The tens of trillions of microorganisms that live in our intestines and form the intestinal microbiota are not only used to digest food. They also play an important role in brain health, according to researchers at Washington University School of Medicine in St. Louis.
- People with the APOE4 genetic variant are three to four times more likely to develop Alzheimer’s disease than those with the APOE3 variant.
- The intestinal microbiota is made up of thousands of species: viruses, parasites, non-pathogenic fungi… However, the most common are bacteria.
- This microbiota is mainly located in the small intestine and the colon.
The intestines are often called the “second human brain”. This nickname was mainly given because they constitute the second nervous system of the organism. However, a new study, conducted at Washington University School of Medicine in St. Louis, confirms that the gut microbiota also plays a vital role in brain health.
Alzheimer’s: the composition of the microbiota may increase the risk of lesions
Previous work has shown that the gut microbiome of patients with Alzheimer’s disease is different from that of healthy people. The Missouri team wanted to determine more precisely the influence of these bacteria on the evolution of neurodegenerative pathology.
To do this, the researchers reorganized the microbiota of mice predisposed to developing brain damage and cognitive disorders of the Alzheimer type. They were genetically engineered to express a mutant form of the human brain tau protein that accumulates and causes neuron damage and brain atrophy at nine months of age. They also carried a variant of the human APOE gene, a risk factor for Alzheimer’s disease.
“We gave the young mice antibiotics for just one week, and we saw a permanent change in their gut microbiomes, their immune responses, and the amount of tau-related neurodegeneration they suffered with age.”explained lead author Prof. David Holtzman.
The scientist discovered that gut bacteria – in part by producing compounds such as short-chain fatty acids – affect the behavior of immune cells throughout the body, including those in the brain. They can damage brain tissue and exacerbate neurodegeneration in conditions such as Alzheimer’s disease.
Microbiota and the brain: differences between the sexes
The research, published in the journal Science on January 13, 2023, also highlighted that the protective effects of the microbiota differ according to gender. While its modification via antibiotics was more beneficial in male mice carrying the APOE3 variant than those with the high-risk APOE4 variant, the treatment had no significant effect on neurodegeneration in females.
“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 stimuli”explained Dr. Holtzman. “So it’s not terribly surprising that when we manipulated the microbiome, we found a gender difference in response, although it’s hard to say exactly what this means for men and women living with the condition. Alzheimer’s disease and related disorders”.
Altering the microbiome to protect the brain
According to the researchers, three specific short-chain fatty acids — rare in mice with gut microbiomes altered by antibiotic treatment and undetectable in rodents without gut microbiomes — appeared to trigger neurodegeneration. They activated immune cells in the blood, which in turn activated immune cells in the brain to damage brain tissue.
“When middle-aged mice with no microbiome were fed the three short-chain fatty acids, their brain immune cells became more responsive, and their brains showed more signs of tau-related damage”explain the authors.
This discovery could lead to the development of treatments against Alzheimer’s disease. “What’s exciting is that manipulating the gut microbiota could be a way to have an effect on the brain without putting anything directly into the brain”rejoices Professor David Holtzman.