The Gut Microbiome and Brain Health
Bacteroides, Bifidobacteirum, Faecalibacterium, Ruminococcus– these are the names of some of the 100 trillion bacteria who are living and working in your gut. These microscopic critters, collectively known as the microbiome, help our body to digest food, process nutrients, make vitamins B and K, and produce immune molecules that fight inflammation and heal wounds. The most impressive role of this busy workforce may be, surprisingly, in the brain.
While the digestive tract and the brain feel far apart in your body, they are actually connected via a 24/7 direct line of biochemical communication, set up by special nerve cells and immune pathways. It’s called the gut-brain axis. Down in the gut, bacteria make neuroactive compounds, including 90% of our neurotransmitter serotonin, which regulate our emotions. In turn, the brain can send signals to the gastrointestinal system, for example, to stimulate or suppress digestion.
A healthy microbiome is a diverse microbiome. A rich community of varied species protects against one dominating and causing trouble in our gut and beyond. Shifts in the composition or function of the microbiome have been implicated in inflammatory bowel disease, autism, and blood cancers. Researchers are now discovering that a disrupted microbiome, in certain contexts, may contribute to Alzheimer’s disease and related conditions that cause dementia.
“The role of the microbiome in health and disease is an exciting area at the forefront of science, but the field is in its infancy,” says Dr. William Depaolo, a UW Medicine gastroenterologist and director of the UW Center for Microbiome Sciences & Therapeutics. “I think about the microbiome like a biologist thinks about the deep sea. We know there’s something down there, and we finally have the technology to help us see who’s actually there and how they are influencing our bodies and brains.”
Advanced tools of ‘multi-omics’ technology allow researchers to identify species in the human gut and analyze the bacterial genes and protein products that affect our brain health. Recently, NIH-funded research conducted at the Wisconsin Alzheimer’s Disease Research Center examined the microbiomes of people with Alzheimer’s disease. The team, led by Barbara Bendlin, PhD, and Frederico Rey, PhD, collected stool samples from participants and used genetic sequencing technology to identify the bacterial species present, and assess the microbial richness and diversity.
They found that people living with Alzheimer’s disease have a unique, and less diverse, community of gut microorganisms than their healthy counterparts. Specifically, the microbiomes of people with Alzheimer’s disease showed specific increases and decreases in common gut bacteria, especially decreases in Bifidobacterium, an important inhabitant of the healthy human gut. They also linked the abnormal levels of these microbe families to the amount of Alzheimer’s disease proteins in the participants’ spinal fluid.
The authors suggest that the unique microbiome of people with Alzheimer’s disease could be contributing to the progression of their disease, through the gut-brain axis. Such findings in human and mouse models point to the tantalizing prospect that restoring healthy gut bacterial composition could prevent or slow the development of Alzheimer’s in at-risk populations.
The microbiome field is optimistic about this therapeutic approach. “We know that diet can profoundly affect the microbiome,” says Dr. Depaolo, whose UW lab studies the influence of the microbiome on health and many diseases.“We know that bacterial cells are more sensitive to drugs than human cells, so we can target them without hitting human cells. So, there is a lot of excitement here in using multi-omics technology to identify microorganisms that we could promote in specific people or find strategies to manipulate the microbiome.”
But, as with all quests to create precise, targeted therapeutics for Alzheimer’s disease, it all comes down to genetics.
It’s in the Genes
The composition of every person’s microbiome is unique as a fingerprint, shaped by early life, diet, and environmental exposures over time. But it is our genetic background that influences how bacteria actually function in the human gut. What’s more, bacteria themselves express different genes and make proteins that may predispose certain individuals to gut inflammation or other conditions.
In one striking example, recent NIH-funded research conducted by researchers in the NeuroGenetics Research Consortium suggested that Corynebacterium helps cause Parkinson’s disease, but only in people with a specific genotype.
