as statins to lower a harmful blood marker and reduce disease risk.
However, the study does not show that lowering ImP will prevent Alzheimer’s disease. Researchers will need to prove that ImP directly contributes to disease in humans and then test whether blocking its production or increasing its removal actually protects the brain.
Simply avoiding foods rich in histidine is also unlikely to be a sensible solution. Histidine is an essential nutrient found in many healthy foods, so the goal would be to target the bacterial process or the ImP molecule rather than remove an important nutrient from the diet.
The study is compelling because it combines animal experiments, blood measurements, brain-related markers, long-term cognitive testing and genetic evidence. Still, Alzheimer’s disease has many causes and risk factors, and ImP is unlikely to explain every case.
If future research confirms a direct role, the gut-produced molecule could become a useful blood marker or drug target. That would turn an unusual chemical made by intestinal bacteria into a potentially important new piece of the Alzheimer’s prevention puzzle.
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Source: University of Wisconsin–Madison.
