A study once again clarifies the importance of the “gut-brain axis”: researchers have used mice as a model to provide new information on how an imbalance of bacteria in the digestive system is linked to Alzheimer’s disease. Their research results indicate that optimizing the intestinal flora through better nutrition or food supplements could inhibit the development of dementia.
The importance of intestinal flora for human health is increasingly becoming the focus of science. Recent research has shown that the composition of bacterial populations in the digestive tract is not only linked to the immune system and purely physical illnesses, but also to psychological or neurodegenerative illnesses – including Alzheimer’s. In this dementia disease associated with aging and other risk factors, so-called beta-amyloid plaques are formed, which impair the function of nerve cells and cause them to die.
Tracking down the gut-brain axis
Studies of the intestinal flora of Alzheimer’s patients have already shown that their bacterial communities differ from those of healthy people: the diversity is reduced and some types of microbes are over- or under-represented. In addition, animal experiments have already provided evidence of the importance of the gut-brain axis in the development of Alzheimer’s. However, the mechanisms behind these links have so far largely remained unclear.
The current study was based on preliminary investigations by several co-authors: They were able to show that in neurons a transcription factor called C / EBPβ triggers the production of the enzyme asparagine endopeptidase (AEP), which triggers the formation of deposits and thus the progress of Alzheimer’s disease. Disease is involved. Chun Chen’s team has now investigated the question of whether the activity of the C / EBPβ / AEP signaling pathway is also linked to the composition of the intestinal flora.
As part of their study, the researchers used special mouse breeding lines that were developed for Alzheimer’s research. At an advanced age of around twelve months, they develop an Alzheimer’s disease, which also causes the typical deposits in the brain. The scientists first investigated the extent to which the intestinal flora of “Alzheimer’s mice” differs from that of “normal” mice.
Notes on the mechanism of the relationship
By genetically characterizing the types of bacteria in the animals’ faeces, they were able to show that in mice up to six months old, the composition of the bacterial communities still differs little. But when Alzheimer’s mice develop the first symptoms at an advanced age, there are also changes in the intestinal flora – a so-called dysbiosis: the proportion of bacteria that are considered to be rather negative increases, the results show. Using analyzes, the researchers were then able to show that the imbalance in the intestinal flora of the Alzheimer’s mice is actually linked to increased activity of the C / EBP / AEP signaling pathway.
Next, the scientists investigated to what extent this process can be influenced by the transmission of intestinal bacteria. As they explain, microbial transfer between mice can occur naturally if the animals are kept together. The scientists socialized young Alzheimer’s mice either with aged “normal” conspecifics or with seniors from their own breeding line who had a dysbiotic intestinal flora. It turned out that when they were housed together with older Alzheimer’s mice, the young developed Alzheimer’s disease more quickly than their siblings who were housed with the healthy wild-type mice. Once again, the researchers were able to show that this was accompanied by activation of the C / EBP / AEP signaling pathway.
Influencing seems possible
The fact that the C / EBP / AEP system is related to bacterial colonization also underpinned antibiotic treatments in Alzheimer’s mice. The associated reset of the intestinal microbial populations suppressed the signaling pathway associated with Alzheimer’s symptoms, the scientists report. The same was achieved by a drug that blocks C / EBPβ / AEP activity, further trials have shown. “Our results thus support the hypothesis that intestinal dysbiosis activates the C / EBP / AEP signal transmission, which plays a role in Alzheimer’s pathologies,” sum up the scientists.
As Chen and his colleagues emphasize, however, further studies are now necessary to investigate the extent to which the findings from the mouse model can be transferred to humans. However, the results at least raise hope that an optimized diet or special nutritional supplements could favor the establishment of an intestinal flora that counteracts the development of Alzheimer’s disease or restricts the progression.