Fascinating new research sheds more light on how the trillions of microbes in our gut may affect our brain health. found that mice engineered to develop Alzheimer’s disease had significantly reduced signs of neurodegeneration when kept without gut bacteria. This suggests that the microbiome may play an important role in the development of neurodegenerative diseases.
A landmark study published in 2017 reported a bizarre relationship between gut bacteria and the accumulation of toxic proteins associated with Alzheimer’s disease in mice. In this study, we found that mice engineered to develop amyloid protein plaques had less brain amyloid aggregation when reared so as not to carry gut bacteria.
This new study follows on from research investigating the relationship between the microbiome and tau accumulation, another major pathogenic manifestation of Alzheimer’s disease. In this study, we also examined what neurodegenerative differences are indeed detected between mice with and without gut microbiota.
The first test looked at mice that were kept in a completely sterile environment from birth. These animals, called germ-free mice, grow without developing any gut microbiota. When engineered to express large amounts of tau protein, these germ-free mice were found to have significantly less neurodegeneration at 40 weeks of age compared to animals raised under normal conditions. .
The next test looked at normally bred mice that were given high doses of antibiotics to eliminate their microbiome at 2 weeks of age. This is where things started to get a little complicated when gender differences between animals became apparent.
Administration of antibiotics to 2-week-old male mice resulted in less brain damage than expected by 40 weeks of age. Female mice, however, did not show a similar protective effect, and antibiotics did not reduce the level of brain damage at 40 weeks.
“We already know from studies of brain tumors, normal brain development, and related topics that immune cells in male and female brains respond very differently to stimulation,” said the study’s lead author. said David Holtzman, “Thus, it is not too surprising that we found gender differences in responses when manipulating the microbiome, but it is difficult to say what exactly this means for men and women living with Alzheimer’s disease and related disorders. Is difficult.”
Following clues from previous studies, researchers also examined the effects of several specific gut bacterial metabolites on neurodegeneration. SCFA).
When these metabolites were added to the drinking water of germ-free mice, the animals subsequently developed significant levels of neurodegeneration. The next enigma, however, was how these SCFAs were causing neuroinflammation when key brain immune cells lacked receptors to respond to these specific metabolites.
Here, the researchers hypothesize that there may be a chain reaction in which peripheral circulating immune cells are activated by SCFAs and subsequently stimulate immune activity in the brain. And this mechanism could be that gut bacteria play a role in triggering neurodegeneration.
Of course, these findings are still many years away from providing concrete insight into how to therapeutically manipulate the microbiome to treat neurodegenerative diseases. It is not realistic to simply lower the level of Because these metabolites are important for other healthy physiological functions. In fact, a recent hypertension study found that artificial fiber supplements designed to increase SCFA production in the gut can effectively lower blood pressure in humans.
Holzmann is still convinced there may be ways to manipulate the microbiome to slow or even prevent neurodegeneration. , there is still much to learn.
“What I would like to know is that if we take a mouse that is genetically destined to develop a neurodegenerative disease and manipulate the microbiome just before the animal begins to show signs of damage, we can slow or prevent neurodegeneration. Or rather,” Holtzman speculated. “It’s the same as starting treatment in late middle-aged people who are still cognitively normal but are on the verge of developing the disorder. These types of neurodegeneration can be treated before neurodegeneration is first apparent.” If we can start a treatment in a genetically sensitized adult animal model and show it works, it could be something that can be tested in humans.
A new study was published in chemistry.
Source: Washington University School of Medicine in St. Louis
