Brain Health Basics
For most of medical history, the brain was considered sovereign — sealed off, self-contained, running things from the top down. That picture has changed dramatically. Your gut, it turns out, has a great deal to say.
There are more microbial cells in your gut than there are human cells in your entire body. These bacteria, fungi, and other microorganisms — collectively known as the microbiome — were long assumed to be passive residents, quietly helping to digest food and little else. Over the past two decades, that assumption has been overturned entirely. The microbiome is now understood to be a dynamic, metabolically active community that communicates continuously with the brain, influencing mood, cognition, inflammation, and neurological health in ways scientists are only beginning to map.
The connection between gut and brain is not metaphorical. It is anatomical, biochemical, and bidirectional. The gut contains its own extensive nervous system — the enteric nervous system, sometimes called the "second brain" — comprising around 500 million neurons embedded in the gastrointestinal tract. This system connects to the central nervous system via the vagus nerve, a direct physical channel running from the brainstem to the abdomen, through which signals travel in both directions.
But the vagus nerve is only one of several routes through which gut and brain communicate:
Metabolites
Gut bacteria produce small molecules that enter the bloodstream and can cross into the brain, directly influencing neuronal function.
Vagus nerve
A direct neural highway carrying signals between the enteric nervous system and the brainstem — in both directions.
Immune signals
The gut hosts around 70% of the body's immune cells. Microbial imbalance can trigger systemic inflammation that reaches the brain.
The metabolite channel is particularly significant for brain health. Gut bacteria are prolific chemical factories, producing hundreds of compounds that the human body cannot synthesise on its own, including several that neurons depend on for energy metabolism, repair, and protection against oxidative stress. When the microbial community is healthy and diverse, this supply is steady. When it is disrupted — through poor diet, antibiotic use, chronic stress, or ageing — the supply falters, and the consequences for neurological health can be measurable.
The relationship between microbiome disruption and Alzheimer's disease is an active and rapidly developing area of research. Studies have found consistent differences in the gut microbial composition of Alzheimer's patients compared to healthy controls. AD patients had reduced gut diversity and lower levels of anti-inflammatory and neuroprotective bacteria. Whether these differences are a cause or a consequence of the disease — or both — remains a subject of investigation, but the evidence for a meaningful bidirectional relationship is growing.
What is clear is that the gut represents an accessible point of intervention in a disease whose primary site — the brain — is extraordinarily difficult to reach pharmacologically. Influencing the brain's chemical environment via the gut sidesteps the blood-brain barrier and offers a route that is inherently safer and more practical than most existing therapeutic approaches.
How OneCarbon uses this
Our probiotic, 1C-01, was developed specifically to exploit the gut-brain metabolite pathway. Using directed evolution, we engineered a bacterial strain that continuously produces the key metabolites of the one-carbon pathway in the gut — molecules that neurons use to maintain energy and resilience under stress. In our pilot study, 1C-01 successfully colonised the gut and raised one-carbon metabolite levels in the blood, demonstrating that the delivery mechanism works. We are now investigating its clinical efficacy in a larger randomised controlled trial. 1C-01 has not been proven to prevent or treat Alzheimer's disease.